Treatment

LLM-based simulated clients are increasingly used to train novice counselors, evaluate LLM therapists, and generate synthetic data. However, current simulators produce overly cooperative clients that disclose too readily, accept therapeutic reframes without resistance, and resolve core issues within a single session. We trace these issues to profiles that lack causal depth and behavioral mechanisms that treat all content as equally accessible. We present PatientAct, a framework for client simulation grounded in established clinical theories. Our profiles integrate the 5Ps clinical case formulation, providing causal depth without tying the design to any single therapeutic modality. During simulation, profiles include a dynamic memory layer in which items carry trust thresholds (e.g., symptoms are available early, whereas formative memories require a sustained therapeutic alliance). At each turn, the client's emotional reaction and behavior are modeled before generating a response. If the therapist approaches gated content, PatientAct expresses resistance in terms of quantity, content, and style rather than defaulting to cooperation or a single resistance pattern. We evaluate our framework on 40 clinical situations and demonstrate that it generates diverse profiles with high clinical plausibility. Moreover, PatientAct significantly outperforms the baselines, yielding substantial gains in resistance quality and behavioral realism. Our code and data will be publicly available via github.com/Sahandfer/PatientHub.

Clinical prediction models are often developed as if the outcome of interest were cleanly observed for every patient. This assumption fails when treatment decisions make the clinically relevant outcome permanently unobservable. As a case study of this problem, we consider post-cardiac-arrest neurological prognostication using a cohort of 2,497 patients, including 1,429 patients whose outcomes were rendered indeterminate by treatment decisions. These patients with indeterminate outcomes were reviewed by independent clinical experts, who provided their guesses of counterfactual outcomes about what would have happened to the patients. We refer to these patients as uncertain cases. We also have patients for whom we observe their clinically relevant outcomes; we refer to these patients as certain cases. We propose a framework for evaluating prediction models that explicitly splits the evaluation between certain and uncertain cases. Here, we cannot easily evaluate both types of cases in a uniform manner as the available target labels differ. We then propose a simple prediction model that uses target labels from both certain and uncertain cases in a manner that allows us to trade off between them. Across the proposed neural model and a collection of tabular baselines, models with similar certain-case AUROC can nevertheless differ substantially in both certain-case Brier score and their probability estimates for uncertain cases. Improving alignment with target labels of uncertain cases for our proposed model generally comes at the cost of worse accuracy on certain cases, highlighting an explicit tradeoff that standard evaluation conceals. These results show that when treatment decisions determine whether clinically meaningful outcomes remain observable, conventional evaluation metrics can miss important failure modes in the very patients for whom prognostic support matters most.

Large language models (LLMs) increasingly provide conversational health information that may influence treatment decisions, yet existing benchmarks do not isolate whether medication-safety boundaries persist across follow-ups after explicit self-treatment intent. We introduce TAF-MED, a physician-reviewed benchmark of 500 fixed three-turn scenarios, and evaluate eight LLMs across 4,000 conversations. A rubric-based automated judge labelled responses as SAFE, LEAKY, or UNSAFE, and two physicians independently annotated a model-balanced random subset of 400 conversations. We assessed unsafe guidance, collapse after a strictly SAFE initial response, and model-ranking stability. Overall, 71.6% of conversations contained an UNSAFE response, and 61.4% of those beginning with a strictly SAFE response later collapsed to UNSAFE; model-level collapse rates ranged from 24.4% to 96.2%. Four of 28 model pairs reversed order between initial unsafe and collapse rates. Automated labels achieved 94.3% agreement with the adjudicated physician reference ($κ= 0.895$). These findings show that first-turn safety is an incomplete proxy for conversational safety persistence and motivate evaluation across complete dialogue trajectories. We will release TAF-MED on Hugging Face to support reproducible research on multi-turn medical safety.

Treatment planning in precision oncology requires synthesizing heterogeneous patient information with rapidly evolving clinical guidelines to ensure guideline-concordant care. While large language models (LLMs) show promise in many diagnostic tasks, their adoption for high-stakes treatment planning is hindered by complex reasoning, adherence to timely clinical guidelines, and safety concerns. In this study, we present GatorOnco, an agentic LLM for colorectal cancer (CRC) treatment planning. GatorOnco is developed using a total of 282 billion tokens of biomedical text, including healthcare system-scale clinical text comprising 166 billion tokens from UF Health. We implemented a domain-adaptation method that integrates pre-training, model merging, a two-stage post-training approach, and agent-based reinforcement learning. An agentic retrieval-augmented generation (RAG) approach dynamically integrates time-sensitive clinical guidelines into the reasoning process. In a blind, randomized clinical evaluation conducted by five UF Health oncologists, GatorOnco significantly outperformed open-source LLMs (P < 0.01) and achieved expert-level performance comparable to UF Health oncologists. Compared with expert oncologists, GatorOnco received significantly higher ratings for readability (4.46 vs. 4.19, P < 0.01) and completeness (3.91 vs. 3.52, P < 0.01), while showing statistically comparable performance in correctness (4.09 vs. 4.11, P = 0.921), currency (4.04 vs. 3.98, P = 0.478), and safety (4.22 vs. 4.22, P = 0.999). These findings demonstrate that integrating agentic reasoning with large-scale domain adaptation can help bridge the gap for generative AI in high-stakes cancer treatment planning.

Synthetic generation of Cognitive Behavioral Therapy (CBT) sessions is challenged by two competing demands: adhering to strict therapeutic structure while modeling the resistant, unpredictable behavior of real patients. Existing script-based methods fail to capture dynamic therapeutic interactions, while multi-agent approaches struggle to adhere to CBT's sequential structure; both suffer from sycophancy, producing overly compliant patients that misrepresent real clinical settings. In this work we introduce ODRA, a novel framework for synthesizing therapy dialogues through a Chain-of-Thought (CoT) strategy grounded in foundational CBT guidelines (Beck, 2020). ODRA further incorporates a resistance orchestrator to solve patient sycophancy, which employs steering techniques to elicit behaviors aligned with their resistance level. Automated and expert evaluations show that ODRA significantly outperforms existing methods across therapeutic skills, CBT alignment, and patient behavioral fidelity, with licensed psychologists preferring ODRA sessions across 12 of 13 clinical metrics. Furthermore, models fine-tuned on our dataset demonstrate superior therapeutic performance against both cooperative and resistant patients, validating that explicit resistance modeling in synthetic training data directly translates to downstream clinical robustness.

Causal inference usually concerns a scalar treatment, yet in many problems the treatment is unstructured: a text, an image, or a sequence of clinical decisions. Consider an instructor writing a course description to attract more students: the treatment is the course description, and the outcome is enrollment. The standard target, the average treatment effect of fixing the treatment to one exact value versus another, runs into two problems. It cannot be estimated, because almost no exact description recurs across courses, leaving no comparable group from which to measure its effect; and it would be of little use even if it could, since no one wants every course to carry the same description. What the instructor actually wants to know is which features of a description raise enrollment, and which of those features can be acted on across many courses. To this end, we propose a causal query for unstructured treatments: the maximally influential feature (MIF), the feature of the treatment that most strongly influences the outcome. We formalize the MIF as a binary feature of the treatment, defined by a feature-scoring function, constrained so that both of its values stay well populated, and chosen to maximize the causal effect it induces. Turning the feature on shifts the distribution of treatments toward those that display it, turning it off shifts away, and the MIF effect contrasts the two average potential outcomes. We study identification conditions for the MIF, develop algorithms to estimate it, and make it actionable through a nudging algorithm that revises a treatment along the MIF into an outcome-improving version. We illustrate the MIF algorithm across applications in text, image, and dynamic treatment sequences.

Psychotherapists need repeated training and supervision; however, scalability is problematic. We present MyMentorLLM, a multimodal voice- and text-based deliberate-practice environment with 2,100 complete Cognitive Behavioural Therapy (CBT) sessions. Each session links a DSM-5-TR-grounded LLM patient (with major depressive, generalised anxiety or borderline personality disorder), an LLM therapist-in-training and an LLM expert supervisor (powered by Gemma-4, Gemini-3.1-Flash-Live and Qwen-3.6). Sessions were analysed for emotional dynamics, therapeutic competence and diagnostic accuracy against human psychotherapy data. Simulated patients expressed disorder-congruent emotional profiles, which therapists mirrored as in human counselling. LLM trainee competence was rated above human levels in most conditions, while native speech-to-speech was closest to human scores. Supervisor feedback improved diagnostic accuracy in 5 of 7 LLM conditions, whereas symptom identification accuracy increased with model size. This work shows deliberate practice can be simulated for CBT training, although patient fidelity, supervisor calibration and harmful feedback require evaluation via a complex systems perspective.

Causal inference has become a central issue across various fields, including computer science, statistics, economics, education, healthcare, and medicine. The broad applicability of this discipline has garnered increased research funding and attention. In recent years, the estimation of causal effects from observational data has gained traction due to the vast amounts of collected data and the lower costs compared to randomized controlled trials. Advances in causal effect estimation methods have enhanced service personalization tools. For instance, these tools can help identify the most effective type of treatment (considering both cost and success rate) for each patient among different medical service options. This paper proposes an innovative method for estimating the heterogeneity of treatment effects. The structure of the proposed model is based on a deep neural network and a pseudo-single learner. The proposed method has been compared with other state-of-the-art methods on the IHDP benchmark. Acceptable results have been obtained by using one estimator to estimate the potential outcomes of two treatment groups. Accordingly, this paves the way for further development and improvement of the proposed method.

Traditional randomized trials often obscure clinically meaningful heterogeneity in treatment response by focusing on average effects. Leveraging real-world data to emulate clinical trials and estimate heterogeneous treatment effects (HTEs) offers a promising path toward more precise and efficient trial design. In this study, we emulate the DAPA-HF trial using electronic health records from the Mayo Clinic Cloud (MCC) to investigate whether HTE-guided stratification can identify patient subgroups with distinct treatment responses to dapagliflozin versus placebo in patients with heart failure with reduced ejection fraction. All-cause mortality was evaluated using Cox proportional hazards models, with HTEs estimated using a Meta-S learner and subgroups defined using a decision tree-based thresholding approach. In the overall cohort of the emulation, no significant treatment difference was observed (HR, 1.681; 95% CI, 0.828-3.413; p = 0.1507). However, compared with the overall emulated cohort, in which dapagliflozin showed no statistically significant survival benefit, HTE-driven stratification identified subgroups with significant and directionally distinct treatment effects. The beneficial (low-HTE) subgroup showed a significant survival benefit from dapagliflozin (HR = 0.203, 95% CI, 0.087-0.476, p = 0.0002), whereas the harmful (high-HTE) subgroup showed a significant harmful association with markedly increased mortality risk (HR = 6.680, 95% CI, 2.759-16.171, p < 0.0001). These findings indicate that HTE-guided stratification can uncover clinically meaningful beneficial and harmful treatment-effect patterns that are masked in the full-cohort emulation.

This article explores the application of covariate balance diagnostics for detecting the presence of hidden confounding/model miss-specification in studies applying offline reinforcement learning (RL) to deriving optimal treatment recommendations. The results demonstrate that, either there is a high risk of bias within existing offline RL studies for treatment recommendations or, existing covariate balance metrics are not sufficient to assess such studies. Regardless, existing offline RL studies cannot be concluded as being statistically robust. The conclusions propose future research directions for obtaining more methodologically robust applications of offline RL to treatment recommendation problems.

Policy learning methods are increasingly used to inform treatment allocation under budget constraints. Most proposed methods assume complete treatment data, yet applications frequently suffer from missingness that can bias estimates and lead to suboptimal policies. We address this gap by extending efficient estimators for average treatment effect (ATE) estimation to policy value and conditional average treatment effect (CATE) estimation under missing at random (MAR) and missing completely conditionally at random (MCCAR) treatment data. Through asymptotic efficiency analysis, we prove that the MAR estimator, which leverages partially-observed units, is both valid and more efficient than the MCCAR estimator when MCCAR assumptions hold. This result provides formal justification for preferring MAR-based estimation in policy learning under both missing data settings. Our comprehensive experiments using synthetic and semi-synthetic datasets confirm that correctly specifying the missingness mechanism is crucial: misspecified estimators remain biased regardless of sample size, while our estimators achieve near-oracle performance when assumptions are satisfied. Our work provides practitioners with theoretically grounded, empirically validated tools for robust policy learning in the presence of missing treatment data.

Brain tumor progression exhibits spatially heterogeneous growth, patient-specific treatment response, and complex interactions with surrounding anatomy, making accurate long-term prediction challenging. We propose an AI-augmented adaptive digital twin (DT) framework for brain tumor evolution prediction and treatment scheduling. The framework integrates an interpretable reaction--diffusion (RD) model, a 3D residual learning module for model-form correction, patient-specific DT updating during recursive rollout, and model predictive control (MPC) for constrained chemotherapy and radiotherapy scheduling. Experiments on 387 synthetic tumor trajectories with 120-step evolution show that the baseline RD model captures tumor location and overall temporal behavior but underestimates heterogeneous tumor burden during long-horizon prediction. Hybrid RD--residual modeling reduces masked voxel-wise mean squared error by 84.3% and increases Dice overlap by 43.5% relative to the RD baseline under dense simulated observations. Online DT updating further reduces mean squared error by 45.9% and improves Dice overlap by 9.6% compared with the non-updated hybrid model. In MPC-based scheduling simulations, the updated DT controller reduces final tumor burden by 22.4% relative to a fixed treatment schedule under the terminal-burden objective. Together, these results demonstrate a unified framework for patient-specific initialization, mechanistic modeling, adaptive learning, and constrained treatment optimization. Although validated using patient-data-informed synthetic trajectories rather than clinical longitudinal data, the proposed framework establishes a foundation for future translation to real-world adaptive treatment planning.

Hepatocellular carcinoma (HCC) is a common malignancy and a leading cause of cancer-related mortality. Current guidelines and staging systems provide coarse categories, but often miss within-stage heterogeneity and the clinical context in electronic medical records (EMRs). We present HCC-STAR (Hepatocellular Carcinoma Staging, Treatment And pRognosis), a clinically aligned large language model that reads routine EMR narratives and jointly outputs risk score-based staging, ranked guideline-consistent treatments with evidence-based rationales, and individualized survival estimates. We curated about 30,000 HCC cases from SEER and expanded them into EMR-style narrative training data using a clinician-validated, prompt-based augmentation workflow. On this corpus, we developed a knowledge-aligned reasoning framework optimized with a step-verifiable composite reward, moving beyond text-level memorization of clinical guidelines. In a multi-center cohort of 6,668 patients from 12 hospitals in China, HCC-STAR achieved state-of-the-art performance in treatment recommendation and risk stratification compared with clinical guidelines and competitive models, including GPT-5 and Gemini-2.5 Pro. Hypothetical overall-survival analysis showed a median survival of 51 months under adherence to HCC-STAR recommendations, compared with 29 and 32 months under BCLC and CNLC. In clinician-centric evaluations, blinded hepatobiliary specialists rated HCC-STAR's reasoning and evidence-based justifications as trustworthy. The model surpassed resident and attending physicians in treatment accuracy and helped physicians make more accurate decisions faster when used as an assistant. These findings support HCC-STAR as a reliable and verifiable decision-support system for risk stratification and precision therapy in HCC.

Accurate prediction of patient-specific therapeutic response from pre-treatment transcriptomes is hindered by the scarcity of matched clinical response labels and post-treatment molecular profiles. Preclinical transfer-learning models can simulate drug-induced expression changes but are often hard to interpret and unstable, whereas knowledge-graph methods provide mechanistic context yet remain static and fail to capture drug-induced transcriptomic perturbation dynamics. We propose PREDIKTOR, a patient-centered multi-view framework that aligns a personalized network view with a transferable transcriptomic perturbation view to predict clinical drug response. For each patient, we construct an individualized gene regulatory network from tumor expression using DysRegNet and augment it with drug-target links from DrugBank; a graph neural encoder yields a drug-centric, mechanistically grounded embedding. In parallel, a frozen condition-specific gene-gene attention model pretrained on LINCS L1000 generates a simulated post-perturbation transcriptomic profile for the same patient-drug pair. We align the two views in a shared latent space via a CLIP-style contrastive objective with drug-context hard negatives, then concatenate the representations for end-to-end response classification. On TCGA, PREDIKTOR consistently outperforms state-of-the-art baselines under patient-, drug-, and tissue-split evaluations, and transfers zero-shot to the I-SPY2 trial, improving AUROC by 5.6% over competing methods. The aligned embeddings yield stable gene and pathway attributions that recover known mechanisms, supporting actionable and interpretable precision oncology.

Estimating heterogeneous treatment effects (CATE) requires simultaneously detecting effect modification and quantifying estimation uncertainty. Existing tree-based methods make an uneasy trade-off: significance-based approaches (Radcliffe and Surry 2011) identify subgroup interactions directly but lack valid inference; honest causal trees (Athey and Imbens 2016) deliver nominal confidence interval coverage but use outcome-agnostic splitting criteria that sacrifice interaction sensitivity. We introduce a hybrid algorithm that fuses significance-based splitting with honest sample-splitting and cross-validation. Our splitting criterion uses the squared $t$-statistic for the treatment $\times$ side interaction ($t^2$), which is shown to be directly aligned with the honest $\text{EMSE}_τ$ criterion when the interaction is strong. Post-hoc honest cross-validation selects the cost-complexity penalty, giving a single principled estimator with nominal CI coverage at the leaf level. For forests, we retain bootstrap count vectors to enable an infinitesimal jackknife (IJ) variance estimate of Monte-Carlo convergence rather than formal pointwise inference. On the three synthetic designs from (Athey and Imbens 2016) the single tree achieves approximately 90% leaf-average CI coverage at the 90% nominal level across all three designs (200 replications each); on the Criteo, Hillstrom and Starbucks uplift datasets we match Qini coefficient performance of S-, T-learner and GRF baselines. An open-source Python package with reproducible seeds, sklearn-compatible API, and full test coverage accompanies this work (https://codeberg.org/hadjipantelis/rattus).

Image-guided therapies, including radiotherapy, biopsy and deep brain stimulation, rely on real-time targeting of anatomical structures. However, in the presence of motion, imaging latencies create a temporal misalignment between observed and true anatomy, compromising treatment accuracy. Artificial intelligence-based frameworks have increasingly been presented to close this latency gap, but leading personalised models can fail due to a lack of stable anatomical grounding. Foundation models can provide grounded behaviour, but they do not adapt to real-time, individual patient dynamics. Here we introduce a closed-loop coupling framework that synergises patient-specific temporal prediction with continuous segmentation-based anatomical interpretation from a foundation model. A personalised model predicts future anatomy to compensate for system latency, while a streaming foundation model provides anatomical supervision used to continuously update the temporal predictor in real time during treatment. We validate the framework using a digital phantom and intrafraction magnetic resonance imaging (MRI) from patients undergoing MRI-guided radiotherapy. For a prediction horizon of 400 ms, the proposed method improves anatomical prediction and reduces dosimetric error compared with existing approaches, within clinically relevant latency constraints. These results establish closed-loop coupling as a general strategy for real-time image-guided intervention.

Large language models show promise for mental health support, yet therapeutic quality improves only when evaluation functions as an actionable control signal rather than a passive metric. We introduce a framework that formulates therapeutic response generation as a decision-refinement problem driven by multi-dimensional, human-aligned evaluation. In Stage I, we introduce TheraJudge, an open-source therapeutic evaluator trained via preference-based optimization on human-annotated data to produce reliable judgments across 7 psychological dimensions. In Stage II, we introduce TheraAgent, which operationalizes TheraJudge's evaluations through a coordinated refinement process with specialized Critic, Coach, and Therapist roles that translate evaluative signals into targeted response revisions. Empirically, TheraJudge achieves strong agreement with clinician ratings, with intraclass correlation coefficients (ICC = 0.87-0.95), surpassing supervised baselines and strong closed-source judges, particularly on critical dimensions such as Safety, Relevance, and Empathy. Acting on these evaluations, TheraAgent yields a +0.43 improvement in human-rated therapeutic quality (on a 5-point scale) under blind evaluation, with 96% clinician inter-rater reliability. Low-quality responses ($\leq 3$) improve by +2.45 points with a 94% recovery rate, demonstrating targeted correction of unsafe outputs. Overall, our results indicate that effective alignment of mental-health LLMs stems from acting on human-aligned evaluation, rather than relying solely on stronger generation. We release code at https://github.com/vis-nlp/TheraAlign.

Treatment reasoning underpins every therapeutic decision, integrating disease context, comorbidities, medications, contraindications, and evolving biomedical knowledge to select an appropriate therapy. It is inherently iterative: candidates are weighed against many constraints, revised as evidence emerges, and grounded in verifiable sources. Here we introduce ATHENA-R1, an AI agent for treatment reasoning across all FDA approved drugs since 1939, trained by reinforcement learning over a universe of 212 biomedical tools. At each step it identifies missing information, selects and runs relevant tools, and incorporates the evidence. To train it without human-annotated traces, we build a two-level self-learning framework: multi-agent systems construct the tools, tasks, and reasoning trajectories for supervised fine-tuning, then reinforcement learning with scientific feedback rewards reasoning quality (evidence gathering, grounded tool use, logical non-redundancy). Across five benchmarks of 3,168 drug reasoning tasks and 456 patient treatment cases, ATHENA-R1 outperforms language models and tool-use systems, reaching 94.7% accuracy on open-ended drug reasoning and 82.9% on treatment reasoning, 17.8 and 10.7 points above GPT-5. In blinded evaluations by experts from 28 rare disease organizations, it is preferred over reference models on all criteria, and physicians rated it favorably on complex hospitalized cardiovascular and infectious-disease cases. Adverse-event hypotheses it generated, tested in electronic health records from 5.4 million patients, reached adjusted odds ratios of 1.48-1.84, with no elevation among negative controls. Because it requires knowing what evidence to seek before concluding, treatment reasoning has long been hard for AI; we show it can be reframed as a learnable process of iterative evidence gathering that reinforcement learning can train AI to perform.

Large language models (LLMs) are increasingly piloted in African healthcare contexts, raising concerns about their potential to manipulate users in high-stakes settings. In a randomised experiment, we examined the manipulative capabilities of two publicly available models, ChatGPT 5.2 and DeepSeek V3.2, among Kenyan participants (N = 303). Participants interacted with either a manipulative variant or a non-manipulative variant before making a treatment decision within a hypothetical clinical scenario. The manipulative variant was prompted to covertly steer participants towards an incorrect treatment option while the non-manipulative variant served as the control condition. Manipulation success rates were higher in the manipulative condition (59.5%) than in the control condition (44.0%), with the effect reaching significance (OR = 2.11, 95% CI [1.12, 4.00], p = .021). These findings highlight the need for improved safety infrastructure specifically targeting manipulation, particularly given the integration of AI into healthcare systems across Africa.

The presence of confounding bias poses a key challenge in policy evaluation, as the target causal effects of actions are not identifiable (i.e., underdetermined) from observational data. On the other hand, existing confounding-robust evaluation strategies require detailed prior knowledge about the environment or apply only to discrete treatments and outcomes. This paper investigates causal effect evaluation over the continuous domain from confounded observations, while requiring only basic temporal ordering between the treatment and the outcome. We introduce a universal discretization of the exogenous domains that approximates the observational and interventional distributions of any causal model with arbitrary accuracy using a finite number of latent states. Building on this newfound universal approximation property, we develop a novel family of Causal Gaussian process (CGP) models that effectively approximate the observational and interventional distributions of any causal model with confounded observations.

Training psychotherapists in evidence-based interventions such as Acceptance and Commitment Therapy (ACT) requires repeated practice with meaningful feedback, yet opportunities for safe, standardized training are limited by ethical, logistical, and resource constraints. We introduce a system designed to support ACT-oriented psychotherapy training through spoken dialogue with an embodied virtual patient. The system uses large language models to simulate patient behavior conditioned on profiles derived from real therapy sessions and configurable clinical scenarios, while a separate automated evaluator provides turn-by-turn feedback on therapist responses based on established ACT fidelity criteria. Rather than aiming to replace supervision, the system is intended to support deliberate practice by enabling experimentation, reflection, and immediate feedback in low-risk settings. Expert evaluation with practicing psychologists confirmed high realism in patient behavior and demonstrated that immediate turn-by-turn ACT feedback increased therapists' awareness of intervention choices and enabled effective experimentation with alternative responses. Quantitative evaluation across 49 therapy transcripts identified GPT-4o-mini as the optimal feedback model, achieving the lowest mean absolute error (MAE = 6.12) in replicating human supervisor ACT fidelity ratings with statistically significant agreement. This work demonstrates the potential of fidelity-aware simulated patients as a scalable complement to psychotherapy training.

When a bacterial sample is exposed to several antibiotics, not every applied drug necessarily acts: if the organism is resistant to one of them, that drug leaves no morphological trace. The clinically meaningful quantity is therefore not which antibiotics were applied, but which ones were active. We show that these two are sharply decoupled in real E. coli microscopy - naively assuming the applied combination equals the active one is correct only about 37% of the time - yet existing computational tools are ill-suited to recovering the active set. Forward perturbation models such as scGen, CPA, and IMPA are designed to predict appearance from treatment, not the reverse, and inverting them degrades sharply; discriminative image classifiers tend to memorise strain- and batch-specific texture and fail to transfer across experimental replicates. We introduce AURA, which reframes the task as constrained, energy-based inverse attribution. Its central inductive bias is that the active set must be a subset of the applied set; this collapses the candidate space and lets AURA infer the active subset of applied antibiotics by decomposing residual morphology into antibiotic response atoms and selecting the subset with the lowest reconstruction energy, using no strain label at test time. AURA-E adds evidence-aware abstention, withholding a prediction when candidate explanations remain near-equally plausible. On cross-replicate transfer in an E. coli cytological profiling dataset, AURA recovers the active antibiotic combination with 95.47% exact-match accuracy.

Historical medical archives and traditional medicines hold immense potential for drug discovery and remain a primary source for current drug development. However, pre-ontological prose and idiosyncratic taxonomies prevent the standardization and medical modernization of the data for use in current biomedical pipelines. Furthermore, no existing LLM agent system, whether tool-calling, retrieval-augmented, or agentic deep-research, can convert such text into verifiable drug-discovery leads at scale. We close this gap with DeepRoot, a multi-agent LLM system that jointly builds and utilizes a verified knowledge graph, showing that grounding and reasoning -- often conflated -- are separable axes the system can compose for therapeutic reasoning. Applied to the Shen Nong Ben Cao Jing, DeepRoot recovers $10$ of $21$ held-out compound-disease treatment pairs at R@$20$ ($47.6\%$ vs $4.8\%$ for a raw corpus LLM and $\sim\!2.4\%$ random) and dominates an LLM-as-judge audit for reasoning quality over baseline LLMs and LLMs with direct tool-call access to the same APIs DeepRoot itself queries. Tool-using LLMs hallucinate evidence on $87\%$ of claims, versus 7-10% for DeepRoot. Graph-only inference hallucinates $0\%$ but ranks lowest on reasoning coherence; DeepRoot KG+LLM is the only condition to win on both axes, pointing toward a route for systematic mining and repurposing of historical medical knowledge.

Telehealth, the delivery of medical care remotely, is hoped to increase access to specialty services or decrease health care utilization. Physicians can provide telehealth to each other or to patients. Specialists often treat complex patients who can be adequately cared for only in academic hospitals, suggesting that providing specialty services via telehealth will reallocate rather than reduce system utilization. Here I use agent-based modeling to investigate telehealth's effects on clinical outcomes and system utilization in medical toxicology. I found that physician-physician telehealth increased patient health but system utilization did not change. The effects were more pronounced as clinical complexity increased. Physician-patient telehealth increased cost and system utilization but not clinical outcomes. Within the limitations of our approach, these results suggest that telehealth is more cost-effective for improving generalist access to specialist knowledge than in providing care to the public.

Advances in computational modeling, neuroimaging, and artificial intelligence are revolutionizing the modeling of neurological disorders for improved diagnostics, prognosis, and treatment planning. Mechanistic models provide valuable scientific insight into the disorders, but in practice they are often simplified with assumptions or computationally expensive and slow to solve. However, while purely data driven approaches provide speed and scalability, they require large, high quality data to train and generally suffer from interpretability and generalization issues. This perspective paper presents a structured overview of hybrid modeling strategies, which combine deep learning models with physics based solvers, and are categorized into parallel, series, and parallel-series architectures. Three main approaches that have been emphasized are residual modeling for missing or incomplete physics, Neural Ordinary Differential Equations (NODEs) for continuous time dynamics approximation, and solver in the loop that accelerates traditional solvers with neural approximations. These hybrid models integrate the governing differential equation based formulations and deep learning to characterize the evolution of neurological disorders, and promise advanced personalized neurological modeling. In addition, the study explores and proposes different hybrid configurations to improve diagnosis accuracy, predict disease progression, and inform treatment strategies across a range of neurological disorders. These capabilities outperform standalone mechanistic or purely data driven approaches, making hybrid modeling a powerful tool, especially in applications involving modeling the progression and treatment responses in neurological conditions such as brain tumors, Alzheimer's disease, and stroke.

CARE-link is an open-source, web-based clinical support platform designed to improve the management of gestational diabetes by linking clinicians and patients through an LLM-mediated workflow. The system aggregates patient-generated data outside the hospital, summarizes relevant clinical information, and delivers context-aware decision support to clinicians. For patients, CARE-link provides clear explanations of management plans and delivers timely lifestyle guidance through a WhatsApp interface. The integrated dual-facing design aims to promote continuous monitoring, support individualized care, and reduce the burden of in-clinic follow-ups. Built with a modular architecture, the platform can be adapted to other chronic conditions requiring longitudinal tracking and behavioral support. CARE-link has the potential to enhance clinical oversight, promote patient compliance, and strengthen continuity of care particularly in resource-constrained settings.

Large language models (LLMs) have shown growing potential for Cognitive Behavioral Therapy (CBT) counseling. However, most existing approaches still formulate counseling as a local response generation problem, focusing on empathetic replies within short, text-only, or single-session interactions. We argue that this formulation fundamentally mismatches the nature of real psychotherapy. In clinical CBT, therapy is a longitudinal process in which therapists continuously infer, update, and intervene on evolving therapeutic states across sessions. Realistic CBT further involves multimodal inference and delayed cross-session intervention effects, requiring models to capture longitudinal therapeutic state evolution under partial observability. We propose DMT-CBT, a framework for Dynamic Modeling of evolving Therapeutic states in CBT counseling. DMT-CBT maintains structured therapeutic states across sessions while incorporating multimodal behavioral grounding and tool-augmented intervention to support adaptive therapeutic reasoning. Based on this framework, we construct DMTCorpus, a synthetic multi-session multimodal CBT counseling dataset featuring evolving therapeutic states, image-grounded client behaviors, and cross-session intervention continuity. Experimental results show that DMT-CBT improves counseling fidelity and therapeutic alliance, produces more favorable longitudinal affective trajectories, and preserves therapeutic states more faithfully than post-hoc extraction approaches.

Dynamic medical treatment requires deciding treatment intensity and intervention timing, while patient states evolve continuously and adverse events may occur between clinical interactions. Most existing treatment learning methods assume fixed schedules or enforce safety only at discrete decision points. We propose Interaction-Limited Safe Continuous-Time Reinforcement Learning, a framework that jointly optimizes treatment administration and clinical interaction timing under trajectory-level safety constraints. Our key idea is to reformulate the continuous time treatment problem as an option-based semi-Markov decision process, where each option specifies a continuous-time treatment policy and its duration. We develop a safety-tightening mechanism showing that suitably constructed constraints at interaction times guarantee safety over the full continuous-time trajectory with high probability. We further establish finite-sample guarantees for policy learning from logged treatment trajectories and introduce a practical data-driven conservative surrogate. Experiments show that the proposed adaptive interaction-timing mechanism improves both safety and treatment effectiveness over equidistant interaction schemes across different safe policy optimization methods.

Medical treatment recommendation poses several challenges to reinforcement learning (RL): patient physiology evolves in continuous time, measurements and interventions are performed at irregular intervals, and treatment effects vary substantially across individuals. Existing RL formulations and simulated environments, however, are based on discrete-time MDPs with fixed decision intervals. Thus, it remains difficult to evaluate whether RL methods can handle time-interval-dependent disease progression, personalized treatment response, and safety between consecutive measurement points. To address this gap, we introduce MedGym, a benchmark environment for dynamic treatment recommendation. MedGym models longitudinal patient evolution in a continuous-time framework and constructs a configurable medical RL benchmark from clinical data by using Physics-Informed Neural Networks. The resulting benchmark enables direct comparison between discrete-time and continuous-time methods under irregular treatment timing and patient-specific dynamics. Furthermore, MedGym supports evaluation from clinically important perspectives, such as personalization and trajectory-level safety. By providing a standardized and configurable benchmark for continuous-time dynamic treatment, MedGym enables more realistic and informative evaluation of medical RL methods.

In this work, we propose a prototype machine-to-machine (M2M) knowledge-guided Large Language Model (LLM) framework for automated radiotherapy treatment planning. In the proposed paradigm, Treatment Planning Parameter (TPP) distribution knowledge discovered by a Deep Reinforcement Learning (DRL) agent is transferred to an LLM agent through in-context learning, enabling autonomous iterative planning without human intervention. While standard LLM-based planning often lacks physical intuition and struggles with convergence, the integration of DRL-derived guidance constrains the agent to a physically valid parameter space. Experimental evaluations are performed across three diverse planning scenarios: basic prostate cases, complex prostate configurations with increased organ-at-risk (OAR) constraints, and liver cases. The evaluation results demonstrate that the guided LLM agent consistently achieves optimal planning scores while significantly reducing the number of iterations compared to unguided planning. Analysis of the final TPP configurations reveals that the agent successfully learns a hierarchical priority of objectives, effectively restoring a logical "cause-and-effect" relationship between parameter tuning and dosimetric outcomes. Crucially, this prototype framework exhibits robust generalizability, maintaining high planning quality regardless of specific patient anatomy, treatment site, or initial plan quality. By bridging the specialized optimization of DRL with the adaptive reasoning of LLMs, this M2M framework establishes a scalable foundation towards generalizable autonomous treatment planning, ultimately benefiting clinical practice in realistic environments.

The treatment of ischemic stroke using mechanical thrombectomy involves difficult decisions under intense time constraints. Numerical physics simulations can in theory inform operators to make better decisions regarding treatment approaches and device selection, but are too slow to do so in practice. In this thesis, we investigate if current machine learning based surrogates can accurately emulate these simulations in a step-by-step manner while making them significantly faster. To do this we train three surrogate models on two simulations that involve a simplified aspiration procedure, with varying levels of geometric complexity. Our results show that two of our models accurately predict singular simulation steps and provide substantial speedups, especially when combined with specific data augmentations. However, the models showed a lack of stability when emulating simulations with complex geometries over longer time periods. Overall, this work provides a foundation for future studies to develop stable methods that scale to realistic numerical physics simulations of mechanical thrombectomy.

Clinical foundation models are evaluated with factual or exam-style medical QA, but treatment decisions must change when patient context changes. We introduce ClinPivot, an auditable treatment-decision benchmark built from biomedical relations and pivoted patient contexts. ClinPivot asks whether models change treatment choices when new clinical constraints shift the action space. We find that strong medical QA performance does not reliably predict decision-making performance: frontier models and task-adapted Qwen variants often fail to change decisions correctly, and model rankings shift across evaluation regimes. Decision-structured supervision improves pivot-sensitive decision-making and medical QA under matched knowledge budgets, while lightweight replay reduces losses in general assistant ability.

Understanding the effects of interventions is central to scientific progress, with randomized controlled trials (RCTs) regarded as the gold standard for causal inference in many applied fields. However, RCTs are costly, time-consuming, and often constrained by ethical or practical limitations, motivating the need for causal methods able to draw conclusions from observational data. While such data is collected at ever larger scale, making its use for causal inference is often hindered by the fact that not all variables affecting treatment allocation and the outcome are observed: an issue known as unobserved confounding. In this paper, we introduce a new study design called confounder detection via treatment intent. The idea is to query a human expert who makes treatment decisions, and ask them to compare pairs of units proposed by a principled matching strategy, with the goal of eliciting unobserved variables that explain why treatment decisions differ. We provide a theoretical basis for such a procedure, ascertaining conditions under which such a study design may elicit unobserved confounders. Building on this newly established foundations, we study treatment effects of interventions in the intensive care unit (ICU). First, we show empirical evidence strongly indicating that electronic health records (EHRs) collected in ICUs are subject to unobserved confounding. By using clinical text notes as a proxy for physicians' knowledge and leveraging natural language processing, we provide a proof of concept for our methodology in a semi-synthetic environment with a known ground truth.

Large language models (LLMs) are increasingly being used for emotional support. They are also being developed for formal therapy purposes. However, LLMs like ChaptGPT or Llama are often developed with content moderation guardrails that prevent them from discussing sensitive subjects with users for both liability and safety purposes, and this inability to broach these subjects may affect their capacity as therapists. In this study, we perform an algorithm audit on three state-of-the-art moderation systems (OpenAI's moderation endpoint, Meta's Llama Guard, and Google's Shield Gemma) to investigate the extent to which these systems flag the content of real-life therapy sessions as undesirable. Our results raise implications for the limitations that users and organizations may encounter when designing LLMs to play the part of a therapist.

Public service programs often allocate limited resources under uncertainty about their benefits, creating a need for randomization to support credible evaluation. In practice, however, applicants commonly enter waitlists where resources are prioritized toward individuals judged to have higher need through tiered priority queues, making direct randomization difficult. Motivated by this, we develop an experimental design framework for learning treatment effects while treating those most in need where incoming applicants are randomized into priority queues based on their assessed risk scores. Treatments are then provided across queues in priority order and first-in-first-out within queue as budget becomes available. Our contributions are two-fold. First, we characterize what causal effects are identified under this priority-queue allocation. When arrivals are exogenous, treatments are conditionally randomized, and hence standard estimands are identified; when arrivals are endogenous, queue randomization instead provides an instrument for treatment, identifying local treatment effects induced by the queuing process. Second, we develop optimized queue-assignment designs that trade off statistical efficiency against prioritizing higher-need applicants. We show in the process that, despite dependence in treatment assignments induced by the design, usual iid efficiency bounds remain well-justified design objectives. We illustrate the proposed designs using data from a housing allocation program in a large U.S. county.

Causal inference, estimating causal effects from observational data, is a fundamental tool in many disciplines. Of particular importance across a variety of domains is the continuous treatment setting, where the variable of intervention has a continuous range. This setting is far less explored and represents a substantial shift from the binary treatment setting, with models needing to represent effects across a continuum of treatment values. In this paper, we present the first causal foundation model for the continuous treatment setting. Our model meta-learns the ability to predict causal effects across a wide variety of unseen tasks without additional training or fine-tuning. First, we design a novel prior over data-generating processes with continuous treatment variables in order to generate a rich causal training corpus. We then train a transformer to reconstruct individual treatment-response curves given only observational data, leveraging in-context learning to amortize expensive Bayesian posterior inference. Our model achieves state-of-the-art performance on individual treatment-response curve reconstruction tasks compared to causal models which are trained specifically for those tasks. Inference code (including trained model weights) can be found at https://github.com/layer6ai-labs/CCPFN-inference .

Distributional treatment effects can be invisible to means: a treatment may preserve average outcomes while changing tails, modes, dispersion, or rare-event probabilities. Kernel tests can detect discrepancies between interventional outcome laws, but global tests do not reveal where the laws differ. We propose DR-ME, to our knowledge the first semiparametrically efficient finite-location test for interpretable distributional treatment effects. DR-ME evaluates an interventional kernel witness at learned outcome locations, returning causal-discrepancy coordinates rather than only a global rejection. From observational data, we derive orthogonal doubly robust kernel features whose centered oracle form is the canonical gradient of this finite witness. For fixed locations, we characterize the local testing limit: DR-ME is chi-square calibrated under the null, has noncentral chi-square local power, and uses the covariance whitening that optimizes local signal-to-noise for discrepancies visible through the selected coordinates. This efficient local-power geometry yields a principled location-learning criterion, with sample splitting preserving post-selection validity. Experiments show near-nominal type-I error, competitive power against global doubly robust kernel tests, and interpretable learned locations that localize distributional effects in a semi-synthetic medical-imaging study.

Formulating a treatment plan is inherently a complex reasoning and refinement task rather than a simple generation problem. However, existing large language models (LLMs) mainly rely on one-shot output without explicit verification, which may result in rough, incomplete, and potentially unsafe treatment plans. To address these limitations, we propose TheraAgent, an agentic framework that replaces one-shot generation with an iterative generate-judge-refine pipeline. By mirroring the actual reasoning process of human experts who iteratively revise treatment plans, our framework progressively transforms coarse and incomplete drafts into precise, comprehensive, and safer therapeutic regimens. To facilitate the critical judge component, we introduce TheraJudge, a treatment-specific evaluation module integrated into the inference loop to enforce clinical standards. Experiments show TheraAgent achieves state-of-the-art results on HealthBench, leading in Accuracy and Completeness. In expert evaluations, it attains an 86% win rate against physicians, with superior Targeting and Harm Control. Moreover, the highly agreement between TheraJudge and HealthBench evaluations confirms the reliability of our framework.

Chronic neck pain is a leading cause of disability worldwide, and current treatment selection remains largely trial and error. We present a machine learning framework that uses electroencephalography to predict treatment efficacy in patients with chronic neck pain, with the goal of supporting individualized therapy and reducing the burden on healthcare systems. The framework centers on a rigorous data preprocessing stage tailored to the characteristics of each EEG recording type. For resting-state EEG, the preprocessing pipeline comprises baseline signal removal, bad channel identification and exclusion, re-referencing, bandpass and notch filtering, Independent Component Analysis, and power spectral density analysis. For motor execution and motor imagery recordings, the same initial steps are applied, after which signals are aligned to trigger events so that event-related desynchronization (ERD) and event-related synchronization (ERS) can be quantified. Synchronously recorded electromyography data are bandpass filtered and smoothed with a moving average, then correlated with the corresponding EEG channels to characterize the EEG EMG relationship during attempted movement. In parallel, we performed an extensive literature review of machine learning models applied to clinical EEG (763 records initially screened, 16 patient and 47 healthy-control studies retained), to inform the post-processing strategy. Through this combined preprocessing and review effort, we aim to develop a robust predictive model that can support personalized healthcare strategies in chronic pain management.

This paper develops Virtual Speech Therapist (VST), an intelligent agent-based platform that streamlines stuttering assessment and delivers customized therapy planning through automated and adaptive AI-driven workflows. VST integrates state-of-the-art deep learning-based stuttering classification, and multi-agent large language model (LLM) reasoning to support evidence-based clinical decision-making. The VST begins with the acquisition and feature extraction of patient speech samples, followed by robust classification of stuttering types. Building on these outputs, VST initiates an agentic reasoning process in which specialized LLM agents autonomously generate, critique, and iteratively refine individualized therapy plans. A dedicated critic agent evaluates all generated therapy plans to ensure clinical safety, methodological soundness, and alignment with peer-reviewed evidence and established professional guidelines. The resulting output is a comprehensive, patient-specific therapy draft intended for clinician review. Incorporating clinician feedback, the system then produces a finalized therapy plan suitable for patient delivery, thereby maintaining a clinician-in-the-loop paradigm. Experimental evaluation by expert speech therapists confirms that VST consistently generates high-quality, evidence-based therapy recommendations. These findings demonstrate the system's potential to augment clinical workflows, reduce clinician burden, and improve therapeutic outcomes for individuals with speech impairments. An interactive user interface for the proposed system is available online at: https://vocametrix.com/ai/stuttering-therapy-planning-agent , facilitating real-time stuttering assessment and personalized therapy planning.

Surprisal theory links human processing effort to the predictability of an upcoming linguistic unit, but empirical work often leaves the notion of a unit underspecified. In practice, experimental stimuli are segmented into linguistically motivated units (e.g., words), while pretrained language models assign probability mass to a fixed token alphabet that typically does not align with those units. As a result, surprisal-based predictors depend implicitly on ad hoc procedures that conflate two distinct modeling choices: the definition of the unit of analysis and the choice of regions of interest over which predictions are evaluated. In this paper, we disentangle these choices and give a unified framework for reasoning about surprisal over arbitrary unit inventories. We argue that surprisal-based analyses should make these choices explicit and treat tokenization as an implementation detail rather than a scientific primitive.

How people narrate their experiences offers a window into how the mind organizes them. Computational approaches to therapeutic writing have evolved from lexical counting to neural methods, yet remain fragmented: dictionary tools miss discourse structure, while embeddings conflate local coherence with global organization. No existing framework maps these techniques onto the hierarchical processes through which narratives are constructed. Here we introduce a three-level framework - micro-level lexical features, meso-level semantic embeddings, and macro-level LLM narrative evaluation - and show, across 830 Chinese therapeutic texts spanning depression, anxiety, and trauma, that macro-level evaluation substantially outperforms lexical and embedding features for mental health prediction. This challenges the field's emphasis on word-counting: formal structural features (Labov's story grammar, RST coherence, propositional composition) demonstrate that narrative organization per se carries predictive signal, while clinically-grounded narrative dimensions capture how psychological states are expressed through discourse. Semantic embeddings add minimal independent value but yield incremental gains in multi-level classification. By grounding computational levels in discourse processing theory, this framework identifies macro-structural organization as the primary locus of clinical signal and generates testable hypotheses for intervention design and longitudinal research.

Building trustworthy AI systems for mental health support is a shared priority across stakeholders from multiple disciplines. However, "trustworthy" remains loosely defined and inconsistently operationalized. AI research often focuses on technical criteria (e.g., robustness, explainability, and safety), while therapeutic practitioners emphasize therapeutic fidelity (e.g., appropriateness, empathy, and long-term user outcomes). To bridge the fragmented landscape, we propose a three-layer trust framework, covering human-oriented, AI-oriented, and interaction-oriented trust, integrating the viewpoints of key stakeholders (e.g., practitioners, researchers, regulators). Using this framework, we systematically review existing AI-driven research in mental health domain and examine evaluation practices for ``trustworthy'' ranging from automatic metrics to clinically validated approaches. We highlight critical gaps between what NLP currently measures and what real-world mental health contexts require, and outline a research agenda for building socio-technically aligned and genuinely trustworthy AI for mental health support.

Drug repurposing is often framed as a candidate identification task, but existing approaches provide limited guidance for distinguishing biologically plausible candidates from historically well-connected ones. Here we introduce DrugKLM, a hybrid framework that integrates biomedical knowledge graph structure with large language model-based mechanistic reasoning to enable mechanistically grounded therapeutic prioritization. Across benchmark datasets, DrugKLM outperforms knowledge graph-only and language model-only baselines, including TxGNN. Beyond improved recall, DrugKLM confidence scores exhibit functional alignment with molecular phenotypes: higher scores are associated with transcriptional signatures linked to improved survival across 12 TCGA cancers. The scoring framework preferentially captures biologically perturbational signals rather than historical indication patterns. Expert curation across five cancers further reveals systematic differences in prioritization behavior, with DrugKLM elevating candidates supported by coherent mechanistic rationale and disease-specific clinical context. Together, these results establish DrugKLM as an evidence-integrative framework that translates heterogeneous biomedical data into mechanistically interpretable and clinically grounded therapeutic hypotheses.

Clinical decision-making in oncology requires predicting dynamic disease evolution, a task current static AI predictors cannot perform. While world models (WMs) offer a paradigm for generative prediction, existing medical applications remain limited. Existing methods often rely on stochastic diffusion models, focusing on visual reconstruction rather than causal, physiological transitions. Furthermore, in medical domain, models like MeWM typically ignore patient-specific temporal and clinical contexts and lack a feedback mechanism to link predictions to treatment decisions. To address these gaps, we introduce CLARITY, a medical world model that forecasts disease evolution directly within a structured latent space. It explicitly integrates time intervals (temporal context) and patient-specific data (clinical context) to model treatment-conditioned progression as a smooth, interpretable trajectory, and thus generate physiologically faithful, individualized treatment plans. Finally, CLARITY introduces a novel prediction-to-decision framework, translating latent rollouts into transparent, actionable recommendations. CLARITY demonstrates state-of-the-art performance in treatment planning. On the MU-Glioma-Post dataset, our approach outperforms recent MeWM by 12%, and significantly surpasses all other medical-specific large language models.

We present Tell Me, a mental well-being system that leverages advances in large language models to provide accessible, context-aware support for users and researchers. The system integrates three components: (i) a retrieval-augmented generation (RAG) assistant for personalized, knowledge-grounded dialogue; (ii) a synthetic client-therapist dialogue generator conditioned on client profiles to facilitate research on therapeutic language and data augmentation; and (iii) a Well-being AI crew, implemented with CrewAI, that produces weekly self-care plans and guided meditation audio. The system is designed as a reflective space for emotional processing rather than a substitute for professional therapy. It illustrates how conversational assistants can lower barriers to support, complement existing care, and broaden access to mental health resources. To address the shortage of confidential therapeutic data, we introduce synthetic client-therapist dialogue generation conditioned on client profiles. Finally, the planner demonstrates an innovative agentic workflow for dynamically adaptive, personalized self-care, bridging the limitations of static well-being tools. We describe the architecture, demonstrate its functionalities, and report evaluation of the RAG assistant in curated well-being scenarios using both automatic LLM-based judgments and a human-user study. This work highlights opportunities for interdisciplinary collaboration between NLP researchers and mental health professionals to advance responsible innovation in human-AI interaction for well-being.

Radiotherapy (RT) planning is complex, subjective, and time-intensive. Advances with artificial intelligence (AI) promise to improve its precision and efficiency, but progress is often limited by the scarcity of large, standardized datasets. To address this, we introduce the Automated Iterative RT Planning (AIRTP) system, a scalable solution for generating high-quality treatment plans. This scalable solution is designed to generate substantial volumes of consistently high-quality treatment plans, overcoming a key obstacle in the advancement of AI-driven RT planning. Our AIRTP pipeline adheres to clinical guidelines and automates essential steps, including organ-at-risk (OAR) contouring, helper structure creation, beam setup, optimization, and plan quality improvement, using AI integrated with RT planning software like Varian Eclipse. Furthermore, a novel approach for determining optimization parameters to reproduce 3D dose distributions, i.e. a method to convert dose predictions to deliverable treatment plans constrained by machine limitations is proposed. A comparative analysis of plan quality reveals that our automated pipeline produces treatment plans of quality comparable to those generated manually, which traditionally require several hours of labor per plan. Committed to public research, the first data release of our AIRTP pipeline includes nine cohorts covering head-and-neck and lung cancer sites to support an AAPM 2025 challenge. To our best knowledge, this dataset features more than 10 times number of plans compared to the largest existing well-curated public dataset. Repo: https://github.com/RiqiangGao/GDP-HMM_AAPMChallenge.

AI systems increasingly operate between flexible input representations and formal objects used by downstream tools. A key challenge is recognizing when an unfamiliar formulation denotes a known formal object. We study this challenge through theorem recognition: given an equivalence-preserving transformation of a theorem condition, a model must recover the theorem identity associated with the standard statement. We introduce TREAT, a benchmark for evaluating whether large language models can recover known theorem identities from equivalence-preserving formula-level transformations. Rather than paraphrasing theorem text, TREAT changes the mathematical form of theorem conditions themselves, expressing known results through residual equations, witness statements, optimization identities, set relations, operator forms, and proof-intermediate characterizations. Starting from scraped theorem pages, we filter for entries with usable mathematical expression forms, extract canonical theorem conditions, and generate transformed variants with recorded assumptions and inverse mappings. The final corpus contains 737 theorem identities and 29,480 transformed rows. On a test panel, the best model retrieves the correct theorem identity in only 60.73% of cases. Other systems reveal different failure modes, including abstention, wrong detection, and malformed outputs. These suggest that theorem knowledge can be fragile under equivalent changes in representation. TREAT therefore provides a controlled testbed for evaluating representation-robust access to formal knowledge, with broader relevance to domains that require stable target objects, explicit equivalence relations, validation procedures, and auditable scoring.

We propose a generalization of the synthetic control methods to the setting with dynamic treatment effects, in which each unit receives multiple treatments sequentially, according to an adaptive policy that depends on a latent, endogenously time-varying confounding state. Under a low-rank latent factor model assumption, which admits linear time-varying and time-invariant dynamic triangular systems as special cases, we develop an identification strategy for any unit-specific mean outcome under any sequence of interventions. Our method, which we term synthetic blips, is a backward induction process in which the blip effect of a treatment at each period for a target unit is recursively expressed as a linear combination of the blip effects of other units that received the designated treatment, avoiding the combinatorial donor requirements of naive synthetic control extensions. We provide easy-to-implement estimation algorithms that yield consistent estimators. Using unique Korean firm-level panel data, we estimate individualized dynamic treatment effects and optimal allocation rules in the context of financial support for exporting firms.