搜索结果：therapeutic

We report the design, fabrication and characterization of evanescent mid-infrared germanium-on-silicon waveguide sensors for therapeutic drug monitoring (TDM). TDM requires rapid and accurate quantification of serum drug levels but existing clinical assays rely on laboratory-based instrumentation that limits point-of-care deployment. In this work, tunable diode laser absorption spectroscopy was used to analyze dried samples of the anti-seizure medication phenytoin in the spectral region of $λ$ = 5.6 - 6.0 $μ$m. A limit of detection of 2.20 mg/L was achieved for extracted samples, where phenytoin was first added to human serum and subsequently isolated using liquid-liquid extraction. This limit is significantly below the therapeutic window of 10 - 20 mg/L for phenytoin, enabling detection of sub-therapeutic concentrations. At the same time, the sensor maintains a consistent dose-dependent response up to 40 mg/L, demonstrating its capability to quantify concentrations across the therapeutic window and above the upper therapeutic limit. This validates the use of silicon photonics for biomedical infrared spectroscopy for patients undergoing drug therapy, whether the serum-drug concentr

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) un

Therapeutic art activities, such as expressive drawing and painting, require the synergy between creative visual production and interactive dialogue. Recent advancements in Multimodal Large Language Models (MLLMs) have expanded the capacity of computing systems to interpret both textual and visual data, offering a new frontier for AI-mediated therapeutic support. This work-in-progress paper introduces an MLLM-powered chatbot that analyzes visual creation in real-time while engaging the creator in reflective conversations. We conducted an evaluation with five experts in art therapy and related fields, which demonstrated the chatbot's potential to facilitate therapeutic engagement, and highlighted several areas for future development, including entryways and risk management, bespoke alignment of user profile and therapeutic style, balancing conversational depth and width, and enriching visual interactivity. These themes provide a design roadmap for designing the future AI-mediated creative expression tools.

While large language models (LLMs) excel at open-ended dialogue, effective psychotherapy requires structured progression and adherence to clinical protocols, making the design of psychotherapist chatbots challenging. We investigate how different LLM-based designs shape perceived therapeutic dialogue in a chatbot grounded in the Self-Attachment Technique (SAT), a novel self-administered psychotherapy rooted in attachment theory. We compare three architectural variants: (1) a multi-agent system utilizing finite state machine aligned with therapeutic stages and a shared long-term memory, (2) a single-agent using identical knowledge-base and the same prompts, and (3) an unguided LLM. In an eight-day randomized controlled trial (RCT) with N=66 Farsi-speaking participants, balanced across the three chatbots, the multi-agent system is perceived as significantly more natural and human-like than the other variants and achieves higher ratings across most other metrics. These findings demonstrate that for therapeutic AI, architectural orchestration is as critical as prompt engineering in fostering natural, engaging dialogue.

The increasing use of large language models in mental health applications calls for principled evaluation frameworks that assess alignment with psychotherapeutic best practices beyond surface-level fluency. While recent systems exhibit conversational competence, they lack structured mechanisms to evaluate adherence to core therapeutic principles. In this paper, we study the problem of evaluating AI-generated therapist-like responses for clinically grounded appropriateness and effectiveness. We assess each therapists utterance along six therapeutic principles: non-judgmental acceptance, warmth, respect for autonomy, active listening, reflective understanding, and situational appropriateness using a fine-grained ordinal scale. We introduce FAITH-M, a benchmark annotated with expert-assigned ordinal ratings, and propose CARE, a multi-stage evaluation framework that integrates intra-dialogue context, contrastive exemplar retrieval, and knowledge-distilled chain-of-thought reasoning. Experiments show that CARE achieves an F-1 score of 63.34 versus the strong baseline Qwen3 F-1 score of 38.56 which is a 64.26 improvement, which also serves as its backbone, indicating that gains arise fro

Therapeutic development is a costly and high-risk endeavor that is often plagued by high failure rates. To address this, we introduce TxGemma, a suite of efficient, generalist large language models (LLMs) capable of therapeutic property prediction as well as interactive reasoning and explainability. Unlike task-specific models, TxGemma synthesizes information from diverse sources, enabling broad application across the therapeutic development pipeline. The suite includes 2B, 9B, and 27B parameter models, fine-tuned from Gemma-2 on a comprehensive dataset of small molecules, proteins, nucleic acids, diseases, and cell lines. Across 66 therapeutic development tasks, TxGemma achieved superior or comparable performance to the state-of-the-art generalist model on 64 (superior on 45), and against state-of-the-art specialist models on 50 (superior on 26). Fine-tuning TxGemma models on therapeutic downstream tasks, such as clinical trial adverse event prediction, requires less training data than fine-tuning base LLMs, making TxGemma suitable for data-limited applications. Beyond these predictive capabilities, TxGemma features conversational models that bridge the gap between general LLMs an

Identifying conditions that a certain drug takes therapeutic effect on a target disease is crucial for clinical decision-making support. However, most existing biomedical information extraction methods have focused on identifying only relations between drugs and diseases, while largely overlooking the context-specific conditions where such relations can apply. To address this problem, we introduce the task of applicability condition extraction for therapeutic drug-disease relations from biomedical research literature. We create the first dataset that has manually annotated triples of drugs, diseases, and applicability conditions on biomedical paper abstracts with 1,119 drug-disease pairs. Using this dataset, we systematically evaluate the performance of a range of existing methods. In addition, we propose a new method that enhances LoRA to consider relations between drugs and diseases. Our method consistently outperforms strong baselines across different evaluation settings.

While large language models show promise in mental healthcare, evaluating their therapeutic competence remains challenging due to the unstructured and longitudinal nature of counseling. We argue that current evaluation paradigms suffer from an unanchored defect, leading to two forms of instability: process drift, where unsteered client simulation wanders away from specific counseling goals, and standard drift, where static pointwise scoring lacks the stability for reliable judgment. To address this, we introduce Ps, a unified framework that calibrates the therapeutic competence of LLMs via trajectory-anchored tournaments. We first anchor the interaction trajectory in simulation, where clients precisely control the fluid consultation process to probe multifaceted capabilities. We then anchor the battle trajectory in judgments through an efficient Swiss-system tournament, utilizing dynamic pairwise battles to yield robust Elo ratings. Beyond ranking, we demonstrate that tournament trajectories can be transformed into credible reward signals, enabling on-policy reinforcement learning to enhance LLMs' performance. Extensive experiments validate the effectiveness of PsychePass and its s

Large language models (LLMs) hold significant potential for mental health support, capable of generating empathetic responses and simulating therapeutic conversations. However, existing LLM-based approaches often lack the clinical grounding necessary for real-world psychological counseling, particularly in explicit diagnostic reasoning aligned with standards like the DSM/ICD and incorporating diverse therapeutic modalities beyond basic empathy or single strategies. To address these critical limitations, we propose PsyLLM, the first large language model designed to systematically integrate both diagnostic and therapeutic reasoning for mental health counseling. To develop PsyLLM, we design a novel automated data synthesis pipeline that processes real-world mental health posts collected from Reddit, where users frequently share psychological distress and seek community support. This pipeline processes real-world mental health posts, generates multi-turn dialogue structures, and leverages LLMs guided by international diagnostic standards (e.g., DSM/ICD) and multiple therapeutic frameworks (e.g., CBT, ACT, psychodynamic) to simulate detailed clinical reasoning processes. Rigorous multi-

Spatially Fractionated Radiation Therapy (SFRT) produces highly heterogeneous dose distributions, for which conventional metrics such as peak, valley, or average dose can yield ambiguous or inconsistent estimates of therapeutic window changes. These dose descriptors are not uniquely linked to biological outcome, complicating comparisons between modalities. We introduce the Biologically Effective Particle Number Ratio (BPNR), a model-independent and outcome-based framework that quantifies therapeutic window changes using directly measurable delivery quantities rather than spatial dose metrics. BPNR is defined as the ratio of total particle numbers (proportional to monitor units, MU) required to reach specified levels of tumor control probability (TCP) and normal tissue complication probability (NTCP). The relative BPNR (RBPNR) compares therapeutic windows across modalities and avoids ambiguities of spatial dose averaging by relying solely on biological endpoints. As an illustration, we apply the framework to preclinical proton minibeam radiotherapy (pMBRT) versus conventional proton therapy. The absence of normal tissue complications at the highest tested MU in the pMBRT arm yields

Mental health disorders impose a substantial global socioeconomic burden. While large language models (LLMs) offer 24/7, non-judgmental interactions to address this gap, pretrained models lack contextual coherence and emotional alignment for appropriate therapeutic dialogue. Existing methods suffer from three critical methodological gaps: 1) Supervised Fine-Tuning (SFT) produces repetitive, context-insensitive outputs that fail to balance clinical accuracy with genuine empathy; 2) Reinforcement Learning (RL)-based therapeutic systems rely on generic reward functions (e.g., BLEU, ROUGE) that prioritise lexical similarity over clinical-specific emotional appropriateness and contextual relevance; 3) LLMs are resource-intensive and pose data privacy risks, making local deployment in clinical settings infeasible. To address these gaps, this study investigates the application of SFT and RL techniques to enhance GPT-2's capacity for therapeutic dialogue generation. The methodology restructured input formats to enable simultaneous processing of contextual information and emotional states alongside user input, employing a novel multi-component reward function that explicitly aligns model ou

Proactive questioning, where therapists deliberately initiate structured, cognition-guiding inquiries, is a cornerstone of cognitive behavioral therapy (CBT). Yet, current psychological large language models (LLMs) remain overwhelmingly reactive, defaulting to empathetic but superficial responses that fail to surface latent beliefs or guide behavioral change. To bridge this gap, we propose the \textbf{Socratic Inquiry Framework (SIF)}, a lightweight, plug-and-play therapeutic intent planner that transforms LLMs from passive listeners into active cognitive guides. SIF decouples \textbf{when to ask} (via Strategy Anchoring) from \textbf{what to ask} (via Template Retrieval), enabling context-aware, theory-grounded questioning without end-to-end retraining. Complementing SIF, we introduce \textbf{Socratic-QA}, a high-quality dataset of strategy-aligned Socratic sequences that provides explicit supervision for proactive reasoning. Experiments show that SIF significantly enhances proactive questioning frequency, conversational depth, and therapeutic alignment, marking a clear shift from reactive comfort to proactive exploration. Our work establishes a new paradigm for psychologically in

Diffusion models have emerged as a leading framework in generative modeling, poised to transform the traditionally slow and costly process of drug discovery. This review provides a systematic comparison of their application in designing two principal therapeutic modalities: small molecules and therapeutic peptides. We dissect how the unified framework of iterative denoising is adapted to the distinct molecular representations, chemical spaces, and design objectives of each modality. For small molecules, these models excel at structure-based design, generating novel, pocket-fitting ligands with desired physicochemical properties, yet face the critical hurdle of ensuring chemical synthesizability. Conversely, for therapeutic peptides, the focus shifts to generating functional sequences and designing de novo structures, where the primary challenges are achieving biological stability against proteolysis, ensuring proper folding, and minimizing immunogenicity. Despite these distinct challenges, both domains face shared hurdles: the scarcity of high-quality experimental data, the reliance on inaccurate scoring functions for validation, and the crucial need for experimental validation. We

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 ac

Therapeutic decision-making in clinical medicine constitutes a high-stakes domain in which AI guidance interacts with complex interactions among patient characteristics, disease processes, and pharmacological agents. Tasks such as drug recommendation, treatment planning, and adverse-effect prediction demand robust, multi-step reasoning grounded in reliable biomedical knowledge. Agentic AI methods, exemplified by TxAgent, address these challenges through iterative retrieval-augmented generation (RAG). TxAgent employs a fine-tuned Llama-3.1-8B model that dynamically generates and executes function calls to a unified biomedical tool suite (ToolUniverse), integrating FDA Drug API, OpenTargets, and Monarch resources to ensure access to current therapeutic information. In contrast to general-purpose RAG systems, medical applications impose stringent safety constraints, rendering the accuracy of both the reasoning trace and the sequence of tool invocations critical. These considerations motivate evaluation protocols treating token-level reasoning and tool-usage behaviors as explicit supervision signals. This work presents insights derived from our participation in the CURE-Bench NeurIPS 2

AI-driven discovery can greatly reduce design time and enhance new therapeutics' effectiveness. Models using simulators explore broad design spaces but risk violating implicit constraints due to a lack of experimental priors. For example, in a new analysis we performed on a diverse set of models on the GuacaMol benchmark using supervised classifiers, over 60\% of molecules proposed had high probability of being mutagenic. In this work, we introduce Medex, a dataset of priors for design problems extracted from literature describing compounds used in lab settings. It is constructed with LLM pipelines for discovering therapeutic entities in relevant paragraphs and summarizing information in concise fair-use facts. Medex consists of 32.3 million pairs of natural language facts, and appropriate entity representations (i.e. SMILES or refseq IDs). To demonstrate the potential of the data, we train LLM, CLIP, and LLava architectures to reason jointly about text and design targets and evaluate on tasks from the Therapeutic Data Commons (TDC). Medex is highly effective for creating models with strong priors: in supervised prediction problems that use our data as pretraining, our best models

Robust therapeutic relationships between counselors and clients are fundamental to counseling effectiveness. The assessment of therapeutic alliance is well-established in traditional face-to-face therapy but may not directly translate to text-based settings. With millions of individuals seeking support through online text-based counseling, understanding the relationship in such contexts is crucial. In this paper, we present an automatic approach using large language models (LLMs) to understand the development of therapeutic alliance in text-based counseling. We adapt a theoretically grounded framework specifically to the context of online text-based counseling and develop comprehensive guidelines for characterizing the alliance. We collect a comprehensive counseling dataset and conduct multiple expert evaluations on a subset based on this framework. Our LLM-based approach, combined with guidelines and simultaneous extraction of supportive evidence underlying its predictions, demonstrates effectiveness in identifying the therapeutic alliance. Through further LLM-based evaluations on additional conversations, our findings underscore the challenges counselors face in cultivating stron

Metabolic disorders, particularly type 2 diabetes mellitus (T2DM), represent a significant global health burden, disproportionately impacting genetically predisposed populations such as the Pima Indians (a Native American tribe from south central Arizona). This study introduces a novel machine learning (ML) framework that integrates predictive modeling with gene-agnostic pathway mapping to identify high-risk individuals and uncover potential therapeutic targets. Using the Pima Indian dataset, logistic regression and t-tests were applied to identify key predictors of T2DM, yielding an overall model accuracy of 78.43%. To bridge predictive analytics with biological relevance, we developed a pathway mapping strategy that links identified predictors to critical signaling networks, including insulin signaling, AMPK, and PPAR pathways. This approach provides mechanistic insights without requiring direct molecular data. Building upon these connections, we propose therapeutic strategies such as dual GLP-1/GIP receptor agonists, AMPK activators, SIRT1 modulators, and phytochemical, further validated through pathway enrichment analyses. Overall, this framework advances precision medicine by

Chatbots or conversational agents (CAs) are increasingly used to improve access to digital psychotherapy. Many current systems rely on rigid, rule-based designs, heavily dependent on expert-crafted dialogue scripts for guiding therapeutic conversations. Although advances in large language models (LLMs) offer potential for more flexible interactions, their lack of controllability and explanability poses challenges in high-stakes contexts like psychotherapy. To address this, we conducted two studies in this work to explore how aligning LLMs with expert-crafted scripts can enhance psychotherapeutic chatbot performance. In Study 1 (N=43), an online experiment with a within-subjects design, we compared rule-based, pure LLM, and LLMs aligned with expert-crafted scripts via fine-tuning and prompting. Results showed that aligned LLMs significantly outperformed the other types of chatbots in empathy, dialogue relevance, and adherence to therapeutic principles. Building on findings, we proposed ``Script-Strategy Aligned Generation (SSAG)'', a more flexible alignment approach that reduces reliance on fully scripted content while maintaining LLMs' therapeutic adherence and controllability. In