Daily Papers

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

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

Skin conditions affect an estimated 1.9 billion people worldwide. A shortage of dermatologists causes long wait times and leads patients to seek dermatologic care from general practitioners. However, the diagnostic accuracy of general practitioners has been reported to be only 0.24-0.70 (compared to 0.77-0.96 for dermatologists), resulting in referral errors, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 skin conditions that represent roughly 80% of the volume of skin conditions seen in primary care. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively. For a random subset of the validation set (n=963 cases), 18 clinicians reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs. These results highlight the potential of the DLS to augment general practitioners to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.

Retinal imaging has emerged as a powerful, non-invasive modality for detecting and quantifying biomarkers of systemic diseases-ranging from diabetes and hypertension to Alzheimer's disease and cardiovascular disorders but current insights remain dispersed across platforms and specialties. Recent technological advances in optical coherence tomography (OCT/OCTA) and adaptive optics (AO) now deliver ultra-high-resolution scans (down to 5 {\mu}m ) with superior contrast and spatial integration, allowing early identification of microvascular abnormalities and neurodegenerative changes. At the same time, AI-driven and machine learning (ML) algorithms have revolutionized the analysis of large-scale retinal datasets, increasing sensitivity and specificity; for example, deep learning models achieve > 90 \% sensitivity for diabetic retinopathy and AUC = 0.89 for the prediction of cardiovascular risk from fundus photographs. The proliferation of mobile health technologies and telemedicine platforms further extends access, reduces costs, and facilitates community-based screening and longitudinal monitoring. Despite these breakthroughs, translation into routine practice is hindered by heterogeneous imaging protocols, limited external validation of AI models, and integration challenges within clinical workflows. In this review, we systematically synthesize the latest OCT/OCT and AO developments, AI/ML approaches, and mHealth/Tele-ophthalmology initiatives and quantify their diagnostic performance across disease domains. Finally, we propose a roadmap for multicenter protocol standardization, prospective validation trials, and seamless incorporation of retinal screening into primary and specialty care pathways-paving the way for precision prevention, early intervention, and ongoing treatment of life-threatening systemic diseases.

The rapid advancement of native multi-modal models and omni-models, exemplified by GPT-4o, Gemini, and o3, with their capability to process and generate content across modalities such as text and images, marks a significant milestone in the evolution of intelligence. Systematic evaluation of their multi-modal output capabilities in visual thinking processes (also known as multi-modal chain of thought, M-CoT) becomes critically important. However, existing benchmarks for evaluating multi-modal models primarily focus on assessing multi-modal inputs and text-only reasoning while neglecting the importance of reasoning through multi-modal outputs. In this paper, we present a benchmark, dubbed RBench-V, designed to assess models' vision-indispensable reasoning abilities. To construct RBench-V, we carefully hand-pick 803 questions covering math, physics, counting, and games. Unlike previous benchmarks that typically specify certain input modalities, RBench-V presents problems centered on multi-modal outputs, which require image manipulation such as generating novel images and constructing auxiliary lines to support the reasoning process. We evaluate numerous open- and closed-source models on RBench-V, including o3, Gemini 2.5 Pro, Qwen2.5-VL, etc. Even the best-performing model, o3, achieves only 25.8% accuracy on RBench-V, far below the human score of 82.3%, highlighting that current models struggle to leverage multi-modal reasoning. Data and code are available at https://evalmodels.github.io/rbenchv

The teaching career shares common global characteristics, such as internal promotion, performance evaluation, recruitment of top candidates, continuous training, specialization, and peer learning. This study aims to describe the factors associated with the value placed on the teaching career in Peru. A total of 28217 public school teachers were analyzed using data from the 2020 National Teacher Survey. A variable measuring the "value of the teaching career" was constructed using eight indicators and categorized as low, medium, or high. Another variable, vision of the future, was classified as pessimistic, conformist, or optimistic. This observational, cross-sectional, and analytical study included variables related to in-service training, working conditions, professional recognition, and sociodemographic characteristics. Among the teachers surveyed, 45.8 % expressed an optimistic outlook on the future of the profession, 48 % held a conformist view, and only 6.2 % reported a pessimistic perspective. A generalized linear model revealed that the value placed on the teaching career was significantly associated with male gender (p = 0.002), a professional career (p < 0.001), an optimistic outlook (p = 0.033), and working at the primary level (p < 0.001). It was concluded that Peruvian teachers predominantly hold conformist or optimistic views of their profession. This highlights the need to reinforce merit-based advancement, competency-based training, intrinsic motivation, and ongoing professional development

Why do brains have inhibitory connections? Why do deep networks have negative weights? We propose an answer from the perspective of representation capacity. We believe representing functions is the primary role of both (i) the brain in natural intelligence, and (ii) deep networks in artificial intelligence. Our answer to why there are inhibitory/negative weights is: to learn more functions. We prove that, in the absence of negative weights, neural networks with non-decreasing activation functions are not universal approximators. While this may be an intuitive result to some, to the best of our knowledge, there is no formal theory, in either machine learning or neuroscience, that demonstrates why negative weights are crucial in the context of representation capacity. Further, we provide insights on the geometric properties of the representation space that non-negative deep networks cannot represent. We expect these insights will yield a deeper understanding of more sophisticated inductive priors imposed on the distribution of weights that lead to more efficient biological and machine learning.

In practical settings, differentially private Federated learning (DP-FL) is the dominant method for training models from private, on-device client data. Recent work has suggested that DP-FL may be enhanced or outperformed by methods that use DP synthetic data (Wu et al., 2024; Hou et al., 2024). The primary algorithms for generating DP synthetic data for FL applications require careful prompt engineering based on public information and/or iterative private client feedback. Our key insight is that the private client feedback collected by prior DP synthetic data methods (Hou et al., 2024; Xie et al., 2024) can be viewed as an RL (reinforcement learning) reward. Our algorithm, Policy Optimization for Private Data (POPri) harnesses client feedback using policy optimization algorithms such as Direct Preference Optimization (DPO) to fine-tune LLMs to generate high-quality DP synthetic data. To evaluate POPri, we release LargeFedBench, a new federated text benchmark for uncontaminated LLM evaluations on federated client data. POPri substantially improves the utility of DP synthetic data relative to prior work on LargeFedBench datasets and an existing benchmark from Xie et al. (2024). POPri closes the gap between next-token prediction accuracy in the fully-private and non-private settings by up to 58%, compared to 28% for prior synthetic data methods, and 3% for state-of-the-art DP federated learning methods. The code and data are available at https://github.com/meiyuw/POPri.

In the domain of Multimodal Large Language Models (MLLMs), achieving human-centric video understanding remains a formidable challenge. Existing benchmarks primarily emphasize object and action recognition, often neglecting the intricate nuances of human emotions, behaviors, and speech visual alignment within video content. We present HumanVBench, an innovative benchmark meticulously crafted to bridge these gaps in the evaluation of video MLLMs. HumanVBench comprises 17 carefully designed tasks that explore two primary dimensions: inner emotion and outer manifestations, spanning static and dynamic, basic and complex, as well as single-modal and cross-modal aspects. With two advanced automated pipelines for video annotation and distractor-included QA generation, HumanVBench utilizes diverse state-of-the-art (SOTA) techniques to streamline benchmark data synthesis and quality assessment, minimizing human annotation dependency tailored to human-centric multimodal attributes. A comprehensive evaluation across 16 SOTA video MLLMs reveals notable limitations in current performance, especially in cross-modal and temporal alignment, underscoring the necessity for further refinement toward achieving more human-like understanding. HumanVBench is open-sourced to facilitate future advancements and real-world applications in video MLLMs.

Text-to-image diffusion models are typically trained to optimize the log-likelihood objective, which presents challenges in meeting specific requirements for downstream tasks, such as image aesthetics and image-text alignment. Recent research addresses this issue by refining the diffusion U-Net using human rewards through reinforcement learning or direct backpropagation. However, many of them overlook the importance of the text encoder, which is typically pretrained and fixed during training. In this paper, we demonstrate that by finetuning the text encoder through reinforcement learning, we can enhance the text-image alignment of the results, thereby improving the visual quality. Our primary motivation comes from the observation that the current text encoder is suboptimal, often requiring careful prompt adjustment. While fine-tuning the U-Net can partially improve performance, it remains suffering from the suboptimal text encoder. Therefore, we propose to use reinforcement learning with low-rank adaptation to finetune the text encoder based on task-specific rewards, referred as TexForce. We first show that finetuning the text encoder can improve the performance of diffusion models. Then, we illustrate that TexForce can be simply combined with existing U-Net finetuned models to get much better results without additional training. Finally, we showcase the adaptability of our method in diverse applications, including the generation of high-quality face and hand images.

Retrieval-augmented Generation (RAG) enhances Large Language Models (LLMs) by integrating external knowledge to reduce hallucinations and incorporate up-to-date information without retraining. As an essential part of RAG, external knowledge bases are commonly built by extracting structured data from unstructured PDF documents using Optical Character Recognition (OCR). However, given the imperfect prediction of OCR and the inherent non-uniform representation of structured data, knowledge bases inevitably contain various OCR noises. In this paper, we introduce OHRBench, the first benchmark for understanding the cascading impact of OCR on RAG systems. OHRBench includes 350 carefully selected unstructured PDF documents from six real-world RAG application domains, along with Q&As derived from multimodal elements in documents, challenging existing OCR solutions used for RAG To better understand OCR's impact on RAG systems, we identify two primary types of OCR noise: Semantic Noise and Formatting Noise and apply perturbation to generate a set of structured data with varying degrees of each OCR noise. Using OHRBench, we first conduct a comprehensive evaluation of current OCR solutions and reveal that none is competent for constructing high-quality knowledge bases for RAG systems. We then systematically evaluate the impact of these two noise types and demonstrate the vulnerability of RAG systems. Furthermore, we discuss the potential of employing Vision-Language Models (VLMs) without OCR in RAG systems. Code: https://github.com/opendatalab/OHR-Bench

The prevalence and importance of algorithmic two-sided marketplaces has drawn attention to the issue of fairness in such settings. Algorithmic decisions are used in assigning students to schools, users to advertisers, and applicants to job interviews. These decisions should heed the preferences of individuals, and simultaneously be fair with respect to their merits (synonymous with fit, future performance, or need). Merits conditioned on observable features are always uncertain, a fact that is exacerbated by the widespread use of machine learning algorithms to infer merit from the observables. As our key contribution, we carefully axiomatize a notion of individual fairness in the two-sided marketplace setting which respects the uncertainty in the merits; indeed, it simultaneously recognizes uncertainty as the primary potential cause of unfairness and an approach to address it. We design a linear programming framework to find fair utility-maximizing distributions over allocations, and we show that the linear program is robust to perturbations in the estimated parameters of the uncertain merit distributions, a key property in combining the approach with machine learning techniques.

Recent advances in image generation, particularly via diffusion models, have led to impressive improvements in image synthesis quality. Despite this, diffusion models are still challenged by model-induced artifacts and limited stability in image fidelity. In this work, we hypothesize that the primary cause of this issue is the improper resampling operation that introduces aliasing in the diffusion model and a careful alias-free resampling dictated by image processing theory can improve the model's performance in image synthesis. We propose the integration of alias-free resampling layers into the UNet architecture of diffusion models without adding extra trainable parameters, thereby maintaining computational efficiency. We then assess whether these theory-driven modifications enhance image quality and rotational equivariance. Our experimental results on benchmark datasets, including CIFAR-10, MNIST, and MNIST-M, reveal consistent gains in image quality, particularly in terms of FID and KID scores. Furthermore, we propose a modified diffusion process that enables user-controlled rotation of generated images without requiring additional training. Our findings highlight the potential of theory-driven enhancements such as alias-free resampling in generative models to improve image quality while maintaining model efficiency and pioneer future research directions to incorporate them into video-generating diffusion models, enabling deeper exploration of the applications of alias-free resampling in generative modeling.

Large Language Models (LLMs) have demonstrated considerable potential in general practice. However, existing benchmarks and evaluation frameworks primarily depend on exam-style or simplified question-answer formats, lacking a competency-based structure aligned with the real-world clinical responsibilities encountered in general practice. Consequently, the extent to which LLMs can reliably fulfill the duties of general practitioners (GPs) remains uncertain. In this work, we propose a novel evaluation framework to assess the capability of LLMs to function as GPs. Based on this framework, we introduce a general practice benchmark (GPBench), whose data are meticulously annotated by domain experts in accordance with routine clinical practice standards. We evaluate ten state-of-the-art LLMs and analyze their competencies. Our findings indicate that current LLMs are not yet ready for deployment in such settings without human oversight, and further optimization specifically tailored to the daily responsibilities of GPs is essential.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

Urgent care clinics and emergency departments around the world periodically suffer from extended wait times beyond patient expectations due to inadequate staffing levels. These delays have been linked with adverse clinical outcomes. Previous research into forecasting demand this domain has mostly used a collection of statistical techniques, with machine learning approaches only now beginning to emerge in recent literature. The forecasting problem for this domain is difficult and has also been complicated by the COVID-19 pandemic which has introduced an additional complexity to this estimation due to typical demand patterns being disrupted. This study explores the ability of machine learning methods to generate accurate patient presentations at two large urgent care clinics located in Auckland, New Zealand. A number of machine learning algorithms were explored in order to determine the most effective technique for this problem domain, with the task of making forecasts of daily patient demand three months in advance. The study also performed an in-depth analysis into the model behaviour in respect to the exploration of which features are most effective at predicting demand and which features are capable of adaptation to the volatility caused by the COVID-19 pandemic lockdowns. The results showed that ensemble-based methods delivered the most accurate and consistent solutions on average, generating improvements in the range of 23%-27% over the existing in-house methods for estimating the daily demand.

Recent advancements in large language model(LLM) performance on medical multiple choice question (MCQ) benchmarks have stimulated interest from healthcare providers and patients globally. Particularly in low-and middle-income countries (LMICs) facing acute physician shortages and lack of specialists, LLMs offer a potentially scalable pathway to enhance healthcare access and reduce costs. However, their effectiveness in the Global South, especially across the African continent, remains to be established. In this work, we introduce AfriMed-QA, the first large scale Pan-African English multi-specialty medical Question-Answering (QA) dataset, 15,000 questions (open and closed-ended) sourced from over 60 medical schools across 16 countries, covering 32 medical specialties. We further evaluate 30 LLMs across multiple axes including correctness and demographic bias. Our findings show significant performance variation across specialties and geographies, MCQ performance clearly lags USMLE (MedQA). We find that biomedical LLMs underperform general models and smaller edge-friendly LLMs struggle to achieve a passing score. Interestingly, human evaluations show a consistent consumer preference for LLM answers and explanations when compared with clinician answers.

Large Language models have demonstrated excellent domain-specific question-answering capabilities when finetuned with a particular dataset of that specific domain. However, fine-tuning the models requires a significant amount of training time and a considerable amount of hardware. In this work, we propose CARE (Customer Assistance and Response Engine), a lightweight model made by fine-tuning Phi3.5-mini on very minimal hardware and data, designed to handle queries primarily across three domains: telecommunications support, medical support, and banking support. For telecommunications and banking, the chatbot addresses issues and problems faced by customers regularly in the above-mentioned domains. In the medical domain, CARE provides preliminary support by offering basic diagnoses and medical suggestions that a user might take before consulting a healthcare professional. Since CARE is built on Phi3.5-mini, it can be used even on mobile devices, increasing its usability. Our research also shows that CARE performs relatively well on various medical benchmarks, indicating that it can be used to make basic medical suggestions.

We aim to present a comprehensive overview of the latest advancements in utilizing Large Language Models (LLMs) within the healthcare sector, emphasizing their transformative impact across various medical domains. LLMs have become pivotal in supporting healthcare, including physicians, healthcare providers, and patients. Our review provides insight into the applications of Large Language Models (LLMs) in healthcare, specifically focusing on diagnostic and treatment-related functionalities. We shed light on how LLMs are applied in cancer care, dermatology, dental care, neurodegenerative disorders, and mental health, highlighting their innovative contributions to medical diagnostics and patient care. Throughout our analysis, we explore the challenges and opportunities associated with integrating LLMs in healthcare, recognizing their potential across various medical specialties despite existing limitations. Additionally, we offer an overview of handling diverse data types within the medical field.