Danielle S. Bitterman

Marco Guevara, Shan Chen, Spencer Thomas et al. · harvard

Social determinants of health (SDoH) have an important impact on patient outcomes but are incompletely collected from the electronic health records (EHR). This study researched the ability of large language models to extract SDoH from free text in EHRs, where they are most commonly documented, and explored the role of synthetic clinical text for improving the extraction of these scarcely documented, yet extremely valuable, clinical data. 800 patient notes were annotated for SDoH categories, and several transformer-based models were evaluated. The study also experimented with synthetic data generation and assessed for algorithmic bias. Our best-performing models were fine-tuned Flan-T5 XL (macro-F1 0.71) for any SDoH, and Flan-T5 XXL (macro-F1 0.70). The benefit of augmenting fine-tuning with synthetic data varied across model architecture and size, with smaller Flan-T5 models (base and large) showing the greatest improvements in performance (delta F1 +0.12 to +0.23). Model performance was similar on the in-hospital system dataset but worse on the MIMIC-III dataset. Our best-performing fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models for both tasks. These fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p<0.05). At the patient-level, our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. Our method can effectively extracted SDoH information from clinic notes, performing better compare to GPT zero- and few-shot settings. These models could enhance real-world evidence on SDoH and aid in identifying patients needing social support.

Shan Chen, Yingya Li, Sheng Lu et al. · harvard

Recent advances in large language models (LLMs) have shown impressive ability in biomedical question-answering, but have not been adequately investigated for more specific biomedical applications. This study investigates the performance of LLMs such as the ChatGPT family of models (GPT-3.5s, GPT-4) in biomedical tasks beyond question-answering. Because no patient data can be passed to the OpenAI API public interface, we evaluated model performance with over 10000 samples as proxies for two fundamental tasks in the clinical domain - classification and reasoning. The first task is classifying whether statements of clinical and policy recommendations in scientific literature constitute health advice. The second task is causal relation detection from the biomedical literature. We compared LLMs with simpler models, such as bag-of-words (BoW) with logistic regression, and fine-tuned BioBERT models. Despite the excitement around viral ChatGPT, we found that fine-tuning for two fundamental NLP tasks remained the best strategy. The simple BoW model performed on par with the most complex LLM prompting. Prompt engineering required significant investment.

Shan Chen, Marco Guevara, Nicolas Ramirez et al. · harvard

Radiotherapy (RT) toxicities can impair survival and quality-of-life, yet remain under-studied. Real-world evidence holds potential to improve our understanding of toxicities, but toxicity information is often only in clinical notes. We developed natural language processing (NLP) models to identify the presence and severity of esophagitis from notes of patients treated with thoracic RT. We fine-tuned statistical and pre-trained BERT-based models for three esophagitis classification tasks: Task 1) presence of esophagitis, Task 2) severe esophagitis or not, and Task 3) no esophagitis vs. grade 1 vs. grade 2-3. Transferability was tested on 345 notes from patients with esophageal cancer undergoing RT. Fine-tuning PubmedBERT yielded the best performance. The best macro-F1 was 0.92, 0.82, and 0.74 for Task 1, 2, and 3, respectively. Selecting the most informative note sections during fine-tuning improved macro-F1 by over 2% for all tasks. Silver-labeled data improved the macro-F1 by over 3% across all tasks. For the esophageal cancer notes, the best macro-F1 was 0.73, 0.74, and 0.65 for Task 1, 2, and 3, respectively, without additional fine-tuning. To our knowledge, this is the first effort to automatically extract esophagitis toxicity severity according to CTCAE guidelines from clinic notes. The promising performance provides proof-of-concept for NLP-based automated detailed toxicity monitoring in expanded domains.

Weipeng Zhou, Danielle Bitterman, Majid Afshar et al.

Large language models (LLMs) like ChatGPT have excited scientists across fields; in medicine, one source of excitement is the potential applications of LLMs trained on electronic health record (EHR) data. But there are tough questions we must first answer if health care institutions are interested in having LLMs trained on their own data; should they train an LLM from scratch or fine-tune it from an open-source model? For healthcare institutions with a predefined budget, what are the biggest LLMs they can afford? In this study, we take steps towards answering these questions with an analysis on dataset sizes, model sizes, and costs for LLM training using EHR data. This analysis provides a framework for thinking about these questions in terms of data scale, compute scale, and training budgets.

Sheng Lu, Shan Chen, Yingya Li et al. · harvard

In-context learning (ICL) is a new learning paradigm that has gained popularity along with the development of large language models. In this work, we adapt a recently proposed hardness metric, pointwise $\mathcal{V}$-usable information (PVI), to an in-context version (in-context PVI). Compared to the original PVI, in-context PVI is more efficient in that it requires only a few exemplars and does not require fine-tuning. We conducted a comprehensive empirical analysis to evaluate the reliability of in-context PVI. Our findings indicate that in-context PVI estimates exhibit similar characteristics to the original PVI. Specific to the in-context setting, we show that in-context PVI estimates remain consistent across different exemplar selections and numbers of shots. The variance of in-context PVI estimates across different exemplar selections is insignificant, which suggests that in-context PVI are stable. Furthermore, we demonstrate how in-context PVI can be employed to identify challenging instances. Our work highlights the potential of in-context PVI and provides new insights into the capabilities of ICL.

Shan Chen, Marco Guevara, Shalini Moningi et al.

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

Yanjun Gao, Skatje Myers, Shan Chen et al.

The introduction of Large Language Models (LLMs) has advanced data representation and analysis, bringing significant progress in their use for medical questions and answering. Despite these advancements, integrating tabular data, especially numerical data pivotal in clinical contexts, into LLM paradigms has not been thoroughly explored. In this study, we examine the effectiveness of vector representations from last hidden states of LLMs for medical diagnostics and prognostics using electronic health record (EHR) data. We compare the performance of these embeddings with that of raw numerical EHR data when used as feature inputs to traditional machine learning (ML) algorithms that excel at tabular data learning, such as eXtreme Gradient Boosting. We focus on instruction-tuned LLMs in a zero-shot setting to represent abnormal physiological data and evaluating their utilities as feature extractors to enhance ML classifiers for predicting diagnoses, length of stay, and mortality. Furthermore, we examine prompt engineering techniques on zero-shot and few-shot LLM embeddings to measure their impact comprehensively. Although findings suggest the raw data features still prevails in medical ML tasks, zero-shot LLM embeddings demonstrate competitive results, suggesting a promising avenue for future research in medical applications.

Shan Chen, Mingye Gao, Kuleen Sasse et al. · harvard

Background: Large language models (LLMs) are trained to follow directions, but this introduces a vulnerability to blindly comply with user requests even if they generate wrong information. In medicine, this could accelerate the generation of misinformation that impacts human well-being. Objectives/Methods: We analyzed compliance to requests to generate misleading content about medications in settings where models know the request is illogical. We investigated whether in-context directions and instruction-tuning of LLMs to prioritize logical reasoning over compliance reduced misinformation risk. Results: While all frontier LLMs complied with misinformation requests, both prompt-based and parameter-based approaches can improve the detection of logic flaws in requests and prevent the dissemination of medical misinformation. Conclusion: Shifting LLMs to prioritize logic over compliance could reduce risks of exploitation for medical misinformation.

Xiaoye Wang, Nicole Xi Zhang, Hongyu He et al.

Recent advancements in artificial intelligence (AI), particularly in large language models (LLMs), have unlocked significant potential to enhance the quality and efficiency of medical care. By introducing a novel way to interact with AI and data through natural language, LLMs offer new opportunities for medical practitioners, patients, and researchers. However, as AI and LLMs become more powerful and especially achieve superhuman performance in some medical tasks, public concerns over their safety have intensified. These concerns about AI safety have emerged as the most significant obstacles to the adoption of AI in medicine. In response, this review examines emerging risks in AI utilization during the LLM era. First, we explore LLM-specific safety challenges from functional and communication perspectives, addressing issues across data collection, model training, and real-world application. We then consider inherent safety problems shared by all AI systems, along with additional complications introduced by LLMs. Last, we discussed how safety issues of using AI in clinical practice and healthcare system operation would undermine trust among patient, clinicians and the public, and how to build confidence in these systems. By emphasizing the development of safe AI, we believe these technologies can be more rapidly and reliably integrated into everyday medical practice to benefit both patients and clinicians.

Jack Gallifant, Shan Chen, Kuleen Sasse et al.

Sparse Autoencoders (SAEs) provide potentials for uncovering structured, human-interpretable representations in Large Language Models (LLMs), making them a crucial tool for transparent and controllable AI systems. We systematically analyze SAE for interpretable feature extraction from LLMs in safety-critical classification tasks. Our framework evaluates (1) model-layer selection and scaling properties, (2) SAE architectural configurations, including width and pooling strategies, and (3) the effect of binarizing continuous SAE activations. SAE-derived features achieve macro F1 > 0.8, outperforming hidden-state and BoW baselines while demonstrating cross-model transfer from Gemma 2 2B to 9B-IT models. These features generalize in a zero-shot manner to cross-lingual toxicity detection and visual classification tasks. Our analysis highlights the significant impact of pooling strategies and binarization thresholds, showing that binarization offers an efficient alternative to traditional feature selection while maintaining or improving performance. These findings establish new best practices for SAE-based interpretability and enable scalable, transparent deployment of LLMs in real-world applications. Full repo: https://github.com/shan23chen/MOSAIC.

Katherine C. Kellogg, Bingyang Ye, Yifan Hu et al.

The rapid adoption of large language models (LLMs) in healthcare has been accompanied by scrutiny of their oversight. Existing monitoring approaches, inherited from traditional machine learning (ML), are task-based and founded on assumed performance degradation arising from dataset drift. In contrast, with LLMs, inevitable model degradation due to changes in populations compared to the training dataset cannot be assumed, because LLMs were not trained for any specific task in any given population. We therefore propose a new organizing principle guiding generalist LLM monitoring that is scalable and grounded in how these models are developed and used in practice: capability-based monitoring. Capability-based monitoring is motivated by the fact that LLMs are generalist systems whose overlapping internal capabilities are reused across numerous downstream tasks. Instead of evaluating each downstream task independently, this approach organizes monitoring around shared model capabilities, such as summarization, reasoning, translation, or safety guardrails, in order to enable cross-task detection of systemic weaknesses, long-tail errors, and emergent behaviors that task-based monitoring may miss. We describe considerations for developers, organizational leaders, and professional societies for implementing a capability-based monitoring approach. Ultimately, capability-based monitoring will provide a scalable foundation for safe, adaptive, and collaborative monitoring of LLMs and future generalist artificial intelligence models in healthcare.

Mingxuan Liu, Yuhe Ke, Wentao Zhu et al.

The integration of large language models (LLMs) into healthcare holds promise to enhance clinical decision-making, yet their susceptibility to biases remains a critical concern. Gender has long influenced physician behaviors and patient outcomes, raising concerns that LLMs assuming human-like roles, such as clinicians or medical educators, may replicate or amplify gender-related biases. Using case studies from the New England Journal of Medicine Challenge (NEJM), we assigned genders (female, male, or unspecified) to multiple open-source and proprietary LLMs. We evaluated their response consistency across LLM-gender assignments regarding both LLM-based diagnosis and models' judgments on the clinical relevance or necessity of patient gender. In our findings, diagnoses were relatively consistent across LLM genders for most models. However, for patient gender's relevance and necessity in LLM-based diagnosis, all models demonstrated substantial inconsistency across LLM genders, particularly for relevance judgements. Some models even displayed a systematic female-male disparity in their interpretation of patient gender. These findings present an underexplored bias that could undermine the reliability of LLMs in clinical practice, underscoring the need for routine checks of identity-assignment consistency when interacting with LLMs to ensure reliable and equitable AI-supported clinical care.

Jirui Qi, Shan Chen, Zidi Xiong et al.

Recent Large Reasoning Models (LRMs) with thinking traces have shown strong performance on English reasoning tasks. However, their ability to think in other languages is less studied. This capability is as important as answer accuracy for real world applications because users may find the reasoning trace useful for oversight only when it is expressed in their own language. We comprehensively evaluate two leading families of LRMs on our XReasoning benchmark and find that even the most advanced models often revert to English or produce fragmented reasoning in other languages, revealing a substantial gap in multilingual reasoning. Prompt based interventions that force models to reason in the users language improve readability and oversight but reduce answer accuracy, exposing an important trade off. We further show that targeted post training on just 100 examples mitigates this mismatch, though some accuracy loss remains. Our results highlight the limited multilingual reasoning capabilities of current LRMs and outline directions for future work. Code and data are available at https://github.com/Betswish/mCoT-XReasoning.

Jack Gallifant, Shan Chen, Pedro Moreira et al.

Medical knowledge is context-dependent and requires consistent reasoning across various natural language expressions of semantically equivalent phrases. This is particularly crucial for drug names, where patients often use brand names like Advil or Tylenol instead of their generic equivalents. To study this, we create a new robustness dataset, RABBITS, to evaluate performance differences on medical benchmarks after swapping brand and generic drug names using physician expert annotations. We assess both open-source and API-based LLMs on MedQA and MedMCQA, revealing a consistent performance drop ranging from 1-10\%. Furthermore, we identify a potential source of this fragility as the contamination of test data in widely used pre-training datasets. All code is accessible at https://github.com/BittermanLab/RABBITS, and a HuggingFace leaderboard is available at https://huggingface.co/spaces/AIM-Harvard/rabbits-leaderboard.

João Matos, Shan Chen, Siena Placino et al.

Multimodal/vision language models (VLMs) are increasingly being deployed in healthcare settings worldwide, necessitating robust benchmarks to ensure their safety, efficacy, and fairness. Multiple-choice question and answer (QA) datasets derived from national medical examinations have long served as valuable evaluation tools, but existing datasets are largely text-only and available in a limited subset of languages and countries. To address these challenges, we present WorldMedQA-V, an updated multilingual, multimodal benchmarking dataset designed to evaluate VLMs in healthcare. WorldMedQA-V includes 568 labeled multiple-choice QAs paired with 568 medical images from four countries (Brazil, Israel, Japan, and Spain), covering original languages and validated English translations by native clinicians, respectively. Baseline performance for common open- and closed-source models are provided in the local language and English translations, and with and without images provided to the model. The WorldMedQA-V benchmark aims to better match AI systems to the diverse healthcare environments in which they are deployed, fostering more equitable, effective, and representative applications.

Shan Chen, Pedro Moreira, Yuxin Xiao et al.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

David Restrepo, Chenwei Wu, Zhengxu Tang et al.

Current ophthalmology clinical workflows are plagued by over-referrals, long waits, and complex and heterogeneous medical records. Large language models (LLMs) present a promising solution to automate various procedures such as triaging, preliminary tests like visual acuity assessment, and report summaries. However, LLMs have demonstrated significantly varied performance across different languages in natural language question-answering tasks, potentially exacerbating healthcare disparities in Low and Middle-Income Countries (LMICs). This study introduces the first multilingual ophthalmological question-answering benchmark with manually curated questions parallel across languages, allowing for direct cross-lingual comparisons. Our evaluation of 6 popular LLMs across 7 different languages reveals substantial bias across different languages, highlighting risks for clinical deployment of LLMs in LMICs. Existing debiasing methods such as Translation Chain-of-Thought or Retrieval-augmented generation (RAG) by themselves fall short of closing this performance gap, often failing to improve performance across all languages and lacking specificity for the medical domain. To address this issue, We propose CLARA (Cross-Lingual Reflective Agentic system), a novel inference time de-biasing method leveraging retrieval augmented generation and self-verification. Our approach not only improves performance across all languages but also significantly reduces the multilingual bias gap, facilitating equitable LLM application across the globe.

Jasmine Chiat Ling Ong, Yilin Ning, Mingxuan Liu et al.

The integration of generative AI (GenAI) and large language models (LLMs) in healthcare presents both unprecedented opportunities and challenges, necessitating innovative regulatory approaches. GenAI and LLMs offer broad applications, from automating clinical workflows to personalizing diagnostics. However, the non-deterministic outputs, broad functionalities and complex integration of GenAI and LLMs challenge existing medical device regulatory frameworks, including the total product life cycle (TPLC) approach. Here we discuss the constraints of the TPLC approach to GenAI and LLM-based medical device regulation, and advocate for global collaboration in regulatory science research. This serves as the foundation for developing innovative approaches including adaptive policies and regulatory sandboxes, to test and refine governance in real-world settings. International harmonization, as seen with the International Medical Device Regulators Forum, is essential to manage implications of LLM on global health, including risks of widening health inequities driven by inherent model biases. By engaging multidisciplinary expertise, prioritizing iterative, data-driven approaches, and focusing on the needs of diverse populations, global regulatory science research enables the responsible and equitable advancement of LLM innovations in healthcare.

Yanjun Gao, Skatje Myers, Shan Chen et al.

Large language models (LLMs) are being explored for diagnostic decision support, yet their ability to estimate pre-test probabilities, vital for clinical decision-making, remains limited. This study evaluates two LLMs, Mistral-7B and Llama3-70B, using structured electronic health record data on three diagnosis tasks. We examined three current methods of extracting LLM probability estimations and revealed their limitations. We aim to highlight the need for improved techniques in LLM confidence estimation.

Lasse Hyldig Hansen, Nikolaj Andersen, Jack Gallifant et al.

Background Advancements in Large Language Models (LLMs) hold transformative potential in healthcare, however, recent work has raised concern about the tendency of these models to produce outputs that display racial or gender biases. Although training data is a likely source of such biases, exploration of disease and demographic associations in text data at scale has been limited. Methods We conducted a large-scale textual analysis using a dataset comprising diverse web sources, including Arxiv, Wikipedia, and Common Crawl. The study analyzed the context in which various diseases are discussed alongside markers of race and gender. Given that LLMs are pre-trained on similar datasets, this approach allowed us to examine the potential biases that LLMs may learn and internalize. We compared these findings with actual demographic disease prevalence as well as GPT-4 outputs in order to evaluate the extent of bias representation. Results Our findings indicate that demographic terms are disproportionately associated with specific disease concepts in online texts. gender terms are prominently associated with disease concepts, while racial terms are much less frequently associated. We find widespread disparities in the associations of specific racial and gender terms with the 18 diseases analyzed. Most prominently, we see an overall significant overrepresentation of Black race mentions in comparison to population proportions. Conclusions Our results highlight the need for critical examination and transparent reporting of biases in LLM pretraining datasets. Our study suggests the need to develop mitigation strategies to counteract the influence of biased training data in LLMs, particularly in sensitive domains such as healthcare.

Mingye Gao, Aman Varshney, Shan Chen et al.

Cancer clinical trials often face challenges in recruitment and engagement due to a lack of participant-facing informational and educational resources. This study investigated the potential of Large Language Models (LLMs), specifically GPT4, in generating patient-friendly educational content from clinical trial informed consent forms. Using data from ClinicalTrials.gov, we employed zero-shot learning for creating trial summaries and one-shot learning for developing multiple-choice questions, evaluating their effectiveness through patient surveys and crowdsourced annotation. Results showed that GPT4-generated summaries were both readable and comprehensive, and may improve patients' understanding and interest in clinical trials. The multiple-choice questions demonstrated high accuracy and agreement with crowdsourced annotators. For both resource types, hallucinations were identified that require ongoing human oversight. The findings demonstrate the potential of LLMs "out-of-the-box" to support the generation of clinical trial education materials with minimal trial-specific engineering, but implementation with a human-in-the-loop is still needed to avoid misinformation risks.

Shan Chen, Jack Gallifant, Marco Guevara et al.

Generative models have been showing potential for producing data in mass. This study explores the enhancement of clinical natural language processing performance by utilizing synthetic data generated from advanced language models. Promising results show feasible applications in such a high-stakes domain.

Mingxuan Liu, Yilin Ning, Haoyuan Wang et al.

As machine learning models become increasingly integrated into healthcare, structural inequities and social biases embedded in clinical data can be perpetuated or even amplified by data-driven models. In survival analysis, censoring and time dynamics can further add complexity to fair model development. Additionally, algorithmic fairness approaches often overlook disparities in cross-group rankings, e.g., high-risk Black patients may be ranked below lower-risk White patients who do not experience the event of mortality. Such misranking can reinforce biological essentialism and undermine equitable care. We propose a Fairness-Aware Survival Modeling (FASM), designed to mitigate algorithmic bias regarding both intra-group and cross-group risk rankings over time. Using breast cancer prognosis as a representative case and applying FASM to SEER breast cancer data, we show that FASM substantially improves fairness while preserving discrimination performance comparable to fairness-unaware survival models. Time-stratified evaluations show that FASM maintains stable fairness over a 10-year horizon, with the greatest improvements observed during the mid-term of follow-up. Our approach enables the development of survival models that prioritize both accuracy and equity in clinical decision-making, advancing fairness as a core principle in clinical care.

Jack Gallifant, Katherine C. Kellogg, Matt Butler et al.

Large language models (LLMs) integrated into agent-driven workflows hold immense promise for healthcare, yet a significant gap exists between their potential and practical implementation within clinical settings. To address this, we present a practitioner-oriented field manual for deploying generative agents that use electronic health record (EHR) data. This guide is informed by our experience deploying the "irAE-Agent", an automated system to detect immune-related adverse events from clinical notes at Mass General Brigham, and by structured interviews with 20 clinicians, engineers, and informatics leaders involved in the project. Our analysis reveals a critical misalignment in clinical AI development: less than 20% of our effort was dedicated to prompt engineering and model development, while over 80% was consumed by the sociotechnical work of implementation. We distill this effort into five "heavy lifts": data integration, model validation, ensuring economic value, managing system drift, and governance. By providing actionable solutions for each of these challenges, this field manual shifts the focus from algorithmic development to the essential infrastructure and implementation work required to bridge the "valley of death" and successfully translate generative AI from pilot projects into routine clinical care.

Fridolin Haugg, Grace Lee, John He et al.

Background: Facial appearance offers a noninvasive window into health. We built FAHR-Face, a foundation model trained on >40 million facial images and fine-tuned it for two distinct tasks: biological age estimation (FAHR-FaceAge) and survival risk prediction (FAHR-FaceSurvival). Methods: FAHR-FaceAge underwent a two-stage, age-balanced fine-tuning on 749,935 public images; FAHR-FaceSurvival was fine-tuned on 34,389 photos of cancer patients. Model robustness (cosmetic surgery, makeup, pose, lighting) and independence (saliency mapping) was tested extensively. Both models were clinically tested in two independent cancer patient datasets with survival analyzed by multivariable Cox models and adjusted for clinical prognostic factors. Findings: For age estimation, FAHR-FaceAge had the lowest mean absolute error of 5.1 years on public datasets, outperforming benchmark models and maintaining accuracy across the full human lifespan. In cancer patients, FAHR-FaceAge outperformed a prior facial age estimation model in survival prognostication. FAHR-FaceSurvival demonstrated robust prediction of mortality, and the highest-risk quartile had more than triple the mortality of the lowest (adjusted hazard ratio 3.22; P<0.001). These findings were validated in the independent cohort and both models showed generalizability across age, sex, race and cancer subgroups. The two algorithms provided distinct, complementary prognostic information; saliency mapping revealed each model relied on distinct facial regions. The combination of FAHR-FaceAge and FAHR-FaceSurvival improved prognostic accuracy. Interpretation: A single foundation model can generate inexpensive, scalable facial biomarkers that capture both biological ageing and disease-related mortality risk. The foundation model enabled effective training using relatively small clinical datasets.

Yuxin Xiao, Shan Chen, Jack Gallifant et al.

Characterizing a large language model's (LLM's) knowledge of a given question is challenging. As a result, prior work has primarily examined LLM behavior under knowledge conflicts, where the model's internal parametric memory contradicts information in the external context. However, this does not fully reflect how well the model knows the answer to the question. In this paper, we first introduce a taxonomy of five knowledge statuses based on the consistency and correctness of LLM knowledge modes. We then propose KScope, a hierarchical framework of statistical tests that progressively refines hypotheses about knowledge modes and characterizes LLM knowledge into one of these five statuses. We apply KScope to nine LLMs across four datasets and systematically establish: (1) Supporting context narrows knowledge gaps across models. (2) Context features related to difficulty, relevance, and familiarity drive successful knowledge updates. (3) LLMs exhibit similar feature preferences when partially correct or conflicted, but diverge sharply when consistently wrong. (4) Context summarization constrained by our feature analysis, together with enhanced credibility, further improves update effectiveness and generalizes across LLMs.

Luis Felipe, Carlos Garcia, Issam El Naqa et al.

The need for robust and diverse data sets to train clinical large language models (cLLMs) is critical given that currently available public repositories often prove too limited in size or scope for comprehensive medical use. While resources like PubMed provide foundational medical literature, they capture only a narrow range of formal publications and omit the broader medical discourse on the internet. To address these deficits, we introduce TheBlueScrubs-v1, a curated dataset of over 25 billion medical tokens - nearly three times larger than PubMed - drawn from a broad-scale internet corpus. Our two-stage filtering pipeline employs a Logistic Regression model for document screening (achieving an AUC of approximately 0.95 on external validation), followed by verification via a 70B-parameter Llama 3.1 instruct model. Each text is assigned three LLM-based quality scores encompassing medical relevance, precision and factual detail, and safety and ethical standards. Clinician reviews confirm high concordance with these automated evaluations, and a specialized cancer classifier further labels approximately 11 billion oncology tokens. Two demonstration tasks highlight the dataset's practical value: first, we distill the safety evaluations to a smaller BERT-style model that reaches an AUC near 0.96 on unseen data; second, we fine-tune a compact LLM on a filtered subset, showing measurable improvements over standard baselines in medical benchmarks as well as private ones. This Data Descriptor details the dataset's creation and validation, underscoring its potential utility for medical AI research.

Kuleen Sasse, Shan Chen, Jackson Pond et al.

As Vision Language Models (VLMs) gain widespread use, their fairness remains under-explored. In this paper, we analyze demographic biases across five models and six datasets. We find that portrait datasets like UTKFace and CelebA are the best tools for bias detection, finding gaps in performance and fairness for both LLaVa and CLIP models. Scene-based datasets like PATA and VLStereoSet fail to be useful benchmarks for bias due to their text prompts allowing the model to guess the answer without a picture. As for pronoun-based datasets like VisoGender, we receive mixed signals as only some subsets of the data are useful in providing insights. To alleviate these two problems, we introduce a more rigorous evaluation dataset and a debiasing method based on Sparse Autoencoders to help reduce bias in models. We find that our data set generates more meaningful errors than the previous data sets. Furthermore, our debiasing method improves fairness, gaining 5-15 points in performance over the baseline. This study displays the problems with the current benchmarks for measuring demographic bias in Vision Language Models and introduces both a more effective dataset for measuring bias and a novel and interpretable debiasing method based on Sparse Autoencoders.

Rui Yang, Yilin Ning, Emilia Keppo et al.

Generative artificial intelligence (AI) has brought revolutionary innovations in various fields, including medicine. However, it also exhibits limitations. In response, retrieval-augmented generation (RAG) provides a potential solution, enabling models to generate more accurate contents by leveraging the retrieval of external knowledge. With the rapid advancement of generative AI, RAG can pave the way for connecting this transformative technology with medical applications and is expected to bring innovations in equity, reliability, and personalization to health care.

Shan Chen, Jack Gallifant, Mingye Gao et al.

Large language models (LLMs) are increasingly essential in processing natural languages, yet their application is frequently compromised by biases and inaccuracies originating in their training data. In this study, we introduce Cross-Care, the first benchmark framework dedicated to assessing biases and real world knowledge in LLMs, specifically focusing on the representation of disease prevalence across diverse demographic groups. We systematically evaluate how demographic biases embedded in pre-training corpora like $ThePile$ influence the outputs of LLMs. We expose and quantify discrepancies by juxtaposing these biases against actual disease prevalences in various U.S. demographic groups. Our results highlight substantial misalignment between LLM representation of disease prevalence and real disease prevalence rates across demographic subgroups, indicating a pronounced risk of bias propagation and a lack of real-world grounding for medical applications of LLMs. Furthermore, we observe that various alignment methods minimally resolve inconsistencies in the models' representation of disease prevalence across different languages. For further exploration and analysis, we make all data and a data visualization tool available at: www.crosscare.net.