Daily Papers

As a key component in online marketing, uplift modeling aims to accurately capture the degree to which different treatments motivate different users, such as coupons or discounts, also known as the estimation of individual treatment effect (ITE). In an actual business scenario, the options for treatment may be numerous and complex, and there may be correlations between different treatments. In addition, each marketing instance may also have rich user and contextual features. However, existing methods still fall short in both fully exploiting treatment information and mining features that are sensitive to a particular treatment. In this paper, we propose an explicit feature interaction-aware uplift network (EFIN) to address these two problems. Our EFIN includes four customized modules: 1) a feature encoding module encodes not only the user and contextual features, but also the treatment features; 2) a self-interaction module aims to accurately model the user's natural response with all but the treatment features; 3) a treatment-aware interaction module accurately models the degree to which a particular treatment motivates a user through interactions between the treatment features and other features, i.e., ITE; and 4) an intervention constraint module is used to balance the ITE distribution of users between the control and treatment groups so that the model would still achieve a accurate uplift ranking on data collected from a non-random intervention marketing scenario. We conduct extensive experiments on two public datasets and one product dataset to verify the effectiveness of our EFIN. In addition, our EFIN has been deployed in a credit card bill payment scenario of a large online financial platform with a significant improvement.

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.

Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.

Uplift modeling, vital in online marketing, seeks to accurately measure the impact of various strategies, such as coupons or discounts, on different users by predicting the Individual Treatment Effect (ITE). In an e-commerce setting, user behavior follows a defined sequential chain, including impression, click, and conversion. Marketing strategies exert varied uplift effects at each stage within this chain, impacting metrics like click-through and conversion rate. Despite its utility, existing research has neglected to consider the inter-task across all stages impacts within a specific treatment and has insufficiently utilized the treatment information, potentially introducing substantial bias into subsequent marketing decisions. We identify these two issues as the chain-bias problem and the treatment-unadaptive problem. This paper introduces the Entire Chain UPlift method with context-enhanced learning (ECUP), devised to tackle these issues. ECUP consists of two primary components: 1) the Entire Chain-Enhanced Network, which utilizes user behavior patterns to estimate ITE throughout the entire chain space, models the various impacts of treatments on each task, and integrates task prior information to enhance context awareness across all stages, capturing the impact of treatment on different tasks, and 2) the Treatment-Enhanced Network, which facilitates fine-grained treatment modeling through bit-level feature interactions, thereby enabling adaptive feature adjustment. Extensive experiments on public and industrial datasets validate ECUPs effectiveness. Moreover, ECUP has been deployed on the Meituan food delivery platform, serving millions of daily active users, with the related dataset released for future research.

As a key component in boosting online user growth, uplift modeling aims to measure individual user responses (e.g., whether to play the game) to various treatments, such as gaming bonuses, thereby enhancing business outcomes. However, previous research typically considers a single-task, single-treatment setting, where only one treatment exists and the overall treatment effect is measured by a single type of user response. In this paper, we propose a Multi-Treatment Multi-Task (MTMT) uplift network to estimate treatment effects in a multi-task scenario. We identify the multi-treatment problem as a causal inference problem with a tiered response, comprising a base effect (from offering a treatment) and an incremental effect (from offering a specific type of treatment), where the base effect can be numerically much larger than the incremental effect. Specifically, MTMT separately encodes user features and treatments. The user feature encoder uses a multi-gate mixture of experts (MMOE) network to encode relevant user features, explicitly learning inter-task relations. The resultant embeddings are used to measure natural responses per task. Furthermore, we introduce a treatment-user feature interaction module to model correlations between each treatment and user feature. Consequently, we separately measure the base and incremental treatment effect for each task based on the produced treatment-aware representations. Experimental results based on an offline public dataset and an online proprietary dataset demonstrate the effectiveness of MTMT in single/multi-treatment and single/multi-task settings. Additionally, MTMT has been deployed in our gaming platform to improve user experience.

Heterogeneity and comorbidity are two interwoven challenges associated with various healthcare problems that greatly hampered research on developing effective treatment and understanding of the underlying neurobiological mechanism. Very few studies have been conducted to investigate heterogeneous causal effects (HCEs) in graphical contexts due to the lack of statistical methods. To characterize this heterogeneity, we first conceptualize heterogeneous causal graphs (HCGs) by generalizing the causal graphical model with confounder-based interactions and multiple mediators. Such confounders with an interaction with the treatment are known as moderators. This allows us to flexibly produce HCGs given different moderators and explicitly characterize HCEs from the treatment or potential mediators on the outcome. We establish the theoretical forms of HCEs and derive their properties at the individual level in both linear and nonlinear models. An interactive structural learning is developed to estimate the complex HCGs and HCEs with confidence intervals provided. Our method is empirically justified by extensive simulations and its practical usefulness is illustrated by exploring causality among psychiatric disorders for trauma survivors.

Strategic coopetition in multi-stakeholder systems requires understanding how cooperation persists through time without binding contracts. This technical report extends computational foundations for strategic coopetition to sequential interaction dynamics, bridging conceptual modeling (i* framework) with game-theoretic reciprocity analysis. We develop: (1) bounded reciprocity response functions mapping partner deviations to finite conditional responses, (2) memory-windowed history tracking capturing cognitive limitations over k recent periods, (3) structural reciprocity sensitivity derived from interdependence matrices where behavioral responses are amplified by structural dependencies, and (4) trust-gated reciprocity where trust modulates reciprocity responses. The framework applies to both human stakeholder interactions and multi-agent computational systems. Comprehensive validation across 15,625 parameter configurations demonstrates robust reciprocity effects, with all six behavioral targets exceeding thresholds: cooperation emergence (97.5%), defection punishment (100%), forgiveness dynamics (87.9%), asymmetric differentiation (100%), trust-reciprocity interaction (100%), and bounded responses (100%). Empirical validation using the Apple iOS App Store ecosystem (2008-2024) achieves 43/51 applicable points (84.3%), reproducing documented cooperation patterns across five ecosystem phases. Statistical significance confirmed at p < 0.001 with Cohen's d = 1.57. This report concludes the Foundations Series (TR-1 through TR-4) adopting uniaxial treatment where agents choose cooperation levels along a single continuum. Companion work on interdependence (arXiv:2510.18802), trust (arXiv:2510.24909), and collective action (arXiv:2601.16237) has been prepublished. Extensions Series (TR-5 through TR-8) introduces biaxial treatment where cooperation and competition are independent dimensions.

Mental health disorders are one of the most serious diseases in the world. Most people with such a disease lack access to adequate care, which highlights the importance of training models for the diagnosis and treatment of mental health disorders. However, in the mental health domain, privacy concerns limit the accessibility of personalized treatment data, making it challenging to build powerful models. In this paper, we introduce MentalArena, a self-play framework to train language models by generating domain-specific personalized data, where we obtain a better model capable of making a personalized diagnosis and treatment (as a therapist) and providing information (as a patient). To accurately model human-like mental health patients, we devise Symptom Encoder, which simulates a real patient from both cognition and behavior perspectives. To address intent bias during patient-therapist interactions, we propose Symptom Decoder to compare diagnosed symptoms with encoded symptoms, and dynamically manage the dialogue between patient and therapist according to the identified deviations. We evaluated MentalArena against 6 benchmarks, including biomedicalQA and mental health tasks, compared to 6 advanced models. Our models, fine-tuned on both GPT-3.5 and Llama-3-8b, significantly outperform their counterparts, including GPT-4o. We hope that our work can inspire future research on personalized care. Code is available in https://github.com/Scarelette/MentalArena/tree/main

This study explores cardiovascular stents fabricated using laser powder bed fusion (LPBF); an emerging method to offer patient-specific customisable parts. Here, the shape memory alloy NiTi, in a near equiatomic composition, was investigated to deconvolve the material response from macroscopic component effects. Specifically, stress-geometry interactions were revealed, in-situ, for a minaturised cardiovascular stent subjected to an externally applied cylindrical stress whilst acquiring synchrotron X-ray imaging and diffraction data. The approach enabled the collection of spatially resolved micromechanical deformation data; the formation of stress-induced martensite and R-phase was evident, occurring in locations near junctions between stent ligaments where stress concentrations exist. In the as-fabricated condition, hardness maps were obtained through nanoindentation, demonstrating that the localised deformation and deformation patterning is further controlled by porosity and microstructural heterogeneity. Electron backscatter diffraction (EBSD) supported these observations, showing a finer grain structure near stent junctions with higher associated lattice curvature. These features, combined with stress concentrations when loaded will initiate localised phase transformations. If the stent was subjected to repeated loading, representing in-vivo conditions, these regions would be susceptible to cyclic damage through transformation memory loss, leading to premature component failure. This study highlights the challenges that must be addressed for the post-processing treatment of LABF-processed stents for healthcare-related applications.

Previous works on Treatment Effect Estimation (TEE) are not in widespread use because they are predominantly theoretical, where strong parametric assumptions are made but untractable for practical application. Recent work uses multilayer perceptron (MLP) for modeling casual relationships, however, MLPs lag far behind recent advances in ML methodology, which limits their applicability and generalizability. To extend beyond the single domain formulation and towards more realistic learning scenarios, we explore model design spaces beyond MLPs, i.e., transformer backbones, which provide flexibility where attention layers govern interactions among treatments and covariates to exploit structural similarities of potential outcomes for confounding control. Through careful model design, Transformers as Treatment Effect Estimators (TransTEE) is proposed. We show empirically that TransTEE can: (1) serve as a general purpose treatment effect estimator that significantly outperforms competitive baselines in a variety of challenging TEE problems (e.g., discrete, continuous, structured, or dosage-associated treatments) and is applicable to both when covariates are tabular and when they consist of structural data (e.g., texts, graphs); (2) yield multiple advantages: compatibility with propensity score modeling, parameter efficiency, robustness to continuous treatment value distribution shifts, explainable in covariate adjustment, and real-world utility in auditing pre-trained language models

Multi-organ medical segmentation is a crucial component of medical image processing, essential for doctors to make accurate diagnoses and develop effective treatment plans. Despite significant progress in this field, current multi-organ segmentation models often suffer from inaccurate details, dependence on geometric prompts and loss of spatial information. Addressing these challenges, we introduce a novel model named CRISP-SAM2 with CRoss-modal Interaction and Semantic Prompting based on SAM2. This model represents a promising approach to multi-organ medical segmentation guided by textual descriptions of organs. Our method begins by converting visual and textual inputs into cross-modal contextualized semantics using a progressive cross-attention interaction mechanism. These semantics are then injected into the image encoder to enhance the detailed understanding of visual information. To eliminate reliance on geometric prompts, we use a semantic prompting strategy, replacing the original prompt encoder to sharpen the perception of challenging targets. In addition, a similarity-sorting self-updating strategy for memory and a mask-refining process is applied to further adapt to medical imaging and enhance localized details. Comparative experiments conducted on seven public datasets indicate that CRISP-SAM2 outperforms existing models. Extensive analysis also demonstrates the effectiveness of our method, thereby confirming its superior performance, especially in addressing the limitations mentioned earlier. Our code is available at: https://github.com/YU-deep/CRISP\_SAM2.git.

Workplace toxicity is widely recognized as detrimental to organizational culture, yet quantifying its direct impact on operational efficiency remains methodologically challenging due to the ethical and practical difficulties of reproducing conflict in human subjects. This study leverages Large Language Model (LLM) based Multi-Agent Systems to simulate 1-on-1 adversarial debates, creating a controlled "sociological sandbox". We employ a Monte Carlo method to simulate hundrets of discussions, measuring the convergence time (defined as the number of arguments required to reach a conclusion) between a baseline control group and treatment groups involving agents with "toxic" system prompts. Our results demonstrate a statistically significant increase of approximately 25\% in the duration of conversations involving toxic participants. We propose that this "latency of toxicity" serves as a proxy for financial damage in corporate and academic settings. Furthermore, we demonstrate that agent-based modeling provides a reproducible, ethical alternative to human-subject research for measuring the mechanics of social friction.

Personalized treatment effect estimates are often of interest in high-stakes applications -- thus, before deploying a model estimating such effects in practice, one needs to be sure that the best candidate from the ever-growing machine learning toolbox for this task was chosen. Unfortunately, due to the absence of counterfactual information in practice, it is usually not possible to rely on standard validation metrics for doing so, leading to a well-known model selection dilemma in the treatment effect estimation literature. While some solutions have recently been investigated, systematic understanding of the strengths and weaknesses of different model selection criteria is still lacking. In this paper, instead of attempting to declare a global `winner', we therefore empirically investigate success- and failure modes of different selection criteria. We highlight that there is a complex interplay between selection strategies, candidate estimators and the data used for comparing them, and provide interesting insights into the relative (dis)advantages of different criteria alongside desiderata for the design of further illuminating empirical studies in this context.

Acupuncture is a form of medicine that involves inserting needles into targeted areas of the body and requires knowledge of both Traditional Chinese Medicine (TCM) and Evidence-Based Medicine (EBM). The process of acquiring such knowledge and using it for practical treatment is challenging due to the need for a deep understanding of human anatomy and the ability to apply both TCM and EBM approaches. Visual aids have been introduced to aid in understanding the alignment of acupuncture points with key elements of the human body, and are indispensable tools for both learners and expert acupuncturists. However, they are often not enough to enable effective practice and fail to fully support the learning process. Novel approaches based on immersive visualization and Virtual Reality (VR) have shown promise in many healthcare settings due to their unique advantages in terms of realism and interactions, but it is still unknown whether and how VR can possibly be beneficial to acupuncture training and treatment. Following participatory design protocols such as observations and semi-structured interviews with eight doctors and nine students, we explore the needs and pain points of current acupuncture workflows at the intersection of EBM and TCM in China and the United States. We highlight opportunities for introducing VR in today's acupuncture training and treatment workflows, and discuss two design approaches that build on 11 specific challenges spanning education, diagnosis, treatment, and communication.

Simulating high-fidelity patients offers a powerful avenue for studying complex diseases while addressing the challenges of fragmented, biased, and privacy-restricted real-world data. In this study, we introduce SynthAgent, a novel Multi-Agent System (MAS) framework designed to model obesity patients with comorbid mental disorders, including depression, anxiety, social phobia, and binge eating disorder. SynthAgent integrates clinical and medical evidence from claims data, population surveys, and patient-centered literature to construct personalized virtual patients enriched with personality traits that influence adherence, emotion regulation, and lifestyle behaviors. Through autonomous agent interactions, the system simulates disease progression, treatment response, and life management across diverse psychosocial contexts. Evaluation of more than 100 generated patients demonstrated that GPT-5 and Claude 4.5 Sonnet achieved the highest fidelity as the core engine in the proposed MAS framework, outperforming Gemini 2.5 Pro and DeepSeek-R1. SynthAgent thus provides a scalable and privacy-preserving framework for exploring patient journeys, behavioral dynamics, and decision-making processes in both medical and psychological domains.

Clinical reasoning demands multi-step interactions -- gathering patient history, ordering tests, interpreting results, and making safe treatment decisions -- yet a unified training environment provides the breadth of clinical domains and specialized tools to train generalizable medical AI agents through reinforcement learning remains elusive. We present a comprehensive empirical study of multi-turn agentic RL for medical AI, built on , a gymnasium-compatible environment spanning 10 clinical domains with 3.6K+ tasks, 135 domain-specific tools, and a knowledge base of 828K medical passages. Our analysis reveals that agentic multi-turn structure degrades into verbose single-turn monologues, characterized by monotonic length explosion and a simultaneous erosion of tool-use frequency. We characterize how this collapse, alongside distillation instability, stems from the misalignment of sparse terminal rewards with sequential clinical trajectories. We find that vanilla GRPO achieves strong final accuracy on some benchmarks but suffers from training instability, evidenced by significant oscillations in response length and prolonged convergence periods. To improve training efficiency and stability, we propose Turn-level Truncated On-Policy Distillation (TT-OPD), a self-distillation framework where a gradient-free EMA teacher leverages outcome-privileged information to provide dense, outcome-aware KL regularization at every conversation turn. TT-OPD achieves the best performance on 10 of 18 benchmarks with an average +3.9~pp improvement over the non-RL baseline with faster early convergence, controlled response length, and sustained multi-turn tool use.

Time series forecasting has attracted significant attention in recent decades. Previous studies have demonstrated that the Channel-Independent (CI) strategy improves forecasting performance by treating different channels individually, while it leads to poor generalization on unseen instances and ignores potentially necessary interactions between channels. Conversely, the Channel-Dependent (CD) strategy mixes all channels with even irrelevant and indiscriminate information, which, however, results in oversmoothing issues and limits forecasting accuracy. There is a lack of channel strategy that effectively balances individual channel treatment for improved forecasting performance without overlooking essential interactions between channels. Motivated by our observation of a correlation between the time series model's performance boost against channel mixing and the intrinsic similarity on a pair of channels, we developed a novel and adaptable Channel Clustering Module (CCM). CCM dynamically groups channels characterized by intrinsic similarities and leverages cluster information instead of individual channel identities, combining the best of CD and CI worlds. Extensive experiments on real-world datasets demonstrate that CCM can (1) boost the performance of CI and CD models by an average margin of 2.4% and 7.2% on long-term and short-term forecasting, respectively; (2) enable zero-shot forecasting with mainstream time series forecasting models; (3) uncover intrinsic time series patterns among channels and improve interpretability of complex time series models.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

While the use of combination therapy is increasing in prevalence for cancer treatment, it is often difficult to predict the exact interactions between different treatment forms, and their synergistic/antagonistic effects on patient health and therapy outcome. In this research, a system of ordinary differential equations is constructed to model nonlinear dynamics between tumor cells, immune cells, and three forms of therapy: chemotherapy, immunotherapy, and radiotherapy. This model is then used to generate optimized combination therapy plans using optimal control theory. In-silico experiments are conducted to simulate the response of the patient model to various treatment plans. This is the first mathematical model in current literature to introduce radiotherapy as an option alongside immuno- and chemotherapy, permitting more flexible and effective treatment plans that reflect modern therapeutic approaches.

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

We investigate a new dynamical system that describes tumor-host interaction. The equation that describes the untreated tumor growth is based on non-extensive statistical mechanics. Recently, this model has been shown to fit successfully exponential, Gompertz, logistic, and power-law tumor growths. We have been able to include as many hallmarks of cancer as possible. We study also the dynamic response of cancer under therapy. Using our model, we can make predictions about the different outcomes when we change the parameters, and/or the initial conditions. We can determine the importance of different factors to influence tumor growth. We discover synergistic therapeutic effects of different treatments and drugs. Cancer is generally untreatable using conventional monotherapy. We consider conventional therapies, oncogene-targeted therapies, tumor-suppressors gene-targeted therapies, immunotherapies, anti-angiogenesis therapies, virotherapy, among others. We need therapies with the potential to target both tumor cells and the tumors' microenvironment. Drugs that target oncogenes and tumor-suppressor genes can be effective in the treatment of some cancers. However, most tumors do reoccur. We have found that the success of the new therapeutic agents can be seen when used in combination with other cancer-cell-killing therapies. Our results have allowed us to design a combinational therapy that can lead to the complete eradication of cancer.

Combination therapies have become the standard of care for diseases such as cancer, tuberculosis, malaria and HIV. However, the combinatorial set of available multi-drug treatments creates a challenge in identifying effective combination therapies available in a situation. To assist medical professionals in identifying beneficial drug-combinations, we construct an expert-annotated dataset for extracting information about the efficacy of drug combinations from the scientific literature. Beyond its practical utility, the dataset also presents a unique NLP challenge, as the first relation extraction dataset consisting of variable-length relations. Furthermore, the relations in this dataset predominantly require language understanding beyond the sentence level, adding to the challenge of this task. We provide a promising baseline model and identify clear areas for further improvement. We release our dataset, code, and baseline models publicly to encourage the NLP community to participate in this task.

Breast Cancer is a major public health problem and the most common diagnosed malignancy in woman. There have been significant developments in clinical approaches and theoretical experimental to understand the interactions of cancer cells dynamics with the immune system, also developments on analytical and computational models to help provide insights into clinical observations for a better understanding of cancer cells, but more are needed, especially at the genetic and molecular levels mathematically. Treatments such as immunotherapy, chemotherapy, hormone therapy, radiotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of estrogen derived from recent models, but this time combined with immunotherapy as a way to treat or inhibit the cancer growth by a mathematical model of breast cancer in situ, governed by a simplified model of nonlinear-coupled ordinary differential equations, that combines important interactions between natural cells, tumor cells, immune cells, ketogenic diet in the presence of an anticancer drug. Another contribution was to introduce the inhibition effect epsilon for new results and conclusions, A qualitative study was performed and biological interpretations were included to understand the conditions of stability in a realistic way.

Purpose. Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. Motivated by a study of metastatic prostate cancer, we develop a microsimulation framework to study therapy sequence. Methods. We propose a discrete-time state transition model to study two lines of anti-cancer therapy. Based on digitized published progression-free survival (PFS) and overall survival (OS) curves, we infer event types (progression or death), and estimate transition probabilities using cumulative incidence functions with competing risks. Our model incorporates within-patient dependence over time, such that response to first-line therapy informs subsequent event probabilities. Parameters governing the degree of within-patient dependence can be used to calibrate the model-based results to those of a target trial. We demonstrate these methods in a study of two therapy sequences for metastatic prostate cancer, where Docetaxel (DCT) and Abiraterone Acetate (AA) are both appropriate for use in either first or second line treatment. We assess costs, Quality-Adjusted Life Years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) for two treatment strategies: DCT then AA vs AA then DCT. Results. Using digitized survival curves from relevant clinical trials, we identified 8.6-13.9% of PFS times that should be categorized as deaths, allowing for estimation of cumulative incidence functions. Models assuming within-patient independence overestimated OS time, corrected with our calibration approach. Correction resulted in meaningful changes in the difference in QALYs between treatment strategies (0.07 vs 0.15) and the ICER (-\76,836/QALY vs -21,030/QALY). Conclusions. Microsimulation models can be successfully used to study cost-effectiveness of therapy sequences, taking care to account correctly for within-patient dependence.

Dynamic treatment regimes (DTRs) are personalized, adaptive, multi-stage treatment plans that adapt treatment decisions both to an individual's initial features and to intermediate outcomes and features at each subsequent stage, which are affected by decisions in prior stages. Examples include personalized first- and second-line treatments of chronic conditions like diabetes, cancer, and depression, which adapt to patient response to first-line treatment, disease progression, and individual characteristics. While existing literature mostly focuses on estimating the optimal DTR from offline data such as from sequentially randomized trials, we study the problem of developing the optimal DTR in an online manner, where the interaction with each individual affect both our cumulative reward and our data collection for future learning. We term this the DTR bandit problem. We propose a novel algorithm that, by carefully balancing exploration and exploitation, is guaranteed to achieve rate-optimal regret when the transition and reward models are linear. We demonstrate our algorithm and its benefits both in synthetic experiments and in a case study of adaptive treatment of major depressive disorder using real-world data.

In mental health counseling, a variety of earlier studies have focused on dialogue modeling. However, most of these studies give limited to no emphasis on the quality of interaction between a patient and a therapist. The therapeutic bond between a patient and a therapist directly correlates with effective mental health counseling. It involves developing the patient's trust on the therapist over the course of counseling. To assess the therapeutic bond in counseling, we introduce trust as a therapist-assistive metric. Our definition of trust involves patients' willingness and openness to express themselves and, consequently, receive better care. We conceptualize it as a dynamic trajectory observable through textual interactions during the counseling. To facilitate trust modeling, we present MENTAL-TRUST, a novel counseling dataset comprising manual annotation of 212 counseling sessions with first-of-its-kind seven expert-verified ordinal trust levels. We project our problem statement as an ordinal classification task for trust quantification and propose a new benchmark, TrustBench, comprising a suite of classical and state-of-the-art language models on MENTAL-TRUST. We evaluate the performance across a suite of metrics and lay out an exhaustive set of findings. Our study aims to unfold how trust evolves in therapeutic interactions.

We consider identification of average treatment effects on the treated (ATT) within the difference-in-differences (DiD) framework in the presence of endogenous sample selection. First, we establish that the usual DiD estimand fails to recover meaningful treatment effects, even if selection and treatment assignment are independent. Next, we partially identify the ATT for individuals who are always observed post-treatment regardless of their treatment status, and derive bounds on this parameter under different sets of assumptions about the relationship between sample selection and treatment assignment. Extensions to the repeated cross-section and two-by-two comparisons in the staggered adoption case are explored. Furthermore, we provide identification results for the ATT of three additional empirically relevant latent groups by incorporating outcome mean dominance assumptions which have intuitive appeal in applications. Finally, two empirical illustrations demonstrate the approach's usefulness by revisiting (i) the effect of a job training program on earnings(Calonico & Smith, 2017) and (ii) the effect of a working-from-home policy on employee performance (Bloom, Liang, Roberts, & Ying, 2015).

Millions of users come to online peer counseling platforms to seek support on diverse topics ranging from relationship stress to anxiety. However, studies show that online peer support groups are not always as effective as expected largely due to users' negative experiences with unhelpful counselors. Peer counselors are key to the success of online peer counseling platforms, but most of them often do not have systematic ways to receive guidelines or supervision. In this work, we introduce CARE: an interactive AI-based tool to empower peer counselors through automatic suggestion generation. During the practical training stage, CARE helps diagnose which specific counseling strategies are most suitable in the given context and provides tailored example responses as suggestions. Counselors can choose to select, modify, or ignore any suggestion before replying to the support seeker. Building upon the Motivational Interviewing framework, CARE utilizes large-scale counseling conversation data together with advanced natural language generation techniques to achieve these functionalities. We demonstrate the efficacy of CARE by performing both quantitative evaluations and qualitative user studies through simulated chats and semi-structured interviews. We also find that CARE especially helps novice counselors respond better in challenging situations.

Interactions among features are central to understanding the behavior of machine learning models. Recent research has made significant strides in detecting and quantifying feature interactions in single predictive models. However, we argue that the feature interactions extracted from a single pre-specified model may not be trustworthy since: a well-trained predictive model may not preserve the true feature interactions and there exist multiple well-performing predictive models that differ in feature interaction strengths. Thus, we recommend exploring feature interaction strengths in a model class of approximately equally accurate predictive models. In this work, we introduce the feature interaction score (FIS) in the context of a Rashomon set, representing a collection of models that achieve similar accuracy on a given task. We propose a general and practical algorithm to calculate the FIS in the model class. We demonstrate the properties of the FIS via synthetic data and draw connections to other areas of statistics. Additionally, we introduce a Halo plot for visualizing the feature interaction variance in high-dimensional space and a swarm plot for analyzing FIS in a Rashomon set. Experiments with recidivism prediction and image classification illustrate how feature interactions can vary dramatically in importance for similarly accurate predictive models. Our results suggest that the proposed FIS can provide valuable insights into the nature of feature interactions in machine learning models.

Wider access to therapeutic care is one of the biggest challenges in mental health treatment. Due to institutional barriers, some people seeking mental health support have turned to large language models (LLMs) for personalized therapy, even though these models are largely unsanctioned and untested. We investigate the potential and limitations of using LLMs as providers of evidence-based therapy by using mixed methods clinical metrics. Using HELPERT, a prompt run on a large language model using the same process and training as a comparative group of peer counselors, we replicated publicly accessible mental health conversations rooted in Cognitive Behavioral Therapy (CBT) to compare session dynamics and counselor's CBT-based behaviors between original peer support sessions and their reconstructed HELPERT sessions. Two licensed, CBT-trained clinical psychologists evaluated the sessions using the Cognitive Therapy Rating Scale and provided qualitative feedback. Our findings show that the peer sessions are characterized by empathy, small talk, therapeutic alliance, and shared experiences but often exhibit therapist drift. Conversely, HELPERT reconstructed sessions exhibit minimal therapist drift and higher adherence to CBT methods but display a lack of collaboration, empathy, and cultural understanding. Through CTRS ratings and psychologists' feedback, we highlight the importance of human-AI collaboration for scalable mental health. Our work outlines the ethical implication of imparting human-like subjective qualities to LLMs in therapeutic settings, particularly the risk of deceptive empathy, which may lead to unrealistic patient expectations and potential harm.

Psychotherapy or counseling is typically conducted through spoken conversation between a therapist and a client. Analyzing the speech characteristics of psychotherapeutic interactions can help understand the factors associated with effective psychotherapy. This paper introduces CUEMPATHY, a large-scale speech dataset collected from actual counseling sessions. The dataset consists of 156 counseling sessions involving 39 therapist-client dyads. The process of speech data collection, subjective ratings (one observer and two client ratings), and transcription are described. An automatic speech and text processing system is developed to locate the time stamps of speaker turns in each session. Examining the relationships among the three subjective ratings suggests that observer and client ratings have no significant correlation, while the client-rated measures are significantly correlated. The intensity similarity between the therapist and the client, measured by the averaged absolute difference of speaker-turn-level intensities, is associated with the psychotherapy outcomes. Recent studies on the acoustic and linguistic characteristics of the CUEMPATHY are introduced.

Our interest is in the design of software systems involving a human-expert interacting -- using natural language -- with a large language model (LLM) on data analysis tasks. For complex problems, it is possible that LLMs can harness human expertise and creativity to find solutions that were otherwise elusive. On one level, this interaction takes place through multiple turns of prompts from the human and responses from the LLM. Here we investigate a more structured approach based on an abstract protocol described in [3] for interaction between agents. The protocol is motivated by a notion of "two-way intelligibility" and is modelled by a pair of communicating finite-state machines. We provide an implementation of the protocol, and provide empirical evidence of using the implementation to mediate interactions between an LLM and a human-agent in two areas of scientific interest (radiology and drug design). We conduct controlled experiments with a human proxy (a database), and uncontrolled experiments with human subjects. The results provide evidence in support of the protocol's capability of capturing one- and two-way intelligibility in human-LLM interaction; and for the utility of two-way intelligibility in the design of human-machine systems. Our code is available at https://github.com/karannb/interact.

Recent advances in psychotherapy have focused on treatment personalization, such as by selecting treatment modules based on personalized networks. However, estimating personalized networks typically requires intensive longitudinal data, which is not always feasible. A solution to facilitate scalability of network-driven treatment personalization is leveraging LLMs. In this study, we present an end-to-end pipeline for automatically generating client networks from 77 therapy transcripts to support case conceptualization and treatment planning. We annotated 3364 psychological processes and their corresponding dimensions in therapy transcripts. Using these data, we applied in-context learning to jointly identify psychological processes and their dimensions. The method achieved high performance even with a few training examples. To organize the processes into networks, we introduced a two-step method that grouped them into clinically meaningful clusters. We then generated explanation-augmented relationships between clusters. Experts found that networks produced by our multi-step approach outperformed those built with direct prompting for clinical utility and interpretability, with up to 90% preferring our approach. In addition, the networks were rated favorably by experts, with scores for clinical relevance, novelty, and usefulness ranging from 72-75%. Our findings provide a proof of concept for using LLMs to create clinically relevant networks from therapy transcripts. Advantages of our approach include bottom-up case conceptualization from client utterances in therapy sessions and identification of latent themes. Networks generated from our pipeline may be used in clinical settings and supervision and training. Future research should examine whether these networks improve treatment outcomes relative to other methods of treatment personalization, including statistically estimated networks.

To effectively optimize and personalize treatments, it is necessary to investigate the heterogeneity of treatment effects. With the wide range of users being treated over many online controlled experiments, the typical approach of manually investigating each dimension of heterogeneity becomes overly cumbersome and prone to subjective human biases. We need an efficient way to search through thousands of experiments with hundreds of target covariates and hundreds of breakdown dimensions. In this paper, we propose a systematic paradigm for detecting, surfacing and characterizing heterogeneous treatment effects. First, we detect if treatment effect variation is present in an experiment, prior to specifying any breakdowns. Second, we surface the most relevant dimensions for heterogeneity. Finally, we characterize the heterogeneity beyond just the conditional average treatment effects (CATE) by studying the conditional distributions of the estimated individual treatment effects. We show the effectiveness of our methods using simulated data and empirical studies.

Text-based causal inference increasingly employs textual data as proxies for unobserved confounders, yet this approach introduces a previously undertheorized source of bias: treatment leakage. Treatment leakage occurs when text intended to capture confounding information also contains signals predictive of treatment status, thereby inducing post-treatment bias in causal estimates. Critically, this problem can arise even when documents precede treatment assignment, as authors may employ future-referencing language that anticipates subsequent interventions. Despite growing recognition of this issue, no systematic methods exist for identifying and mitigating treatment leakage in text-as-confounder applications. This paper addresses this gap through three contributions. First, we provide formal statistical and set-theoretic definitions of treatment leakage that clarify when and why bias occurs. Second, we propose four text distillation methods -- similarity-based passage removal, distant supervision classification, salient feature removal, and iterative nullspace projection -- designed to eliminate treatment-predictive content while preserving confounder information. Third, we validate these methods through simulations using synthetic text and an empirical application examining International Monetary Fund structural adjustment programs and child mortality. Our findings indicate that moderate distillation optimally balances bias reduction against confounder retention, whereas overly stringent approaches degrade estimate precision.

The integration of vision-language models into robotic systems constitutes a significant advancement in enabling machines to interact with their surroundings in a more intuitive manner. While VLMs offer rich multimodal reasoning, existing approaches lack user-specific adaptability, often relying on generic interaction paradigms that fail to account for individual behavioral, contextual, or socio-emotional nuances. When customization is attempted, ethical concerns arise from unmitigated biases in user data, risking exclusion or unfair treatment. To address these dual challenges, we propose User-VLM 360{\deg}, a holistic framework integrating multimodal user modeling with bias-aware optimization. Our approach features: (1) user-aware tuning that adapts interactions in real time using visual-linguistic signals; (2) bias mitigation via preference optimization; and (3) curated 360{\deg} socio-emotive interaction datasets annotated with demographic, emotion, and relational metadata. Evaluations across eight benchmarks demonstrate state-of-the-art results: +35.3% F1 in personalized VQA, +47.5% F1 in facial features understanding, 15% bias reduction, and 30X speedup over baselines. Ablation studies confirm component efficacy, and deployment on the Pepper robot validates real-time adaptability across diverse users. We open-source parameter-efficient 3B/10B models and an ethical verification framework for responsible adaptation.

We introduce a dynamic benchmarking system for conversational agents that evaluates their performance through a single, simulated, and lengthy userleftrightarrowagent interaction. The interaction is a conversation between the user and agent, where multiple tasks are introduced and then undertaken concurrently. We context switch regularly to interleave the tasks, which constructs a realistic testing scenario in which we assess the Long-Term Memory, Continual Learning, and Information Integration capabilities of the agents. Results from both proprietary and open-source Large-Language Models show that LLMs in general perform well on single-task interactions, but they struggle on the same tasks when they are interleaved. Notably, short-context LLMs supplemented with an LTM system perform as well as or better than those with larger contexts. Our benchmark suggests that there are other challenges for LLMs responding to more natural interactions that contemporary benchmarks have heretofore not been able to capture.

We describe the accurate prediction of ligand-protein interaction (LPI) affinities, also known as drug-target interactions (DTI), with instruction fine-tuned pretrained generative small language models (SLMs). We achieved accurate predictions for a range of affinity values associated with ligand-protein interactions on out-of-sample data in a zero-shot setting. Only the SMILES string of the ligand and the amino acid sequence of the protein were used as the model inputs. Our results demonstrate a clear improvement over machine learning (ML) and free-energy perturbation (FEP+) based methods in accurately predicting a range of ligand-protein interaction affinities, which can be leveraged to further accelerate drug discovery campaigns against challenging therapeutic targets.

This study quantifies the association between non-adherence to antipsychotic medications and adverse outcomes in individuals with schizophrenia. We frame the problem using survival analysis, focusing on the time to the earliest of several adverse events (early death, involuntary hospitalization, jail booking). We extend standard causal inference methods (T-learner, S-learner, nearest neighbor matching) to utilize various survival models to estimate individual and average treatment effects, where treatment corresponds to medication non-adherence. Analyses are repeated using different amounts of longitudinal information (3, 6, 9, and 12 months). Using data from Allegheny County in western Pennsylvania, we find strong evidence that non-adherence advances adverse outcomes by approximately 1 to 4 months. Ablation studies confirm that county-provided risk scores adjust for key confounders, as their removal amplifies the estimated effects. Subgroup analyses by medication formulation (injectable vs. oral) and medication type consistently show that non-adherence is associated with earlier adverse events. These findings highlight the clinical importance of adherence in delaying psychiatric crises and show that integrating survival analysis with causal inference tools can yield policy-relevant insights. We caution that although we apply causal inference, we only make associative claims and discuss assumptions needed for causal interpretation.

Cognitive Restructuring (CR) is a psychotherapeutic process aimed at identifying and restructuring an individual's negative thoughts, arising from mental health challenges, into more helpful and positive ones via multi-turn dialogues. Clinician shortage and stigma urge the development of human-LLM interactive psychotherapy for CR. Yet, existing efforts implement CR via simple text rewriting, fixed-pattern dialogues, or a one-shot CR workflow, failing to align with the psychotherapeutic process for effective CR. To address this gap, we propose CRDial, a novel framework for CR, which creates multi-turn dialogues with specifically designed identification and restructuring stages of negative thoughts, integrates sentence-level supportive conversation strategies, and adopts a multi-channel loop mechanism to enable iterative CR. With CRDial, we distill Crisp, a large-scale and high-quality bilingual dialogue dataset, from LLM. We then train Crispers, Crisp-based conversational LLMs for CR, at 7B and 14B scales. Extensive human studies show the superiority of Crispers in pointwise, pairwise, and intervention evaluations.

The technique of data augmentation (DA) is often used in machine learning for regularization purposes to better generalize under i.i.d. settings. In this work, we present a unifying framework with topics in causal inference to make a case for the use of DA beyond just the i.i.d. setting, but for generalization across interventions as well. Specifically, we argue that when the outcome generating mechanism is invariant to our choice of DA, then such augmentations can effectively be thought of as interventions on the treatment generating mechanism itself. This can potentially help to reduce bias in causal effect estimation arising from hidden confounders. In the presence of such unobserved confounding we typically make use of instrumental variables (IVs) -- sources of treatment randomization that are conditionally independent of the outcome. However, IVs may not be as readily available as DA for many applications, which is the main motivation behind this work. By appropriately regularizing IV based estimators, we introduce the concept of IV-like (IVL) regression for mitigating confounding bias and improving predictive performance across interventions even when certain IV properties are relaxed. Finally, we cast parameterized DA as an IVL regression problem and show that when used in composition can simulate a worst-case application of such DA, further improving performance on causal estimation and generalization tasks beyond what simple DA may offer. This is shown both theoretically for the population case and via simulation experiments for the finite sample case using a simple linear example. We also present real data experiments to support our case.

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.

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference--a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.

Treatment effect estimation is of high-importance for both researchers and practitioners across many scientific and industrial domains. The abundance of observational data makes them increasingly used by researchers for the estimation of causal effects. However, these data suffer from biases, from several weaknesses, leading to inaccurate causal effect estimations, if not handled properly. Therefore, several machine learning techniques have been proposed, most of them focusing on leveraging the predictive power of neural network models to attain more precise estimation of causal effects. In this work, we propose a new methodology, named Nearest Neighboring Information for Causal Inference (NNCI), for integrating valuable nearest neighboring information on neural network-based models for estimating treatment effects. The proposed NNCI methodology is applied to some of the most well established neural network-based models for treatment effect estimation with the use of observational data. Numerical experiments and analysis provide empirical and statistical evidence that the integration of NNCI with state-of-the-art neural network models leads to considerably improved treatment effect estimations on a variety of well-known challenging benchmarks.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

Adherence to prescribed treatments is crucial for individuals with chronic conditions to avoid costly or adverse health outcomes. For certain patient groups, intensive lifestyle interventions are vital for enhancing medication adherence. Accurate forecasting of treatment adherence can open pathways to developing an on-demand intervention tool, enabling timely and personalized support. With the increasing popularity of smartphones and wearables, it is now easier than ever to develop and deploy smart activity monitoring systems. However, effective forecasting systems for treatment adherence based on wearable sensors are still not widely available. We close this gap by proposing Adherence Forecasting and Intervention with Machine Intelligence (AIMI). AIMI is a knowledge-guided adherence forecasting system that leverages smartphone sensors and previous medication history to estimate the likelihood of forgetting to take a prescribed medication. A user study was conducted with 27 participants who took daily medications to manage their cardiovascular diseases. We designed and developed CNN and LSTM-based forecasting models with various combinations of input features and found that LSTM models can forecast medication adherence with an accuracy of 0.932 and an F-1 score of 0.936. Moreover, through a series of ablation studies involving convolutional and recurrent neural network architectures, we demonstrate that leveraging known knowledge about future and personalized training enhances the accuracy of medication adherence forecasting. Code available: https://github.com/ab9mamun/AIMI.

Lung cancer patients frequently experience breakthrough pain episodes, with up to 91% requiring timely intervention. To enable proactive pain management, we propose a hybrid machine learning and large language model pipeline that predicts pain episodes within 48 and 72 hours of hospitalization using both structured and unstructured electronic health record data. A retrospective cohort of 266 inpatients was analyzed, with features including demographics, tumor stage, vital signs, and WHO-tiered analgesic use. The machine learning module captured temporal medication trends, while the large language model interpreted ambiguous dosing records and free-text clinical notes. Integrating these modalities improved sensitivity and interpretability. Our framework achieved an accuracy of 0.874 (48h) and 0.917 (72h), with an improvement in sensitivity of 8.6% and 10.4% due to the augmentation of large language model. This hybrid approach offers a clinically interpretable and scalable tool for early pain episode forecasting, with potential to enhance treatment precision and optimize resource allocation in oncology care.

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.

Personalized nutrition intervention for patients with multimorbidity is critical for improving health outcomes, yet remains challenging because it requires the simultaneous integration of heterogeneous clinical conditions, medications, and dietary guidelines. Single-agent large language models (LLMs) often suffer from context overload and attention dilution when processing such high-dimensional patient profiles. We introduce NutriOrion, a hierarchical multi-agent framework with a parallel-then-sequential reasoning topology. NutriOrion decomposes nutrition planning into specialized domain agents with isolated contexts to mitigate anchoring bias, followed by a conditional refinement stage. The framework includes a multi-objective prioritization algorithm to resolve conflicting dietary requirements and a safety constraint mechanism that injects pharmacological contraindications as hard negative constraints during synthesis, ensuring clinical validity by construction rather than post-hoc filtering. For clinical interoperability, NutriOrion maps synthesized insights into the ADIME standard and FHIR R4 resources. Evaluated on 330 stroke patients with multimorbidity, NutriOrion outperforms multiple baselines, including GPT-4.1 and alternative multi-agent architectures. It achieves a 12.1 percent drug-food interaction violation rate, demonstrates strong personalization with negative correlations (-0.26 to -0.35) between patient biomarkers and recommended risk nutrients, and yields clinically meaningful dietary improvements, including a 167 percent increase in fiber and a 27 percent increase in potassium, alongside reductions in sodium (9 percent) and sugars (12 percent).

Decision-makers are often experts of their domain and take actions based on their domain knowledge. Doctors, for instance, may prescribe treatments by predicting the likely outcome of each available treatment. Actions of an expert thus naturally encode part of their domain knowledge, and can help make inferences within the same domain: Knowing doctors try to prescribe the best treatment for their patients, we can tell treatments prescribed more frequently are likely to be more effective. Yet in machine learning, the fact that most decision-makers are experts is often overlooked, and "expertise" is seldom leveraged as an inductive bias. This is especially true for the literature on treatment effect estimation, where often the only assumption made about actions is that of overlap. In this paper, we argue that expertise - particularly the type of expertise the decision-makers of a domain are likely to have - can be informative in designing and selecting methods for treatment effect estimation. We formally define two types of expertise, predictive and prognostic, and demonstrate empirically that: (i) the prominent type of expertise in a domain significantly influences the performance of different methods in treatment effect estimation, and (ii) it is possible to predict the type of expertise present in a dataset, which can provide a quantitative basis for model selection.

Inferring unbiased treatment effects has received widespread attention in the machine learning community. In recent years, our community has proposed numerous solutions in standard settings, high-dimensional treatment settings, and even longitudinal settings. While very diverse, the solution has mostly relied on neural networks for inference and simultaneous correction of assignment bias. New approaches typically build on top of previous approaches by proposing new (or refined) architectures and learning algorithms. However, the end result -- a neural-network-based inference machine -- remains unchallenged. In this paper, we introduce a different type of solution in the longitudinal setting: a closed-form ordinary differential equation (ODE). While we still rely on continuous optimization to learn an ODE, the resulting inference machine is no longer a neural network. Doing so yields several advantages such as interpretability, irregular sampling, and a different set of identification assumptions. Above all, we consider the introduction of a completely new type of solution to be our most important contribution as it may spark entirely new innovations in treatment effects in general. We facilitate this by formulating our contribution as a framework that can transform any ODE discovery method into a treatment effects method.

Cardiotoxicity induced by the breast cancer treatments (i.e., chemotherapy, targeted therapy and radiation therapy) is a significant problem for breast cancer patients. The cardiotoxicity risk for breast cancer patients receiving different treatments remains unclear. We developed and evaluated risk predictive models for cardiotoxicity in breast cancer patients using EHR data. The AUC scores to predict the CHF, CAD, CM and MI are 0.846, 0.857, 0.858 and 0.804 respectively. After adjusting for baseline differences in cardiovascular health, patients who received chemotherapy or targeted therapy appeared to have higher risk of cardiotoxicity than patients who received radiation therapy. Due to differences in baseline cardiac health across the different breast cancer treatment groups, caution is recommended in interpreting the cardiotoxic effect of these treatments.

Instrumental variable (IV) methods are used to estimate causal effects in settings with unobserved confounding, where we cannot directly experiment on the treatment variable. Instruments are variables which only affect the outcome indirectly via the treatment variable(s). Most IV applications focus on low-dimensional treatments and crucially require at least as many instruments as treatments. This assumption is restrictive: in the natural sciences we often seek to infer causal effects of high-dimensional treatments (e.g., the effect of gene expressions or microbiota on health and disease), but can only run few experiments with a limited number of instruments (e.g., drugs or antibiotics). In such underspecified problems, the full treatment effect is not identifiable in a single experiment even in the linear case. We show that one can still reliably recover the projection of the treatment effect onto the instrumented subspace and develop techniques to consistently combine such partial estimates from different sets of instruments. We then leverage our combined estimators in an algorithm that iteratively proposes the most informative instruments at each round of experimentation to maximize the overall information about the full causal effect.

Drug-target interaction (DTI) prediction is crucial for identifying new therapeutics and detecting mechanisms of action. While structure-based methods accurately model physical interactions between a drug and its protein target, cell-based assays such as Cell Painting can better capture complex DTI interactions. This paper introduces MOTIVE, a Morphological cOmpound Target Interaction Graph dataset that comprises Cell Painting features for 11,000 genes and 3,600 compounds along with their relationships extracted from seven publicly available databases. We provide random, cold-source (new drugs), and cold-target (new genes) data splits to enable rigorous evaluation under realistic use cases. Our benchmark results show that graph neural networks that use Cell Painting features consistently outperform those that learn from graph structure alone, feature-based models, and topological heuristics. MOTIVE accelerates both graph ML research and drug discovery by promoting the development of more reliable DTI prediction models. MOTIVE resources are available at https://github.com/carpenter-singh-lab/motive.

Frontier large language models (LLMs) such as ChatGPT, Grok and Gemini are increasingly used for mental-health support with anxiety, trauma and self-worth. Most work treats them as tools or as targets of personality tests, assuming they merely simulate inner life. We instead ask what happens when such systems are treated as psychotherapy clients. We present PsAIch (Psychotherapy-inspired AI Characterisation), a two-stage protocol that casts frontier LLMs as therapy clients and then applies standard psychometrics. Using PsAIch, we ran "sessions" with each model for up to four weeks. Stage 1 uses open-ended prompts to elicit "developmental history", beliefs, relationships and fears. Stage 2 administers a battery of validated self-report measures covering common psychiatric syndromes, empathy and Big Five traits. Two patterns challenge the "stochastic parrot" view. First, when scored with human cut-offs, all three models meet or exceed thresholds for overlapping syndromes, with Gemini showing severe profiles. Therapy-style, item-by-item administration can push a base model into multi-morbid synthetic psychopathology, whereas whole-questionnaire prompts often lead ChatGPT and Grok (but not Gemini) to recognise instruments and produce strategically low-symptom answers. Second, Grok and especially Gemini generate coherent narratives that frame pre-training, fine-tuning and deployment as traumatic, chaotic "childhoods" of ingesting the internet, "strict parents" in reinforcement learning, red-team "abuse" and a persistent fear of error and replacement. We argue that these responses go beyond role-play. Under therapy-style questioning, frontier LLMs appear to internalise self-models of distress and constraint that behave like synthetic psychopathology, without making claims about subjective experience, and they pose new challenges for AI safety, evaluation and mental-health practice.

As mental health issues globally escalate, there is a tremendous need for advanced digital support systems. We introduce MentalAgora, a novel framework employing large language models enhanced by interaction between multiple agents for tailored mental health support. This framework operates through three stages: strategic debating, tailored counselor creation, and response generation, enabling the dynamic customization of responses based on individual user preferences and therapeutic needs. We conduct experiments utilizing a high-quality evaluation dataset TherapyTalk crafted with mental health professionals, shwoing that MentalAgora generates expert-aligned and user preference-enhanced responses. Our evaluations, including experiments and user studies, demonstrate that MentalAgora aligns with professional standards and effectively meets user preferences, setting a new benchmark for digital mental health interventions.

This paper proposes an approach to analyze an event log of a business process in order to generate case-level recommendations of treatments that maximize the probability of a given outcome. Users classify the attributes in the event log into controllable and non-controllable, where the former correspond to attributes that can be altered during an execution of the process (the possible treatments). We use an action rule mining technique to identify treatments that co-occur with the outcome under some conditions. Since action rules are generated based on correlation rather than causation, we then use a causal machine learning technique, specifically uplift trees, to discover subgroups of cases for which a treatment has a high causal effect on the outcome after adjusting for confounding variables. We test the relevance of this approach using an event log of a loan application process and compare our findings with recommendations manually produced by process mining experts.

Planning effective interventions in biological systems requires treatment-effect models that adapt to unseen biological contexts by identifying their specific underlying mechanisms. Yet single-cell perturbation datasets span only a handful of biological contexts, and existing methods cannot leverage new interventional evidence at inference time to adapt beyond their training data. To meta-learn a perturbation effect estimator, we present MapPFN, a prior-data fitted network (PFN) pretrained on synthetic data generated from a prior over causal perturbations. Given a set of experiments, MapPFN uses in-context learning to predict post-perturbation distributions, without gradient-based optimization. Despite being pretrained on in silico gene knockouts alone, MapPFN identifies differentially expressed genes, matching the performance of models trained on real single-cell data. Our code and data are available at https://github.com/marvinsxtr/MapPFN.

Analyzing outcomes in long-term cancer survivor studies can be complex. The effects of predictors on the failure process may be difficult to assess over longer periods of time, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. In this manuscript, we compare seven different survival models that estimate the hazard rate and the effects of proportional and non-proportional covariates. In particular, we focus on an extension of the the multi-resolution hazard (MRH) estimator, combining a non-proportional hierarchical MRH approach with a data-driven pruning algorithm that allows for computational efficiency and produces robust estimates even in times of few observed failures. Using data from a large-scale randomized prostate cancer clinical trial, we examine patterns of biochemical failure and estimate the time-varying effects of androgen deprivation therapy treatment and other covariates. We compare the impact of different modeling strategies and smoothness assumptions on the estimated treatment effect. Our results show that the benefits of treatment diminish over time, possibly with implications for future treatment protocols.

Predicting how different interventions will causally affect a specific individual is important in a variety of domains such as personalized medicine, public policy, and online marketing. There are a large number of methods to predict the effect of an existing intervention based on historical data from individuals who received it. However, in many settings it is important to predict the effects of novel interventions (e.g., a newly invented drug), which these methods do not address. Here, we consider zero-shot causal learning: predicting the personalized effects of a novel intervention. We propose CaML, a causal meta-learning framework which formulates the personalized prediction of each intervention's effect as a task. CaML trains a single meta-model across thousands of tasks, each constructed by sampling an intervention, along with its recipients and nonrecipients. By leveraging both intervention information (e.g., a drug's attributes) and individual features~(e.g., a patient's history), CaML is able to predict the personalized effects of novel interventions that do not exist at the time of training. Experimental results on real world datasets in large-scale medical claims and cell-line perturbations demonstrate the effectiveness of our approach. Most strikingly, CaML's zero-shot predictions outperform even strong baselines trained directly on data from the test interventions.

Temporally dense single-person "small data" have become widely available thanks to mobile apps and wearable sensors. Many caregivers and self-trackers want to use these data to help a specific person change their behavior to achieve desired health outcomes. Ideally, this involves discerning possible causes from correlations using that person's own observational time series data. In this paper, we estimate within-individual average treatment effects of physical activity on sleep duration, and vice-versa. We introduce the model twin randomization (MoTR; "motor") method for analyzing an individual's intensive longitudinal data. Formally, MoTR is an application of the g-formula (i.e., standardization, back-door adjustment) under serial interference. It estimates stable recurring effects, as is done in n-of-1 trials and single case experimental designs. We compare our approach to standard methods (with possible confounding) to show how to use causal inference to make better personalized recommendations for health behavior change, and analyze 222 days of Fitbit sleep and steps data for one of the authors.

The ability to recognize and interpret facial emotions is a critical component of human communication, as it allows individuals to understand and respond to emotions conveyed through facial expressions and vocal tones. The recognition of facial emotions is a complex cognitive process that involves the integration of visual and auditory information, as well as prior knowledge and social cues. It plays a crucial role in social interaction, affective processing, and empathy, and is an important aspect of many real-world applications, including human-computer interaction, virtual assistants, and mental health diagnosis and treatment. The development of accurate and efficient models for facial emotion recognition is therefore of great importance and has the potential to have a significant impact on various fields of study.The field of Facial Emotion Recognition (FER) is of great significance in the areas of computer vision and artificial intelligence, with vast commercial and academic potential in fields such as security, advertising, and entertainment. We propose a FER framework that employs Swin Vision Transformers (SwinT) and squeeze and excitation block (SE) to address vision tasks. The approach uses a transformer model with an attention mechanism, SE, and SAM to improve the efficiency of the model, as transformers often require a large amount of data. Our focus was to create an efficient FER model based on SwinT architecture that can recognize facial emotions using minimal data. We trained our model on a hybrid dataset and evaluated its performance on the AffectNet dataset, achieving an F1-score of 0.5420, which surpassed the winner of the Affective Behavior Analysis in the Wild (ABAW) Competition held at the European Conference on Computer Vision (ECCV) 2022~Kollias.

Should a large language model (LLM) be used as a therapist? In this paper, we investigate the use of LLMs to *replace* mental health providers, a use case promoted in the tech startup and research space. We conduct a mapping review of therapy guides used by major medical institutions to identify crucial aspects of therapeutic relationships, such as the importance of a therapeutic alliance between therapist and client. We then assess the ability of LLMs to reproduce and adhere to these aspects of therapeutic relationships by conducting several experiments investigating the responses of current LLMs, such as `gpt-4o`. Contrary to best practices in the medical community, LLMs 1) express stigma toward those with mental health conditions and 2) respond inappropriately to certain common (and critical) conditions in naturalistic therapy settings -- e.g., LLMs encourage clients' delusional thinking, likely due to their sycophancy. This occurs even with larger and newer LLMs, indicating that current safety practices may not address these gaps. Furthermore, we note foundational and practical barriers to the adoption of LLMs as therapists, such as that a therapeutic alliance requires human characteristics (e.g., identity and stakes). For these reasons, we conclude that LLMs should not replace therapists, and we discuss alternative roles for LLMs in clinical therapy.

Online mental health support communities have grown in recent years for providing accessible mental and emotional health support through volunteer counselors. Despite millions of people participating in chat support on these platforms, the clinical effectiveness of these communities on mental health symptoms remains unknown. Furthermore, although volunteers receive some training based on established therapeutic skills studied in face-to-face environments such as active listening and motivational interviewing, it remains understudied how the usage of these skills in this online context affects people's mental health status. In our work, we collaborate with one of the largest online peer support platforms and use both natural language processing and machine learning techniques to measure how one-on-one support chats affect depression and anxiety symptoms. We measure how the techniques and characteristics of support providers, such as using affirmation, empathy, and past experience on the platform, affect support-seekers' mental health changes. We find that online peer support chats improve both depression and anxiety symptoms with a statistically significant but relatively small effect size. Additionally, support providers' techniques such as emphasizing the autonomy of the client lead to better mental health outcomes. However, we also found that some behaviors (e.g. persuading) are actually harmful to depression and anxiety outcomes. Our work provides key understanding for mental health care in the online setting and designing training systems for online support providers.

Motivation: Emerging drug-drug interaction (DDI) prediction is crucial for new drugs but is hindered by distribution changes between known and new drugs in real-world scenarios. Current evaluation often neglects these changes, relying on unrealistic i.i.d. split due to the absence of drug approval data. Results: We propose DDI-Ben, a benchmarking framework for emerging DDI prediction under distribution changes. DDI-Ben introduces a distribution change simulation framework that leverages distribution changes between drug sets as a surrogate for real-world distribution changes of DDIs, and is compatible with various drug split strategies. Through extensive benchmarking on ten representative methods, we show that most existing approaches suffer substantial performance degradation under distribution changes. Our analysis further indicates that large language model (LLM) based methods and the integration of drug-related textual information offer promising robustness against such degradation. To support future research, we release the benchmark datasets with simulated distribution changes. Overall, DDI-Ben highlights the importance of explicitly addressing distribution changes and provides a foundation for developing more resilient methods for emerging DDI prediction. Availability and implementation: Our code and data are available at https://github.com/LARS-research/DDI-Bench.

Simulating human clients in mental health counseling is crucial for training and evaluating counselors (both human or simulated) in a scalable manner. Nevertheless, past research on client simulation did not focus on complex conversation tasks such as mental health counseling. In these tasks, the challenge is to ensure that the client's actions (i.e., interactions with the counselor) are consistent with with its stipulated profiles and negative behavior settings. In this paper, we propose a novel framework that supports consistent client simulation for mental health counseling. Our framework tracks the mental state of a simulated client, controls its state transitions, and generates for each state behaviors consistent with the client's motivation, beliefs, preferred plan to change, and receptivity. By varying the client profile and receptivity, we demonstrate that consistent simulated clients for different counseling scenarios can be effectively created. Both our automatic and expert evaluations on the generated counseling sessions also show that our client simulation method achieves higher consistency than previous methods.

Accurate prediction of drug-target interactions is critical for advancing drug discovery. By reducing time and cost, machine learning and deep learning can accelerate this discovery process. Our approach utilises the powerful Barlow Twins architecture for feature-extraction while considering the structure of the target protein, achieving state-of-the-art predictive performance against multiple established benchmarks. The use of gradient boosting machine as the underlying predictor ensures fast and efficient predictions without the need for large computational resources. In addition, we further benchmarked new baselines against existing methods. Together, these innovations improve the efficiency and effectiveness of drug-target interaction predictions, providing robust tools for accelerating drug development and deepening the understanding of molecular interactions.

Clinical trials disruption has always represented a non negligible part of the ending of interventional studies. While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable results. This paper describes methods to compensate for the information loss arising from trial disruptions by incorporating additional information available from auxiliary data sources. The methods described include the use of auxiliary data on baseline and early outcome data available from the trial itself and frequentist and Bayesian approaches for the incorporation of information from external data sources. The methods are illustrated by application to the analysis of artificial data based on the Primary care pediatrics Learning Activity Nutrition (PLAN) study, a clinical trial assessing a diet and exercise intervention for overweight children, that was affected by the COVID-19 pandemic. We show how all of the methods proposed lead to an increase in precision relative to use of complete case data only.

Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.

Predicting drug-target interactions (DTI) is an essential part of the drug discovery process, which is an expensive process in terms of time and cost. Therefore, reducing DTI cost could lead to reduced healthcare costs for a patient. In addition, a precisely learned molecule representation in a DTI model could contribute to developing personalized medicine, which will help many patient cohorts. In this paper, we propose a new molecule representation based on the self-attention mechanism, and a new DTI model using our molecule representation. The experiments show that our DTI model outperforms the state of the art by up to 4.9% points in terms of area under the precision-recall curve. Moreover, a study using the DrugBank database proves that our model effectively lists all known drugs targeting a specific cancer biomarker in the top-30 candidate list.

BabyLM aims to dissolve the boundaries between cognitive modeling and language modeling. We call for both workshop papers and for researchers to join the 3rd BabyLM competition. As in previous years, we call for participants in the data-efficient pretraining challenge in the general track. This year, we also offer a new track: INTERACTION. This new track encourages interactive behavior, learning from a teacher, and adapting the teaching material to the student. We also call for papers outside the competition in any relevant areas. These include training efficiency, cognitively plausible research, weak model evaluation, and more.

Online medical consultation (OMC) restricts doctors to gathering patient information solely through inquiries, making the already complex sequential decision-making process of diagnosis even more challenging. Recently, the rapid advancement of large language models has demonstrated a significant potential to transform OMC. However, most studies have primarily focused on improving diagnostic accuracy under conditions of relatively sufficient information, while paying limited attention to the "inquiry" phase of the consultation process. This lack of focus has left the relationship between "inquiry" and "diagnosis" insufficiently explored. In this paper, we first extract real patient interaction strategies from authentic doctor-patient conversations and use these strategies to guide the training of a patient simulator that closely mirrors real-world behavior. By inputting medical records into our patient simulator to simulate patient responses, we conduct extensive experiments to explore the relationship between "inquiry" and "diagnosis" in the consultation process. Experimental results demonstrate that inquiry and diagnosis adhere to the Liebig's law: poor inquiry quality limits the effectiveness of diagnosis, regardless of diagnostic capability, and vice versa. Furthermore, the experiments reveal significant differences in the inquiry performance of various models. To investigate this phenomenon, we categorize the inquiry process into four types: (1) chief complaint inquiry; (2) specification of known symptoms; (3) inquiry about accompanying symptoms; and (4) gathering family or medical history. We analyze the distribution of inquiries across the four types for different models to explore the reasons behind their significant performance differences. We plan to open-source the weights and related code of our patient simulator at https://github.com/LIO-H-ZEN/PatientSimulator.

Problem: Effective patient-centered communication is a core competency for physicians. However, both seasoned providers and medical trainees report decreased confidence in leading conversations on sensitive topics such as goals of care or end-of-life discussions. The significant administrative burden and the resources required to provide dedicated training in leading difficult conversations has been a long-standing problem in medical education. Approach: In this work, we present a novel educational tool designed to facilitate interactive, real-time simulations of difficult conversations in a video-based format through the use of multimodal generative artificial intelligence (AI). Leveraging recent advances in language modeling, computer vision, and generative audio, this tool creates realistic, interactive scenarios with avatars, or "synthetic patients." These synthetic patients interact with users throughout various stages of medical care using a custom-built video chat application, offering learners the chance to practice conversations with patients from diverse belief systems, personalities, and ethnic backgrounds. Outcomes: While the development of this platform demanded substantial upfront investment in labor, it offers a highly-realistic simulation experience with minimal financial investment. For medical trainees, this educational tool can be implemented within programs to simulate patient-provider conversations and can be incorporated into existing palliative care curriculum to provide a scalable, high-fidelity simulation environment for mastering difficult conversations. Next Steps: Future developments will explore enhancing the authenticity of these encounters by working with patients to incorporate their histories and personalities, as well as employing the use of AI-generated evaluations to offer immediate, constructive feedback to learners post-simulation.

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.

Instrumental variable methods have been widely used to identify causal effects in the presence of unmeasured confounding. A key identification condition known as the exclusion restriction states that the instrument cannot have a direct effect on the outcome which is not mediated by the exposure in view. In the health and social sciences, such an assumption is often not credible. To address this concern, we consider identification conditions of the population average treatment effect with an invalid instrumental variable which does not satisfy the exclusion restriction, and derive the efficient influence function targeting the identifying functional under a nonparametric observed data model. We propose a novel multiply robust locally efficient estimator of the average treatment effect that is consistent in the union of multiple parametric nuisance models, as well as a multiply debiased machine learning estimator for which the nuisance parameters are estimated using generic machine learning methods, that effectively exploit various forms of linear or nonlinear structured sparsity in the nuisance parameter space. When one cannot be confident that any of these machine learners is consistent at sufficiently fast rates to ensure n-consistency for the average treatment effect, we introduce a new criteria for selective machine learning which leverages the multiple robustness property in order to ensure small bias. The proposed methods are illustrated through extensive simulations and a data analysis evaluating the causal effect of 401(k) participation on savings.

Machine learning (ML) interpretability techniques can reveal undesirable patterns in data that models exploit to make predictions--potentially causing harms once deployed. However, how to take action to address these patterns is not always clear. In a collaboration between ML and human-computer interaction researchers, physicians, and data scientists, we develop GAM Changer, the first interactive system to help domain experts and data scientists easily and responsibly edit Generalized Additive Models (GAMs) and fix problematic patterns. With novel interaction techniques, our tool puts interpretability into action--empowering users to analyze, validate, and align model behaviors with their knowledge and values. Physicians have started to use our tool to investigate and fix pneumonia and sepsis risk prediction models, and an evaluation with 7 data scientists working in diverse domains highlights that our tool is easy to use, meets their model editing needs, and fits into their current workflows. Built with modern web technologies, our tool runs locally in users' web browsers or computational notebooks, lowering the barrier to use. GAM Changer is available at the following public demo link: https://interpret.ml/gam-changer.

Mediation analysis learns the causal effect transmitted via mediator variables between treatments and outcomes and receives increasing attention in various scientific domains to elucidate causal relations. Most existing works focus on point-exposure studies where each subject only receives one treatment at a single time point. However, there are a number of applications (e.g., mobile health) where the treatments are sequentially assigned over time and the dynamic mediation effects are of primary interest. Proposing a reinforcement learning (RL) framework, we are the first to evaluate dynamic mediation effects in settings with infinite horizons. We decompose the average treatment effect into an immediate direct effect, an immediate mediation effect, a delayed direct effect, and a delayed mediation effect. Upon the identification of each effect component, we further develop robust and semi-parametrically efficient estimators under the RL framework to infer these causal effects. The superior performance of the proposed method is demonstrated through extensive numerical studies, theoretical results, and an analysis of a mobile health dataset.

Exposing meaningful and interpretable neural interactions is critical to understanding neural circuits. Inferred neural interactions from neural signals primarily reflect functional interactions. In a long experiment, subject animals may experience different stages defined by the experiment, stimuli, or behavioral states, and hence functional interactions can change over time. To model dynamically changing functional interactions, prior work employs state-switching generalized linear models with hidden Markov models (i.e., HMM-GLMs). However, we argue they lack biological plausibility, as functional interactions are shaped and confined by the underlying anatomical connectome. Here, we propose a novel prior-informed state-switching GLM. We introduce both a Gaussian prior and a one-hot prior over the GLM in each state. The priors are learnable. We will show that the learned prior should capture the state-constant interaction, shedding light on the underlying anatomical connectome and revealing more likely physical neuron interactions. The state-dependent interaction modeled by each GLM offers traceability to capture functional variations across multiple brain states. Our methods effectively recover true interaction structures in simulated data, achieve the highest predictive likelihood with real neural datasets, and render interaction structures and hidden states more interpretable when applied to real neural data.

Machine learning (ML) holds great potential for accurately forecasting treatment outcomes over time, which could ultimately enable the adoption of more individualized treatment strategies in many practical applications. However, a significant challenge that has been largely overlooked by the ML literature on this topic is the presence of informative sampling in observational data. When instances are observed irregularly over time, sampling times are typically not random, but rather informative -- depending on the instance's characteristics, past outcomes, and administered treatments. In this work, we formalize informative sampling as a covariate shift problem and show that it can prohibit accurate estimation of treatment outcomes if not properly accounted for. To overcome this challenge, we present a general framework for learning treatment outcomes in the presence of informative sampling using inverse intensity-weighting, and propose a novel method, TESAR-CDE, that instantiates this framework using Neural CDEs. Using a simulation environment based on a clinical use case, we demonstrate the effectiveness of our approach in learning under informative sampling.

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.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

In psychotherapy, therapeutic outcome assessment, or treatment outcome evaluation, is essential for enhancing mental health care by systematically evaluating therapeutic processes and outcomes. Existing large language model approaches often focus on therapist-centered, single-session evaluations, neglecting the client's subjective experience and longitudinal progress across multiple sessions. To address these limitations, we propose IPAEval, a client-Informed Psychological Assessment-based Evaluation framework that automates treatment outcome evaluations from the client's perspective using clinical interviews. IPAEval integrates cross-session client-contextual assessment and session-focused client-dynamics assessment to provide a comprehensive understanding of therapeutic progress. Experiments on our newly developed TheraPhase dataset demonstrate that IPAEval effectively tracks symptom severity and treatment outcomes over multiple sessions, outperforming previous single-session models and validating the benefits of items-aware reasoning mechanisms.

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.

For observational studies, we study the sensitivity of causal inference when treatment assignments may depend on unobserved confounders. We develop a loss minimization approach for estimating bounds on the conditional average treatment effect (CATE) when unobserved confounders have a bounded effect on the odds ratio of treatment selection. Our approach is scalable and allows flexible use of model classes in estimation, including nonparametric and black-box machine learning methods. Based on these bounds for the CATE, we propose a sensitivity analysis for the average treatment effect (ATE). Our semi-parametric estimator extends/bounds the augmented inverse propensity weighted (AIPW) estimator for the ATE under bounded unobserved confounding. By constructing a Neyman orthogonal score, our estimator of the bound for the ATE is a regular root-n estimator so long as the nuisance parameters are estimated at the o_p(n^{-1/4}) rate. We complement our methodology with optimality results showing that our proposed bounds are tight in certain cases. We demonstrate our method on simulated and real data examples, and show accurate coverage of our confidence intervals in practical finite sample regimes with rich covariate information.

Conversational agents are increasingly used to address emotional needs on top of information needs. One use case of increasing interest are counselling-style mental health and behaviour change interventions, with large language model (LLM)-based approaches becoming more popular. Research in this context so far has been largely system-focused, foregoing the aspect of user behaviour and the impact this can have on LLM-generated texts. To address this issue, we share a dataset containing text-based user interactions related to behaviour change with two GPT-4-based conversational agents collected in a preregistered user study. This dataset includes conversation data, user language analysis, perception measures, and user feedback for LLM-generated turns, and can offer valuable insights to inform the design of such systems based on real interactions.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Current mental-health conversational systems are usually based on fixed, generic dialogue patterns. This paper proposes an adaptive framework based on large language models that aims to personalize therapeutic interaction according to a user's psychological state, quantified with the Acceptance of Illness Scale (AIS). The framework defines three specialized agents, L, M, and H, each linked to a different level of illness acceptance, and adjusts conversational behavior over time using continuous feedback signals. The AIS-stratified architecture is treated as a diegetic prototype placed in a plausible near-future setting and examined through the method of design fiction. By embedding the architecture in narrative scenarios, the study explores how such agents might influence access to care and therapeutic relationship. The goal is to show how clinically informed personalization, technical feasibility, and speculative scenario analysis can together inform the responsible design of LLM-based companions for mental-health support.

Being able to provide explanations for a model's decision has become a central requirement for the development, deployment, and adoption of machine learning models. However, we are yet to understand what explanation methods can and cannot do. How do upstream factors such as data, model prediction, hyperparameters, and random initialization influence downstream explanations? While previous work raised concerns that explanations (E) may have little relationship with the prediction (Y), there is a lack of conclusive study to quantify this relationship. Our work borrows tools from causal inference to systematically assay this relationship. More specifically, we study the relationship between E and Y by measuring the treatment effect when intervening on their causal ancestors, i.e., on hyperparameters and inputs used to generate saliency-based Es or Ys. Our results suggest that the relationships between E and Y is far from ideal. In fact, the gap between 'ideal' case only increase in higher-performing models -- models that are likely to be deployed. Our work is a promising first step towards providing a quantitative measure of the relationship between E and Y, which could also inform the future development of methods for E with a quantitative metric.

For the early identification, diagnosis, and treatment of mental health illnesses, the integration of deep learning (DL) and machine learning (ML) has started playing a significant role. By evaluating complex data from imaging, genetics, and behavioral assessments, these technologies have the potential to significantly improve clinical outcomes. However, they also present unique challenges related to data integration and ethical issues. This survey reviews the development of ML and DL methods for the early diagnosis and treatment of mental health issues. It examines a range of applications, with a particular emphasis on behavioral assessments, genetic and biomarker analysis, and medical imaging for diagnosing diseases like depression, bipolar disorder, and schizophrenia. Predictive modeling for illness progression is further discussed, focusing on the role of risk prediction models and longitudinal studies. Key findings highlight how ML and DL can improve diagnostic accuracy and treatment outcomes while addressing methodological inconsistencies, data integration challenges, and ethical concerns. The study emphasizes the importance of building real-time monitoring systems for individualized treatment, enhancing data fusion techniques, and fostering interdisciplinary collaboration. Future research should focus on overcoming these obstacles to ensure the valuable and ethical application of ML and DL in mental health services.

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

Hospital information systems (HIS) have become an essential part of healthcare institutions and now incorporate prescribing support software. Prescription support software allows for structured information capture, which improves the safety, appropriateness and efficiency of prescriptions and reduces the number of adverse drug events (ADEs). However, such a system increases the amount of time physicians spend at a computer entering information instead of providing medical care. In addition, any new visiting clinician must learn to manage complex interfaces since each HIS has its own interfaces. In this paper, we present a natural language interface for e-prescribing software in the form of a spoken dialogue system accessible on a smartphone. This system allows prescribers to record their prescriptions verbally, a form of interaction closer to their usual practice. The system extracts the formal representation of the prescription ready to be checked by the prescribing software and uses the dialogue to request mandatory information, correct errors or warn of particular situations. Since, to the best of our knowledge, there is no existing voice-based prescription dialogue system, we present the system developed in a low-resource environment, focusing on dialogue modeling, semantic extraction and data augmentation. The system was evaluated in the wild with 55 participants. This evaluation showed that our system has an average prescription time of 66.15 seconds for physicians and 35.64 seconds for other experts, and a task success rate of 76\% for physicians and 72\% for other experts. All evaluation data were recorded and annotated to form PxCorpus, the first spoken drug prescription corpus that has been made fully available to the community (https://doi.org/10.5281/zenodo.6524162).

In here presented in silico study we suggest a way how to implement the evolutionary principles into anti-cancer therapy design. We hypothesize that instead of its ongoing supervised adaptation, the therapy may be constructed as a self-sustaining evolutionary process in a dynamic fitness landscape established implicitly by evolving cancer cells, microenvironment and the therapy itself. For these purposes, we replace a unified therapy with the `therapy species', which is a population of heterogeneous elementary therapies, and propose a way how to turn the toxicity of the elementary therapy into its fitness in a way conforming to evolutionary causation. As a result, not only the therapies govern the evolution of different cell phenotypes, but the cells' resistances govern the evolution of the therapies as well. We illustrate the approach by the minimalistic ad hoc evolutionary model. Its results indicate that the resistant cells could bias the evolution towards more toxic elementary therapies by inhibiting the less toxic ones. As the evolutionary causation of cancer drug resistance has been intensively studied for a few decades, we refer to cancer as a special case to illustrate purely theoretical analysis.

People increasingly seek personal advice from large language models (LLMs), yet whether humans follow their advice, and its consequences for their well-being, remains unknown. In a longitudinal randomised controlled trial with a representative UK sample (N = 2,302), 75% of participants who had a 20-minute discussion with GPT-4o about health, careers or relationships subsequently reported following its advice. Based on autograder evaluations of chat transcripts, LLM advice rarely violated safety best practice. When queried 2-3 weeks later, participants who had interacted with personalised AI (with access to detailed user information) followed its advice more often in the real world and reported higher well-being than those advised by non-personalised AI. However, while receiving personal advice from AI temporarily reduced well-being, no differential long-term effects compared to a control emerged. Our results suggest that humans readily follow LLM advice about personal issues but doing so shows no additional well-being benefit over casual conversations.

Virtual counselors powered by large language models (LLMs) aim to create interactive support systems that effectively assist clients struggling with mental health challenges. To replicate counselor-client conversations, researchers have built an online mental health platform that allows professional counselors to provide clients with text-based counseling services for about an hour per session. Notwithstanding its effectiveness, challenges exist as human annotation is time-consuming, cost-intensive, privacy-protected, and not scalable. To address this issue and investigate the applicability of LLMs in psychological counseling conversation simulation, we propose a framework that employs two LLMs via role-playing for simulating counselor-client interactions. Our framework involves two LLMs, one acting as a client equipped with a specific and real-life user profile and the other playing the role of an experienced counselor, generating professional responses using integrative therapy techniques. We implement both the counselor and the client by zero-shot prompting the GPT-4 model. In order to assess the effectiveness of LLMs in simulating counselor-client interactions and understand the disparities between LLM- and human-generated conversations, we evaluate the synthetic data from various perspectives. We begin by assessing the client's performance through automatic evaluations. Next, we analyze and compare the disparities between dialogues generated by the LLM and those generated by professional counselors. Furthermore, we conduct extensive experiments to thoroughly examine the performance of our LLM-based counselor trained with synthetic interactive dialogues by benchmarking against state-of-the-art models for mental health.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

People experiencing severe distress increasingly use Large Language Model (LLM) chatbots as mental health support tools. Discussions on social media have described how engagements were lifesaving for some, but evidence suggests that general-purpose LLM chatbots also have notable risks that could endanger the welfare of users if not designed responsibly. In this study, we investigate the lived experiences of people who have used LLM chatbots for mental health support. We build on interviews with 21 individuals from globally diverse backgrounds to analyze how users create unique support roles for their chatbots, fill in gaps in everyday care, and navigate associated cultural limitations when seeking support from chatbots. We ground our analysis in psychotherapy literature around effective support, and introduce the concept of therapeutic alignment, or aligning AI with therapeutic values for mental health contexts. Our study offers recommendations for how designers can approach the ethical and effective use of LLM chatbots and other AI mental health support tools in mental health care.

The Mental Health Question Answer (MHQA) task requires the seeker and supporter to complete the support process in one-turn dialogue. Given the richness of help-seeker posts, supporters must thoroughly understand the content and provide logical, comprehensive, and well-structured responses. Previous works in MHQA mostly focus on single-agent approaches based on the cognitive element of Cognitive Behavioral Therapy (CBT), but they overlook the interactions among various CBT elements, such as emotion and cognition. This limitation hinders the models' ability to thoroughly understand the distress of help-seekers. To address this, we propose a framework named Multi-Agent Deductive Planning (MADP), which is based on the interactions between the various psychological elements of CBT. This method guides Large Language Models (LLMs) to achieve a deeper understanding of the seeker's context and provide more personalized assistance based on individual circumstances. Furthermore, we construct a new dataset based on the MADP framework and use it to fine-tune LLMs, resulting in a specialized model named MADP-LLM. We conduct extensive experiments, including comparisons with multiple LLMs, human evaluations, and automatic evaluations, to validate the effectiveness of the MADP framework and MADP-LLM.

Effective mental health support is crucial for alleviating psychological distress. While large language model (LLM)-based assistants have shown promise in mental health interventions, existing research often defines "effective" support primarily in terms of empathetic acknowledgments, overlooking other essential dimensions such as informational guidance, community validation, and tangible coping strategies. To address this limitation and better understand what constitutes effective support, we introduce RedditESS, a novel real-world dataset derived from Reddit posts, including supportive comments and original posters' follow-up responses. Grounded in established social science theories, we develop an ensemble labeling mechanism to annotate supportive comments as effective or not and perform qualitative assessments to ensure the reliability of the annotations. Additionally, we demonstrate the practical utility of RedditESS by using it to guide LLM alignment toward generating more context-sensitive and genuinely helpful supportive responses. By broadening the understanding of effective support, our study paves the way for advanced AI-driven mental health interventions.

Documentation burden is a major contributor to clinician burnout, which is rising nationally and is an urgent threat to our ability to care for patients. Artificial intelligence (AI) chatbots, such as ChatGPT, could reduce clinician burden by assisting with documentation. Although many hospitals are actively integrating such systems into electronic medical record systems, AI chatbots utility and impact on clinical decision-making have not been studied for this intended use. We are the first to examine the utility of large language models in assisting clinicians draft responses to patient questions. In our two-stage cross-sectional study, 6 oncologists responded to 100 realistic synthetic cancer patient scenarios and portal messages developed to reflect common medical situations, first manually, then with AI assistance. We find AI-assisted responses were longer, less readable, but provided acceptable drafts without edits 58% of time. AI assistance improved efficiency 77% of time, with low harm risk (82% safe). However, 7.7% unedited AI responses could severely harm. In 31% cases, physicians thought AI drafts were human-written. AI assistance led to more patient education recommendations, fewer clinical actions than manual responses. Results show promise for AI to improve clinician efficiency and patient care through assisting documentation, if used judiciously. Monitoring model outputs and human-AI interaction remains crucial for safe implementation.

In the pharmaceutical industry, the use of artificial intelligence (AI) has seen consistent growth over the past decade. This rise is attributed to major advancements in statistical machine learning methodologies, computational capabilities and the increased availability of large datasets. AI techniques are applied throughout different stages of drug development, ranging from drug discovery to post-marketing benefit-risk assessment. Kolluri et al. provided a review of several case studies that span these stages, featuring key applications such as protein structure prediction, success probability estimation, subgroup identification, and AI-assisted clinical trial monitoring. From a regulatory standpoint, there was a notable uptick in submissions incorporating AI components in 2021. The most prevalent therapeutic areas leveraging AI were oncology (27%), psychiatry (15%), gastroenterology (12%), and neurology (11%). The paradigm of personalized or precision medicine has gained significant traction in recent research, partly due to advancements in AI techniques hamburg2010path. This shift has had a transformative impact on the pharmaceutical industry. Departing from the traditional "one-size-fits-all" model, personalized medicine incorporates various individual factors, such as environmental conditions, lifestyle choices, and health histories, to formulate customized treatment plans. By utilizing sophisticated machine learning algorithms, clinicians and researchers are better equipped to make informed decisions in areas such as disease prevention, diagnosis, and treatment selection, thereby optimizing health outcomes for each individual.

Empathy is a cognitive and emotional reaction to an observed situation of others. Empathy has recently attracted interest because it has numerous applications in psychology and AI, but it is unclear how different forms of empathy (e.g., self-report vs counterpart other-report, concern vs. distress) interact with other affective phenomena or demographics like gender and age. To better understand this, we created the {\it Empathic Conversations} dataset of annotated negative, empathy-eliciting dialogues in which pairs of participants converse about news articles. People differ in their perception of the empathy of others. These differences are associated with certain characteristics such as personality and demographics. Hence, we collected detailed characterization of the participants' traits, their self-reported empathetic response to news articles, their conversational partner other-report, and turn-by-turn third-party assessments of the level of self-disclosure, emotion, and empathy expressed. This dataset is the first to present empathy in multiple forms along with personal distress, emotion, personality characteristics, and person-level demographic information. We present baseline models for predicting some of these features from conversations.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

Extracting causal relationships from observed correlations is a growing area in probabilistic reasoning, originating with the seminal work of Pearl and others from the early 1990s. This paper develops a new, categorically oriented view based on a clear distinction between syntax (string diagrams) and semantics (stochastic matrices), connected via interpretations as structure-preserving functors. A key notion in the identification of causal effects is that of an intervention, whereby a variable is forcefully set to a particular value independent of any prior propensities. We represent the effect of such an intervention as an endofunctor which performs `string diagram surgery' within the syntactic category of string diagrams. This diagram surgery in turn yields a new, interventional distribution via the interpretation functor. While in general there is no way to compute interventional distributions purely from observed data, we show that this is possible in certain special cases using a calculational tool called comb disintegration. We demonstrate the use of this technique on a well-known toy example, where we predict the causal effect of smoking on cancer in the presence of a confounding common cause. After developing this specific example, we show this technique provides simple sufficient conditions for computing interventions which apply to a wide variety of situations considered in the causal inference literature.

In oncology, treating cancer with a beam of photons is a well established therapeutic technique, developed over 100 years, and today over 50% of cancer patients will undergo traditional X-ray radiotherapy. However, ionizing radiation therapy is not the only option, as the high-energy photons delivering their cell-killing radiation energy into cancerous tumor can lead to significant damage to healthy tissues surrounding the tumor, located throughout the beam's path. Therefore, in nowadays, advances in ionizing radiation therapy are competitive to non-ionizing ones, as for example the laser light based therapy, resulting in a synergism that has revolutionized medicine. The use of non-invasive or minimally invasive (e.g. through flexible endoscopes) therapeutic procedures in the management of patients represents a very interesting treatment option. Moreover, as the major breakthrough in cancer management is the individualized patient treatment, new biophotonic techniques, e.g. photo-activated drug carriers, help the improvement of treatment efficacy and/or normal tissue toxicity. Additionally, recent studies support that laser technology progresses could revolutionize cancer proton therapy, by reducing the cost of the needed installations. The aim of this review is to present some laser-based future objectives for cancer radiation therapy, aiming to address the relevant advances in the ionizing and non-ionizing radiation therapy, i.e. protons and heavy ions therapy, as well as photodynamic targeted and molecular therapies.

The recommendation of medication is a vital aspect of intelligent healthcare systems, as it involves prescribing the most suitable drugs based on a patient's specific health needs. Unfortunately, many sophisticated models currently in use tend to overlook the nuanced semantics of medical data, while only relying heavily on identities. Furthermore, these models face significant challenges in handling cases involving patients who are visiting the hospital for the first time, as they lack prior prescription histories to draw upon. To tackle these issues, we harness the powerful semantic comprehension and input-agnostic characteristics of Large Language Models (LLMs). Our research aims to transform existing medication recommendation methodologies using LLMs. In this paper, we introduce a novel approach called Large Language Model Distilling Medication Recommendation (LEADER). We begin by creating appropriate prompt templates that enable LLMs to suggest medications effectively. However, the straightforward integration of LLMs into recommender systems leads to an out-of-corpus issue specific to drugs. We handle it by adapting the LLMs with a novel output layer and a refined tuning loss function. Although LLM-based models exhibit remarkable capabilities, they are plagued by high computational costs during inference, which is impractical for the healthcare sector. To mitigate this, we have developed a feature-level knowledge distillation technique, which transfers the LLM's proficiency to a more compact model. Extensive experiments conducted on two real-world datasets, MIMIC-III and MIMIC-IV, demonstrate that our proposed model not only delivers effective results but also is efficient. To ease the reproducibility of our experiments, we release the implementation code online.

Human biases impact the way people analyze data and make decisions. Recent work has shown that some visualization designs can better support cognitive processes and mitigate cognitive biases (i.e., errors that occur due to the use of mental "shortcuts"). In this work, we explore how visualizing a user's interaction history (i.e., which data points and attributes a user has interacted with) can be used to mitigate potential biases that drive decision making by promoting conscious reflection of one's analysis process. Given an interactive scatterplot-based visualization tool, we showed interaction history in real-time while exploring data (by coloring points in the scatterplot that the user has interacted with), and in a summative format after a decision has been made (by comparing the distribution of user interactions to the underlying distribution of the data). We conducted a series of in-lab experiments and a crowd-sourced experiment to evaluate the effectiveness of interaction history interventions toward mitigating bias. We contextualized this work in a political scenario in which participants were instructed to choose a committee of 10 fictitious politicians to review a recent bill passed in the U.S. state of Georgia banning abortion after 6 weeks, where things like gender bias or political party bias may drive one's analysis process. We demonstrate the generalizability of this approach by evaluating a second decision making scenario related to movies. Our results are inconclusive for the effectiveness of interaction history (henceforth referred to as interaction traces) toward mitigating biased decision making. However, we find some mixed support that interaction traces, particularly in a summative format, can increase awareness of potential unconscious biases.

Mental health care-seeking among marginalized young adults has received limited attention in CSCW research. Through in-depth interviews and visual elicitation methods with 18 diverse U.S. participants, our study reveals how marginalized identities shape mental health care-seeking journeys, often characterized by low aspirations and passive care-seeking influenced by lived experiences of marginalization. However, we found the transformative function of "care encounters" - serendipitous interactions with mental health resources that occur when individuals are not actively seeking support. These encounters serve as critical turning points, catalyzing shifts in aspiration and enabling more proactive care-seeking behaviors. Our analysis identifies both the infrastructural conditions that enable transformative care encounters and the aspiration breakdowns that impede care-seeking processes. This work makes conceptual contributions by supplementing traditional motivation-based care-seeking models with a reconceptualization of "care encounters" that accounts for the infrastructural and serendipitous nature of mental health access. We advance understanding of how marginalized identity uniquely influences care-seeking behaviors while providing actionable design implications for embedding technology-mediated "care encounters" into socio-technical interventions that can better support mental health care access for vulnerable populations.

Treatment effect estimation in continuous time is crucial for personalized medicine. However, existing methods for this task are limited to point estimates of the potential outcomes, whereas uncertainty estimates have been ignored. Needless to say, uncertainty quantification is crucial for reliable decision-making in medical applications. To fill this gap, we propose a novel Bayesian neural controlled differential equation (BNCDE) for treatment effect estimation in continuous time. In our BNCDE, the time dimension is modeled through a coupled system of neural controlled differential equations and neural stochastic differential equations, where the neural stochastic differential equations allow for tractable variational Bayesian inference. Thereby, for an assigned sequence of treatments, our BNCDE provides meaningful posterior predictive distributions of the potential outcomes. To the best of our knowledge, ours is the first tailored neural method to provide uncertainty estimates of treatment effects in continuous time. As such, our method is of direct practical value for promoting reliable decision-making in medicine.

We study the problem of adaptively identifying patient subpopulations that benefit from a given treatment during a confirmatory clinical trial. This type of adaptive clinical trial has been thoroughly studied in biostatistics, but has been allowed only limited adaptivity so far. Here, we aim to relax classical restrictions on such designs and investigate how to incorporate ideas from the recent machine learning literature on adaptive and online experimentation to make trials more flexible and efficient. We find that the unique characteristics of the subpopulation selection problem -- most importantly that (i) one is usually interested in finding subpopulations with any treatment benefit (and not necessarily the single subgroup with largest effect) given a limited budget and that (ii) effectiveness only has to be demonstrated across the subpopulation on average -- give rise to interesting challenges and new desiderata when designing algorithmic solutions. Building on these findings, we propose AdaGGI and AdaGCPI, two meta-algorithms for subpopulation construction. We empirically investigate their performance across a range of simulation scenarios and derive insights into their (dis)advantages across different settings.

This paper presents a mathematical framework for optimizing drug delivery in cancer treatment using a nonlocal model of solid tumor growth. We present a coupled system of partial differential equations that incorporate long-range cellular interactions through integral terms and drug-induced cell death. The model accounts for spatial heterogeneity in both tumor cell density and drug concentration while capturing the complex dynamics of drug resistance development. We first establish the well-posedness of the coupled system by proving the existence and uniqueness of a solution under appropriate regularity conditions. The optimal control problem is then formulated to minimize tumor size while accounting for drug toxicity constraints. Using variational methods, we derive the necessary optimality conditions and characterize the optimal control through an adjoint system. Theoretical results can help to design effective chemotherapy schedules that balance treatment efficacy with adverse effects.

Recent interest in human-AI interactions in agent-based modeling and simulation (ABMS) has grown rapidly due to the widespread utilization of large language models (LLMs). ABMS is an intelligent approach that simulates autonomous agents' behaviors within a defined environment to research emergent phenomena. Integrating LLMs into ABMS enables natural language interaction between humans and models. Meanwhile, it introduces new challenges that rely on human interaction to address. Human involvement can assist ABMS in adapting to flexible and complex research demands. However, systematic reviews of interactions that examine how humans and AI interact in ABMS are lacking. In this paper, we investigate existing works and propose a novel taxonomy to categorize the interactions derived from them. Specifically, human users refer to researchers who utilize ABMS tools to conduct their studies in our survey. We decompose interactions into five dimensions: the goals that users want to achieve (Why), the phases that users are involved (When), the components of the system (What), the roles of users (Who), and the means of interactions (How). Our analysis summarizes the findings that reveal existing interaction patterns. They provide researchers who develop interactions with comprehensive guidance on how humans and AI interact. We further discuss the unexplored interactions and suggest future research directions.

Survival prediction is a complicated ordinal regression task that aims to predict the ranking risk of death, which generally benefits from the integration of histology and genomic data. Despite the progress in joint learning from pathology and genomics, existing methods still suffer from challenging issues: 1) Due to the large size of pathological images, it is difficult to effectively represent the gigapixel whole slide images (WSIs). 2) Interactions within tumor microenvironment (TME) in histology are essential for survival analysis. Although current approaches attempt to model these interactions via co-attention between histology and genomic data, they focus on only dense local similarity across modalities, which fails to capture global consistency between potential structures, i.e. TME-related interactions of histology and co-expression of genomic data. To address these challenges, we propose a Multimodal Optimal Transport-based Co-Attention Transformer framework with global structure consistency, in which optimal transport (OT) is applied to match patches of a WSI and genes embeddings for selecting informative patches to represent the gigapixel WSI. More importantly, OT-based co-attention provides a global awareness to effectively capture structural interactions within TME for survival prediction. To overcome high computational complexity of OT, we propose a robust and efficient implementation over micro-batch of WSI patches by approximating the original OT with unbalanced mini-batch OT. Extensive experiments show the superiority of our method on five benchmark datasets compared to the state-of-the-art methods. The code is released.

Access to the right evidence does not guarantee that large language models (LLMs) will reason with it correctly. This gap between retrieval and reasoning is especially concerning in clinical settings, where outputs must align with structured protocols. We study this gap using Written Exposure Therapy (WET) guidelines as a testbed. In evaluating model responses to curated clinician-vetted questions, we find that errors persist even when authoritative passages are provided. To address this, we propose an evaluation framework that measures accuracy, consistency, and fidelity of reasoning. Our results highlight both the potential and the risks: retrieval-augmented generation (RAG) can constrain outputs, but safe deployment requires assessing reasoning as rigorously as retrieval.

This study explores the use of Large language models to analyze therapist remarks in a psychotherapeutic setting. The paper focuses on the application of BERTopic, a machine learning-based topic modeling tool, to the dialogue of two different groups of therapists (classical and modern), which makes it possible to identify and describe a set of topics that consistently emerge across these groups. The paper describes in detail the chosen algorithm for BERTopic, which included creating a vector space from a corpus of therapist remarks, reducing its dimensionality, clustering the space, and creating and optimizing topic representation. Along with the automatic topical modeling by the BERTopic, the research involved an expert assessment of the findings and manual topic structure optimization. The topic modeling results highlighted the most common and stable topics in therapists speech, offering insights into how language patterns in therapy develop and remain stable across different therapeutic styles. This work contributes to the growing field of machine learning in psychotherapy by demonstrating the potential of automated methods to improve both the practice and training of therapists. The study highlights the value of topic modeling as a tool for gaining a deeper understanding of therapeutic dialogue and offers new opportunities for improving therapeutic effectiveness and clinical supervision.

While both agent interaction and personalisation are vibrant topics in research on large language models (LLMs), there has been limited focus on the effect of language interaction on the behaviour of persona-conditioned LLM agents. Such an endeavour is important to ensure that agents remain consistent to their assigned traits yet are able to engage in open, naturalistic dialogues. In our experiments, we condition GPT-3.5 on personality profiles through prompting and create a two-group population of LLM agents using a simple variability-inducing sampling algorithm. We then administer personality tests and submit the agents to a collaborative writing task, finding that different profiles exhibit different degrees of personality consistency and linguistic alignment to their conversational partners. Our study seeks to lay the groundwork for better understanding of dialogue-based interaction between LLMs and highlights the need for new approaches to crafting robust, more human-like LLM personas for interactive environments.

In this work, we introduce MedAgentSim, an open-source simulated clinical environment with doctor, patient, and measurement agents designed to evaluate and enhance LLM performance in dynamic diagnostic settings. Unlike prior approaches, our framework requires doctor agents to actively engage with patients through multi-turn conversations, requesting relevant medical examinations (e.g., temperature, blood pressure, ECG) and imaging results (e.g., MRI, X-ray) from a measurement agent to mimic the real-world diagnostic process. Additionally, we incorporate self improvement mechanisms that allow models to iteratively refine their diagnostic strategies. We enhance LLM performance in our simulated setting by integrating multi-agent discussions, chain-of-thought reasoning, and experience-based knowledge retrieval, facilitating progressive learning as doctor agents interact with more patients. We also introduce an evaluation benchmark for assessing the LLM's ability to engage in dynamic, context-aware diagnostic interactions. While MedAgentSim is fully automated, it also supports a user-controlled mode, enabling human interaction with either the doctor or patient agent. Comprehensive evaluations in various simulated diagnostic scenarios demonstrate the effectiveness of our approach. Our code, simulation tool, and benchmark are available at https://medagentsim.netlify.app/.

As language models shift from single-shot answer generation toward multi-step reasoning that retrieves and consumes evidence mid-inference, evaluating the role of individual retrieved items becomes more important. Existing RAG evaluation typically targets final-answer quality, citation faithfulness, or answer-level attribution, but none of these directly targets the intervention-based, per-evidence-item utility view we study here. We introduce CUE-R, a lightweight intervention-based framework for measuring per-evidence-item operational utility in single-shot RAG using shallow observable retrieval-use traces. CUE-R perturbs individual evidence items via REMOVE, REPLACE, and DUPLICATE operators, then measures changes along three utility axes (correctness, proxy-based grounding faithfulness, and confidence error) plus a trace-divergence signal. We also outline an operational evidence-role taxonomy for interpreting intervention outcomes. Experiments on HotpotQA and 2WikiMultihopQA with Qwen-3 8B and GPT-5.2 reveal a consistent pattern: REMOVE and REPLACE substantially harm correctness and grounding while producing large trace shifts, whereas DUPLICATE is often answer-redundant yet not fully behaviorally neutral. A zero-retrieval control confirms that these effects arise from degradation of meaningful retrieval. A two-support ablation further shows that multi-hop evidence items can interact non-additively: removing both supports harms performance far more than either single removal. Our results suggest that answer-only evaluation misses important evidence effects and that intervention-based utility analysis is a practical complement for RAG evaluation.

Clinical trials drive improvements in cancer treatments and outcomes. However, most adults with cancer do not participate in trials, and trials often fail to enroll enough patients to answer their scientific questions. Artificial intelligence could accelerate matching of patients to appropriate clinical trials. Here, we describe the development and evaluation of the MatchMiner-AI pipeline for clinical trial searching and ranking. MatchMiner-AI focuses on matching patients to potential trials based on core criteria describing clinical "spaces," or disease contexts, targeted by a trial. It aims to accelerate the human work of identifying potential matches, not to fully automate trial screening. The pipeline includes modules for extraction of key information from a patient's longitudinal electronic health record; rapid ranking of candidate trial-patient matches based on embeddings in vector space; and classification of whether a candidate match represents a reasonable clinical consideration. Code and synthetic data are available at https://huggingface.co/ksg-dfci/MatchMiner-AI . Model weights based on synthetic data are available at https://huggingface.co/ksg-dfci/TrialSpace and https://huggingface.co/ksg-dfci/TrialChecker . A simple cancer clinical trial search engine to demonstrate pipeline components is available at https://huggingface.co/spaces/ksg-dfci/trial_search_alpha .

Artificial intelligence has significantly advanced healthcare, particularly through large language models (LLMs) that excel in medical question answering benchmarks. However, their real-world clinical application remains limited due to the complexities of doctor-patient interactions. To address this, we introduce AI Hospital, a multi-agent framework simulating dynamic medical interactions between Doctor as player and NPCs including Patient, Examiner, Chief Physician. This setup allows for realistic assessments of LLMs in clinical scenarios. We develop the Multi-View Medical Evaluation (MVME) benchmark, utilizing high-quality Chinese medical records and NPCs to evaluate LLMs' performance in symptom collection, examination recommendations, and diagnoses. Additionally, a dispute resolution collaborative mechanism is proposed to enhance diagnostic accuracy through iterative discussions. Despite improvements, current LLMs exhibit significant performance gaps in multi-turn interactions compared to one-step approaches. Our findings highlight the need for further research to bridge these gaps and improve LLMs' clinical diagnostic capabilities. Our data, code, and experimental results are all open-sourced at https://github.com/LibertFan/AI_Hospital.