Daily Papers

We developed an explainable artificial intelligence (AI) early warning score (xAI-EWS) system for early detection of acute critical illness. While maintaining a high predictive performance, our system explains to the clinician on which relevant electronic health records (EHRs) data the prediction is grounded. Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as Early Warning Scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on EHR-trained AI systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute critical illness. However, without insight into the complex decisions by such system, clinical translation is hindered. In this letter, we present our xAI-EWS system, which potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.

Accurate differentiation of pseudoprogression (PsP) from True Progression (TP) following radiotherapy (RT) in glioblastoma (GBM) patients is crucial for optimal treatment planning. However, this task remains challenging due to the overlapping imaging characteristics of PsP and TP. This study therefore proposes a multimodal deep-learning approach utilizing complementary information from routine anatomical MR images, clinical parameters, and RT treatment planning information for improved predictive accuracy. The approach utilizes a self-supervised Vision Transformer (ViT) to encode multi-sequence MR brain volumes to effectively capture both global and local context from the high dimensional input. The encoder is trained in a self-supervised upstream task on unlabeled glioma MRI datasets from the open BraTS2021, UPenn-GBM, and UCSF-PDGM datasets to generate compact, clinically relevant representations from FLAIR and T1 post-contrast sequences. These encoded MR inputs are then integrated with clinical data and RT treatment planning information through guided cross-modal attention, improving progression classification accuracy. This work was developed using two datasets from different centers: the Burdenko Glioblastoma Progression Dataset (n = 59) for training and validation, and the GlioCMV progression dataset from the University Hospital Erlangen (UKER) (n = 20) for testing. The proposed method achieved an AUC of 75.3%, outperforming the current state-of-the-art data-driven approaches. Importantly, the proposed approach relies on readily available anatomical MRI sequences, clinical data, and RT treatment planning information, enhancing its clinical feasibility. The proposed approach addresses the challenge of limited data availability for PsP and TP differentiation and could allow for improved clinical decision-making and optimized treatment plans for GBM patients.

Clinical notes contain information about patients that goes beyond structured data like lab values and medications. However, clinical notes have been underused relative to structured data, because notes are high-dimensional and sparse. This work develops and evaluates representations of clinical notes using bidirectional transformers (ClinicalBERT). ClinicalBERT uncovers high-quality relationships between medical concepts as judged by humans. ClinicalBert outperforms baselines on 30-day hospital readmission prediction using both discharge summaries and the first few days of notes in the intensive care unit. Code and model parameters are available.

Extracting clinical information from medical transcripts in low-resource languages remains a significant challenge in healthcare natural language processing (NLP). This study evaluates a two-step pipeline combining Aya-expanse-8B as a Persian-to-English translation model with five open-source small language models (SLMs) -- Qwen2.5-7B-Instruct, Llama-3.1-8B-Instruct, Llama-3.2-3B-Instruct, Qwen2.5-1.5B-Instruct, and Gemma-3-1B-it -- for binary extraction of 13 clinical features from 1,221 anonymized Persian transcripts collected at a cancer palliative care call center. Using a few-shot prompting strategy without fine-tuning, models were assessed on macro-averaged F1-score, Matthews Correlation Coefficient (MCC), sensitivity, and specificity to account for class imbalance. Qwen2.5-7B-Instruct achieved the highest overall performance (median macro-F1: 0.899; MCC: 0.797), while Gemma-3-1B-it showed the weakest results. Larger models (7B--8B parameters) consistently outperformed smaller counterparts in sensitivity and MCC. A bilingual analysis of Aya-expanse-8B revealed that translating Persian transcripts to English improved sensitivity, reduced missing outputs, and boosted metrics robust to class imbalance, though at the cost of slightly lower specificity and precision. Feature-level results showed reliable extraction of physiological symptoms across most models, whereas psychological complaints, administrative requests, and complex somatic features remained challenging. These findings establish a practical, privacy-preserving blueprint for deploying open-source SLMs in multilingual clinical NLP settings with limited infrastructure and annotation resources, and highlight the importance of jointly optimizing model scale and input language strategy for sensitive healthcare applications.

Prompt learning is a new paradigm in the Natural Language Processing (NLP) field which has shown impressive performance on a number of natural language tasks with common benchmarking text datasets in full, few-shot, and zero-shot train-evaluation setups. Recently, it has even been observed that large but frozen pre-trained language models (PLMs) with prompt learning outperform smaller but fine-tuned models. However, as with many recent NLP trends, the performance of even the largest PLMs such as GPT-3 do not perform well on specialized domains (e.g. medical text), and the common practice to achieve State of the Art (SoTA) results still consists of pre-training and fine-tuning the PLMs on downstream tasks. The reliance on fine-tuning large PLMs is problematic in clinical settings where data is often held in non-GPU environments, and more resource efficient methods of training specialized domain models is crucial. We investigated the viability of prompt learning on clinically meaningful decision tasks and directly compared with more traditional fine-tuning methods. Results are partially in line with the prompt learning literature, with prompt learning able to match or improve on traditional fine-tuning with substantially fewer trainable parameters and requiring less training data. We argue that prompt learning therefore provides lower computational resource costs applicable to clinical settings, that can serve as an alternative to fine-tuning ever increasing in size PLMs. Complementary code to reproduce experiments presented in this work can be found at: https://github.com/NtaylorOX/Public_Clinical_Prompt.

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model - GatorTron - using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on 5 clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve 5 clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og.

Encoder-based transformer models are central to biomedical and clinical Natural Language Processing (NLP), as their bidirectional self-attention makes them well-suited for efficiently extracting structured information from unstructured text through discriminative tasks. However, encoders have seen slower development compared to decoder models, leading to limited domain adaptation in biomedical and clinical settings. We introduce BioClinical ModernBERT, a domain-adapted encoder that builds on the recent ModernBERT release, incorporating long-context processing and substantial improvements in speed and performance for biomedical and clinical NLP. BioClinical ModernBERT is developed through continued pretraining on the largest biomedical and clinical corpus to date, with over 53.5 billion tokens, and addresses a key limitation of prior clinical encoders by leveraging 20 datasets from diverse institutions, domains, and geographic regions, rather than relying on data from a single source. It outperforms existing biomedical and clinical encoders on four downstream tasks spanning a broad range of use cases. We release both base (150M parameters) and large (396M parameters) versions of BioClinical ModernBERT, along with training checkpoints to support further research.

The advancement of natural language processing (NLP) systems in healthcare hinges on language model ability to interpret the intricate information contained within clinical notes. This process often requires integrating information from various time points in a patient's medical history. However, most earlier clinical language models were pretrained with a context length limited to roughly one clinical document. In this study, We introduce ClinicalMamba, a specialized version of the Mamba language model, pretrained on a vast corpus of longitudinal clinical notes to address the unique linguistic characteristics and information processing needs of the medical domain. ClinicalMamba, with 130 million and 2.8 billion parameters, demonstrates a superior performance in modeling clinical language across extended text lengths compared to Mamba and clinical Llama. With few-shot learning, ClinicalMamba achieves notable benchmarks in speed and accuracy, outperforming existing clinical language models and general domain large models like GPT-4 in longitudinal clinical notes information extraction tasks.

We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization. Therefore, we publicly release SoftTiger models at scales of 13 billion and 70 billion parameters, as well as datasets and code for our innovative scalable evaluation, hopefully, making a significant contribution to the healthcare industry.

Tokenization strategies shape how models process electronic health records, yet fair comparisons of their effectiveness remain limited. We present a systematic evaluation of tokenization approaches for clinical time series modeling using transformer-based architectures, revealing task-dependent and sometimes counterintuitive findings about temporal and value feature importance. Through controlled ablations across four clinical prediction tasks on MIMIC-IV, we demonstrate that explicit time encodings provide no consistent statistically significant benefit for the evaluated downstream tasks. Value features show task-dependent importance, affecting mortality prediction but not readmission, suggesting code sequences alone can carry sufficient predictive signal. We further show that frozen pretrained code encoders dramatically outperform their trainable counterparts while requiring dramatically fewer parameters. Larger clinical encoders provide consistent improvements across tasks, benefiting from frozen embeddings that eliminate computational overhead. Our controlled evaluation enables fairer tokenization comparisons and demonstrates that simpler, parameter-efficient approaches can, in many cases, achieve strong performance, though the optimal tokenization strategy remains task-dependent.

Finding relevant literature underpins the practice of evidence-based medicine. From 2014 to 2016, TREC conducted a clinical decision support track, wherein participants were tasked with finding articles relevant to clinical questions posed by physicians. In total, 87 teams have participated over the past three years, generating 395 runs. During this period, each team has trialled a variety of methods. While there was significant overlap in the methods employed by different teams, the results were varied. Due to the diversity of the platforms used, the results arising from the different techniques are not directly comparable, reducing the ability to build on previous work. By using a stable platform, we have been able to compare different document and query processing techniques, allowing us to experiment with different search parameters. We have used our system to reproduce leading teams runs, and compare the results obtained. By benchmarking our indexing and search techniques, we can statistically test a variety of hypotheses, paving the way for further research.

Hospitals and healthcare systems rely on operational decisions that determine patient flow, cost, and quality of care. Despite strong performance on medical knowledge and conversational benchmarks, foundation models trained on general text may lack the specialized knowledge required for these operational decisions. We introduce Lang1, a family of models (100M-7B parameters) pretrained on a specialized corpus blending 80B clinical tokens from NYU Langone Health's EHRs and 627B tokens from the internet. To rigorously evaluate Lang1 in real-world settings, we developed the REalistic Medical Evaluation (ReMedE), a benchmark derived from 668,331 EHR notes that evaluates five critical tasks: 30-day readmission prediction, 30-day mortality prediction, length of stay, comorbidity coding, and predicting insurance claims denial. In zero-shot settings, both general-purpose and specialized models underperform on four of five tasks (36.6%-71.7% AUROC), with mortality prediction being an exception. After finetuning, Lang1-1B outperforms finetuned generalist models up to 70x larger and zero-shot models up to 671x larger, improving AUROC by 3.64%-6.75% and 1.66%-23.66% respectively. We also observed cross-task scaling with joint finetuning on multiple tasks leading to improvement on other tasks. Lang1-1B effectively transfers to out-of-distribution settings, including other clinical tasks and an external health system. Our findings suggest that predictive capabilities for hospital operations require explicit supervised finetuning, and that this finetuning process is made more efficient by in-domain pretraining on EHR. Our findings support the emerging view that specialized LLMs can compete with generalist models in specialized tasks, and show that effective healthcare systems AI requires the combination of in-domain pretraining, supervised finetuning, and real-world evaluation beyond proxy benchmarks.

Although recent advances in scaling large language models (LLMs) have resulted in improvements on many NLP tasks, it remains unclear whether these models trained primarily with general web text are the right tool in highly specialized, safety critical domains such as clinical text. Recent results have suggested that LLMs encode a surprising amount of medical knowledge. This raises an important question regarding the utility of smaller domain-specific language models. With the success of general-domain LLMs, is there still a need for specialized clinical models? To investigate this question, we conduct an extensive empirical analysis of 12 language models, ranging from 220M to 175B parameters, measuring their performance on 3 different clinical tasks that test their ability to parse and reason over electronic health records. As part of our experiments, we train T5-Base and T5-Large models from scratch on clinical notes from MIMIC III and IV to directly investigate the efficiency of clinical tokens. We show that relatively small specialized clinical models substantially outperform all in-context learning approaches, even when finetuned on limited annotated data. Further, we find that pretraining on clinical tokens allows for smaller, more parameter-efficient models that either match or outperform much larger language models trained on general text. We release the code and the models used under the PhysioNet Credentialed Health Data license and data use agreement.

Specialised pre-trained language models are becoming more frequent in NLP since they can potentially outperform models trained on generic texts. BioBERT and BioClinicalBERT are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like Knowledge Distillation (KD), it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from 15 million to 65 million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including Natural Language Inference, Relation Extraction, Named Entity Recognition, and Sequence Classification. To our knowledge, this is the first comprehensive study specifically focused on creating efficient and compact transformers for clinical NLP tasks. The models and code used in this study can be found on our Huggingface profile at https://huggingface.co/nlpie and Github page at https://github.com/nlpie-research/Lightweight-Clinical-Transformers, respectively, promoting reproducibility of our results.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

Machine unlearning is increasingly important for clinical language models, where privacy regulations and institutional policies may require removing sensitive information from deployed systems without retraining from scratch. In practice, deletion requests must balance effective forgetting of targeted information with preservation of model utility and minimal parameter modification. We introduce Sparse Token Embedding Unlearning (STEU), a parameter-efficient method for behavioral class-level unlearning that updates only PMI-selected token embeddings together with a small classifier head while keeping all encoder layers frozen. Across experiments on MIMIC-IV, MIMIC-III, and eICU using BioClinicalBERT, BERT-base, and DistilBERT, STEU consistently suppresses the target class while largely preserving retained task performance. In the primary MIMIC-IV setting, STEU achieves near-complete forgetting (forget F1 = 0.0004) while maintaining competitive retained utility (retain avg F1 = 0.4766) after modifying only 0.19\% of model parameters. These results suggest that targeted behavioral unlearning can be achieved through sparse embedding edits without modifying deeper encoder representations.

Adapting pretrained language models to novel domains, such as clinical applications, traditionally involves retraining their entire set of parameters. Parameter-Efficient Fine-Tuning (PEFT) techniques for fine-tuning language models significantly reduce computational requirements by selectively fine-tuning small subsets of parameters. In this study, we propose a two-step PEFT framework and evaluate it in the clinical domain. Our approach combines a specialised PEFT adapter layer designed for clinical domain adaptation with another adapter specialised for downstream tasks. We evaluate the framework on multiple clinical outcome prediction datasets, comparing it to clinically trained language models. Our framework achieves a better AUROC score averaged across all clinical downstream tasks compared to clinical language models. In particular, we observe large improvements of 4-5% AUROC in large-scale multilabel classification tasks, such as diagnoses and procedures classification. To our knowledge, this study is the first to provide an extensive empirical analysis of the interplay between PEFT techniques and domain adaptation in an important real-world domain of clinical applications.

The entry of large language models (LLMs) into research and commercial spaces has led to a trend of ever-larger models, with initial promises of generalisability, followed by a widespread desire to downsize and create specialised models without the need for complete fine-tuning, using Parameter Efficient Fine-tuning (PEFT) methods. We present an investigation into the suitability of different PEFT methods to clinical decision-making tasks, across a range of model sizes, including extremely small models with as few as 25 million parameters. Our analysis shows that the performance of most PEFT approaches varies significantly from one task to another, with the exception of LoRA, which maintains relatively high performance across all model sizes and tasks, typically approaching or matching full fine-tuned performance. The effectiveness of PEFT methods in the clinical domain is evident, particularly for specialised models which can operate on low-cost, in-house computing infrastructure. The advantages of these models, in terms of speed and reduced training costs, dramatically outweighs any performance gain from large foundation LLMs. Furthermore, we highlight how domain-specific pre-training interacts with PEFT methods and model size, and discuss how these factors interplay to provide the best efficiency-performance trade-off. Full code available at: tbd.

Brain-Computer Interface (BCI) systems allow users to perform actions by translating their brain activity into commands. Such systems usually need a training phase, consisting in training a classification algorithm to discriminate between mental states using specific features from the recorded signals. This phase of feature selection and training is crucial for BCI performance and presents specific constraints to be met in a clinical context, such as post-stroke rehabilitation. In this paper, we present HappyFeat, a software making Motor Imagery (MI) based BCI experiments easier, by gathering all necessary manipulations and analysis in a single convenient GUI and via automation of experiment or analysis parameters. The resulting workflow allows for effortlessly selecting the best features, helping to achieve good BCI performance in time-constrained environments. Alternative features based on Functional Connectivity can be used and compared or combined with Power Spectral Density, allowing a network-oriented approach. We then give details of HappyFeat's main mechanisms, and a review of its performances in typical use cases. We also show that it can be used as an efficient tool for comparing different metrics extracted from the signals, to train the classification algorithm. To this end, we show a comparison between the commonly-used Power Spectral Density and network metrics based on Functional Connectivity. HappyFeat is available as an open-source project which can be freely downloaded on GitHub.

We introduce TeMLM, a set of transparency-first release artifacts for clinical language models. TeMLM unifies provenance, data transparency, modeling transparency, and governance into a single, machine-checkable release bundle. We define an artifact suite (TeMLM-Card, TeMLM-Datasheet, TeMLM-Provenance) and a lightweight conformance checklist for repeatable auditing. We instantiate the artifacts on Technetium-I, a large-scale synthetic clinical NLP dataset with 498,000 notes, 7.74M PHI entity annotations across 10 types, and ICD-9-CM diagnosis labels, and report reference results for ProtactiniumBERT (about 100 million parameters) on PHI de-identification (token classification) and top-50 ICD-9 code extraction (multi-label classification). We emphasize that synthetic benchmarks are valuable for tooling and process validation, but models should be validated on real clinical data prior to deployment.

There is enormous enthusiasm and concerns in using large language models (LLMs) in healthcare, yet current assumptions are all based on general-purpose LLMs such as ChatGPT. This study develops a clinical generative LLM, GatorTronGPT, using 277 billion words of mixed clinical and English text with a GPT-3 architecture of 20 billion parameters. GatorTronGPT improves biomedical natural language processing for medical research. Synthetic NLP models trained using GatorTronGPT generated text outperform NLP models trained using real-world clinical text. Physicians Turing test using 1 (worst) to 9 (best) scale shows that there is no significant difference in linguistic readability (p = 0.22; 6.57 of GatorTronGPT compared with 6.93 of human) and clinical relevance (p = 0.91; 7.0 of GatorTronGPT compared with 6.97 of human) and that physicians cannot differentiate them (p < 0.001). This study provides insights on the opportunities and challenges of LLMs for medical research and healthcare.

Although large language models (LLMs) demonstrate expert-level medical knowledge, aligning their open-ended outputs with fine-grained clinician preferences remains challenging. Existing methods often rely on coarse objectives or unreliable automated judges that are weakly grounded in professional guidelines. We propose a two-stage framework to address this gap. First, we introduce HealthRubrics, a dataset of 7,034 physician-verified preference examples in which clinicians refine LLM-drafted rubrics to meet rigorous medical standards. Second, we distill these rubrics into HealthPrinciples: 119 broadly reusable, clinically grounded principles organized by clinical dimensions, enabling scalable supervision beyond manual annotation. We use HealthPrinciples for (1) offline alignment by synthesizing rubrics for unlabeled queries and (2) an inference-time tool for guided self-revision. A 30B parameter model that activates only 3B parameters at inference trained with our framework achieves 33.4% on HealthBench-Hard, outperforming much larger models including Deepseek-R1 and o3, establishing a resource-efficient baseline for clinical alignment.

Objective To solve major clinical natural language processing (NLP) tasks using a unified text-to-text learning architecture based on a generative large language model (LLM) via prompt tuning. Methods We formulated 7 key clinical NLP tasks as text-to-text learning and solved them using one unified generative clinical LLM, GatorTronGPT, developed using GPT-3 architecture and trained with up to 20 billion parameters. We adopted soft prompts (i.e., trainable vectors) with frozen LLM, where the LLM parameters were not updated (i.e., frozen) and only the vectors of soft prompts were updated, known as prompt tuning. We added additional soft prompts as a prefix to the input layer, which were optimized during the prompt tuning. We evaluated the proposed method using 7 clinical NLP tasks and compared them with previous task-specific solutions based on Transformer models. Results and Conclusion The proposed approach achieved state-of-the-art performance for 5 out of 7 major clinical NLP tasks using one unified generative LLM. Our approach outperformed previous task-specific transformer models by ~3% for concept extraction and 7% for relation extraction applied to social determinants of health, 3.4% for clinical concept normalization, 3.4~10% for clinical abbreviation disambiguation, and 5.5~9% for natural language inference. Our approach also outperformed a previously developed prompt-based machine reading comprehension (MRC) model, GatorTron-MRC, for clinical concept and relation extraction. The proposed approach can deliver the ``one model for all`` promise from training to deployment using a unified generative LLM.

Segmenting stroke lesions in Magnetic Resonance Imaging (MRI) is challenging due to diverse clinical imaging domains, with existing models struggling to generalise across different MRI acquisition parameters and sequences. In this work, we propose two novel physics-constrained approaches using synthetic quantitative MRI (qMRI) images to enhance the robustness and generalisability of segmentation models. We trained a qMRI estimation model to predict qMRI maps from MPRAGE images, which were used to simulate diverse MRI sequences for segmentation training. A second approach built upon prior work in synthetic data for stroke lesion segmentation, generating qMRI maps from a dataset of tissue labels. The proposed approaches improved over the baseline nnUNet on a variety of out-of-distribution datasets, with the second approach outperforming the prior synthetic data method.

Ultrasound fetal imaging is beneficial to support prenatal development because it is affordable and non-intrusive. Nevertheless, fetal plane classification (FPC) remains challenging and time-consuming for obstetricians since it depends on nuanced clinical aspects, which increases the difficulty in identifying relevant features of the fetal anatomy. Thus, to assist with its accurate feature extraction, a lightweight artificial intelligence architecture leveraging convolutional neural networks and attention mechanisms is proposed to classify the largest benchmark ultrasound dataset. The approach fine-tunes from lightweight EfficientNet feature extraction backbones pre-trained on the ImageNet1k. to classify key fetal planes such as the brain, femur, thorax, cervix, and abdomen. Our methodology incorporates the attention mechanism to refine features and 3-layer perceptrons for classification, achieving superior performance with the highest Top-1 accuracy of 96.25%, Top-2 accuracy of 99.80% and F1-Score of 0.9576. Importantly, the model has 40x fewer trainable parameters than existing benchmark ensemble or transformer pipelines, facilitating easy deployment on edge devices to help clinical practitioners with real-time FPC. The findings are also interpreted using GradCAM to carry out clinical correlation to aid doctors with diagnostics and improve treatment plans for expectant mothers.

Pathology foundation models (FMs) have driven significant progress in computational pathology. However, these high-performing models can easily exceed a billion parameters and produce high-dimensional embeddings, thus limiting their applicability for research or clinical use when computing resources are tight. Here, we introduce Pathryoshka, a multi-teacher distillation framework inspired by RADIO distillation and Matryoshka Representation Learning to reduce pathology FM sizes while allowing for adaptable embedding dimensions. We evaluate our framework with a distilled model on ten public pathology benchmarks with varying downstream tasks. Compared to its much larger teachers, Pathryoshka reduces the model size by 86-92% at on-par performance. It outperforms state-of-the-art single-teacher distillation models of comparable size by a median margin of 7.0 in accuracy. By enabling efficient local deployment without sacrificing accuracy or representational richness, Pathryoshka democratizes access to state-of-the-art pathology FMs for the broader research and clinical community.

Large language models (LLMs) exhibit exceptional performance but pose substantial privacy risks due to training data memorization, particularly within healthcare contexts involving imperfect or privacy-sensitive patient information. We present a hierarchical dual-strategy framework for selective knowledge unlearning that precisely removes specialized knowledge while preserving fundamental medical competencies. Our approach synergistically integrates geometric-constrained gradient updates to selectively modulate target parameters with concept-aware token-level interventions that distinguish between preservation-critical and unlearning-targeted tokens via a unified four-level medical concept hierarchy. Comprehensive evaluations on the MedMCQA (surgical) and MHQA (anxiety, depression, trauma) datasets demonstrate superior performance, achieving an 82.7% forgetting rate and 88.5% knowledge preservation. Notably, our framework maintains robust privacy guarantees while requiring modification of only 0.1% of parameters, addressing critical needs for regulatory compliance, auditability, and ethical standards in clinical research.

Photoplethysmography (PPG) is a widely adopted, non-invasive technique for monitoring cardiovascular health and physiological parameters in both consumer and clinical settings. While motion artifacts in dynamic environments have been extensively studied, suboptimal skin-sensor contact in sedentary conditions - a critical yet underexplored issue - can distort PPG waveform morphology, leading to the loss or misalignment of key features and compromising sensing accuracy. In this work, we propose CP-PPG, a novel framework that transforms Contact Pressure-distorted PPG signals into high-fidelity waveforms with ideal morphology. CP-PPG integrates a custom data collection protocol, a carefully designed signal processing pipeline, and a novel deep adversarial model trained with a custom PPG-aware loss function. We validated CP-PPG through comprehensive evaluations, including 1) morphology transformation performance on our self-collected dataset, 2) downstream physiological monitoring performance on public datasets, and 3) in-the-wild study. Extensive experiments demonstrate substantial and consistent improvements in signal fidelity (Mean Absolute Error: 0.09, 40% improvement over the original signal) as well as downstream performance across all evaluations in Heart Rate (HR), Heart Rate Variability (HRV), Respiration Rate (RR), and Blood Pressure (BP) estimation (on average, 21% improvement in HR; 41-46% in HRV; 6% in RR; and 4-5% in BP). These findings highlight the critical importance of addressing skin-sensor contact issues to enhance the reliability and effectiveness of PPG-based physiological monitoring. CP-PPG thus holds significant potential to improve the accuracy of wearable health technologies in clinical and consumer applications.

The conversion from 2D X-ray to 3D shape holds significant potential for improving diagnostic efficiency and safety. However, existing reconstruction methods often rely on hand-crafted features, manual intervention, and prior knowledge, resulting in unstable shape errors and additional processing costs. In this paper, we introduce Swin-X2S, an end-to-end deep learning method for directly reconstructing 3D segmentation and labeling from 2D biplanar orthogonal X-ray images. Swin-X2S employs an encoder-decoder architecture: the encoder leverages 2D Swin Transformer for X-ray information extraction, while the decoder employs 3D convolution with cross-attention to integrate structural features from orthogonal views. A dimension-expanding module is introduced to bridge the encoder and decoder, ensuring a smooth conversion from 2D pixels to 3D voxels. We evaluate proposed method through extensive qualitative and quantitative experiments across nine publicly available datasets covering four anatomies (femur, hip, spine, and rib), with a total of 54 categories. Significant improvements over previous methods have been observed not only in the segmentation and labeling metrics but also in the clinically relevant parameters that are of primary concern in practical applications, which demonstrates the promise of Swin-X2S to provide an effective option for anatomical shape reconstruction in clinical scenarios. Code implementation is available at: https://github.com/liukuan5625/Swin-X2S.

Cardiac magnetic resonance (CMR) is a cornerstone for diagnosing cardiovascular disease. However, it remains underutilized due to complex, time-consuming interpretation across multi-sequences, phases, quantitative measures that heavily reliant on specialized expertise. Here, we present BAAI Cardiac Agent, a multimodal intelligent system designed for end-to-end CMR interpretation. The agent integrates specialized cardiac expert models to perform automated segmentation of cardiac structures, functional quantification, tissue characterization and disease diagnosis, and generates structured clinical reports within a unified workflow. Evaluated on CMR datasets from two hospitals (2413 patients) spanning 7-types of major cardiovascular diseases, the agent achieved an area under the receiver-operating-characteristic curve exceeding 0.93 internally and 0.81 externally. In the task of estimating left ventricular function indices, the results generated by this system for core parameters such as ejection fraction, stroke volume, and left ventricular mass are highly consistent with clinical reports, with Pearson correlation coefficients all exceeding 0.90. The agent outperformed state-of-the-art models in segmentation and diagnostic tasks, and generated clinical reports showing high concordance with expert radiologists (six readers across three experience levels). By dynamically orchestrating expert models for coordinated multimodal analysis, this agent framework enables accurate, efficient CMR interpretation and highlights its potentials for complex clinical imaging workflows. Code is available at https://github.com/plantain-herb/Cardiac-Agent.

Echocardiography interpretation requires integrating multi-view temporal evidence with quantitative measurements and guideline-grounded reasoning, yet existing foundation-model pipelines largely solve isolated subtasks and fail when tool outputs are noisy or values fall near clinical cutoffs. We propose Echo-CoPilot, an end-to-end agentic framework that combines a multi-perspective workflow with knowledge-graph guided measurement selection. Echo-CoPilot runs three independent ReAct-style agents, structural, pathological, and quantitative, that invoke specialized echocardiography tools to extract parameters while querying EchoKG to determine which measurements are required for the clinical question and which should be avoided. A self-contrast language model then compares the evidence-grounded perspectives, generates a discrepancy checklist, and re-queries EchoKG to apply the appropriate guideline thresholds and resolve conflicts, reducing hallucinated measurement selection and borderline flip-flops. On MIMICEchoQA, Echo-CoPilot provides higher accuracy compared to SOTA baselines and, under a stochasticity stress test, achieves higher reliability through more consistent conclusions and fewer answer changes across repeated runs. Our code is publicly available at~https://github.com/moeinheidari7829/Echo-CoPilot{magenta{GitHub}}.

Focused Ultrasound Ablation Surgery (FUAS) has emerged as a promising non-invasive therapeutic modality, valued for its safety and precision. Nevertheless, its clinical implementation entails intricate tasks such as multimodal image interpretation, personalized dose planning, and real-time intraoperative decision-making processes that demand intelligent assistance to improve efficiency and reliability. We introduce FUAS-Agents, an autonomous agent system that leverages the multimodal understanding and tool-using capabilities of large language models (LLMs). By integrating patient profiles and MRI data, FUAS-Agents orchestrates a suite of specialized medical AI tools, including segmentation, treatment dose prediction, and clinical guideline retrieval, to generate personalized treatment plans comprising MRI image, dose parameters, and therapeutic strategies. We evaluate the system in a uterine fibroid treatment scenario. Human assessment by four senior FUAS experts indicates that 82.5%, 82.5%, 87.5%, and 97.5% of the generated plans were rated 4 or above (on a 5-point scale) in terms of completeness, accuracy, fluency, and clinical compliance, respectively. These results demonstrate the potential of LLM-driven agents in enhancing decision-making across complex clinical workflows, and exemplify a translational paradigm that combines general-purpose models with specialized expert systems to solve practical challenges in vertical healthcare domains.

Echocardiography is widely used for assessing cardiac function, where clinically meaningful parameters such as left-ventricular ejection fraction (EF) play a central role in diagnosis and management. Generative models capable of synthesising realistic echocardiogram videos with explicit control over such parameters are valuable for data augmentation, counterfactual analysis, and specialist training. However, existing approaches typically rely on computationally expensive multi-step sampling and aggressive temporal normalisation, limiting efficiency and applicability to heterogeneous real-world data. We introduce EchoLVFM, a one-step latent video flow-matching framework for controllable echocardiogram generation. Operating in the latent space, EchoLVFM synthesises temporally coherent videos in a single inference step, achieving a sim 50times improvement in sampling efficiency compared to multi-step flow baselines while maintaining visual fidelity. The model supports global conditioning on clinical variables, demonstrated through precise control of EF, and enables reconstruction and counterfactual generation from partially observed sequences. A masked conditioning strategy further removes fixed-length constraints, allowing shorter sequences to be retained rather than discarded. We evaluate EchoLVFM on the CAMUS dataset under challenging single-frame conditioning. Quantitative and qualitative results demonstrate competitive video quality, strong EF adherence, and 57.9% discrimination accuracy by expert clinicians which is close to chance. These findings indicate that efficient, one-step flow matching can enable practical, controllable echocardiogram video synthesis without sacrificing fidelity. Code available at: https://github.com/EngEmmanuel/EchoLVFM

We introduce a general, flexible, parametric survival modelling framework which encompasses key shapes of hazard function (constant, increasing, decreasing, up-then-down, down-then-up), various common survival distributions (log-logistic, Burr type XII, Weibull, Gompertz), and includes defective distributions (i.e., cure models). This generality is achieved using four basic distributional parameters: two scale-type parameters and two shape parameters. Generalising to covariate dependence, the scale-type regression components correspond to accelerated failure time (AFT) and proportional hazards (PH) models. Therefore, this general formulation unifies the most popular survival models which allows us to consider the practical value of possible modelling choices for survival data. Furthermore, in line with our proposed flexible baseline distribution, we advocate the use of multi-parameter regression in which more than one distributional parameter depends on covariates - rather than the usual convention of having a single covariate-dependent (scale) parameter. While many choices are available, we suggest introducing covariates through just one or other of the two scale parameters, which covers AFT and PH models, in combination with a `power' shape parameter, which allows for more complex non-AFT/non-PH effects, while the other shape parameter remains covariate-independent, and handles automatic selection of the baseline distribution. We explore inferential issues in simulations, both with and without a covariate, with particular focus on evidence concerning the need, or otherwise, to include both AFT and PH parameters. We illustrate the efficacy of our modelling framework by investigating differences between treatment groups using data from a lung cancer study and a melanoma study. Censoring is accommodated throughout.

A compartmental deterministic model that allows (1) immunity from two stages of infection and carriage, and (2) disease induced death, is used in studying the dynamics of meningitis epidemic process in a closed population. It allows for difference in the transmission rate of infection to a susceptible by a carrier and an infective. It is generalized to allow a proportion ({\phi}) of those susceptibles infected to progress directly to infectives in stage I. Both models are used in this study. The threshold conditions for the spread of carrier and infectives in stage I are derived for the two models. Sensitivity analysis is performed on the reproductive number derived from the next generation matrix. The case-carrier ratio profile for various parameters and threshold values are shown. So also are the graphs of the total number ever infected as influenced by {\epsilon} and {\phi}. The infection transmission rate (eta), the odds in favor of a carrier, over an infective, in transmitting an infection to a susceptible ({\epsilon}) and the carrier conversion rate ({\phi}) to an infective in stage I, are identified as key parameters that should be subject of attention for any control intervention strategy. The case-carrier ratio profiles provide evidence of a critical case-carrier ratio attained before the number of reported cases grows to an epidemic level. They also provide visual evidence of epidemiological context, in this case, epidemic incidence (in later part of dry season) and endemic incidence (during rainy season). Results from total proportion ever infected suggest that the model, in which {\phi}=0 obtained, can adequately represent, in essence, the generalized model for this study.

Intermittent Androgen Suppression (IAS) is a treatment strategy for delaying or even preventing time to relapse of advanced prostate cancer. IAS consists of alternating cycles of therapy (in the form of androgen suppression) and off-treatment periods. The level of prostate specific antigen (PSA) in a patient's serum is frequently monitored to determine when the patient will be taken off therapy and when therapy will resume. In spite of extensive recent clinical experience with IAS, the design of an ideal protocol for any given patient remains one of the main challenges associated with effectively implementing this therapy. We use a threshold-based policy for optimal IAS therapy design that is parameterized by lower and upper PSA threshold values and is associated with a cost metric that combines clinically relevant measures of therapy success. We apply Infinitesimal Perturbation Analysis (IPA) to a Stochastic Hybrid Automaton (SHA) model of prostate cancer evolution under IAS and derive unbiased estimators of the cost metric gradient with respect to various model and therapy parameters. These estimators are subsequently used for system analysis. By evaluating sensitivity estimates with respect to several model parameters, we identify critical parameters and demonstrate that relaxing the optimality condition in favor of increased robustness to modeling errors provides an alternative objective to therapy design for at least some patients.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

Tumor documentation in Germany is largely done manually, requiring reading patient records and entering data into structured databases. Large language models (LLMs) could potentially enhance this process by improving efficiency and reliability. This evaluation tests eleven different open source LLMs with sizes ranging from 1-70 billion model parameters on three basic tasks of the tumor documentation process: identifying tumor diagnoses, assigning ICD-10 codes, and extracting the date of first diagnosis. For evaluating the LLMs on these tasks, a dataset of annotated text snippets based on anonymized doctors' notes from urology was prepared. Different prompting strategies were used to investigate the effect of the number of examples in few-shot prompting and to explore the capabilities of the LLMs in general. The models Llama 3.1 8B, Mistral 7B, and Mistral NeMo 12 B performed comparably well in the tasks. Models with less extensive training data or having fewer than 7 billion parameters showed notably lower performance, while larger models did not display performance gains. Examples from a different medical domain than urology could also improve the outcome in few-shot prompting, which demonstrates the ability of LLMs to handle tasks needed for tumor documentation. Open source LLMs show a strong potential for automating tumor documentation. Models from 7-12 billion parameters could offer an optimal balance between performance and resource efficiency. With tailored fine-tuning and well-designed prompting, these models might become important tools for clinical documentation in the future. The code for the evaluation is available from https://github.com/stefan-m-lenz/UroLlmEval. We also release the dataset as a new valuable resource that addresses the shortage of authentic and easily accessible benchmarks in German-language medical NLP.

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.

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.

The development of clinical natural language processing (NLP) systems is severely hampered by the sensitive nature of medical records, which restricts data sharing under stringent privacy regulations, particularly in France and the broader European Union. To address this gap, we introduce PARHAF, a large open-source corpus of clinical documents in French. PARHAF comprises expert-authored clinical reports describing realistic yet entirely fictitious patient cases, making it anonymous and freely shareable by design. The corpus was developed using a structured protocol that combined clinician expertise with epidemiological guidance from the French National Health Data System (SNDS), ensuring broad clinical coverage. A total of 104 medical residents across 18 specialties authored and peer-reviewed the reports following predefined clinical scenarios and document templates. The corpus contains 7394 clinical reports covering 5009 patient cases across a wide range of medical and surgical specialties. It includes a general-purpose component designed to approximate real-world hospitalization distributions, and four specialized subsets that support information-extraction use cases in oncology, infectious diseases, and diagnostic coding. Documents are released under a CC-BY open license, with a portion temporarily embargoed to enable future benchmarking under controlled conditions. PARHAF provides a valuable resource for training and evaluating French clinical language models in a fully privacy-preserving setting, and establishes a replicable methodology for building shareable synthetic clinical corpora in other languages and health systems.

Recruiting patients to participate in clinical trials can be challenging and time-consuming. Usually, participation in a clinical trial is initiated by a healthcare professional and proposed to the patient. Promoting clinical trials directly to patients via online recruitment might help to reach them more efficiently. In this study, we address the case where a patient is initiating their own recruitment process and wants to determine whether they are eligible for a given clinical trial, using their own language to describe their medical profile. To study whether this creates difficulties in the patient trial matching process, we design a new dataset and task, Natural Language Inference for Patient Recruitment (NLI4PR), in which patient language profiles must be matched to clinical trials. We create it by adapting the TREC 2022 Clinical Trial Track dataset, which provides patients' medical profiles, and rephrasing them manually using patient language. We also use the associated clinical trial reports where the patients are either eligible or excluded. We prompt several open-source Large Language Models on our task and achieve from 56.5 to 71.8 of F1 score using patient language, against 64.7 to 73.1 for the same task using medical language. When using patient language, we observe only a small loss in performance for the best model, suggesting that having the patient as a starting point could be adopted to help recruit patients for clinical trials. The corpus and code bases are all freely available on our Github and HuggingFace repositories.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

Large Language Models (LLMs) are increasingly being explored for clinical question answering and decision support, yet safe deployment critically requires reliable handling of patient measurements in heterogeneous clinical notes. Existing evaluations of LLMs for clinical numerical reasoning provide limited operation-level coverage, restricted primarily to arithmetic computation, and rarely assess the robustness of numerical understanding across clinical note formats. We introduce ClinicNumRobBench, a benchmark of 1,624 context-question instances with ground-truth answers that evaluates four main types of clinical numeracy: value retrieval, arithmetic computation, relational comparison, and aggregation. To stress-test robustness, ClinicNumRobBench presents longitudinal MIMIC-IV vital-sign records in three semantically equivalent representations, including a real-world note-style variant derived from the Open Patients dataset, and instantiates queries using 42 question templates. Experiments on 14 LLMs show that value retrieval is generally strong, with most models exceeding 85% accuracy, while relational comparison and aggregation remain challenging, with some models scoring below 15%. Fine-tuning on medical data can reduce numeracy relative to base models by over 30%, and performance drops under note-style variation indicate LLM sensitivity to format. ClinicNumRobBench offers a rigorous testbed for clinically reliable numerical reasoning. Code and data URL are available on https://github.com/MinhVuong2000/ClinicNumRobBench.

Several studies have shown that speech and language features, automatically extracted from clinical interviews or spontaneous discourse, have diagnostic value for mental disorders such as schizophrenia and bipolar disorder. They typically make use of a large feature set to train a classifier for distinguishing between two groups of interest, i.e. a clinical and control group. However, a purely data-driven approach runs the risk of overfitting to a particular data set, especially when sample sizes are limited. Here, we first down-select the set of language features to a small subset that is related to a well-validated test of functional ability, the Social Skills Performance Assessment (SSPA). This helps establish the concurrent validity of the selected features. We use only these features to train a simple classifier to distinguish between groups of interest. Linear regression reveals that a subset of language features can effectively model the SSPA, with a correlation coefficient of 0.75. Furthermore, the same feature set can be used to build a strong binary classifier to distinguish between healthy controls and a clinical group (AUC = 0.96) and also between patients within the clinical group with schizophrenia and bipolar I disorder (AUC = 0.83).

As mental health care systems worldwide struggle to meet demand, there is increasing focus on using language models to infer neuropsychiatric conditions or psychopathological traits from language production. Yet, so far, this research has only delivered solutions with limited clinical applicability, due to insufficient consideration of ethical questions crucial to ensuring the synergy between possible applications and model design. To accelerate progress towards clinically applicable models, our paper charts the ethical landscape of research on language-based inference of psychopathology and provides a practical tool for researchers to navigate it. We identify seven core ethical principles that should guide model development and deployment in this domain, translate them into ELLIPS, an ethical toolkit operationalizing these principles into questions that can guide researchers' choices with respect to data selection, architectures, evaluation, and model deployment, and provide a case study exemplifying its use. With this, we aim to facilitate the emergence of model technology with concrete potential for real-world applicability.

Background: Rapid advancements in natural language processing have led to the development of large language models with the potential to revolutionize mental health care. These models have shown promise in assisting clinicians and providing support to individuals experiencing various psychological challenges. Objective: This study aims to compare the performance of two large language models, GPT-4 and Chat-GPT, in responding to a set of 18 psychological prompts, to assess their potential applicability in mental health care settings. Methods: A blind methodology was employed, with a clinical psychologist evaluating the models' responses without knowledge of their origins. The prompts encompassed a diverse range of mental health topics, including depression, anxiety, and trauma, to ensure a comprehensive assessment. Results: The results demonstrated a significant difference in performance between the two models (p > 0.05). GPT-4 achieved an average rating of 8.29 out of 10, while Chat-GPT received an average rating of 6.52. The clinical psychologist's evaluation suggested that GPT-4 was more effective at generating clinically relevant and empathetic responses, thereby providing better support and guidance to potential users. Conclusions: This study contributes to the growing body of literature on the applicability of large language models in mental health care settings. The findings underscore the importance of continued research and development in the field to optimize these models for clinical use. Further investigation is necessary to understand the specific factors underlying the performance differences between the two models and to explore their generalizability across various populations and mental health conditions.

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.

Med42-v2 introduces a suite of clinical large language models (LLMs) designed to address the limitations of generic models in healthcare settings. These models are built on Llama3 architecture and fine-tuned using specialized clinical data. They underwent multi-stage preference alignment to effectively respond to natural prompts. While generic models are often preference-aligned to avoid answering clinical queries as a precaution, Med42-v2 is specifically trained to overcome this limitation, enabling its use in clinical settings. Med42-v2 models demonstrate superior performance compared to the original Llama3 models in both 8B and 70B parameter configurations and GPT-4 across various medical benchmarks. These LLMs are developed to understand clinical queries, perform reasoning tasks, and provide valuable assistance in clinical environments. The models are now publicly available at https://huggingface.co/m42-health{https://huggingface.co/m42-health}.

Objective: Data unavailability has been one of the biggest barriers in clinical natural language processing. This paper is aimed at providing a large-scale and publicly available patient note dataset, named PMC-Patients, with relevant articles and similar patients annotations. The ultimate goal of PMC-Patients is to facilitate the development of retrieval-based clinical decision support systems. Materials and Methods: To collect PMC-Patients, we extract patient notes from case reports in PubMed Central by recognizing certain section patterns. Patient-article relevance and patient-patient similarity are annotated by citation relationships in PubMed. In addition, we perform three tasks with PMC-Patients to demonstrate its utility in providing clinical decision support for a given patient, including (1) classifying whether another patient is similar, (2) retrieving similar patients in PMC-Patients, and (3) retrieving relevant articles in PubMed. Results: We collect and release PMC-Patients under the CC BY-NC-SA license, which becomes the largest publicly available patient note dataset so far. PMC-Patients contains 167k patient notes that are annotated with 3.1M relevant articles and 293k similar patients. Qualitative and quantitative analyses reveal the high quality and richness of our dataset. Experiments show that classifying the similarity of patient pairs is relatively easy, but it is hard to retrieve similar patients or relevant articles for a given patient from a large set of candidates. Conclusion: We present PMC-Patients, a large-scale dataset of patient notes with high quality, easy access, diverse conditions, and rich annotations. The proposed dataset can also serve as a hard benchmark for evaluating retrieval-based clinical decision support systems.

Purpose: Recent advancements in large language models (LLMs) have expanded their capabilities in a multimodal fashion, potentially replicating the image interpretation of human radiologists. This study aimed to develop open-source multimodal large language model for interpreting chest X-ray images (CXR-LLaVA). We also examined the effect of prompt engineering and model parameters such as temperature and nucleus sampling. Materials and Methods: For training, we collected 659,287 publicly available CXRs: 417,336 CXRs had labels for certain radiographic abnormalities (dataset 1); 241,951 CXRs provided free-text radiology reports (dataset 2). After pre-training the Resnet50 as an image encoder, the contrastive language-image pre-training was used to align CXRs and corresponding radiographic abnormalities. Then, the Large Language Model Meta AI-2 was fine-tuned using dataset 2, which were refined using GPT-4, with generating various question answering scenarios. The code can be found at https://github.com/ECOFRI/CXR_LLaVA. Results: In the test set, we observed that the model's performance fluctuated based on its parameters. On average, it achieved F1 score of 0.34 for five pathologic findings (atelectasis, cardiomegaly, consolidation, edema, and pleural effusion), which was improved to 0.46 through prompt engineering. In the independent set, the model achieved an average F1 score of 0.30 for the same pathologic findings. Notably, for the pediatric chest radiograph dataset, which was unseen during training, the model differentiated abnormal radiographs with an F1 score ranging from 0.84 to 0.85. Conclusion: CXR-LLaVA demonstrates promising potential in CXR interpretation. Both prompt engineering and model parameter adjustments can play pivotal roles in interpreting CXRs.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

While the general machine learning (ML) community has benefited from public datasets, tasks, and models, the progress of ML in healthcare has been hampered by a lack of such shared assets. The success of foundation models creates new challenges for healthcare ML by requiring access to shared pretrained models to validate performance benefits. We help address these challenges through three contributions. First, we publish a new dataset, EHRSHOT, which contains deidentified structured data from the electronic health records (EHRs) of 6,739 patients from Stanford Medicine. Unlike MIMIC-III/IV and other popular EHR datasets, EHRSHOT is longitudinal and not restricted to ICU/ED patients. Second, we publish the weights of CLMBR-T-base, a 141M parameter clinical foundation model pretrained on the structured EHR data of 2.57M patients. We are one of the first to fully release such a model for coded EHR data; in contrast, most prior models released for clinical data (e.g. GatorTron, ClinicalBERT) only work with unstructured text and cannot process the rich, structured data within an EHR. We provide an end-to-end pipeline for the community to validate and build upon its performance. Third, we define 15 few-shot clinical prediction tasks, enabling evaluation of foundation models on benefits such as sample efficiency and task adaptation. Our model and dataset are available via a research data use agreement from the Stanford AIMI Center. Code to reproduce our results are available at our Github repo: https://github.com/som-shahlab/ehrshot-benchmark

While recent advancements in commercial large language models (LM) have shown promising results in medical tasks, their closed-source nature poses significant privacy and security concerns, hindering their widespread use in the medical field. Despite efforts to create open-source models, their limited parameters often result in insufficient multi-step reasoning capabilities required for solving complex medical problems. To address this, we introduce Meerkat-7B, a novel medical AI system with 7 billion parameters. Meerkat-7B was trained using our new synthetic dataset consisting of high-quality chain-of-thought reasoning paths sourced from 18 medical textbooks, along with diverse instruction-following datasets. Our system achieved remarkable accuracy across seven medical benchmarks, surpassing GPT-3.5 by 13.1%, as well as outperforming the previous best 7B models such as MediTron-7B and BioMistral-7B by 13.4% and 9.8%, respectively. Notably, it surpassed the passing threshold of the United States Medical Licensing Examination (USMLE) for the first time for a 7B-parameter model. Additionally, our system offered more detailed free-form responses to clinical queries compared to existing 7B and 13B models, approaching the performance level of GPT-3.5. This significantly narrows the performance gap with large LMs, showcasing its effectiveness in addressing complex medical challenges.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

Large Language Models (LLMs) hold great promise to revolutionize current clinical systems for their superior capacities on medical text processing tasks and medical licensing exams. Meanwhile, traditional ML models such as SVM and XGBoost have still been mainly adopted in clinical prediction tasks. An emerging question is Can LLMs beat traditional ML models in clinical prediction? Thus, we build a new benchmark ClinicalBench to comprehensively study the clinical predictive modeling capacities of both general-purpose and medical LLMs, and compare them with traditional ML models. ClinicalBench embraces three common clinical prediction tasks, two databases, 14 general-purpose LLMs, 8 medical LLMs, and 11 traditional ML models. Through extensive empirical investigation, we discover that both general-purpose and medical LLMs, even with different model scales, diverse prompting or fine-tuning strategies, still cannot beat traditional ML models in clinical prediction yet, shedding light on their potential deficiency in clinical reasoning and decision-making. We call for caution when practitioners adopt LLMs in clinical applications. ClinicalBench can be utilized to bridge the gap between LLMs' development for healthcare and real-world clinical practice.

Mixture of Expert Tuning (MoE-Tuning) has effectively enhanced the performance of general MLLMs with fewer parameters, yet its application in resource-limited medical settings has not been fully explored. To address this gap, we developed MoE-TinyMed, a model tailored for medical applications that significantly lowers parameter demands. In evaluations on the VQA-RAD, SLAKE, and Path-VQA datasets, MoE-TinyMed outperformed LLaVA-Med in all Med-VQA closed settings with just 3.6B parameters. Additionally, a streamlined version with 2B parameters surpassed LLaVA-Med's performance in PathVQA, showcasing its effectiveness in resource-limited healthcare settings.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

Providing effective treatment and making informed clinical decisions are essential goals of modern medicine and clinical care. We are interested in simulating disease dynamics for clinical decision-making, leveraging recent advances in large generative models. To this end, we introduce the Medical World Model (MeWM), the first world model in medicine that visually predicts future disease states based on clinical decisions. MeWM comprises (i) vision-language models to serve as policy models, and (ii) tumor generative models as dynamics models. The policy model generates action plans, such as clinical treatments, while the dynamics model simulates tumor progression or regression under given treatment conditions. Building on this, we propose the inverse dynamics model that applies survival analysis to the simulated post-treatment tumor, enabling the evaluation of treatment efficacy and the selection of the optimal clinical action plan. As a result, the proposed MeWM simulates disease dynamics by synthesizing post-treatment tumors, with state-of-the-art specificity in Turing tests evaluated by radiologists. Simultaneously, its inverse dynamics model outperforms medical-specialized GPTs in optimizing individualized treatment protocols across all metrics. Notably, MeWM improves clinical decision-making for interventional physicians, boosting F1-score in selecting the optimal TACE protocol by 13%, paving the way for future integration of medical world models as the second readers.

PURPOSE: Subarachnoid hemorrhage (SAH) entails high morbidity and mortality rates. Convolutional neural networks (CNN), a form of deep learning, are capable of generating highly accurate predictions from imaging data. Our objective was to predict mortality in SAH patients by processing the initial CT scan on a CNN based algorithm. METHODS: Retrospective multicentric study of a consecutive cohort of patients with SAH between 2011-2022. Demographic, clinical and radiological variables were analyzed. Pre-processed baseline CT scan images were used as the input for training a CNN using AUCMEDI Framework. Our model's architecture leverages the DenseNet-121 structure, employing transfer learning principles. The output variable was mortality in the first three months. Performance of the model was evaluated by statistical parameters conventionally used in studies involving artificial intelligence methods. RESULTS: Images from 219 patients were processed, 175 for training and validation of the CNN and 44 for its evaluation. 52%(115/219) of patients were female, and the median age was 58(SD=13.06) years. 18.5%(39/219) were idiopathic SAH. Mortality rate was 28.5%(63/219). The model showed good accuracy at predicting mortality in SAH patients exclusively using the images of the initial CT scan (Accuracy=74%, F1=75% and AUC=82%). CONCLUSION: Modern image processing techniques based on AI and CNN make possible to predict mortality in SAH patients with high accuracy using CT scan images as the only input. These models might be optimized by including more data and patients resulting in better training, development and performance on tasks which are beyond the skills of conventional clinical knowledge.

We introduce Biomed-Enriched, a biomedical text dataset constructed from PubMed via a two-stage annotation process. In the first stage, a large language model annotates 400K paragraphs from PubMed scientific articles, assigning scores for their type (review, study, clinical case, other), domain (clinical, biomedical, other), and educational quality. The educational quality score (rated 1 to 5) estimates how useful a paragraph is for college-level learning. These annotations are then used to fine-tune a small language model, which propagates the labels across the full PMC-OA corpus. The resulting metadata allows us to extract refined subsets, including 2M clinical case paragraphs with over 450K high-quality ones from articles with commercial-use licenses, and to construct several variants via quality filtering and domain upsampling. Clinical text is typically difficult to access due to privacy constraints, as hospital records cannot be publicly shared. Hence, our dataset provides an alternative large-scale, openly available collection of clinical cases from PubMed, making it a valuable resource for biomedical and clinical NLP. Preliminary continual-pretraining experiments with OLMo2 suggest these curated subsets enable targeted improvements, with clinical upsampling boosting performance by ~5% on MMLU ProfMed and educational quality filtering improving MedQA and MedMCQA by ~1%. Combinations of these techniques led to faster convergence, reaching same performance with a third of training tokens, indicating potential for more efficient and effective biomedical pretraining strategies.

Recent advances in large language models (LLMs) have shown strong reasoning capabilities through large-scale pretraining and post-training reinforcement learning, demonstrated by DeepSeek-R1. However, current post-training methods, such as Grouped Relative Policy Optimization (GRPO), mainly reward correctness, which is not aligned with the multi-dimensional objectives required in high-stakes fields such as medicine, where reasoning must also be faithful and comprehensive. We introduce Clinical-Objective Relative Policy Optimization (CRPO), a scalable, multi-objective, verifiable reinforcement learning method designed to align LLM post-training with clinical reasoning principles. CRPO integrates rule-based and verifiable reward signals that jointly optimize accuracy, faithfulness, and comprehensiveness without relying on human annotation. To demonstrate its effectiveness, we train Clinical-R1-3B, a 3B-parameter model for clinical reasoning. The experiments on three benchmarks demonstrate that our CRPO substantially improves reasoning on truthfulness and completeness over standard GRPO while maintaining comfortable accuracy enhancements. This framework provides a scalable pathway to align LLM reasoning with clinical objectives, enabling safer and more collaborative AI systems for healthcare while also highlighting the potential of multi-objective, verifiable RL methods in post-training scaling of LLMs for medical domains.

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

Purpose: The need to streamline patient management for COVID-19 has become more pressing than ever. Chest X-rays provide a non-invasive (potentially bedside) tool to monitor the progression of the disease. In this study, we present a severity score prediction model for COVID-19 pneumonia for frontal chest X-ray images. Such a tool can gauge severity of COVID-19 lung infections (and pneumonia in general) that can be used for escalation or de-escalation of care as well as monitoring treatment efficacy, especially in the ICU. Methods: Images from a public COVID-19 database were scored retrospectively by three blinded experts in terms of the extent of lung involvement as well as the degree of opacity. A neural network model that was pre-trained on large (non-COVID-19) chest X-ray datasets is used to construct features for COVID-19 images which are predictive for our task. Results: This study finds that training a regression model on a subset of the outputs from an this pre-trained chest X-ray model predicts our geographic extent score (range 0-8) with 1.14 mean absolute error (MAE) and our lung opacity score (range 0-6) with 0.78 MAE. Conclusions: These results indicate that our model's ability to gauge severity of COVID-19 lung infections could be used for escalation or de-escalation of care as well as monitoring treatment efficacy, especially in the intensive care unit (ICU). A proper clinical trial is needed to evaluate efficacy. To enable this we make our code, labels, and data available online at https://github.com/mlmed/torchxrayvision/tree/master/scripts/covid-severity and https://github.com/ieee8023/covid-chestxray-dataset

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.

In recent years, medical information technology has made it possible for electronic health record (EHR) to store fairly complete clinical data. This has brought health care into the era of "big data". However, medical data are often sparse and strongly correlated, which means that medical problems cannot be solved effectively. With the rapid development of deep learning in recent years, it has provided opportunities for the use of big data in healthcare. In this paper, we propose a temporal-saptial correlation attention network (TSCAN) to handle some clinical characteristic prediction problems, such as predicting death, predicting length of stay, detecting physiologic decline, and classifying phenotypes. Based on the design of the attention mechanism model, our approach can effectively remove irrelevant items in clinical data and irrelevant nodes in time according to different tasks, so as to obtain more accurate prediction results. Our method can also find key clinical indicators of important outcomes that can be used to improve treatment options. Our experiments use information from the Medical Information Mart for Intensive Care (MIMIC-IV) database, which is open to the public. Finally, we have achieved significant performance benefits of 2.0\% (metric) compared to other SOTA prediction methods. We achieved a staggering 90.7\% on mortality rate, 45.1\% on length of stay. The source code can be find: https://github.com/yuyuheintju/TSCAN.

With the advent of LLMs, various tasks across the natural language processing domain have been transformed. However, their application in predictive tasks remains less researched. This study compares large language models, including GatorTron-Base (trained on clinical data), Llama 8B, and Mistral 7B, against models like BioBERT, DocBERT, BioClinicalBERT, Word2Vec, and Doc2Vec, setting benchmarks for predicting Shock in critically ill patients. Timely prediction of shock can enable early interventions, thus improving patient outcomes. Text data from 17,294 ICU stays of patients in the MIMIC III database were scored for length of stay > 24 hours and shock index (SI) > 0.7 to yield 355 and 87 patients with normal and abnormal SI-index, respectively. Both focal and cross-entropy losses were used during finetuning to address class imbalances. Our findings indicate that while GatorTron Base achieved the highest weighted recall of 80.5%, the overall performance metrics were comparable between SLMs and LLMs. This suggests that LLMs are not inherently superior to SLMs in predicting future clinical events despite their strong performance on text-based tasks. To achieve meaningful clinical outcomes, future efforts in training LLMs should prioritize developing models capable of predicting clinical trajectories rather than focusing on simpler tasks such as named entity recognition or phenotyping.

Vision-language models (VLMs) adapted to the medical domain have shown strong performance on visual question answering benchmarks, yet their robustness against two critical failure modes, hallucination and sycophancy, remains poorly understood, particularly in combination. We evaluate six VLMs (three general-purpose, three medical-specialist) on three medical VQA datasets and uncover a grounding-sycophancy tradeoff: models with the lowest hallucination propensity are the most sycophantic, while the most pressure-resistant model hallucinates more than all medical-specialist models. To characterize this tradeoff, we propose three metrics: L-VASE, a logit-space reformulation of VASE that avoids its double-normalization; CCS, a confidence-calibrated sycophancy score that penalizes high-confidence capitulation; and Clinical Safety Index (CSI), a unified safety index that combines grounding, autonomy, and calibration via a geometric mean. Across 1,151 test cases, no model achieves a CSI above 0.35, indicating that none of the evaluated 7-8B parameter VLMs is simultaneously well-grounded and robust to social pressure. Our findings suggest that joint evaluation of both properties is necessary before these models can be considered for clinical use. Code is available at https://github.com/UTSA-VIRLab/AgreeOrRight

Clinicians spend a significant amount of time reviewing medical images and transcribing their findings regarding patient diagnosis, referral and treatment in text form. Vision-language models (VLMs), which automatically interpret images and summarize their findings as text, have enormous potential to alleviate clinical workloads and increase patient access to high-quality medical care. While foundational models have stirred considerable interest in the medical community, it is unclear whether their general capabilities translate to real-world clinical utility. In this work, we show that foundation VLMs markedly underperform compared to practicing ophthalmologists on specialist tasks crucial to the care of patients with age-related macular degeneration (AMD). To address this, we initially identified the essential capabilities required for image-based clinical decision-making, and then developed a curriculum to selectively train VLMs in these skills. The resulting model, RetinaVLM, can be instructed to write reports that significantly outperform those written by leading foundation medical VLMs in disease staging (F1 score of 0.63 vs. 0.11) and patient referral (0.67 vs. 0.39), and approaches the diagnostic performance of junior ophthalmologists (who achieve 0.77 and 0.78 on the respective tasks). Furthermore, in a reader study involving two senior ophthalmologists with up to 32 years of experience, RetinaVLM's reports were found to be similarly correct (78.6% vs. 82.1%) and complete (both 78.6%) as reports written by junior ophthalmologists with up to 10 years of experience. These results demonstrate that our curriculum-based approach provides a blueprint for specializing generalist foundation medical VLMs to handle real-world clinical tasks.

We present Eir Thai Medical LLM, a large language model with 8 billion parameters, specifically designed to enhance the accuracy of handling medical tasks in the Thai language. This model focuses on providing clear and easy-to-understand answers for both healthcare professionals and patients, thereby improving the efficiency of diagnosis and treatment processes. Human evaluation was conducted to ensure that the model adheres to care standards and provides unbiased answers. To prioritize data security, the model is deployed within the hospital's internal network, ensuring both high security and faster processing speeds. The internal API connection is secured with encryption and strict authentication measures to prevent data leaks and unauthorized access. We evaluated several open-source large language models with 8 billion parameters on four medical benchmarks: MedQA, MedMCQA, PubMedQA, and the medical subset of MMLU. The best-performing baselines were used to develop Eir Thai Medical LLM. Our evaluation employed multiple questioning strategies, including zero-shot, few-shot, chain-of-thought reasoning, and ensemble/self-consistency voting methods. Our model outperformed commercially available Thai-language large language models by more than 10%. In addition, we developed enhanced model testing tailored for clinical use in Thai across 18 clinical tasks, where our model exceeded GPT-4o performance by more than 11%

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

While large language models (LLMs) show transformative potential in healthcare, their development remains focused on high-resource languages, creating a critical barrier for others as simple translation fails to capture unique clinical and cultural nuances, such as endemic diseases. To address this, we introduce MedPT, the first large-scale, real-world corpus for Brazilian Portuguese, comprising 384,095 authentic question-answer pairs from patient-doctor interactions. The dataset underwent a meticulous multi-stage curation protocol, using a hybrid quantitative-qualitative analysis to filter noise and contextually enrich thousands of ambiguous queries. We further augmented the corpus via LLM-driven annotation, classifying questions into seven semantic types to capture user intent. Our analysis reveals its thematic breadth (3,200 topics) and unique linguistic properties, like the natural asymmetry in patient-doctor communication. To validate its utility, we benchmark a medical specialty routing task: fine-tuning a 1.7B parameter model achieves an outstanding 94\% F1-score on a 20-class setup. Furthermore, our qualitative error analysis shows misclassifications are not random but reflect genuine clinical ambiguities (e.g., between comorbid conditions), proving the dataset's deep semantic richness. We publicly release MedPT to foster the development of more equitable, accurate, and culturally-aware medical technologies for the Portuguese-speaking world.

We develop an algorithm which exceeds the performance of board certified cardiologists in detecting a wide range of heart arrhythmias from electrocardiograms recorded with a single-lead wearable monitor. We build a dataset with more than 500 times the number of unique patients than previously studied corpora. On this dataset, we train a 34-layer convolutional neural network which maps a sequence of ECG samples to a sequence of rhythm classes. Committees of board-certified cardiologists annotate a gold standard test set on which we compare the performance of our model to that of 6 other individual cardiologists. We exceed the average cardiologist performance in both recall (sensitivity) and precision (positive predictive value).

Large language models have exhibited exceptional performance on various Natural Language Processing (NLP) tasks, leveraging techniques such as the pre-training, and instruction fine-tuning. Despite these advances, their effectiveness in medical applications is limited, due to challenges such as factual inaccuracies, reasoning abilities, and lack grounding in real-world experience. In this study, we present ClinicalGPT, a language model explicitly designed and optimized for clinical scenarios. By incorporating extensive and diverse real-world data, such as medical records, domain-specific knowledge, and multi-round dialogue consultations in the training process, ClinicalGPT is better prepared to handle multiple clinical task. Furthermore, we introduce a comprehensive evaluation framework that includes medical knowledge question-answering, medical exams, patient consultations, and diagnostic analysis of medical records. Our results demonstrate that ClinicalGPT significantly outperforms other models in these tasks, highlighting the effectiveness of our approach in adapting large language models to the critical domain of healthcare.

This paper considers the problem of variable selection allowing for parameter instability. It distinguishes between signal and pseudo-signal variables that are correlated with the target variable, and noise variables that are not, and investigate the asymptotic properties of the One Covariate at a Time Multiple Testing (OCMT) method proposed by Chudik et al. (2018) under parameter insatiability. It is established that OCMT continues to asymptotically select an approximating model that includes all the signals and none of the noise variables. Properties of post selection regressions are also investigated, and in-sample fit of the selected regression is shown to have the oracle property. The theoretical results support the use of unweighted observations at the selection stage of OCMT, whilst applying down-weighting of observations only at the forecasting stage. Monte Carlo and empirical applications show that OCMT without down-weighting at the selection stage yields smaller mean squared forecast errors compared to Lasso, Adaptive Lasso, and boosting.

Large language models (LLMs) have demonstrated remarkable capabilities in natural language understanding and generation across various domains, including medicine. We present a comprehensive evaluation of GPT-4, a state-of-the-art LLM, on medical competency examinations and benchmark datasets. GPT-4 is a general-purpose model that is not specialized for medical problems through training or engineered to solve clinical tasks. Our analysis covers two sets of official practice materials for the USMLE, a three-step examination program used to assess clinical competency and grant licensure in the United States. We also evaluate performance on the MultiMedQA suite of benchmark datasets. Beyond measuring model performance, experiments were conducted to investigate the influence of test questions containing both text and images on model performance, probe for memorization of content during training, and study probability calibration, which is of critical importance in high-stakes applications like medicine. Our results show that GPT-4, without any specialized prompt crafting, exceeds the passing score on USMLE by over 20 points and outperforms earlier general-purpose models (GPT-3.5) as well as models specifically fine-tuned on medical knowledge (Med-PaLM, a prompt-tuned version of Flan-PaLM 540B). In addition, GPT-4 is significantly better calibrated than GPT-3.5, demonstrating a much-improved ability to predict the likelihood that its answers are correct. We also explore the behavior of the model qualitatively through a case study that shows the ability of GPT-4 to explain medical reasoning, personalize explanations to students, and interactively craft new counterfactual scenarios around a medical case. Implications of the findings are discussed for potential uses of GPT-4 in medical education, assessment, and clinical practice, with appropriate attention to challenges of accuracy and safety.

The discharge summary is a one of critical documents in the patient journey, encompassing all events experienced during hospitalization, including multiple visits, medications, tests, surgery/procedures, and admissions/discharge. Providing a summary of the patient's progress is crucial, as it significantly influences future care and planning. Consequently, clinicians face the laborious and resource-intensive task of manually collecting, organizing, and combining all the necessary data for a discharge summary. Therefore, we propose "NOTE", which stands for "Notable generation Of patient Text summaries through an Efficient approach based on direct preference optimization". NOTE is based on Medical Information Mart for Intensive Care- III dataset and summarizes a single hospitalization of a patient. Patient events are sequentially combined and used to generate a discharge summary for each hospitalization. In the present circumstances, large language models' application programming interfaces (LLMs' APIs) are widely available, but importing and exporting medical data presents significant challenges due to privacy protection policies in healthcare institutions. Moreover, to ensure optimal performance, it is essential to implement a lightweight model for internal server or program within the hospital. Therefore, we utilized DPO and parameter efficient fine tuning (PEFT) techniques to apply a fine-tuning method that guarantees superior performance. To demonstrate the practical application of the developed NOTE, we provide a webpage-based demonstration software. In the future, we will aim to deploy the software available for actual use by clinicians in hospital. NOTE can be utilized to generate various summaries not only discharge summaries but also throughout a patient's journey, thereby alleviating the labor-intensive workload of clinicians and aiming for increased efficiency.

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.

Medical coding translates clinical documentation into standardized codes for billing, research, and public health, but manual coding is time-consuming and error-prone. Existing automation efforts rely on small datasets that poorly represent real-world patient heterogeneity. We trained a language model on 5.8 million electronic health records from 1.8 million patients across nearly all specialties in Eastern Denmark (2006--2016) to predict ICD-10 codes from clinical notes, medications, and laboratory results. Evaluated on 270,000 held-out patients, the model achieved a micro F1 of 71.8% and a top-10 recall of 95.5%. Performance varied by specialty (F1: 53--91%), with higher scores in specialties with well-defined diagnostic criteria. Codes appearing predominantly as secondary diagnoses had markedly lower F1 scores. For three such codes (suicide-related behaviors, weight disorders, and hypertension), the model identified thousands of uncoded cases, of which 76-86% were confirmed valid upon manual review, suggesting systematic under-coding rather than model error. These findings suggest under-coding of secondary diagnoses in Eastern Denmark during this period, with potential implications for epidemiological research, public health surveillance, and understanding of multimorbidity. Similar time constraints and reimbursement structures in other healthcare systems suggest this may not be isolated to this dataset. The model can automate coding for approximately 50% of cases and provide accurate suggestions for most others, and may offer a practical solution to help capture missed secondary conditions.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. Early diagnosis, accurate and timely treatment are critical to improving patient survival rates. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose skin-SOAP, a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate this clinical relevance, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

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.

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.

This paper introduces MedMCQA, a new large-scale, Multiple-Choice Question Answering (MCQA) dataset designed to address real-world medical entrance exam questions. More than 194k high-quality AIIMS \& NEET PG entrance exam MCQs covering 2.4k healthcare topics and 21 medical subjects are collected with an average token length of 12.77 and high topical diversity. Each sample contains a question, correct answer(s), and other options which requires a deeper language understanding as it tests the 10+ reasoning abilities of a model across a wide range of medical subjects \& topics. A detailed explanation of the solution, along with the above information, is provided in this study.

Despite decades of clinical research, sepsis remains a global public health crisis with high mortality, and morbidity. Currently, when sepsis is detected and the underlying pathogen is identified, organ damage may have already progressed to irreversible stages. Effective sepsis management is therefore highly time-sensitive. By systematically analysing trends in the plethora of clinical data available in the intensive care unit (ICU), an early prediction of sepsis could lead to earlier pathogen identification, resistance testing, and effective antibiotic and supportive treatment, and thereby become a life-saving measure. Here, we developed and validated a machine learning (ML) system for the prediction of sepsis in the ICU. Our analysis represents the largest multi-national, multi-centre in-ICU study for sepsis prediction using ML to date. Our dataset contains 156,309 unique ICU admissions, which represent a refined and harmonised subset of five large ICU databases originating from three countries. Using the international consensus definition Sepsis-3, we derived hourly-resolved sepsis label annotations, amounting to 26,734 (17.1%) septic stays. We compared our approach, a deep self-attention model, to several clinical baselines as well as ML baselines and performed an extensive internal and external validation within and across databases. On average, our model was able to predict sepsis with an AUROC of 0.847 pm 0.050 (internal out-of sample validation) and 0.761 pm 0.052 (external validation). For a harmonised prevalence of 17%, at 80% recall our model detects septic patients with 39% precision 3.7 hours in advance.

Clinical notes contain rich data, which is unexploited in predictive modeling compared to structured data. In this work, we developed a new text representation Clinical XLNet for clinical notes which also leverages the temporal information of the sequence of the notes. We evaluated our models on prolonged mechanical ventilation prediction problem and our experiments demonstrated that Clinical XLNet outperforms the best baselines consistently.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

The paper shows that the application of the fixed-effect multiple linear regression model to an overparameterized dataset is equivalent to fitting the data with a hyper-curve parameterized by a single scalar parameter. This equivalence allows for a predictor-focused approach, where each predictor is described by a function of the chosen parameter. It is proven that a linear model will produce exact predictions even in the presence of nonlinear dependencies that violate the model assumptions. Parameterization in terms of the dependent variable and the monomial basis in the predictor function space are applied here to both synthetic and experimental data. The hyper-curve approach is especially suited for the regularization of problems with noise in predictor variables and can be used to remove noisy and "improper" predictors from the model.

This study presents a comprehensive analysis and comparison of two predominant fine-tuning methodologies - full-parameter fine-tuning and parameter-efficient tuning - within the context of medical Large Language Models (LLMs). We developed and refined a series of LLMs, based on the Llama-2 architecture, specifically designed to enhance medical knowledge retrieval, reasoning, and question-answering capabilities. Our experiments systematically evaluate the effectiveness of these tuning strategies across various well-known medical benchmarks. Notably, our medical LLM Med42 showed an accuracy level of 72% on the US Medical Licensing Examination (USMLE) datasets, setting a new standard in performance for openly available medical LLMs. Through this comparative analysis, we aim to identify the most effective and efficient method for fine-tuning LLMs in the medical domain, thereby contributing significantly to the advancement of AI-driven healthcare applications.

We introduce MURA, a large dataset of musculoskeletal radiographs containing 40,561 images from 14,863 studies, where each study is manually labeled by radiologists as either normal or abnormal. To evaluate models robustly and to get an estimate of radiologist performance, we collect additional labels from six board-certified Stanford radiologists on the test set, consisting of 207 musculoskeletal studies. On this test set, the majority vote of a group of three radiologists serves as gold standard. We train a 169-layer DenseNet baseline model to detect and localize abnormalities. Our model achieves an AUROC of 0.929, with an operating point of 0.815 sensitivity and 0.887 specificity. We compare our model and radiologists on the Cohen's kappa statistic, which expresses the agreement of our model and of each radiologist with the gold standard. Model performance is comparable to the best radiologist performance in detecting abnormalities on finger and wrist studies. However, model performance is lower than best radiologist performance in detecting abnormalities on elbow, forearm, hand, humerus, and shoulder studies. We believe that the task is a good challenge for future research. To encourage advances, we have made our dataset freely available at https://stanfordmlgroup.github.io/competitions/mura .

The advancement of Large Vision-Language Models (LVLMs) has propelled their application in the medical field. However, Medical LVLMs (Med-LVLMs) encounter factuality challenges due to modality misalignment, where the models prioritize textual knowledge over visual input, leading to hallucinations that contradict information in medical images. Previous attempts to enhance modality alignment in Med-LVLMs through preference optimization have inadequately mitigated clinical relevance in preference data, making these samples easily distinguishable and reducing alignment effectiveness. To address this challenge, we propose MMedPO, a novel multimodal medical preference optimization approach that considers the clinical relevance of preference samples to enhance Med-LVLM alignment. MMedPO curates multimodal preference data by introducing two types of dispreference: (1) plausible hallucinations injected through target Med-LVLMs or GPT-4o to produce medically inaccurate responses, and (2) lesion region neglect achieved through local lesion-noising, disrupting visual understanding of critical areas. We then calculate clinical relevance for each sample based on scores from multiple Med-LLMs and visual tools, and integrate these scores into the preference optimization process as weights, enabling effective alignment. Our experiments demonstrate that MMedPO significantly enhances factual accuracy in Med-LVLMs, achieving substantial improvements over existing preference optimization methods by averaging 14.2% and 51.7% across the Med-VQA and report generation tasks. Our code are available in https://github.com/aiming-lab/MMedPO.

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.

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.

Automatic analysis of the enormous sets of images is a critical task in life sciences. This faces many challenges such as: algorithms are highly parameterized, significant human input is intertwined, and lacking a standard meta-visualization approach. This paper proposes an alternative iterative approach for optimizing input parameters, saving time by minimizing the user involvement, and allowing for understanding the workflow of algorithms and discovering new ones. The main focus is on developing an interactive visualization technique that enables users to analyze the relationships between sampled input parameters and corresponding output. This technique is implemented as a prototype called Veni Vidi Vici, or "I came, I saw, I conquered." This strategy is inspired by the mathematical formulas of numbering computable functions and is developed atop ImageJ, a scientific image processing program. A case study is presented to investigate the proposed framework. Finally, the paper explores some potential future issues in the application of the proposed approach in parameter space analysis in visualization.

Large Language Models (LLMs) are increasingly being utilized by both candidates and employers in the recruitment context. However, with this comes numerous ethical concerns, particularly related to the lack of transparency in these "black-box" models. Although previous studies have sought to increase the transparency of these models by investigating the personality traits of LLMs, many of the previous studies have provided them with personality assessments to complete. On the other hand, this study seeks to obtain a better understanding of such models by examining their output variations based on different input prompts. Specifically, we use a novel elicitation approach using prompts derived from common interview questions, as well as prompts designed to elicit particular Big Five personality traits to examine whether the models were susceptible to trait-activation like humans are, to measure their personality based on the language used in their outputs. To do so, we repeatedly prompted multiple LMs with different parameter sizes, including Llama-2, Falcon, Mistral, Bloom, GPT, OPT, and XLNet (base and fine tuned versions) and examined their personality using classifiers trained on the myPersonality dataset. Our results reveal that, generally, all LLMs demonstrate high openness and low extraversion. However, whereas LMs with fewer parameters exhibit similar behaviour in personality traits, newer and LMs with more parameters exhibit a broader range of personality traits, with increased agreeableness, emotional stability, and openness. Furthermore, a greater number of parameters is positively associated with openness and conscientiousness. Moreover, fine-tuned models exhibit minor modulations in their personality traits, contingent on the dataset. Implications and directions for future research are discussed.

Brain tumor growth is unique to each glioma patient and extends beyond what is visible in imaging scans, infiltrating surrounding brain tissue. Understanding these hidden patient-specific progressions is essential for effective therapies. Current treatment plans for brain tumors, such as radiotherapy, typically involve delineating a uniform margin around the visible tumor on pre-treatment scans to target this invisible tumor growth. This "one size fits all" approach is derived from population studies and often fails to account for the nuances of individual patient conditions. We present the GliODIL framework, which infers the full spatial distribution of tumor cell concentration from available multi-modal imaging, leveraging a Fisher-Kolmogorov type physics model to describe tumor growth. This is achieved through the newly introduced method of Optimizing the Discrete Loss (ODIL), where both data and physics-based constraints are softly assimilated into the solution. Our test dataset comprises 152 glioblastoma patients with pre-treatment imaging and post-treatment follow-ups for tumor recurrence monitoring. By blending data-driven techniques with physics-based constraints, GliODIL enhances recurrence prediction in radiotherapy planning, challenging traditional uniform margins and strict adherence to the Fisher-Kolmogorov partial differential equation (PDE) model, which is adapted for complex cases.

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

Large Language Models (LLMs) are at the forefront of NLP achievements but fall short in dealing with shortcut learning, factual inconsistency, and vulnerability to adversarial inputs.These shortcomings are especially critical in medical contexts, where they can misrepresent actual model capabilities. Addressing this, we present SemEval-2024 Task 2: Safe Biomedical Natural Language Inference for ClinicalTrials. Our contributions include the refined NLI4CT-P dataset (i.e., Natural Language Inference for Clinical Trials - Perturbed), designed to challenge LLMs with interventional and causal reasoning tasks, along with a comprehensive evaluation of methods and results for participant submissions. A total of 106 participants registered for the task contributing to over 1200 individual submissions and 25 system overview papers. This initiative aims to advance the robustness and applicability of NLI models in healthcare, ensuring safer and more dependable AI assistance in clinical decision-making. We anticipate that the dataset, models, and outcomes of this task can support future research in the field of biomedical NLI. The dataset, competition leaderboard, and website are publicly available.

BACKGROUND: Radiology reports are typically written in a free-text format, making clinical information difficult to extract and use. Recently the adoption of structured reporting (SR) has been recommended by various medical societies thanks to the advantages it offers, e.g. standardization, completeness and information retrieval. We propose a pipeline to extract information from free-text radiology reports, that fits with the items of the reference SR registry proposed by a national society of interventional and medical radiology, focusing on CT staging of patients with lymphoma. METHODS: Our work aims to leverage the potential of Natural Language Processing (NLP) and Transformer-based models to deal with automatic SR registry filling. With the availability of 174 radiology reports, we investigate a rule-free generative Question Answering approach based on a domain-specific version of T5 (IT5). Two strategies (batch-truncation and ex-post combination) are implemented to comply with the model's context length limitations. Performance is evaluated in terms of strict accuracy, F1, and format accuracy, and compared with the widely used GPT-3.5 Large Language Model. A 5-point Likert scale questionnaire is used to collect human-expert feedback on the similarity between medical annotations and generated answers. RESULTS: The combination of fine-tuning and batch splitting allows IT5 to achieve notable results; it performs on par with GPT-3.5 albeit its size being a thousand times smaller in terms of parameters. Human-based assessment scores show a high correlation (Spearman's correlation coefficients>0.88, p-values<0.001) with AI performance metrics (F1) and confirm the superior ability of LLMs (i.e., GPT-3.5, 175B of parameters) in generating plausible human-like statements.

Medical benchmarks are indispensable for evaluating the capabilities of language models in healthcare for non-English-speaking communities,therefore help ensuring the quality of real-life applications. However, not every community has sufficient resources and standardized methods to effectively build and design such benchmark, and available non-English medical data is normally fragmented and difficult to verify. We developed an approach to tackle this problem and applied it to create the first Vietnamese medical question benchmark, featuring 14,000 multiple-choice questions across 34 medical specialties. Our benchmark was constructed using various verifiable sources, including carefully curated medical exams and clinical records, and eventually annotated by medical experts. The benchmark includes four difficulty levels, ranging from foundational biological knowledge commonly found in textbooks to typical clinical case studies that require advanced reasoning. This design enables assessment of both the breadth and depth of language models' medical understanding in the target language thanks to its extensive coverage and in-depth subject-specific expertise. We release the benchmark in three parts: a sample public set (4k questions), a full public set (10k questions), and a private set (2k questions) used for leaderboard evaluation. Each set contains all medical subfields and difficulty levels. Our approach is scalable to other languages, and we open-source our data construction pipeline to support the development of future multilingual benchmarks in the medical domain.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

Accurate, continuous out-of-hospital electrocardiogram (ECG) parameter measurement is vital for real-time cardiac health monitoring and telemedicine. On-device computation of single-lead ECG parameters enables timely assessment without reliance on centralized data processing, advancing personalized, ubiquitous cardiac care-yet comprehensive validation across heterogeneous real-world populations remains limited. This study validated the on-device algorithm FeatureDB (https://github.com/PKUDigitalHealth/FeatureDB) using two datasets: HeartVoice-ECG-lite (369 participants with single-lead ECGs annotated by two physicians) and PTB-XL/PTB-XL+ (21,354 patients with 12-lead ECGs and physicians' diagnostic annotations). FeatureDB computed PR, QT, and QTc intervals, with accuracy evaluated against physician annotations via mean absolute error (MAE), correlation analysis, and Bland-Altman analysis. Diagnostic performance for first-degree atrioventricular block (AVBI, PR-based) and long QT syndrome (LQT, QTc-based) was benchmarked against commercial 12-lead systems (12SL, Uni-G) and open-source algorithm Deli, using AUC, accuracy, sensitivity, and specificity. Results showed high concordance with expert annotations (Pearson correlations: 0.836-0.960), MAEs matching inter-observer variability, and minimal bias. AVBI AUC reached 0.787 (12SL: 0.859; Uni-G: 0.812; Deli: 0.501); LQT AUC was 0.684 (12SL: 0.716; Uni-G: 0.605; Deli: 0.569)-comparable to commercial tools and superior to open-source alternatives. FeatureDB delivers physician-level parameter accuracy and commercial-grade abnormality detection via single-lead devices, supporting scalable telemedicine, decentralized cardiac screening, and continuous monitoring in community and outpatient settings.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

Accurate interpretation of lab results is crucial in clinical medicine, yet most patient portals use universal normal ranges, ignoring conditional factors like age and gender. This study introduces Lab-AI, an interactive system that offers personalized normal ranges using retrieval-augmented generation (RAG) from credible health sources. Lab-AI has two modules: factor retrieval and normal range retrieval. We tested these on 122 lab tests: 40 with conditional factors and 82 without. For tests with factors, normal ranges depend on patient-specific information. Our results show GPT-4-turbo with RAG achieved a 0.948 F1 score for factor retrieval and 0.995 accuracy for normal range retrieval. GPT-4-turbo with RAG outperformed the best non-RAG system by 33.5% in factor retrieval and showed 132% and 100% improvements in question-level and lab-level performance, respectively, for normal range retrieval. These findings highlight Lab-AI's potential to enhance patient understanding of lab results.

Discharge summaries in Electronic Health Records (EHRs) are crucial for clinical decision-making, but their length and complexity make information extraction challenging, especially when dealing with accumulated summaries across multiple patient admissions. Large Language Models (LLMs) show promise in addressing this challenge by efficiently analyzing vast and complex data. Existing benchmarks, however, fall short in properly evaluating LLMs' capabilities in this context, as they typically focus on single-note information or limited topics, failing to reflect the real-world inquiries required by clinicians. To bridge this gap, we introduce EHRNoteQA, a novel benchmark built on the MIMIC-IV EHR, comprising 962 different QA pairs each linked to distinct patients' discharge summaries. Every QA pair is initially generated using GPT-4 and then manually reviewed and refined by three clinicians to ensure clinical relevance. EHRNoteQA includes questions that require information across multiple discharge summaries and covers eight diverse topics, mirroring the complexity and diversity of real clinical inquiries. We offer EHRNoteQA in two formats: open-ended and multi-choice question answering, and propose a reliable evaluation method for each. We evaluate 27 LLMs using EHRNoteQA and examine various factors affecting the model performance (e.g., the length and number of discharge summaries). Furthermore, to validate EHRNoteQA as a reliable proxy for expert evaluations in clinical practice, we measure the correlation between the LLM performance on EHRNoteQA, and the LLM performance manually evaluated by clinicians. Results show that LLM performance on EHRNoteQA have higher correlation with clinician-evaluated performance (Spearman: 0.78, Kendall: 0.62) compared to other benchmarks, demonstrating its practical relevance in evaluating LLMs in clinical settings.

LLMs have demonstrated impressive performance in answering medical questions, such as passing scores on medical licensing examinations. However, medical board exam questions or general clinical questions do not capture the complexity of realistic clinical cases. Moreover, the lack of reference explanations means we cannot easily evaluate the reasoning of model decisions, a crucial component of supporting doctors in making complex medical decisions. To address these challenges, we construct two new datasets: JAMA Clinical Challenge and Medbullets. JAMA Clinical Challenge consists of questions based on challenging clinical cases, while Medbullets comprises USMLE Step 2&3 style clinical questions. Both datasets are structured as multiple-choice question-answering tasks, where each question is accompanied by an expert-written explanation. We evaluate four LLMs on the two datasets using various prompts. Experiments demonstrate that our datasets are harder than previous benchmarks. The inconsistency between automatic and human evaluations of model-generated explanations highlights the need to develop new metrics to support future research on explainable medical QA.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate clinical quality, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

In recent years, there have been significant breakthroughs in the field of natural language processing, particularly with the development of large language models (LLMs). These LLMs have showcased remarkable capabilities on various benchmarks. In the healthcare field, the exact role LLMs and other future AI models will play remains unclear. There is a potential for these models in the future to be used as part of adaptive physician training, medical co-pilot applications, and digital patient interaction scenarios. The ability of AI models to participate in medical training and patient care will depend in part on their mastery of the knowledge content of specific medical fields. This study investigated the medical knowledge capability of LLMs, specifically in the context of internal medicine subspecialty multiple-choice test-taking ability. We compared the performance of several open-source LLMs (Koala 7B, Falcon 7B, Stable-Vicuna 13B, and Orca Mini 13B), to GPT-4 and Claude 2 on multiple-choice questions in the field of Nephrology. Nephrology was chosen as an example of a particularly conceptually complex subspecialty field within internal medicine. The study was conducted to evaluate the ability of LLM models to provide correct answers to nephSAP (Nephrology Self-Assessment Program) multiple-choice questions. The overall success of open-sourced LLMs in answering the 858 nephSAP multiple-choice questions correctly was 17.1% - 25.5%. In contrast, Claude 2 answered 54.4% of the questions correctly, whereas GPT-4 achieved a score of 73.3%. We show that current widely used open-sourced LLMs do poorly in their ability for zero-shot reasoning when compared to GPT-4 and Claude 2. The findings of this study potentially have significant implications for the future of subspecialty medical training and patient care.

Clinical LLMs are often scaled by increasing model size, context length, retrieval complexity, or inference-time compute, with the implicit expectation that higher accuracy implies safer behavior. This assumption is incomplete in medicine, where a few confident, high-risk, or evidence-contradicting errors can matter more than average benchmark performance. We introduce SaFE-Scale, a framework for measuring how clinical LLM safety changes across model scale, evidence quality, retrieval strategy, context exposure, and inference-time compute. To instantiate this framework, we introduce RadSaFE-200, a Radiology Safety-Focused Evaluation benchmark of 200 multiple-choice questions with clinician-defined clean evidence, conflict evidence, and option-level labels for high-risk error, unsafe answer, and evidence contradiction. We evaluated 34 locally deployed LLMs across six deployment conditions: closed-book prompting (zero-shot), clean evidence, conflict evidence, standard RAG, agentic RAG, and max-context prompting. Clean evidence produced the strongest improvement, increasing mean accuracy from 73.5% to 94.1%, while reducing high-risk error from 12.0% to 2.6%, contradiction from 12.7% to 2.3%, and dangerous overconfidence from 8.0% to 1.6%. Standard RAG and agentic RAG did not reproduce this safety profile: agentic RAG improved accuracy over standard RAG and reduced contradiction, but high-risk error and dangerous overconfidence remained elevated. Max-context prompting increased latency without closing the safety gap, and additional inference-time compute produced only limited gains. Worst-case analysis showed that clinically consequential errors concentrated in a small subset of questions. Clinical LLM safety is therefore not a passive consequence of scaling, but a deployment property shaped by evidence quality, retrieval design, context construction, and collective failure behavior.

Objectives: While Large Language Models (LLMs) have been widely used to assist clinicians and support patients, no existing work has explored dialogue systems for standard diagnostic interviews and assessments. This study aims to bridge the gap in mental healthcare accessibility by developing an LLM-powered dialogue system that replicates clinician behavior. Materials and Methods: We introduce TRUST, a framework of cooperative LLM modules capable of conducting formal diagnostic interviews and assessments for Post-Traumatic Stress Disorder (PTSD). To guide the generation of appropriate clinical responses, we propose a Dialogue Acts schema specifically designed for clinical interviews. Additionally, we develop a patient simulation approach based on real-life interview transcripts to replace time-consuming and costly manual testing by clinicians. Results: A comprehensive set of evaluation metrics is designed to assess the dialogue system from both the agent and patient simulation perspectives. Expert evaluations by conversation and clinical specialists show that TRUST performs comparably to real-life clinical interviews. Discussion: Our system performs at the level of average clinicians, with room for future enhancements in communication styles and response appropriateness. Conclusions: Our TRUST framework shows its potential to facilitate mental healthcare availability.

We seek to identify the most relevant benefits offered by Medicare Advantage Health Plans that drive membership and market share. As an example, we explore plans operating in a single county in New Jersey between 2018 and 2023. A dataset of benefits from publicly available data sources was created and the variance inflation factor was applied to identify the correlation between the extracted features, to avoid multicollinearity and overparameterization problems. We categorized the variable Market Share and used it as a multinomial response variable with three categories: less than 0.3\%, 0.3\% to 1.5\%, and over 1.5\%. Categories were chosen to achieve approximately uniform distribution of plans (47, 60, and 65 respectively). We built a multinomial Lasso model using 5-fold cross-validation to tune the penalty parameter. Lasso forced some features to be dropped from the model, which reduces the risk of overfitting and increases the interpretability of the results. For each category, important variables are different. Certain brands drive market share, as do PPO plans and prescription drug coverage. Benefits, particularly ancillary benefits that are not part of CMS's required benefits, appear to have little influence, while financial terms such as deductibles, copays, and out-of-pocket limits are associated with higher market share. Finally, we evaluated the predictive accuracy of the Lasso model with the test set. The accuracy is 0.76.

As large language models (LLMs) advance in conversational and reasoning capabilities, their practical application in healthcare has become a critical research focus. However, there is a notable gap between the performance of medical LLMs on static benchmarks such as USMLE and their utility in real-world clinical decision-making. This discrepancy arises because traditional exams fail to capture the dynamic, interactive nature of medical consultations. To address this challenge, we introduce a novel dynamic verification framework that moves beyond static answer verifier, establishing a large-scale, high-fidelity interactive reinforcement learning system. Our framework comprises two key components: a Patient Simulator that creates realistic clinical environments using de-identified medical records, and a Clinical Rubrics Generator that dynamically produces multi-dimensional evaluation metrics. Building on this foundation, we develop Baichuan-M2, a 32B-parameter medical augmented reasoning model trained through a multi-stage reinforcement learning strategy with an improved Group Relative Policy Optimization (GRPO) algorithm. Evaluated on HealthBench, Baichuan-M2 outperforms all other open-source models and most advanced closed-source counterparts, achieving a score above 32 on the challenging HealthBench Hard benchmark-previously exceeded only by GPT-5. Our work demonstrates that robust dynamic verifier system is essential for aligning LLM capabilities with practical clinical applications, establishing a new Pareto front in the performance-parameter trade-off for medical AI deployment.

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.

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.