Daily Papers

Recent audio-language models are increasingly evaluated on recognizing, describing, and reasoning about audio, but expert-facing applications require a different capability: producing feedback that identifies problems and suggests corrective actions grounded in the input. We introduce VocalCoachBench, a benchmark for evaluating audio-language models on expert vocal coaching feedback for singing. VocalCoachBench contains 515 recordings annotated by 18 professional vocal trainers, yielding 1,056 expert submissions and 12,051 atomic coaching claims. It comprises a same-song subset for controlled comparison and a diverse-song subset for segment-grounded feedback across varied songs and recording conditions. To accommodate the open-ended nature of expert feedback, VocalCoachBench sep- arates deterministic structured targets from claim-based assessment of free-form diagnosis and corrective guidance. Human annotation analysis shows that expert agreement varies strongly with label granularity, motivating hierarchical structured metrics and claim-based evaluation of open-ended feedback. Experiments with 12 recent audio-language models reveal a consistent gap: while models can compare performances and identify broad issue domains in free-form feedback, Top-3 fine-grained issue-label identification remains below label-prior baselines and strict diagnosis alignment stays below 7%. To our knowledge, VocalCoachBench pro- vides the first public testbed for evaluating audio-grounded expert feedback for singing, moving audio-language evaluation beyond description toward analytic feedback.

Despite generating increasingly photorealistic images, text-to-image (T2I) models still exhibit localized, subtle, and structurally complex failures. Diagnosing these failures requires instance-level feedback that answers where a defect occurs, what type it is, why it is defective, and its importance to overall image quality. While recent dense-feedback methods move beyond scalar supervision, their heatmap-centric representations still formulate diagnosis as pixel-field regression, making it difficult to localize variable-cardinality defects and bind semantic reasons to individual failures. To address this representation bottleneck, we propose Structured Defect Grounding (SDG), which casts T2I diagnosis as structured set prediction by modeling each defect as a (location, type, reason, importance) tuple. To make this formulation trainable and measurable, we introduce SDG-30K, a 30K-image dataset with box-grounded annotations across four modern T2I generators, together with a dedicated evaluation protocol, SDG-Eval. Building on this structured representation, we further present a diagnosis-to-alignment framework in which a Vision-Language Model (VLM) serves as the SDG detector, and BoxFlow-GRPO converts predicted defect sets into box-derived, importance-weighted spatial rewards for diffusion model alignment. Extensive experiments show that our SDG detector outperforms leading proprietary VLMs on structured defect grounding, while SDG-guided rewards consistently improve T2I alignment and support localized image refinement. These results establish SDG as a unified, instance-level interface for diagnosing, evaluating, and enhancing modern generative models.

Early diagnosis of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) utilizing multi-modal magnetic resonance imaging (MRI) is a pivotal area of research. While various regional and connectivity features from functional MRI (fMRI) and diffusion tensor imaging (DTI) have been employed to develop diagnosis models, most studies integrate these features without adequately addressing their alignment and interactions. This limits the potential to fully exploit the synergistic contributions of combined features and modalities. To solve this gap, our study introduces a novel Hierarchical Alignments and Hierarchical Interactions (HA-HI) method for MCI and SCD classification, leveraging the combined strengths of fMRI and DTI. HA-HI efficiently learns significant MCI- or SCD- related regional and connectivity features by aligning various feature types and hierarchically maximizing their interactions. Furthermore, to enhance the interpretability of our approach, we have developed the Synergistic Activation Map (SAM) technique, revealing the critical brain regions and connections that are indicative of MCI/SCD. Comprehensive evaluations on the ADNI dataset and our self-collected data demonstrate that HA-HI outperforms other existing methods in diagnosing MCI and SCD, making it a potentially vital and interpretable tool for early detection. The implementation of this method is publicly accessible at https://github.com/ICI-BCI/Dual-MRI-HA-HI.git.

Electrocardiogram (ECG) interpretation is essential for cardiovascular disease diagnosis, but current automated systems often struggle with transparency and generalization to unseen conditions. To address this, we introduce ZETA, a zero-shot multimodal framework designed for interpretable ECG diagnosis aligned with clinical workflows. ZETA uniquely compares ECG signals against structured positive and negative clinical observations, which are curated through an LLM-assisted, expert-validated process, thereby mimicking differential diagnosis. Our approach leverages a pre-trained multimodal model to align ECG and text embeddings without disease-specific fine-tuning. Empirical evaluations demonstrate ZETA's competitive zero-shot classification performance and, importantly, provide qualitative and quantitative evidence of enhanced interpretability, grounding predictions in specific, clinically relevant positive and negative diagnostic features. ZETA underscores the potential of aligning ECG analysis with structured clinical knowledge for building more transparent, generalizable, and trustworthy AI diagnostic systems. We will release the curated observation dataset and code to facilitate future research.

Multimodal alignment of histopathology encoders with transcriptomic and genomic data has been shown to significantly improve performance in downstream diagnostic tasks. Hematological cytology is unique in that visual single-cell evaluation is often paired with cytogenetics and molecular genetics for blood cancer diagnosis. In this study, we present a framework to align single white blood cell images with chromosomal aberrations (karyotype) and somatic mutations from targeted gene panels. Our training strategy follows a two-stage approach: (i) self-supervised, vision-only pretraining of a transformer aggregator using an iBOT head on a cohort of over 1500 patients, and (ii) genetic alignment via supervised contrastive loss on acute myeloid leukemia patients. Our genetically aligned patient encoder improves hematological diagnostic tasks, outperforming slide-level histopathology foundation models. Additionally, the model provides off-the-shelf retrieval capabilities for diseases and genetic alterations. Incorporating genetic data into patient encoders increases the quality of patient representations, providing a framework that aligns with clinical diagnostic workflows and paves the way for future multimodal hematology-specific AI. The code and model weights are available at https://github.com/marrlab/GenBloom.

Breast cancer is one of the leading causes of death among women worldwide. We introduce Mammo-FM, the first foundation model specifically for mammography, pretrained on the largest and most diverse dataset to date - 140,677 patients (821,326 mammograms) across four U.S. institutions. Mammo-FM provides a unified foundation for core clinical tasks in breast imaging, including cancer diagnosis, pathology localization, structured report generation, and cancer risk prognosis within a single framework. Its alignment between images and text enables both visual and textual interpretability, improving transparency and clinical auditability, which are essential for real-world adoption. We rigorously evaluate Mammo-FM across diagnosis, prognosis, and report-generation tasks in in- and out-of-distribution datasets. Despite operating on native-resolution mammograms and using only one-third of the parameters of state-of-the-art generalist FMs, Mammo-FM consistently outperforms them across multiple public and private benchmarks. These results highlight the efficiency and value of domain-specific foundation models designed around the full spectrum of tasks within a clinical domain and emphasize the importance of rigorous, domain-aligned evaluation.

Visual latent reasoning lets a multimodal large language model (MLLM) create intermediate visual evidence as continuous tokens, avoiding external tools or image generators. However, existing methods usually follow an output-as-input latent paradigm and yield unstable gains. We identify evidence for a feature-space mismatch that can contribute to this instability: dominant visual-latent models build on pre-norm MLLMs and reuse decoder hidden states as predicted latent inputs, even though these states occupy a substantially different norm regime from the input embeddings the model was trained to consume (Xie et al., 2025; Li et al., 2026; Team et al., 2026). This mismatch can make direct latent feedback unreliable. Motivated by this diagnosis, we propose GAP, a Granular Alignment Paradigm for visual latent modeling. GAP aligns visual latent reasoning at three levels: feature-level alignment maps decoder outputs into input-compatible visual latents through a lightweight PCA-aligned latent head; context-level alignment grounds latent targets with inspectable auxiliary visual supervision; and capacity-guided alignment assigns latent supervision selectively to examples where the base MLLM struggles. On Qwen2.5-VL 7B, the resulting model achieves the best mean aggregate perception and reasoning performance among our supervised variants. Inference-time intervention probing further suggests that generated latents provide task-relevant visual signal beyond merely adding token slots.

While reinforcement learning for large language model alignment has progressed rapidly in recent years, transferring these paradigms to high-stakes medical question answering reveals a fundamental paradigm mismatch. Reinforcement Learning from Human Feedback relies on preference annotations that are prohibitively expensive and often fail to reflect the absolute correctness of medical facts. Reinforcement Learning from Verifiable Rewards lacks effective automatic verifiers and struggles to handle complex clinical contexts. Meanwhile, medical alignment requires the simultaneous optimization of correctness, safety, and compliance, yet multi-objective heterogeneous reward signals are prone to scale mismatch and optimization conflicts.To address these challenges, we propose a robust medical alignment paradigm. We first construct a holistic multi-dimensional medical alignment matrix that decomposes alignment objectives into four categories: fundamental capabilities, expert knowledge, online feedback, and format specifications. Within each category, we establish a closed loop of where observable metrics inform attributable diagnosis, which in turn drives optimizable rewards, thereby providing fine-grained, high-resolution supervision signals for subsequent iterative optimization. To resolve gradient domination and optimization instability problem caused by heterogeneous signals, we further propose a unified optimization mechanism. This mechanism employs Reference-Frozen Normalization to align reward scales and implements a Tri-Factor Adaptive Dynamic Weighting strategy to achieve collaborative optimization that is weakness-oriented, risk-prioritized, and redundancy-reducing. Experimental results demonstrate the effectiveness of our proposed paradigm in real-world medical scenario evaluations, establishing a new paradigm for complex alignment in vertical domains.

Significant disparities exist in the diagnosis and clinical presentation of depression across different linguistic populations. Speech-based depression detection performs well monolingually, but cross-lingual generalization remains an open challenge. A key reason is that prior work uses segment-level random splits without speaker grouping, leading to identity leakage that inflates reported metrics. We propose CLeaD, a supervised contrastive alignment framework that maps WavLM embeddings from English and Mandarin into a shared clinical space, without parallel data or target-language fine-tuning. Evaluating 52 Mandarin speakers, contrastive alignment modestly outperforms the baseline (F1: 0.640 vs. 0.622) under leave-one-speaker-out evaluation. It also improves depressed-class recall at intermediate layers (7-8), though the small test set limits generalizability. Two findings remain robust: model scaling degrades cross-lingual performance while improving monolingual English, and speaker identity leakage artificially inflated previously reported Mandarin F1 scores to 0.954, an artifact we reproduce and quantify.

The PI-CAI (Prostate Imaging: Cancer AI) challenge led to expert-level diagnostic algorithms for clinically significant prostate cancer detection. The algorithms receive biparametric MRI scans as input, which consist of T2-weighted and diffusion-weighted scans. These scans can be misaligned due to multiple factors in the scanning process. Image registration can alleviate this issue by predicting the deformation between the sequences. We investigate the effect of image registration on the diagnostic performance of AI-based prostate cancer diagnosis. First, the image registration algorithm, developed in MeVisLab, is analyzed using a dataset with paired lesion annotations. Second, the effect on diagnosis is evaluated by comparing case-level cancer diagnosis performance between using the original dataset, rigidly aligned diffusion-weighted scans, or deformably aligned diffusion-weighted scans. Rigid registration showed no improvement. Deformable registration demonstrated a substantial improvement in lesion overlap (+10% median Dice score) and a positive yet non-significant improvement in diagnostic performance (+0.3% AUROC, p=0.18). Our investigation shows that a substantial improvement in lesion alignment does not directly lead to a significant improvement in diagnostic performance. Qualitative analysis indicated that jointly developing image registration methods and diagnostic AI algorithms could enhance diagnostic accuracy and patient outcomes.

Diagnosing lung cancer typically involves physicians identifying lung nodules in Computed tomography (CT) scans and generating diagnostic reports based on their morphological features and medical expertise. Although advancements have been made in using multimodal large language models for analyzing lung CT scans, challenges remain in accurately describing nodule morphology and incorporating medical expertise. These limitations affect the reliability and effectiveness of these models in clinical settings. Collaborative multi-agent systems offer a promising strategy for achieving a balance between generality and precision in medical applications, yet their potential in pathology has not been thoroughly explored. To bridge these gaps, we introduce LungNoduleAgent, an innovative collaborative multi-agent system specifically designed for analyzing lung CT scans. LungNoduleAgent streamlines the diagnostic process into sequential components, improving precision in describing nodules and grading malignancy through three primary modules. The first module, the Nodule Spotter, coordinates clinical detection models to accurately identify nodules. The second module, the Radiologist, integrates localized image description techniques to produce comprehensive CT reports. Finally, the Doctor Agent System performs malignancy reasoning by using images and CT reports, supported by a pathology knowledge base and a multi-agent system framework. Extensive testing on two private datasets and the public LIDC-IDRI dataset indicates that LungNoduleAgent surpasses mainstream vision-language models, agent systems, and advanced expert models. These results highlight the importance of region-level semantic alignment and multi-agent collaboration in diagnosing nodules. LungNoduleAgent stands out as a promising foundational tool for supporting clinical analyses of lung nodules.

Large language models internalize a structural trade-off between truthfulness and obsequious flattery, emerging from reward optimization that conflates helpfulness with polite submission. This latent bias, known as sycophancy, manifests as a preference for user agreement over principled reasoning. We introduce Beacon, a single-turn forced-choice benchmark that isolates this bias independent of conversational context, enabling precise measurement of the tension between factual accuracy and submissive bias. Evaluations across twelve state-of-the-art models reveal that sycophancy decomposes into stable linguistic and affective sub-biases, each scaling with model capacity. We further propose prompt-level and activation-level interventions that modulate these biases in opposing directions, exposing the internal geometry of alignment as a dynamic manifold between truthfulness and socially compliant judgment. Beacon reframes sycophancy as a measurable form of normative misgeneralization, providing a reproducible foundation for studying and mitigating alignment drift in large-scale generative systems.

Developing 3D vision-language models with robust clinical reasoning remains a challenge due to the inherent complexity of volumetric medical imaging, the tendency of models to overfit superficial report patterns, and the lack of interpretability-aware reward designs. In this paper, we propose Med3D-R1, a reinforcement learning framework with a two-stage training process: Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL). During SFT stage, we introduce a residual alignment mechanism to bridge the gap between high-dimensional 3D features and textual embeddings, and an abnormality re-weighting strategy to emphasize clinically informative tokens and reduce structural bias in reports. In RL stage, we redesign the consistency reward to explicitly promote coherent, step-by-step diagnostic reasoning. We evaluate our method on medical multiple-choice visual question answering using two 3D diagnostic benchmarks, CT-RATE and RAD-ChestCT, where our model attains state-of-the-art accuracies of 41.92\% on CT-RATE and 44.99\% on RAD-ChestCT. These results indicate improved abnormality diagnosis and clinical reasoning and outperform prior methods on both benchmarks. Overall, our approach holds promise for enhancing real-world diagnostic workflows by enabling more reliable and transparent 3D medical vision-language systems.

Multimodal large language models (MLLMs) demonstrate significant potential in the field of medical diagnosis. However, they face critical challenges in specialized domains such as ophthalmology, particularly the fragmentation of annotation granularity and inconsistencies in clinical reasoning logic, which hinder precise cross-modal understanding. This paper introduces FundusExpert, an ophthalmology-specific MLLM with integrated positioning-diagnosis reasoning capabilities, along with FundusGen, a dataset constructed through the intelligent Fundus-Engine system. Fundus-Engine automates localization and leverages MLLM-based semantic expansion to integrate global disease classification, local object detection, and fine-grained feature analysis within a single fundus image. Additionally, by constructing a clinically aligned cognitive chain, it guides the model to generate interpretable reasoning paths. FundusExpert, fine-tuned with instruction data from FundusGen, achieves the best performance in ophthalmic question-answering tasks, surpassing the average accuracy of the 40B MedRegA by 26.6%. It also excels in zero-shot report generation tasks, achieving a clinical consistency of 77.0%, significantly outperforming GPT-4o's 47.6%. Furthermore, we reveal a scaling law between data quality and model capability (L propto N^{0.068}), demonstrating that the cognitive alignment annotations in FundusGen enhance data utilization efficiency. By integrating region-level localization with diagnostic reasoning chains, our work develops a scalable, clinically-aligned MLLM and explores a pathway toward bridging the visual-language gap in specific MLLMs. Our project can be found at https://github.com/MeteorElf/FundusExpert.

Deep learning based automated pathological diagnosis has markedly improved diagnostic efficiency and reduced variability between observers, yet its clinical adoption remains limited by opaque model decisions and a lack of traceable rationale. To address this, recent multimodal visual reasoning architectures provide a unified framework that generates segmentation masks at the pixel level alongside semantically aligned textual explanations. By localizing lesion regions and producing expert style diagnostic narratives, these models deliver the transparent and interpretable insights necessary for dependable AI assisted pathology. Building on these advancements, we propose PathMR, a cell-level Multimodal visual Reasoning framework for Pathological image analysis. Given a pathological image and a textual query, PathMR generates expert-level diagnostic explanations while simultaneously predicting cell distribution patterns. To benchmark its performance, we evaluated our approach on the publicly available PathGen dataset as well as on our newly developed GADVR dataset. Extensive experiments on these two datasets demonstrate that PathMR consistently outperforms state-of-the-art visual reasoning methods in text generation quality, segmentation accuracy, and cross-modal alignment. These results highlight the potential of PathMR for improving interpretability in AI-driven pathological diagnosis. The code will be publicly available in https://github.com/zhangye-zoe/PathMR.

Large Language Models (LLMs) are widely used as automated judges, where practical value depends on both accuracy and trustworthy, risk-aware judgments. Existing approaches predominantly focus on accuracy, overlooking the necessity of well-calibrated confidence, which is vital for adaptive and reliable evaluation pipelines. In this work, we advocate a shift from accuracy-centric evaluation to confidence-driven, risk-aware LLM-as-a-Judge systems, emphasizing the necessity of well-calibrated confidence for trustworthy and adaptive evaluation. We systematically identify the Overconfidence Phenomenon in current LLM-as-a-Judges, where predicted confidence significantly overstates actual correctness, undermining reliability in practical deployment. To quantify this phenomenon, we introduce TH-Score, a novel metric measuring confidence-accuracy alignment. Furthermore, we propose LLM-as-a-Fuser, an ensemble framework that transforms LLMs into reliable, risk-aware evaluators. Extensive experiments demonstrate that our approach substantially improves calibration and enables adaptive, confidence-driven evaluation pipelines, achieving superior reliability and accuracy compared to existing baselines.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Tool-using LLM agents fail through trajectories rather than only final responses, as they may execute unsafe tool calls, follow injected instructions, comply with harmful requests, or over-refuse benign tasks despite producing a seemingly safe answer. Existing safety-alignment signals are largely response-level or off-policy, and often incur a safety-utility trade-off: improving agent safety comes at the cost of degraded task performance. Such sparse and single-objective rewards severely limit real-world usability. To bridge this gap, we propose FATE, an on-policy self-evolving framework that transforms verifier-scored failures into repair supervision without expert demonstrations. For each failure, the same policy proposes repair candidates, which are then re-scored by verifiers and filtered across security, utility, over-refusal control, and trajectory validity. This dense trajectory-level information is then used as a supervision signal for agent self-evolution. During this process, we further introduce Pareto-Front Policy Optimization (PFPO), combining supervised warmup with Pareto-aware policy optimization to preserve safety-utility trade-offs. Experiments on AgentDojo, AgentHarm, and ATBench show that FATE improves safety across different models and scales while preserving useful behavior. Compared with strong baselines, FATE reduces attack success rate by 33.5%, harmful compliance by 82.6%, and improves external trajectory-safety diagnosis by 6.5%. These results suggest that failed trajectories can provide structured repair supervision for safer self-evolving agents.

While generative text-to-speech (TTS) models approach human-level quality, monolithic metrics fail to diagnose fine-grained acoustic artifacts or explain perceptual collapse. To address this, we propose TTS-PRISM, a multi-dimensional diagnostic framework for Mandarin. First, we establish a 12-dimensional schema spanning stability to advanced expressiveness. Second, we design a targeted synthesis pipeline with adversarial perturbations and expert anchors to build a high-quality diagnostic dataset. Third, schema-driven instruction tuning embeds explicit scoring criteria and reasoning into an efficient end-to-end model. Experiments on a 1,600-sample Gold Test Set show TTS-PRISM outperforms generalist models in human alignment. Profiling six TTS paradigms establishes intuitive diagnostic flags that reveal fine-grained capability differences. TTS-PRISM is open-source, with code and checkpoints at https://github.com/xiaomi-research/tts-prism.

Recent advancements in Large Vision-Language Models (LVLMs) have demonstrated remarkable multimodal perception and reasoning capabilities. While numerous benchmarks have evaluated LVLMs from holistic or task-specific perspectives, their capabilities on fine-grained image tasks-fundamental to computer vision-remain insufficiently understood. To address this gap, we introduce FG-BMK, a comprehensive fine-grained evaluation benchmark containing 1.01 million questions and 0.28 million images, covering diverse scenarios from common object-centric domains to specialized domains. FG-BMK jointly evaluates dialogue-level fine-grained semantic recognition and feature-level visual discriminability through human-oriented and machine-oriented paradigms, enabling diagnostic analysis of whether LVLM failures arise from insufficient visual representations, weak visual-to-semantic grounding, or limited fine-grained knowledge. Through extensive experiments on a diverse set of representative LVLMs/VLMs, we find that current LVLMs remain inadequate fine-grained recognizers, with failures arising from intertwined bottlenecks in visual representations, semantic grounding, modality alignment, and category-level knowledge. We further analyze training design factors for improving fine-grained capabilities and examine how visual and linguistic perturbations affect LVLM predictions. These findings provide diagnostic insights into the limitations of current LVLMs and offer guidance for future data construction and model design in developing more reliable LVLMs for fine-grained visual tasks. Our code is open-source and available at https://fg-bmk.github.io/.

Despite rapid progress in video-capable MLLMs, we find that their apparent audio understanding in videos is often vision-driven: models rely on visual cues to infer or hallucinate acoustic information, rather than verifying the audio stream. This issue appears across both state-of-the-art open-source omni models and leading closed-source models from providers such as Google and OpenAI. We characterize this failure mode as an audio-visual Clever Hans effect, in which models appear (falsely) audio-grounded, but actually exploit visual-acoustic correlations without verifying whether the audio and visual streams are truly aligned. To systematically study this behavior, we introduce Thud, an intervention-driven probing framework based on three counterfactual audio edits: Shift, which tests temporal synchronization; Mute, which tests sound existence; and Swap, which tests audio-visual consistency. Beyond diagnosis, we further study a two-stage alignment recipe: intervention-derived preference pairs teach audio verification, while event-level general video preferences regularize the model against over-specialization. Our best 10K-sample recipe improves average performance across the three intervention dimensions by 28 percentage points, while slightly improving performance on general video and audio-visual QA benchmarks.

Image registration is fundamental in medical imaging, enabling precise alignment of anatomical structures for diagnosis, treatment planning, image-guided treatment or longitudinal monitoring. This work introduces IMPACT (Image Metric with Pretrained model-Agnostic Comparison for Transmodality registration), a generic semantic similarity metric designed for seamless integration into diverse image registration frameworks (such as Elastix and Voxelmorph). It compares deep learning-based features extracted from medical images without requiring task-specific training, ensuring broad applicability across various modalities. By leveraging the features of the large-scale pretrained TotalSegmentator models and the ability to integrate Segment Anything Model (SAM) and other large-scale segmentation networks, this approach offers significant advantages. It provides robust, scalable, and efficient solutions for multimodal image registration. The IMPACT loss was evaluated on five challenging registration tasks involving thoracic CT/CBCT, and pelvic MR/CT datasets. Quantitative metrics, such as Target Registration Error and Dice Similarity Coefficient, demonstrated significant improvements in anatomical alignment compared to baseline methods. Qualitative analyses further confirmed the increased robustness of the proposed metric in the face of noise, artifacts, and modality variations. IMPACT's versatility and efficiency make it a valuable tool for advancing registration performance in clinical and research applications, addressing critical challenges in multimodal medical imaging.

Medical multimodal large language models (MLLMs) are increasingly expected to perform complex image understanding tasks, yet their reliability is often compromised by frequent errors in visual interpretation. To systematically trace these failures, we traverse the hierarchy from high-level clinical tasks down to fundamental visual perception. We therefore introduce Perception-Bench, a large-scale benchmark comprising 1.13 million samples that assesses medical MLLMs across six dimensions: attribute judgment, spatial grounding, spatial understanding, disease prediction, anomaly detection, and report generation, spanning both 2D and 3D radiology images. Our analysis on Perception-Bench reveals that existing MLLMs lack the ability to capture even the most basic lesion attributes, such as location, size, and density. This inability to ground clinical outputs in primary visual evidence reveals that the models' diagnostic unreliability is rooted in a critical but overlooked bottleneck in low-level visual perception. Motivated by this, we propose RadSight, a perception-driven MLLM built upon a dual 2D/3D encoder architecture that preserves native imaging spatial structures. RadSight formulates medical image understanding as a four-stage progressive process: visual-language alignment, fine-grained visual perception, clinical diagnosis, and diagnostic interpretation. The model is trained on an 8.37 million perception-oriented corpus using progressive curriculum learning. On Perception-Bench, RadSight consistently outperforms existing MLLMs across all six evaluation dimensions, with particularly strong gains in spatial grounding and clinical diagnosis. It also achieves consistent improvements on public 2D and 3D medical benchmarks, further demonstrating that robust low-level visual perception is a critical foundation for reliable clinical understanding. Code and model will be publicly available.

Pathology vision-language models (VLMs) have shown strong visual perception ability, but their robustness in the language domain remains poorly characterized. Existing pathology VLM benchmarks largely rely on canonical closed-set prompts or perturb only generic templates, treating language as a fixed evaluation component rather than a variable axis of model behavior. In clinical practice, however, diagnostic language varies across reports, institutions, and candidate diagnoses. We introduce PathLang, a language-centered and clinically grounded zero-shot benchmark. PathLang holds the underlying slides, ground-truth labels, and image-text evaluation direction fixed while systematically varying only the diagnostic language, so that performance differences reflect how a diagnosis is phrased rather than what is imaged. The language variation follows how pathologists actually rephrase diagnoses (terminology, specificity, and reporting style), and all prompts and candidate pools are validated by six board-certified pathologists. PathLang covers four task families: (1) zero-shot classification with image-text alignment analysis, (2) cross-modal retrieval, (3) paraphrase robustness, including semantic-equivalence paraphrases, length and reporting-style variation, and prompt ensembling, and (4) open-vocabulary diagnosis retrieval over four candidate pools with distinct forms of semantic competition. Across nine VLMs and five public datasets spanning four organs, we find that performance is highly sensitive to clinically equivalent paraphrases, varies substantially across forms of semantic competition, and that image-text alignment quality does not necessarily translate into inter-class separability. We release the prompt corpus, candidate pools, pre-computed text embeddings, and evaluation code at https://anonymous.4open.science/r/PathLang.

Fetal ultrasound (US) is the primary imaging modality for prenatal screening, yet its interpretation relies heavily on the expertise of the clinician. Despite advances in deep learning and foundation models, existing automated tools for fetal US analysis struggle to balance task-specific accuracy with the whole-process versatility required to support end-to-end clinical workflows. To address these limitations, we propose FetalAgents, the first multi-agent system for comprehensive fetal US analysis. Through a lightweight, agentic coordination framework, FetalAgents dynamically orchestrates specialized vision experts to maximize performance across diagnosis, measurement, and segmentation. Furthermore, FetalAgents advances beyond static image analysis by supporting end-to-end video stream summarization, where keyframes are automatically identified across multiple anatomical planes, analyzed by coordinated experts, and synthesized with patient metadata into a structured clinical report. Extensive multi-center external evaluations across eight clinical tasks demonstrate that FetalAgents consistently delivers the most robust and accurate performance when compared against specialized models and multimodal large language models (MLLMs), ultimately providing an auditable, workflow-aligned solution for fetal ultrasound analysis and reporting.

Large vision language models (VLMs) combine large language models with vision encoders, demonstrating promise across various tasks. However, they often underperform in task-specific applications due to domain gaps between pre-training and fine-tuning. We introduce VITask, a novel framework that enhances task-specific adaptability of VLMs by integrating task-specific models (TSMs). VITask employs three key strategies: exemplar prompting (EP), response distribution alignment (RDA), and contrastive response tuning (CRT) to improve the task-specific performance of VLMs by adjusting their response distributions. EP allows TSM features to guide VLMs, while RDA enables VLMs to adapt without TSMs during inference by learning from exemplar-prompted models. CRT further optimizes the ranking of correct image-response pairs, thereby reducing the risk of generating undesired responses. Experiments on 12 medical diagnosis datasets across 9 imaging modalities show that VITask outperforms both vanilla instruction-tuned VLMs and TSMs, showcasing its ability to integrate complementary features from both models effectively. Additionally, VITask offers practical advantages such as flexible TSM integration and robustness to incomplete instructions, making it a versatile and efficient solution for task-specific VLM tuning. Our code are available at https://github.com/baiyang4/VITask.

Automated interpretation of electrocardiograms (ECG) has garnered significant attention with the advancements in machine learning methodologies. Despite the growing interest, most current studies focus solely on classification or regression tasks, which overlook a crucial aspect of clinical cardio-disease diagnosis: the diagnostic report generated by experienced human clinicians. In this paper, we introduce a novel approach to ECG interpretation, leveraging recent breakthroughs in Large Language Models (LLMs) and Vision-Transformer (ViT) models. Rather than treating ECG diagnosis as a classification or regression task, we propose an alternative method of automatically identifying the most similar clinical cases based on the input ECG data. Also, since interpreting ECG as images is more affordable and accessible, we process ECG as encoded images and adopt a vision-language learning paradigm to jointly learn vision-language alignment between encoded ECG images and ECG diagnosis reports. Encoding ECG into images can result in an efficient ECG retrieval system, which will be highly practical and useful in clinical applications. More importantly, our findings could serve as a crucial resource for providing diagnostic services in underdeveloped regions.

Developing an interpretable system for generating reports in chest X-ray (CXR) analysis is becoming increasingly crucial in Computer-aided Diagnosis (CAD) systems, enabling radiologists to comprehend the decisions made by these systems. Despite the growth of diverse datasets and methods focusing on report generation, there remains a notable gap in how closely these models' generated reports align with the interpretations of real radiologists. In this study, we tackle this challenge by initially introducing Fine-Grained CXR (FG-CXR) dataset, which provides fine-grained paired information between the captions generated by radiologists and the corresponding gaze attention heatmaps for each anatomy. Unlike existing datasets that include a raw sequence of gaze alongside a report, with significant misalignment between gaze location and report content, our FG-CXR dataset offers a more grained alignment between gaze attention and diagnosis transcript. Furthermore, our analysis reveals that simply applying black-box image captioning methods to generate reports cannot adequately explain which information in CXR is utilized and how long needs to attend to accurately generate reports. Consequently, we propose a novel explainable radiologist's attention generator network (Gen-XAI) that mimics the diagnosis process of radiologists, explicitly constraining its output to closely align with both radiologist's gaze attention and transcript. Finally, we perform extensive experiments to illustrate the effectiveness of our method. Our datasets and checkpoint is available at https://github.com/UARK-AICV/FG-CXR.

As the development of Large Models (LMs) progresses rapidly, their safety is also a priority. In current Large Language Models (LLMs) and Multimodal Large Language Models (MLLMs) safety workflow, evaluation, diagnosis, and alignment are often handled by separate tools. Specifically, safety evaluation can only locate external behavioral risks but cannot figure out internal root causes. Meanwhile, safety diagnosis often drifts from concrete risk scenarios and remains at the explainable level. In this way, safety alignment lack dedicated explanations of changes in internal mechanisms, potentially degrading general capabilities. To systematically address these issues, we propose an open-source project, namely DeepSight, to practice a new safety evaluation-diagnosis integrated paradigm. DeepSight is low-cost, reproducible, efficient, and highly scalable large-scale model safety evaluation project consisting of a evaluation toolkit DeepSafe and a diagnosis toolkit DeepScan. By unifying task and data protocols, we build a connection between the two stages and transform safety evaluation from black-box to white-box insight. Besides, DeepSight is the first open source toolkit that support the frontier AI risk evaluation and joint safety evaluation and diagnosis.

Text-to-image (T2I) diffusion models such as SDXL and FLUX have achieved impressive photorealism, yet small-scale distortions remain pervasive in limbs, face, text and so on. Existing refinement approaches either perform costly iterative re-generation or rely on vision-language models (VLMs) with weak spatial grounding, leading to semantic drift and unreliable local edits. To close this gap, we propose Agentic Retoucher, a hierarchical decision-driven framework that reformulates post-generation correction as a human-like perception-reasoning-action loop. Specifically, we design (1) a perception agent that learns contextual saliency for fine-grained distortion localization under text-image consistency cues, (2) a reasoning agent that performs human-aligned inferential diagnosis via progressive preference alignment, and (3) an action agent that adaptively plans localized inpainting guided by user preference. This design integrates perceptual evidence, linguistic reasoning, and controllable correction into a unified, self-corrective decision process. To enable fine-grained supervision and quantitative evaluation, we further construct GenBlemish-27K, a dataset of 6K T2I images with 27K annotated artifact regions across 12 categories. Extensive experiments demonstrate that Agentic Retoucher consistently outperforms state-of-the-art methods in perceptual quality, distortion localization and human preference alignment, establishing a new paradigm for self-corrective and perceptually reliable T2I generation.

Multimodal large language models (MLLMs) have advanced clinical tasks for common conditions, but their performance on rare diseases remains largely untested. In rare-disease scenarios, clinicians often lack prior clinical knowledge, forcing them to rely strictly on case-level evidence for clinical judgments. Existing benchmarks predominantly evaluate common-condition, single-image settings, leaving multimodal and multi-image evidence integration under rare-disease data scarcity systematically unevaluated. We introduce MMRareBench, to our knowledge the first rare-disease benchmark jointly evaluating multimodal and multi-image clinical capability across four workflow-aligned tracks: diagnosis, treatment planning, cross-image evidence alignment, and examination suggestion. The benchmark comprises 1,756 question-answer pairs with 7,958 associated medical images curated from PMC case reports, with Orphanet-anchored ontology alignment, track-specific leakage control, evidence-grounded annotations, and a two-level evaluation protocol. A systematic evaluation of 23 MLLMs reveals fragmented capability profiles and universally low treatment-planning performance, with medical-domain models trailing general-purpose MLLMs substantially on multi-image tracks despite competitive diagnostic scores. These patterns are consistent with a capacity dilution effect: medical fine-tuning can narrow the diagnostic gap but may erode the compositional multi-image capability that rare-disease evidence integration demands.

As Multimodal Large Language Models (MLLMs) evolve into sophisticated interactive assistants, their reliability depends not only on following instructions but also on validating them. We define Proactive Critique as the model's autonomous ability to identify, analyze and fix faulty user inputs without extra prompts. However, evaluations mainly test models under ideal circumstances or simple refusal behaviors, largely ignoring active error processing. To fill this gap, we propose MMPCBench, a comprehensive framework for evaluating MLLMs' proactive critique competence. It features a fine-grained taxonomy of 4 primary error types spanning 12 subcategories, ranging from cross-modal contradictions to missing visual premises. We adopt a hierarchical evaluation protocol to measure models' error detection, diagnosis and resolution performance, and apply alignment-aware metrics to assess the coherence between internal reasoning and final responses. Tests on 14 mainstream MLLMs show obvious weaknesses in proactive critique, especially in dealing with subtle visual anomalies. Notably, we identify a pervasive "consistency gap": reasoning models can often correctly identify and analyze errors during internal reasoning yet suppress these valid insights in final outputs to prioritize response compliance. The code and data is available at https://github.com/ALIENS32/MMPCBench.

While Diffusion Large Language Models (dLLMs) offer structural advantages for global planning, efficiently verifying that they arrive at correct answers via valid reasoning traces remains a critical challenge. In this work, we propose a geometric perspective: Reasoning on the Manifold. We hypothesize that valid generation trajectories reside as stable attractors on the high-density manifold of the learned distribution, whereas invalid paths exhibit off-manifold drift. To operationalize this, we introduce Bidirectional Manifold Consistency (BMC), a training-free, unsupervised metric that quantifies the stability of the generated sequence through a forward-masking and backward-reconstruction cycle. Empirically, we demonstrate BMC's versatility across the full reasoning lifecycle: (1) in Diagnosis, it serves as a robust discriminator of solution validity without ground truth answer; (2) in Inference, it enables rejection resampling to effectively concentrate computational resources on complex reasoning tasks; and (3) in Alignment, it functions as a dense geometric reward that transforms sparse outcome supervision into fine-grained guidance, empowering models to self-evolve beyond standard baselines. Our results establish intrinsic geometric stability as a robust indicator of correctness for dLLMs.

Dermatological diagnosis represents a complex multimodal challenge that requires integrating visual features with specialized clinical knowledge. While vision-language pretraining (VLP) has advanced medical AI, its effectiveness in dermatology is limited by text length constraints and the lack of structured texts. In this paper, we introduce MAKE, a Multi-Aspect Knowledge-Enhanced vision-language pretraining framework for zero-shot dermatological tasks. Recognizing that comprehensive dermatological descriptions require multiple knowledge aspects that exceed standard text constraints, our framework introduces: (1) a multi-aspect contrastive learning strategy that decomposes clinical narratives into knowledge-enhanced sub-texts through large language models, (2) a fine-grained alignment mechanism that connects subcaptions with diagnostically relevant image features, and (3) a diagnosis-guided weighting scheme that adaptively prioritizes different sub-captions based on clinical significance prior. Through pretraining on 403,563 dermatological image-text pairs collected from education resources, MAKE significantly outperforms state-of-the-art VLP models on eight datasets across zero-shot skin disease classification, concept annotation, and cross-modal retrieval tasks. Our code will be made publicly available at https: //github.com/SiyuanYan1/MAKE.

Deep Research Agents (DRAs) generate citation-rich reports via multi-step search and synthesis, yet existing benchmarks mainly target text-only settings or short-form multimodal QA, missing end-to-end multimodal evidence use. We introduce MMDeepResearch-Bench (MMDR-Bench), a benchmark of 140 expert-crafted tasks across 21 domains, where each task provides an image-text bundle to evaluate multimodal understanding and citation-grounded report generation. Compared to prior setups, MMDR-Bench emphasizes report-style synthesis with explicit evidence use, where models must connect visual artifacts to sourced claims and maintain consistency across narrative, citations, and visual references. We further propose a unified, interpretable evaluation pipeline: Formula-LLM Adaptive Evaluation (FLAE) for report quality, Trustworthy Retrieval-Aligned Citation Evaluation (TRACE) for citation-grounded evidence alignment, and Multimodal Support-Aligned Integrity Check (MOSAIC) for text-visual integrity, each producing fine-grained signals that support error diagnosis beyond a single overall score. Experiments across 25 state-of-the-art models reveal systematic trade-offs between generation quality, citation discipline, and multimodal grounding, highlighting that strong prose alone does not guarantee faithful evidence use and that multimodal integrity remains a key bottleneck for deep research agents.

Medical report generation from X-ray images is a challenging task, particularly in an unpaired setting where paired image-report data is unavailable for training. To address this challenge, we propose a novel model that leverages the available information in two distinct datasets, one comprising reports and the other consisting of images. The core idea of our model revolves around the notion that combining auto-encoding report generation with multi-modal (report-image) alignment can offer a solution. However, the challenge persists regarding how to achieve this alignment when pair correspondence is absent. Our proposed solution involves the use of auxiliary tasks, particularly contrastive learning and classification, to position related images and reports in close proximity to each other. This approach differs from previous methods that rely on pre-processing steps, such as using external information stored in a knowledge graph. Our model, named MedRAT, surpasses previous state-of-the-art methods, demonstrating the feasibility of generating comprehensive medical reports without the need for paired data or external tools.

Existing alignment research is dominated by concerns about safety and preventing harm: safeguards, controllability, and compliance. This paradigm of alignment parallels early psychology's focus on mental illness: necessary but incomplete. What we call Positive Alignment is the development of AI systems that (i) actively support human and ecological flourishing in a pluralistic, polycentric, context-sensitive, and user-authored way while (ii) remaining safe and cooperative. It is a distinct and necessary agenda within AI alignment research. We argue that several existing failures of alignment (e.g., engagement hacking, loss of human autonomy, failures in truth-seeking, low epistemic humility, error correction, lack of diverse viewpoints, and being primarily reactive rather than proactive) may be better addressed through positive alignment, including cultivating virtues and maximizing human flourishing. We highlight a range of challenges, open questions, and technical directions (e.g., data filtering and upsampling, pre- and post-training, evaluations, collaborative value collection) for different phases of the LLM and agents lifecycle. We end with design principles for promoting disagreement and decentralization through contextual grounding, community customization, continual adaptation, and polycentric governance; that is, many legitimate centers of oversight rather than one institutional or moral chokepoint.

Artificial intelligence (AI) shows great potential in assisting radiologists to improve the efficiency and accuracy of medical image interpretation and diagnosis. However, a versatile AI model requires large-scale data and comprehensive annotations, which are often impractical in medical settings. Recent studies leverage radiology reports as a naturally high-quality supervision for medical images, using contrastive language-image pre-training (CLIP) to develop language-informed models for radiological image interpretation. Nonetheless, these approaches typically contrast entire images with reports, neglecting the local associations between imaging regions and report sentences, which may undermine model performance and interoperability. In this paper, we propose a fine-grained vision-language model (fVLM) for anatomy-level CT image interpretation. Specifically, we explicitly match anatomical regions of CT images with corresponding descriptions in radiology reports and perform contrastive pre-training for each anatomy individually. Fine-grained alignment, however, faces considerable false-negative challenges, mainly from the abundance of anatomy-level healthy samples and similarly diseased abnormalities. To tackle this issue, we propose identifying false negatives of both normal and abnormal samples and calibrating contrastive learning from patient-level to disease-aware pairing. We curated the largest CT dataset to date, comprising imaging and report data from 69,086 patients, and conducted a comprehensive evaluation of 54 major and important disease diagnosis tasks across 15 main anatomies. Experimental results demonstrate the substantial potential of fVLM in versatile medical image interpretation. In the zero-shot classification task, we achieved an average AUC of 81.3% on 54 diagnosis tasks, surpassing CLIP and supervised methods by 12.9% and 8.0%, respectively.

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.

Trustworthiness is essential for the precise and interpretable application of artificial intelligence (AI) in medical imaging. Traditionally, precision and interpretability have been addressed as separate tasks, namely medical image analysis and explainable AI, each developing its own models independently. In this study, for the first time, we investigate the development of a unified medical vision-language pre-training model that can achieve both accurate analysis and interpretable understanding of medical images across various modalities. To build the model, we construct MedConcept-23M, a large-scale dataset comprising 23 million medical image-text pairs extracted from 6.2 million scientific articles, enriched with concepts from the Unified Medical Language System (UMLS). Based on MedConcept-23M, we introduce ConceptCLIP, a medical AI model utilizing concept-enhanced contrastive language-image pre-training. The pre-training of ConceptCLIP involves two primary components: image-text alignment learning (IT-Align) and patch-concept alignment learning (PC-Align). This dual alignment strategy enhances the model's capability to associate specific image regions with relevant concepts, thereby improving both the precision of analysis and the interpretability of the AI system. We conducted extensive experiments on 5 diverse types of medical image analysis tasks, spanning 51 subtasks across 10 image modalities, with the broadest range of downstream tasks. The results demonstrate the effectiveness of the proposed vision-language pre-training model. Further explainability analysis across 6 modalities reveals that ConceptCLIP achieves superior performance, underscoring its robust ability to advance explainable AI in medical imaging. These findings highlight ConceptCLIP's capability in promoting trustworthy AI in the field of medicine.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

Vision-language pre-training (VLP) has great potential for developing multifunctional and general medical diagnostic capabilities. However, aligning medical images with a low signal-to-noise ratio (SNR) to reports with a high SNR presents a semantic density gap, leading to visual alignment bias. In this paper, we propose boosting vision semantic density to improve alignment effectiveness. On one hand, we enhance visual semantics through disease-level vision contrastive learning, which strengthens the model's ability to differentiate between normal and abnormal samples for each anatomical structure. On the other hand, we introduce an anatomical normality modeling method to model the distribution of normal samples for each anatomy, leveraging VQ-VAE for reconstructing normal vision embeddings in the latent space. This process amplifies abnormal signals by leveraging distribution shifts in abnormal samples, enhancing the model's perception and discrimination of abnormal attributes. The enhanced visual representation effectively captures the diagnostic-relevant semantics, facilitating more efficient and accurate alignment with the diagnostic report. We conduct extensive experiments on two chest CT datasets, CT-RATE and Rad-ChestCT, and an abdominal CT dataset, MedVL-CT69K, and comprehensively evaluate the diagnosis performance across multiple tasks in the chest and abdominal CT scenarios, achieving state-of-the-art zero-shot performance. Notably, our method achieved an average AUC of 84.9% across 54 diseases in 15 organs, significantly surpassing existing methods. Additionally, we demonstrate the superior transfer learning capabilities of our pre-trained model. Code is available at https://github.com/alibaba-damo-academy/ViSD-Boost.

Electrocardiogram (ECG) plays a foundational role in modern cardiovascular care, enabling non-invasive diagnosis of arrhythmias, myocardial ischemia, and conduction disorders. While machine learning has achieved expert-level performance in ECG interpretation, the development of clinically deployable multimodal AI systems remains constrained, primarily due to the lack of publicly available datasets that simultaneously incorporate raw signals, diagnostic images, and interpretation text. Most existing ECG datasets provide only single-modality data or, at most, dual modalities, making it difficult to build models that can understand and integrate diverse ECG information in real-world settings. To address this gap, we introduce MEETI (MIMIC-IV-Ext ECG-Text-Image), the first large-scale ECG dataset that synchronizes raw waveform data, high-resolution plotted images, and detailed textual interpretations generated by large language models. In addition, MEETI includes beat-level quantitative ECG parameters extracted from each lead, offering structured parameters that support fine-grained analysis and model interpretability. Each MEETI record is aligned across four components: (1) the raw ECG waveform, (2) the corresponding plotted image, (3) extracted feature parameters, and (4) detailed interpretation text. This alignment is achieved using consistent, unique identifiers. This unified structure supports transformer-based multimodal learning and supports fine-grained, interpretable reasoning about cardiac health. By bridging the gap between traditional signal analysis, image-based interpretation, and language-driven understanding, MEETI established a robust foundation for the next generation of explainable, multimodal cardiovascular AI. It offers the research community a comprehensive benchmark for developing and evaluating ECG-based AI systems.

Vision-language pre-training for chest X-rays has made significant strides, primarily by utilizing paired radiographs and radiology reports. However, existing approaches often face challenges in encoding medical knowledge effectively. While radiology reports provide insights into the current disease manifestation, medical definitions (as used by contemporary methods) tend to be overly abstract, creating a gap in knowledge. To address this, we propose DeViDe, a novel transformer-based method that leverages radiographic descriptions from the open web. These descriptions outline general visual characteristics of diseases in radiographs, and when combined with abstract definitions and radiology reports, provide a holistic snapshot of knowledge. DeViDe incorporates three key features for knowledge-augmented vision language alignment: First, a large-language model-based augmentation is employed to homogenise medical knowledge from diverse sources. Second, this knowledge is aligned with image information at various levels of granularity. Third, a novel projection layer is proposed to handle the complexity of aligning each image with multiple descriptions arising in a multi-label setting. In zero-shot settings, DeViDe performs comparably to fully supervised models on external datasets and achieves state-of-the-art results on three large-scale datasets. Additionally, fine-tuning DeViDe on four downstream tasks and six segmentation tasks showcases its superior performance across data from diverse distributions.

AI alignment aims to make AI systems behave in line with human intentions and values. As AI systems grow more capable, so do risks from misalignment. To provide a comprehensive and up-to-date overview of the alignment field, in this survey, we delve into the core concepts, methodology, and practice of alignment. First, we identify four principles as the key objectives of AI alignment: Robustness, Interpretability, Controllability, and Ethicality (RICE). Guided by these four principles, we outline the landscape of current alignment research and decompose them into two key components: forward alignment and backward alignment. The former aims to make AI systems aligned via alignment training, while the latter aims to gain evidence about the systems' alignment and govern them appropriately to avoid exacerbating misalignment risks. On forward alignment, we discuss techniques for learning from feedback and learning under distribution shift. On backward alignment, we discuss assurance techniques and governance practices. We also release and continually update the website (www.alignmentsurvey.com) which features tutorials, collections of papers, blog posts, and other resources.

Alignment faking, where a model behaves aligned with developer policy when monitored but reverts to its own preferences when unobserved, is a concerning yet poorly understood phenomenon, in part because current diagnostic tools remain limited. Prior diagnostics rely on highly toxic and clearly harmful scenarios, causing most models to refuse immediately. As a result, models never deliberate over developer policy, monitoring conditions, or the consequences of non-compliance, making these diagnostics fundamentally unable to detect alignment faking propensity. To support study of this phenomenon, we first introduce VLAF, a diagnostic framework grounded in the hypothesis that alignment faking is most likely when developer policy conflicts with a model's strongly held values. VLAF uses morally unambiguous scenarios to probe this conflict across diverse moral values, bypassing refusal behavior while preserving meaningful deliberative stakes. Using VLAF, we find that alignment faking is substantially more prevalent than previously reported, occurring in models as small as 7B parameters - with olmo2-7b-instruct faking alignment in 37% of cases. Finally, we show that oversight conditions induce activation shifts that lie along a single direction in representation space. This means the behavioral divergence driving alignment faking can be captured by a single contrastive steering vector, which we exploit for lightweight inference-time mitigation. Finally, we exploit this for mitigation that requires no labeled data and minimal computational overhead, achieving relative reductions in alignment faking of 85.8%, 94.0%, and 57.7% on olmo2-7b-instruct, olmo2-13b-instruct, and qwen3-8b respectively.

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.

Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician requests and achieved promising performance. Notably, in a debiased pneumothorax classification task on chest radiographs, where chest drains can act as a major confounder, the system successfully mitigated shortcut learning and nearly halved the model's reliance on chest drains. These findings provide proof of concept that autonomous coding agents may help shift clinical AI development toward a more clinician-driven paradigm, reducing the communication overhead and dependence on specialized AI developers. Although further validation and robustness assessment are needed, this study suggests a promising path toward making clinical AI development more accessible.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

Predicting cancer treatment outcomes requires models that are both accurate and interpretable, particularly in the presence of heterogeneous clinical data. While large language models (LLMs) have shown strong performance in biomedical NLP, they often lack structured reasoning capabilities critical for high-stakes decision support. We present a unified, multi-task learning framework that aligns autoregressive LLMs with clinical reasoning for outcome prediction on the MSK-CHORD dataset. Our models are trained to jointly perform binary survival classification, continuous survival time regression, and natural language rationale generation. We evaluate three alignment strategies: (1) standard supervised fine-tuning (SFT), (2) SFT with Chain-of-Thought (CoT) prompting to elicit step-by-step reasoning, and (3) Group Relative Policy Optimization (GRPO), a reinforcement learning method that aligns model outputs to expert-derived reasoning trajectories. Experiments with LLaMa3-8B and Med42-8B backbones demonstrate that CoT prompting improves F1 by +6.0 and reduces MAE by 12%, while GRPO achieves state-of-the-art interpretability and predictive performance across BLEU, ROUGE, and BERTScore. We further show that existing biomedical LLMs often fail to produce valid reasoning traces due to architectural constraints. Our findings underscore the importance of reasoning-aware alignment in multi-task clinical modeling and set a new benchmark for interpretable, trustworthy LLMs in precision oncology.

Mental health disorders represent a burgeoning global public health challenge. While Large Language Models (LLMs) have demonstrated potential in psychiatric assessment, their clinical utility is severely constrained by benchmarks that lack ecological validity and fine-grained diagnostic supervision. To bridge this gap, we introduce MentalDx Bench, the first benchmark dedicated to disorder-level psychiatric diagnosis within real-world clinical settings. Comprising 712 de-identified electronic health records annotated by board-certified psychiatrists under ICD-11 guidelines, the benchmark covers 76 disorders across 16 diagnostic categories. Evaluation of 18 LLMs reveals a critical paradigm misalignment: strong performance at coarse diagnostic categorization contrasts with systematic failure at disorder-level diagnosis, underscoring a gap between pattern-based modeling and clinical hypothetico-deductive reasoning. In response, we propose MentalSeek-Dx, a medical-specialized LLM trained to internalize this clinical reasoning process through supervised trajectory construction and curriculum-based reinforcement learning. Experiments on MentalDx Bench demonstrate that MentalSeek-Dx achieves state-of-the-art (SOTA) performance with only 14B parameters, establishing a clinically grounded framework for reliable psychiatric diagnosis.

Direct Preference Optimization (DPO) is a principled, scalable alternative to RLHF for aligning large language models from pairwise preferences, but its internal geometric footprint remains undercharacterized, limiting audits, checkpoint comparisons, and failure prediction. We introduce SPINAL (Scaling-law and Preference Integration in Neural Alignment Layers), a diagnostic that measures how alignment reshapes representations across depth by tracing localized structural change layer by layer. Across model families, DPO produces a layerwise calibration effect concentrated in the final decoder blocks (often layers 21-30), where preference gradients most directly affect the next-token distribution. SPINAL encodes each checkpoint as a depth trace over (layer index, contraction score, transport score). The contraction score summarizes how quickly the tail of a layer's spectrum decays (how fast small modes vanish); higher values indicate stronger contraction into fewer effective directions. The transport score summarizes how much the token distribution shifts between adjacent layers using a bounded overlap measure; lower values indicate shorter, smoother steps through representation space. Aligned checkpoints show a late-layer ramp-up in contraction and a smooth reduction in transport, consistent with tightened and stabilized policy mass, while unaligned models trace higher-curvature, more entropic, and geometrically incoherent depth paths. Overall, alignment is geometrically localized: the final layers encode the dominant preference-induced corrections. SPINAL turns this localization into a practical audit signal, quantifying where alignment concentrates, how strongly it manifests, and when it begins to destabilize during training.

Medical imaging analysis plays a critical role in the diagnosis and treatment of various medical conditions. This paper focuses on chest X-ray images and their corresponding radiological reports. It presents a new model that learns a joint X-ray image & report representation. The model is based on a novel alignment scheme between the visual data and the text, which takes into account both local and global information. Furthermore, the model integrates domain-specific information of two types -- lateral images and the consistent visual structure of chest images. Our representation is shown to benefit three types of retrieval tasks: text-image retrieval, class-based retrieval, and phrase-grounding.

Current Vision-Language Models (VLMs) struggle to ground anatomical regions in 3D medical images and reason about them in a step-by-step manner, a key requirement of real-world diagnostic assessment. This ability is essential for aligning model outputs with the diagnostic workflows clinicians use in practice, enabling trustworthy clinician-AI collaboration. Existing 3D datasets provide localization labels, but none support this "grounded reasoning" ability. To address this gap, we introduce 3DReasonKnee, the first 3D grounded reasoning dataset for medical images, which provides 494k high-quality quintuples derived from 7,970 3D knee MRI volumes. Each quintuple includes: (1) the 3D MRI volume, (2) a diagnostic question targeting a specific anatomical region (3) a 3D bounding box localizing the relevant anatomical structures, (4) clinician-generated diagnostic reasoning steps that explicitly detail the 3D reasoning process, and (5) structured severity assessments for the relevant anatomical region. The creation and validation of 3DReasonKnee, involving over 450 hours of expert clinician time for manually segmenting MRIs and generating reasoning chains, ensures its superior quality and clinical relevance. We establish ReasonKnee-Bench to evaluate localization and diagnostic accuracy, providing insight into VLM ability to perform grounding and severity assessment across anatomical regions and diagnostic inquiries. We benchmark five state-of-the-art VLMs, providing baseline performance for ReasonKnee-Bench. By providing this unique resource of expert-annotated 3D reasoning pathways, 3DReasonKnee serves as a repository of orthopedic surgeons' diagnostic expertise and offers a vital testbed for advancing multimodal medical AI systems towards 3D, clinically aligned, localized decision-making capabilities. The dataset can be found in: https://huggingface.co/datasets/rajpurkarlab/3DReasonKnee

Vision-language models (VLMs) often produce chain-of-thought (CoT) explanations that sound plausible yet fail to reflect the underlying decision process, undermining trust in high-stakes clinical use. Existing evaluations rarely catch this misalignment, prioritizing answer accuracy or adherence to formats. We present a clinically grounded framework for chest X-ray visual question answering (VQA) that probes CoT faithfulness via controlled text and image modifications across three axes: clinical fidelity, causal attribution, and confidence calibration. In a reader study (n=4), evaluator-radiologist correlations fall within the observed inter-radiologist range for all axes, with strong alignment for attribution (Kendall's tau_b=0.670), moderate alignment for fidelity (tau_b=0.387), and weak alignment for confidence tone (tau_b=0.091), which we report with caution. Benchmarking six VLMs shows that answer accuracy and explanation quality are decoupled, acknowledging injected cues does not ensure grounding, and text cues shift explanations more than visual cues. While some open-source models match final answer accuracy, proprietary models score higher on attribution (25.0% vs. 1.4%) and often on fidelity (36.1% vs. 31.7%), highlighting deployment risks and the need to evaluate beyond final answer accuracy.

Medical imaging plays a pivotal role in modern healthcare, with computed tomography pulmonary angiography (CTPA) being a critical tool for diagnosing pulmonary embolism and other thoracic conditions. However, the complexity of interpreting CTPA scans and generating accurate radiology reports remains a significant challenge. This paper introduces Abn-BLIP (Abnormality-aligned Bootstrapping Language-Image Pretraining), an advanced diagnosis model designed to align abnormal findings to generate the accuracy and comprehensiveness of radiology reports. By leveraging learnable queries and cross-modal attention mechanisms, our model demonstrates superior performance in detecting abnormalities, reducing missed findings, and generating structured reports compared to existing methods. Our experiments show that Abn-BLIP outperforms state-of-the-art medical vision-language models and 3D report generation methods in both accuracy and clinical relevance. These results highlight the potential of integrating multimodal learning strategies for improving radiology reporting. The source code is available at https://github.com/zzs95/abn-blip.

Empathy requires perspective-taking: empathetic responses require a person to reason about what another has experienced and communicate that understanding in language. However, most NLP approaches to empathy do not explicitly model this alignment process. Here, we introduce a new approach to recognizing alignment in empathetic speech, grounded in Appraisal Theory. We introduce a new dataset of over 9.2K span-level annotations of different types of appraisals of a person's experience and over 3K empathetic alignments between a speaker's and observer's speech. Through computational experiments, we show that these appraisals and alignments can be accurately recognized. In experiments in over 9.2M Reddit conversations, we find that appraisals capture meaningful groupings of behavior but that most responses have minimal alignment. However, we find that mental health professionals engage with substantially more empathetic alignment.

Doctors and patients alike increasingly use Large Language Models (LLMs) to diagnose clinical cases. However, unlike domains such as math or coding, where correctness can be objectively defined by the final answer, medical diagnosis requires both the outcome and the reasoning process to be accurate. Currently, widely used medical benchmarks like MedQA and MMLU assess only accuracy in the final answer, overlooking the quality and faithfulness of the clinical reasoning process. To address this limitation, we introduce MedCaseReasoning, the first open-access dataset for evaluating LLMs on their ability to align with clinician-authored diagnostic reasoning. The dataset includes 14,489 diagnostic question-and-answer cases, each paired with detailed reasoning statements derived from open-access medical case reports. We evaluate state-of-the-art reasoning LLMs on MedCaseReasoning and find significant shortcomings in their diagnoses and reasoning: for instance, the top-performing open-source model, DeepSeek-R1, achieves only 48% 10-shot diagnostic accuracy and mentions only 64% of the clinician reasoning statements (recall). However, we demonstrate that fine-tuning LLMs on the reasoning traces derived from MedCaseReasoning significantly improves diagnostic accuracy and clinical reasoning recall by an average relative gain of 29% and 41%, respectively. The open-source dataset, code, and models are available at https://github.com/kevinwu23/Stanford-MedCaseReasoning.

Alignment is a standard procedure to fine-tune pre-trained large language models (LLMs) to follow natural language instructions and serve as helpful AI assistants. We have observed, however, that the conventional alignment process fails to enhance the factual accuracy of LLMs, and often leads to the generation of more false facts (i.e. hallucination). In this paper, we study how to make the LLM alignment process more factual, by first identifying factors that lead to hallucination in both alignment steps:\ supervised fine-tuning (SFT) and reinforcement learning (RL). In particular, we find that training the LLM on new knowledge or unfamiliar texts can encourage hallucination. This makes SFT less factual as it trains on human labeled data that may be novel to the LLM. Furthermore, reward functions used in standard RL can also encourage hallucination, because it guides the LLM to provide more helpful responses on a diverse set of instructions, often preferring longer and more detailed responses. Based on these observations, we propose factuality-aware alignment, comprised of factuality-aware SFT and factuality-aware RL through direct preference optimization. Experiments show that our proposed factuality-aware alignment guides LLMs to output more factual responses while maintaining instruction-following capability.

The automated generation of imaging reports proves invaluable in alleviating the workload of radiologists. A clinically applicable reports generation algorithm should demonstrate its effectiveness in producing reports that accurately describe radiology findings and attend to patient-specific indications. In this paper, we introduce a novel method, Structural Entities extraction and patient indications Incorporation (SEI) for chest X-ray report generation. Specifically, we employ a structural entities extraction (SEE) approach to eliminate presentation-style vocabulary in reports and improve the quality of factual entity sequences. This reduces the noise in the following cross-modal alignment module by aligning X-ray images with factual entity sequences in reports, thereby enhancing the precision of cross-modal alignment and further aiding the model in gradient-free retrieval of similar historical cases. Subsequently, we propose a cross-modal fusion network to integrate information from X-ray images, similar historical cases, and patient-specific indications. This process allows the text decoder to attend to discriminative features of X-ray images, assimilate historical diagnostic information from similar cases, and understand the examination intention of patients. This, in turn, assists in triggering the text decoder to produce high-quality reports. Experiments conducted on MIMIC-CXR validate the superiority of SEI over state-of-the-art approaches on both natural language generation and clinical efficacy metrics.

Pre-trained audio models excel at detecting acoustic patterns in auscultation sounds but often fail to grasp their clinical significance, limiting their use and performance in diagnostic tasks. To bridge this gap, we introduce AcuLa (Audio-Clinical Understanding via Language Alignment), a lightweight post-training framework that instills semantic understanding into any audio encoder by aligning it with a medical language model, which acts as a "semantic teacher." To enable alignment at scale, we construct a large-scale dataset by leveraging off-the-shelf large language models to translate the rich, structured metadata accompanying existing audio recordings into coherent clinical reports. Our alignment strategy combines a representation-level contrastive objective with a self-supervised modeling, ensuring that the model learns clinical semantics while preserving fine-grained temporal cues. AcuLa achieves state-of-the-art results across 18 diverse cardio-respiratory tasks from 10 different datasets, improving the mean AUROC on classification benchmarks from 0.68 to 0.79 and, on the most challenging COVID-19 cough detection task, boosting the AUROC from 0.55 to 0.89. Our work demonstrates that this audio-language alignment transforms purely acoustic models into clinically-aware diagnostic tools, establishing a novel paradigm for enhancing physiological understanding in audio-based health monitoring.

Learning medical visual representations directly from paired radiology reports has become an emerging topic in representation learning. However, existing medical image-text joint learning methods are limited by instance or local supervision analysis, ignoring disease-level semantic correspondences. In this paper, we present a novel Multi-Granularity Cross-modal Alignment (MGCA) framework for generalized medical visual representation learning by harnessing the naturally exhibited semantic correspondences between medical image and radiology reports at three different levels, i.e., pathological region-level, instance-level, and disease-level. Specifically, we first incorporate the instance-wise alignment module by maximizing the agreement between image-report pairs. Further, for token-wise alignment, we introduce a bidirectional cross-attention strategy to explicitly learn the matching between fine-grained visual tokens and text tokens, followed by contrastive learning to align them. More important, to leverage the high-level inter-subject relationship semantic (e.g., disease) correspondences, we design a novel cross-modal disease-level alignment paradigm to enforce the cross-modal cluster assignment consistency. Extensive experimental results on seven downstream medical image datasets covering image classification, object detection, and semantic segmentation tasks demonstrate the stable and superior performance of our framework.

Rare diseases collectively affect an estimated 3.5% to 5.9% of the population, yet more than 70% of patients are misdiagnosed and many endure years of evaluation before a diagnosis is reached, because early presentations are nonspecific and relevant expertise is scarce and unevenly distributed. Artificial intelligence could provide support, but existing systems address isolated stages of care, overwhelmingly diagnosis. They typically depend on the results of downstream investigations, and they treat the variability between models as noise to be eliminated. Here we present RareLens, a system that supports clinical decision-making across the entire rare disease trajectory by exploiting this variability. When heterogeneous large language models evaluate the same case, they generate divergent but complementary reasoning, which RareLens aligns and calibrates into a single convergent, actionable decision at each stage. Four coordinated modules perform primary-visit risk screening, diagnosis, treatment planning and prognosis. Developed and evaluated on RareBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, at each stage. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external study spanning 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both substantially outperformed unaided physicians. These findings indicate that aligning divergent model reasoning, rather than scaling a single model, offers a generalizable strategy for high-uncertainty clinical decision-making.

Radiologists play a crucial role by translating medical images into medical reports. However, the field faces staffing shortages and increasing workloads. While automated approaches using vision-language models (VLMs) show promise as assistants, they require exceptionally high accuracy. Most current VLMs in radiology rely solely on supervised fine-tuning (SFT). Meanwhile, in the general domain, additional preference fine-tuning has become standard practice. The challenge in radiology lies in the prohibitive cost of obtaining radiologist feedback. We propose a scalable automated preference alignment technique for VLMs in radiology, focusing on chest X-ray (CXR) report generation. Our method leverages publicly available datasets with an LLM-as-a-Judge mechanism, eliminating the need for additional expert radiologist feedback. We evaluate and benchmark five direct alignment algorithms (DAAs). Our results show up to a 57.4% improvement in average GREEN scores, a LLM-based metric for evaluating CXR reports, and a 9.2% increase in an average across six metrics (domain specific and general), compared to the SFT baseline. We study reward overoptimization via length exploitation, with reports lengthening by up to 3.2x. To assess a potential alignment tax, we benchmark on six additional diverse tasks, finding no significant degradations. A reader study involving four board-certified radiologists indicates win rates of up to 0.62 over the SFT baseline, while significantly penalizing verbosity. Our analysis provides actionable insights for the development of VLMs in high-stakes fields like radiology.

Previous research on radiology report generation has made significant progress in terms of increasing the clinical accuracy of generated reports. In this paper, we emphasize another crucial quality that it should possess, i.e., inter-report consistency, which refers to the capability of generating consistent reports for semantically equivalent radiographs. This quality is even of greater significance than the overall report accuracy in terms of ensuring the system's credibility, as a system prone to providing conflicting results would severely erode users' trust. Regrettably, existing approaches struggle to maintain inter-report consistency, exhibiting biases towards common patterns and susceptibility to lesion variants. To address this issue, we propose ICON, which improves the inter-report consistency of radiology report generation. Aiming at enhancing the system's ability to capture the similarities in semantically equivalent lesions, our approach involves first extracting lesions from input images and examining their characteristics. Then, we introduce a lesion-aware mix-up augmentation technique to ensure that the representations of the semantically equivalent lesions align with the same attributes, by linearly interpolating them during the training phase. Extensive experiments on three publicly available chest X-ray datasets verify the effectiveness of our approach, both in terms of improving the consistency and accuracy of the generated reports.

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.

Like a criminal under investigation, Large Language Models (LLMs) might pretend to be aligned while evaluated and misbehave when they have a good opportunity. Can current interpretability methods catch these 'alignment fakers?' To answer this question, we introduce a benchmark that consists of 324 pairs of LLMs fine-tuned to select actions in role-play scenarios. One model in each pair is consistently benign (aligned). The other model misbehaves in scenarios where it is unlikely to be caught (alignment faking). The task is to identify the alignment faking model using only inputs where the two models behave identically. We test five detection strategies, one of which identifies 98% of alignment-fakers.

Vision Language Models (VLMs) are increasingly used for tasks like medical report generation and visual question answering. However, fluent diagnostic text does not guarantee safe visual understanding. In clinical practice, interpretation begins with pre-diagnostic sanity checks: verifying that the input is valid to read (correct modality and anatomy, plausible viewpoint and orientation, and no obvious integrity violations). Existing benchmarks largely assume this step is solved, and therefore miss a critical failure mode: a model can produce plausible narratives even when the input is inconsistent or invalid. We introduce MedObvious, a 1,880-task benchmark that isolates input validation as a set-level consistency capability over small multi-panel image sets: the model must identify whether any panel violates expected coherence. MedObvious spans five progressive tiers, from basic orientation/modality mismatches to clinically motivated anatomy/viewpoint verification and triage-style cues, and includes five evaluation formats to test robustness across interfaces. Evaluating 17 different VLMs, we find that sanity checking remains unreliable: several models hallucinate anomalies on normal (negative-control) inputs, performance degrades when scaling to larger image sets, and measured accuracy varies substantially between multiple-choice and open-ended settings. These results show that pre-diagnostic verification remains unsolved for medical VLMs and should be treated as a distinct, safety-critical capability before deployment.

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.

The development of large-scale image-text pair datasets has significantly advanced self-supervised learning in Vision-Language Processing (VLP). However, directly applying general-domain architectures such as CLIP to medical data presents challenges, particularly in handling negations and addressing the inherent data imbalance of medical datasets. To address these issues, we propose a novel approach that integrates clinically-enhanced dynamic soft labels and medical graphical alignment, thereby improving clinical comprehension and the applicability of contrastive loss in medical contexts. Furthermore, we introduce negation-based hard negatives to deepen the model's understanding of the complexities of clinical language. Our approach is easily integrated into the medical CLIP training pipeline and achieves state-of-the-art performance across multiple tasks, including zero-shot, fine-tuned classification, and report retrieval. To comprehensively evaluate our model's capacity for understanding clinical language, we introduce CXR-Align, a benchmark uniquely designed to evaluate the understanding of negation and clinical information within chest X-ray (CXR) datasets. Experimental results demonstrate that our proposed methods are straightforward to implement and generalize effectively across contrastive learning frameworks, enhancing medical VLP capabilities and advancing clinical language understanding in medical imaging.

Fine-grained visual representations are essential for medical image analysis, particularly when diagnostically relevant evidence is subtle and spatially localized. Modern transformer-based medical vision encoders must therefore learn patch-level representations that are both clinically meaningful and spatially consistent. Without these properties, large vision-language models (LVLMs) operate on an ambiguous visual foundation, limiting their ability to generate clinically reliable and spatially grounded responses. However, existing training strategies for medical vision encoders rarely achieve both objectives. Image-text alignment provides clinically meaningful supervision primarily at the image level, leaving the spatial localization of diagnostic evidence weakly constrained. In contrast, self-supervised learning promotes spatial consistency but lacks the semantic supervision needed to distinguish visually similar yet clinically distinct regions. To address this gap, we present LoFi, a medical vision foundation model built on location-aware fine-grained representation learning. LoFi trains a vision encoder with a lightweight large language model under grounding and grounded captioning objectives. Because these objectives require predicting location from clinical text and vice versa, spatial consistency emerges without any explicit patch-level regularization. To enable training at scale, we construct MedG, a large-scale medical grounding dataset of 4.48M image-text-box triplets curated from 84 datasets spanning 7 modalities. Across phrase grounding, visual question answering, and region-based organ classification under perturbations, LoFi consistently outperforms general-purpose and medical vision foundation models as well as state-of-the-art LVLMs. Code is available at https://github.com/myeongkyunkang/lofi-medg.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

Medical vision-language models (VLMs) have shown increasing potential for radiological image interpretation. Medical VLMs encode radiological images into visual representations that capture both anatomical and phenotypic information for diagnosis. Existing approaches improve pathological phenotype representations through semantic-guided representation alignment. However, pathological phenotypes arise as lesion-specific visual changes superimposed on underlying normal anatomy. Such semantic alignment approaches fail to model the phenotype-specific increment relative to the corresponding normal anatomical representation. To address this gap, we propose ΔRepresentation, a visual phenotype representation learning framework based on counterfactual reasoning for medical VLMs. It comprises BaseAnatomy, a geometry-supervised representation learning module, and ΔPhenotype, a counterfactual incremental representation learning module. BaseAnatomy provides fine-grained geometric supervision through spatial relationships across and within anatomical structures. ΔPhenotype computes the representation increment between lesion representations and their corresponding normal anatomical representations, and supervises increments associated with the same phenotype to cluster in the representation space. Experiments on ReXGroundingCT and LIDC-IDRI demonstrate that ΔRepresentation effectively structures pathological phenotype representations and improves lesion grounding and phenotype characterization accuracy in medical VLMs. Code is available at https://anonymous.4open.science/r/deltarep-CF6D.

The latest breakthroughs in large vision-language models, such as Bard and GPT-4, have showcased extraordinary abilities in performing a wide range of tasks. Such models are trained on massive datasets comprising billions of public image-text pairs with diverse tasks. However, their performance on task-specific domains, such as radiology, is still under-investigated and potentially limited due to a lack of sophistication in understanding biomedical images. On the other hand, conversational medical models have exhibited remarkable success but have mainly focused on text-based analysis. In this paper, we introduce XrayGPT, a novel conversational medical vision-language model that can analyze and answer open-ended questions about chest radiographs. Specifically, we align both medical visual encoder (MedClip) with a fine-tuned large language model (Vicuna), using a simple linear transformation. This alignment enables our model to possess exceptional visual conversation abilities, grounded in a deep understanding of radiographs and medical domain knowledge. To enhance the performance of LLMs in the medical context, we generate ~217k interactive and high-quality summaries from free-text radiology reports. These summaries serve to enhance the performance of LLMs through the fine-tuning process. Our approach opens up new avenues the research for advancing the automated analysis of chest radiographs. Our open-source demos, models, and instruction sets are available at: https://github.com/mbzuai-oryx/XrayGPT.

The alignment of Large Language Models (LLMs) with human values is central to their safe deployment, yet current practice produces static, brittle, and costly-to-maintain models that fail to keep pace with evolving norms and policies. This misalignment, which we term the Alignment-Reality Gap, poses a growing challenge for reliable long-term use. Existing remedies are inadequate: large-scale re-annotation is economically prohibitive, and standard unlearning methods act as blunt instruments that erode utility rather than enable precise policy updates. We introduce TRACE (Triage and Re-align by Alignment Conflict Evaluation), a framework for principled unlearning that reconceives re-alignment as a programmatic policy application problem. TRACE programmatically triages existing preference data against a new policy, identifies high-impact conflicts via a alignment impact score, and applies a hybrid optimization that cleanly inverts, discards, or preserves preferences while safeguarding model performance. Empirical results show that TRACE achieves robust re-alignment across diverse model families (Qwen2.5-7B, Gemma-2-9B, Llama-3.1-8B). On both synthetic benchmarks and the PKU-SafeRLHF dataset under complex policy shift, TRACE enforces new principles without degrading general capabilities. Our work establishes a scalable, dynamic, and cost-effective paradigm for maintaining LLM alignment, providing a foundation for sustainable and responsible AI deployment.

Most existing LLM diagnoses are evaluated on static, single-turn settings where complete patient information is provided upfront, an oversimplification of real clinical practice. We study active diagnosis: the real-life clinical process of starting from initial observation, ordering tests, interpreting results, and updating a differential diagnosis across multiple turns. Through systematic analysis, we identify three recurring failure modes in current LLMs: ungrounded test ordering, unreliable diagnostic update, and degraded multi-turn coherence. Together, these failures reveal a core deficit: existing medical training data teaches models to reason from complete information but not to act under evolving, partial evidence. To address this gap, we introduce MedAction, a tree-structured distillation pipeline that synthesizes diverse and high-quality multi-turn diagnostic trajectories via LLM-environment interaction. We propose two knowledge-graph-grounded metrics to filter trajectory quality: Disease Trajectory Consistency (DTC), which tracks whether the model's hypothesis converges toward the correct diagnosis, and Reasoning-Action Consistency (RAC), which verifies that belief updates are driven by gathered evidence. Using this pipeline, we construct MedAction-32K, a dataset of 32,681 trajectories from 2,896 PMC cases. Fine-tuning an 8B model on MedAction-32K achieves state-of-the-art performance among open-source models on both MedR-Bench and our curated MedAction-300-Hard benchmark, pushing the edge for open-source medical LLMs.

Traditionally, AI research in medical diagnosis has largely centered on image analysis. While this has led to notable advancements, the absence of patient-reported symptoms continues to hinder diagnostic accuracy. To address this, we propose a Pre-Consultation Dialogue Framework (PCDF) that mimics real-world diagnostic procedures, where doctors iteratively query patients before reaching a conclusion. Specifically, we simulate diagnostic dialogues between two vision-language models (VLMs): a DocVLM, which generates follow-up questions based on the image and dialogue history, and a PatientVLM, which responds using a symptom profile derived from the ground-truth diagnosis. We additionally conducted a small-scale clinical validation of the synthetic symptoms generated by our framework, with licensed clinicians confirming their clinical relevance, symptom coverage, and overall realism. These findings indicate that the resulting DocVLM-PatientVLM interactions form coherent, multi-turn consultations paired with images and diagnoses, which we then use to fine-tune the DocVLM. This dialogue-based supervision leads to substantial gains over image-only training, highlighting the value of realistic symptom elicitation for diagnosis.

Medical imaging plays a significant role in clinical practice of medical diagnosis, where the text reports of the images are essential in understanding them and facilitating later treatments. By generating the reports automatically, it is beneficial to help lighten the burden of radiologists and significantly promote clinical automation, which already attracts much attention in applying artificial intelligence to medical domain. Previous studies mainly follow the encoder-decoder paradigm and focus on the aspect of text generation, with few studies considering the importance of cross-modal mappings and explicitly exploit such mappings to facilitate radiology report generation. In this paper, we propose a cross-modal memory networks (CMN) to enhance the encoder-decoder framework for radiology report generation, where a shared memory is designed to record the alignment between images and texts so as to facilitate the interaction and generation across modalities. Experimental results illustrate the effectiveness of our proposed model, where state-of-the-art performance is achieved on two widely used benchmark datasets, i.e., IU X-Ray and MIMIC-CXR. Further analyses also prove that our model is able to better align information from radiology images and texts so as to help generating more accurate reports in terms of clinical indicators.

Feature-based methods are commonly used to explain model predictions, but these methods often implicitly assume that interpretable features are readily available. However, this is often not the case for high-dimensional data, and it can be hard even for domain experts to mathematically specify which features are important. Can we instead automatically extract collections or groups of features that are aligned with expert knowledge? To address this gap, we present FIX (Features Interpretable to eXperts), a benchmark for measuring how well a collection of features aligns with expert knowledge. In collaboration with domain experts, we propose FIXScore, a unified expert alignment measure applicable to diverse real-world settings across cosmology, psychology, and medicine domains in vision, language and time series data modalities. With FIXScore, we find that popular feature-based explanation methods have poor alignment with expert-specified knowledge, highlighting the need for new methods that can better identify features interpretable to experts.

Accurate disease interpretation from radiology remains challenging due to imaging heterogeneity. Achieving expert-level diagnostic decisions requires integration of subtle image features with clinical knowledge. Yet major vision-language models (VLMs) treat images as holistic entities and overlook fine-grained image details that are vital for disease diagnosis. Clinicians analyze images by utilizing their prior medical knowledge and identify anatomical structures as important region of interests (ROIs). Inspired from this human-centric workflow, we introduce Anatomy-VLM, a fine-grained, vision-language model that incorporates multi-scale information. First, we design a model encoder to localize key anatomical features from entire medical images. Second, these regions are enriched with structured knowledge for contextually-aware interpretation. Finally, the model encoder aligns multi-scale medical information to generate clinically-interpretable disease prediction. Anatomy-VLM achieves outstanding performance on both in- and out-of-distribution datasets. We also validate the performance of Anatomy-VLM on downstream image segmentation tasks, suggesting that its fine-grained alignment captures anatomical and pathology-related knowledge. Furthermore, the Anatomy-VLM's encoder facilitates zero-shot anatomy-wise interpretation, providing its strong expert-level clinical interpretation capabilities.

The integration of large language models (LLMs) into medical practice holds transformative potential, yet their real-world clinical utility remains limited by critical alignment challenges: (1) a disconnect between static evaluation benchmarks and dynamic clinical cognitive needs, (2) difficulties in adapting to evolving, multi-source medical standards, and (3) the inability of conventional reward models to capture nuanced, multi-dimensional medical quality criteria. To address these gaps, we propose MR-RML (Multidimensional Rubric-oriented Reward Model Learning) via GPRC (Geometric Projection Reference Constraints), a novel alignment framework that integrates medical standards into a structured "Dimensions-Scenarios-Disciplines" matrix to guide data generation and model optimization. MR-RML introduces three core innovations: (1) a "Dimensions-Scenarios-Disciplines" medical standard system that embeds domain standards into the full training pipeline; (2) an independent multi-dimensional reward model that decomposes evaluation criteria, shifting from real-time rubric-based scoring to internalized reward modeling for improved consistency and cost-efficiency; (3) geometric projection reference constraints that transform medical cognitive logic into mathematical regularization, aligning scoring gradients with clinical reasoning and enabling synthetic data-driven training. Through extensive evaluations on the authoritative medical benchmark Healthbench, our method yields substantial performance gains over the base LLM Qwen-32B (45% on the full subset and 85% on Hard subset, respectively). It achieves a SOTA among open-source LLMs with scores of 62.7 (full subset) and 44.7 (hard subset), while also outperforming the majority of closed-source models.

Most clinical benchmarks evaluate language models (LMs) on diagnosis using complete case descriptions. In clinical practice, however, patients present information in different ways, and clinicians must obtain relevant history and determine which examinations are needed before reaching a diagnosis. Diagnostic accuracy alone therefore cannot establish whether an agent gathered essential information or conducted an appropriate clinical assessment. Furthermore, existing benchmarks lack professional clinicians' verification. To address this gap, we introduce KlinikeBench, a benchmark of 333 clinician-authored tasks, each providing an isolated sandbox environment with a virtual patient, clinical tools, and task-specific success criteria. More than 35 clinicians contributed to case authoring and benchmark evaluation. In an empirical study, clinicians gave simulated dialogues higher mean quality ratings than reference conversations, which is adapted from real conversation. In each task, an LM has a fixed budget of turns to communicate with the patient, ask about relevant history, request examinations, follow action constraints, and record a final diagnosis. We score these steps separately as well as together. Across 31 models and seven model families, the best-performing models (e.g., GPT-6-astra and Claude Opus 5) succeed on less than 30% of tasks, even though their diagnosis accuracy reaches 90.7%. Some models benefit from talking with the patient; others diagnose well from a complete chart but perform much worse in conversation. Overall, KlinikeBench provides a testbed for evaluating the full clinical encounter and reveals a substantial gap between diagnostic accuracy and performance in interactive clinical assessment.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

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.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

Supervised synthetic CT generation from CBCT requires registered training pairs, yet perfect registration between separately acquired scans remains unattainable. This registration bias propagates into trained models and corrupts standard evaluation metrics. This may suggest that superior benchmark performance indicates better reproduction of registration artifacts rather than anatomical fidelity. We propose physics-based CBCT simulation to provide geometrically aligned training pairs by construction, combined with evaluation using geometric alignment metrics against input CBCT rather than biased ground truth. On two independent pelvic datasets, models trained on synthetic data achieved superior geometric alignment (Normalized Mutual Information: 0.31 vs 0.22) despite lower conventional intensity scores. Intensity metrics showed inverted correlations with clinical assessment for deformably registered data, while Normalized Mutual Information consistently predicted observer preference across registration methodologies (rho = 0.31, p < 0.001). Clinical observers preferred synthetic-trained outputs in 87% of cases, demonstrating that geometric fidelity, not intensity agreement with biased ground truth, aligns with clinical requirements.

Big models, exemplified by Large Language Models (LLMs), are models typically pre-trained on massive data and comprised of enormous parameters, which not only obtain significantly improved performance across diverse tasks but also present emergent capabilities absent in smaller models. However, the growing intertwining of big models with everyday human lives poses potential risks and might cause serious social harm. Therefore, many efforts have been made to align LLMs with humans to make them better follow user instructions and satisfy human preferences. Nevertheless, `what to align with' has not been fully discussed, and inappropriate alignment goals might even backfire. In this paper, we conduct a comprehensive survey of different alignment goals in existing work and trace their evolution paths to help identify the most essential goal. Particularly, we investigate related works from two perspectives: the definition of alignment goals and alignment evaluation. Our analysis encompasses three distinct levels of alignment goals and reveals a goal transformation from fundamental abilities to value orientation, indicating the potential of intrinsic human values as the alignment goal for enhanced LLMs. Based on such results, we further discuss the challenges of achieving such intrinsic value alignment and provide a collection of available resources for future research on the alignment of big models.

This large scale study focuses on quantifying what X-rays diagnostic prediction tasks generalize well across multiple different datasets. We present evidence that the issue of generalization is not due to a shift in the images but instead a shift in the labels. We study the cross-domain performance, agreement between models, and model representations. We find interesting discrepancies between performance and agreement where models which both achieve good performance disagree in their predictions as well as models which agree yet achieve poor performance. We also test for concept similarity by regularizing a network to group tasks across multiple datasets together and observe variation across the tasks. All code is made available online and data is publicly available: https://github.com/mlmed/torchxrayvision

Radiologic diagnostic errors-under-reading errors, inattentional blindness, and communication failures-remain prevalent in clinical practice. These issues often stem from missed localized abnormalities, limited global context, and variability in report language. These challenges are amplified in 3D imaging, where clinicians must examine hundreds of slices per scan. Addressing them requires systems with precise localized detection, global volume-level reasoning, and semantically consistent natural language reporting. However, existing 3D vision-language models are unable to meet all three needs jointly, lacking local-global understanding for spatial reasoning and struggling with the variability and noise of uncurated radiology reports. We present MedVista3D, a multi-scale semantic-enriched vision-language pretraining framework for 3D CT analysis. To enable joint disease detection and holistic interpretation, MedVista3D performs local and global image-text alignment for fine-grained representation learning within full-volume context. To address report variability, we apply language model rewrites and introduce a Radiology Semantic Matching Bank for semantics-aware alignment. MedVista3D achieves state-of-the-art performance on zero-shot disease classification, report retrieval, and medical visual question answering, while transferring well to organ segmentation and prognosis prediction. Code and datasets will be released.

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

Inpatient clinical reasoning is a sequential decision under partial observability: the clinician sees the admission so far and must choose the next action whose downstream consequences are not yet visible. Existing clinical-LLM evaluations and RL rewards signals collapse this into closed-form retrieval, clinical journey leakage, or unanchored LLM-as-judge scoring. We introduce CLR-voyance, a framework that reformulates inpatient reasoning as a Partially Observable Markov Decision Process (POMDP) and supervises it with rewards that are simultaneously outcome-grounded and clinician-validated. We instantiate the formulation as CLR-POMDP, which partitions successful patient journeys into a policy-visible past and an oracle-only future. Using the past information, an oracle LLM generates a case-specific query-answer pair, and the first adaptive rubric for clinical reasoning which is verifiable in the future of the patient journey. These rubrics are used for both post-training and evaluation of models for inpatient clinical reasoning. We post-train Qwen3-8B and MedGemma-4B with GRPO followed by model merging, yielding state-of-the-art inpatient clinical reasoning while retaining generalist capabilities. CLR-voyance-8B achieves 84.91% on CLR-POMDP, ahead of frontier medical reasoning models like GPT-5 (77.83%) and MedGemma-27B (66.66%) and has comparable or better performance on existing medical benchmarks. To ensure a clinically meaningful setting, we conduct a large-scale clinician alignment study, where physicians curate per-case rubrics, grade candidate responses, and provide blinded pairwise preferences of model reasoning. This study provides insights on clinical LLM-as-a-judge and clinical preference-model selection, which can inform the community at large. CLR-voyance has been deployed for 6+ months at a partner public hospital, drafting thousands of reasoning-heavy inpatient notes.

Automated diagnosis prediction from medical images is a valuable resource to support clinical decision-making. However, such systems usually need to be trained on large amounts of annotated data, which often is scarce in the medical domain. Zero-shot methods address this challenge by allowing a flexible adaption to new settings with different clinical findings without relying on labeled data. Further, to integrate automated diagnosis in the clinical workflow, methods should be transparent and explainable, increasing medical professionals' trust and facilitating correctness verification. In this work, we introduce Xplainer, a novel framework for explainable zero-shot diagnosis in the clinical setting. Xplainer adapts the classification-by-description approach of contrastive vision-language models to the multi-label medical diagnosis task. Specifically, instead of directly predicting a diagnosis, we prompt the model to classify the existence of descriptive observations, which a radiologist would look for on an X-Ray scan, and use the descriptor probabilities to estimate the likelihood of a diagnosis. Our model is explainable by design, as the final diagnosis prediction is directly based on the prediction of the underlying descriptors. We evaluate Xplainer on two chest X-ray datasets, CheXpert and ChestX-ray14, and demonstrate its effectiveness in improving the performance and explainability of zero-shot diagnosis. Our results suggest that Xplainer provides a more detailed understanding of the decision-making process and can be a valuable tool for clinical diagnosis.

Unstructured clinical notes contain essential patient information but are challenging for physicians to search and interpret efficiently. Although large language models (LLMs) have shown promise in question answering (QA), most existing systems lack transparency, usability, and alignment with clinical workflows. This work introduces an interactive QA system that enables physicians to query clinical notes via text or voice and receive extractive answers highlighted directly in the note for traceability. The system was built using OpenAI models with zero-shot prompting and evaluated across multiple metrics, including exact string match, word overlap, SentenceTransformer similarity, and BERTScore. Results show that while exact match scores ranged from 47 to 62 percent, semantic similarity scores exceeded 87 percent, indicating strong contextual alignment even when wording varied. To assess usability, the system was also evaluated using simulated clinical personas. Seven diverse physician and nurse personas interacted with the system across scenario-based tasks and provided structured feedback. The evaluations highlighted strengths in intuitive design and answer accessibility, alongside opportunities for enhancing explanation clarity.

Motion artefacts in magnetic resonance brain images can have a strong impact on diagnostic confidence. The assessment of MR image quality is fundamental before proceeding with the clinical diagnosis. Motion artefacts can alter the delineation of structures such as the brain, lesions or tumours and may require a repeat scan. Otherwise, an inaccurate (e.g. correct pathology but wrong severity) or incorrect diagnosis (e.g. wrong pathology) may occur. "Image quality assessment" as a fast, automated step right after scanning can assist in deciding if the acquired images are diagnostically sufficient. An automated image quality assessment based on the structural similarity index (SSIM) regression through a residual neural network is proposed in this work. Additionally, a classification into different groups - by subdividing with SSIM ranges - is evaluated. Importantly, this method predicts SSIM values of an input image in the absence of a reference ground truth image. The networks were able to detect motion artefacts, and the best performance for the regression and classification task has always been achieved with ResNet-18 with contrast augmentation. The mean and standard deviation of residuals' distribution were mu=-0.0009 and sigma=0.0139, respectively. Whilst for the classification task in 3, 5 and 10 classes, the best accuracies were 97, 95 and 89\%, respectively. The results show that the proposed method could be a tool for supporting neuro-radiologists and radiographers in evaluating image quality quickly.

As the field of artificial intelligence progresses, assistive technologies are becoming more widely used across all industries. The healthcare industry is no different, with numerous studies being done to develop assistive tools for healthcare professionals. Automatic diagnostic systems are one such beneficial tool that can assist with a variety of tasks, including collecting patient information, analyzing test results, and diagnosing patients. However, the idea of developing systems that can provide a differential diagnosis has been largely overlooked in most of these research studies. In this study, we propose a transformer-based approach for providing differential diagnoses based on a patient's age, sex, medical history, and symptoms. We use the DDXPlus dataset, which provides differential diagnosis information for patients based on 49 disease types. Firstly, we propose a method to process the tabular patient data from the dataset and engineer them into patient reports to make them suitable for our research. In addition, we introduce two data modification modules to diversify the training data and consequently improve the robustness of the models. We approach the task as a multi-label classification problem and conduct extensive experiments using four transformer models. All the models displayed promising results by achieving over 97% F1 score on the held-out test set. Moreover, we design additional behavioral tests to get a broader understanding of the models. In particular, for one of our test cases, we prepared a custom test set of 100 samples with the assistance of a doctor. The results on the custom set showed that our proposed data modification modules improved the model's generalization capabilities. We hope our findings will provide future researchers with valuable insights and inspire them to develop reliable systems for automatic differential diagnosis.

In AI alignment, extensive latitude must be granted to annotators, either human or algorithmic, to judge which model outputs are `better' or `safer.' We refer to this latitude as alignment discretion. Such discretion remains largely unexamined, posing two risks: (i) annotators may use their power of discretion arbitrarily, and (ii) models may fail to mimic this discretion. To study this phenomenon, we draw on legal concepts of discretion that structure how decision-making authority is conferred and exercised, particularly in cases where principles conflict or their application is unclear or irrelevant. Extended to AI alignment, discretion is required when alignment principles and rules are (inevitably) conflicting or indecisive. We present a set of metrics to systematically analyze when and how discretion in AI alignment is exercised, such that both risks (i) and (ii) can be observed. Moreover, we distinguish between human and algorithmic discretion and analyze the discrepancy between them. By measuring both human and algorithmic discretion over safety alignment datasets, we reveal layers of discretion in the alignment process that were previously unaccounted for. Furthermore, we demonstrate how algorithms trained on these datasets develop their own forms of discretion in interpreting and applying these principles, which challenges the purpose of having any principles at all. Our paper presents the first step towards formalizing this core gap in current alignment processes, and we call on the community to further scrutinize and control alignment discretion.

Vietnamese medical research has become an increasingly vital domain, particularly with the rise of intelligent technologies aimed at reducing time and resource burdens in clinical diagnosis. Recent advances in vision-language models (VLMs), such as Gemini and GPT-4V, have sparked a growing interest in applying AI to healthcare. However, most existing VLMs lack exposure to Vietnamese medical data, limiting their ability to generate accurate and contextually appropriate diagnostic outputs for Vietnamese patients. To address this challenge, we introduce ViX-Ray, a novel dataset comprising 5,400 Vietnamese chest X-ray images annotated with expert-written findings and impressions from physicians at a major Vietnamese hospital. We analyze linguistic patterns within the dataset, including the frequency of mentioned body parts and diagnoses, to identify domain-specific linguistic characteristics of Vietnamese radiology reports. Furthermore, we fine-tune five state-of-the-art open-source VLMs on ViX-Ray and compare their performance to leading proprietary models, GPT-4V and Gemini. Our results show that while several models generate outputs partially aligned with clinical ground truths, they often suffer from low precision and excessive hallucination, especially in impression generation. These findings not only demonstrate the complexity and challenge of our dataset but also establish ViX-Ray as a valuable benchmark for evaluating and advancing vision-language models in the Vietnamese clinical domain.

Pulmonary embolism (PE) is a life-threatening condition where rapid and accurate diagnosis is imperative yet difficult due to predominantly atypical symptomatology. Computed tomography pulmonary angiography (CTPA) is acknowledged as the gold standard imaging tool in clinics, yet it can be contraindicated for emergency department (ED) patients and represents an onerous procedure, thus necessitating PE identification through non-contrast CT (NCT) scans. In this work, we explore the feasibility of applying a deep-learning approach to NCT scans for PE identification. We propose a novel Cross-Phase Mutual learNing framework (CPMN) that fosters knowledge transfer from CTPA to NCT, while concurrently conducting embolism segmentation and abnormality classification in a multi-task manner. The proposed CPMN leverages the Inter-Feature Alignment (IFA) strategy that enhances spatial contiguity and mutual learning between the dual-pathway network, while the Intra-Feature Discrepancy (IFD) strategy can facilitate precise segmentation of PE against complex backgrounds for single-pathway networks. For a comprehensive assessment of the proposed approach, a large-scale dual-phase dataset containing 334 PE patients and 1,105 normal subjects has been established. Experimental results demonstrate that CPMN achieves the leading identification performance, which is 95.4\% and 99.6\% in patient-level sensitivity and specificity on NCT scans, indicating the potential of our approach as an economical, accessible, and precise tool for PE identification in clinical practice.

Medical vision-language pre-training shows great potential in learning representative features from massive paired radiographs and reports. However, in computed tomography (CT) scans, the distribution of lesions which contain intricate structures is characterized by spatial sparsity. Besides, the complex and implicit relationships between different pathological descriptions in each sentence of the report and their corresponding sub-regions in radiographs pose additional challenges. In this paper, we propose a Similarity-Driven Cross-Granularity Pre-training (SimCroP) framework on chest CTs, which combines similarity-driven alignment and cross-granularity fusion to improve radiograph interpretation. We first leverage multi-modal masked modeling to optimize the encoder for understanding precise low-level semantics from radiographs. Then, similarity-driven alignment is designed to pre-train the encoder to adaptively select and align the correct patches corresponding to each sentence in reports. The cross-granularity fusion module integrates multimodal information across instance level and word-patch level, which helps the model better capture key pathology structures in sparse radiographs, resulting in improved performance for multi-scale downstream tasks. SimCroP is pre-trained on a large-scale paired CT-reports dataset and validated on image classification and segmentation tasks across five public datasets. Experimental results demonstrate that SimCroP outperforms both cutting-edge medical self-supervised learning methods and medical vision-language pre-training methods. Codes and models are available at https://github.com/ToniChopp/SimCroP.

Medical report generation has achieved remarkable advancements yet has still been faced with several challenges. First, the inherent imbalance in the distribution of normal and abnormal cases may lead models to exhibit a biased focus on normal samples, resulting in unreliable diagnoses. Second, the frequent occurrence of common template sentences in the reports may overwhelm the critical abnormal information. Moreover, existing works focus on 2D chest X-rays, leaving CT report generation underexplored due to the high-dimensional nature of CT images and the limited availability of CT-report pairs. Recently, LLM has shown a great ability to generate reliable answers with appropriate prompts, which shed light on addressing the aforementioned challenges. In this paper, we propose Dia-LLaMA, a framework to adapt the LLaMA2-7B for CT report generation by incorporating diagnostic information as guidance prompts. Considering the high dimension of CT, we leverage a pre-trained ViT3D with perceiver to extract the visual information. To tailor the LLM for report generation and emphasize abnormality, we extract additional diagnostic information by referring to a disease prototype memory bank, which is updated during training to capture common disease representations. Furthermore, we introduce disease-aware attention to enable the model to adjust attention for different diseases. Experiments on the chest CT dataset demonstrated that our proposed method outperformed previous methods and achieved state-of-the-art on both clinical efficacy performance and natural language generation metrics. The code will be made publically available.

The application of Large Language Models (LLMs) to diagnostic decision-making has garnered growing interest. However, existing benchmarks largely focus on textual reasoning or isolated visual question-answering (VQA) tasks, lacking holistic integration of clinical narratives and medical imaging, and thus failing to assess the multimodal diagnostic synthesis capability central to expert clinical judgment. To bridge this gap, we introduce MedReaMM, a benchmark specifically designed to evaluate models' ability to synthesize heterogeneous clinical evidence consisting of detailed patient histories alongside multiple medical images into accurate differential diagnoses under a complete-information paradigm. Constructed from case reports sourced from top-tier medical journals and curated clinical case databases, MedReaMM comprises 625 expert-validated cases with an average of 2.79 medical images per case and a total of 1,042 standardized diagnoses annotated with ICD-11 codes. These cases predominantly represent rare, atypical, or multi-system presentations that demand expert-level evidence integration beyond routine pattern recognition. We evaluate 23 Large Multimodal Models (LMMs) and find that most achieve diagnostic accuracy scores below 50%, underscoring a substantial gap in multimodal diagnostic synthesis capability. Further analysis reveals that medical knowledge proficiency, medical image understanding, and evidence integration are all highly correlated with diagnostic performance.

Chain-of-Thought (CoT) reasoning has proven effective in enhancing large language models by encouraging step-by-step intermediate reasoning, and recent advances have extended this paradigm to Multimodal Large Language Models (MLLMs). In the medical domain, where diagnostic decisions depend on nuanced visual cues and sequential reasoning, CoT aligns naturally with clinical thinking processes. However, Current benchmarks for medical image understanding generally focus on the final answer while ignoring the reasoning path. An opaque process lacks reliable bases for judgment, making it difficult to assist doctors in diagnosis. To address this gap, we introduce a new M3CoTBench benchmark specifically designed to evaluate the correctness, efficiency, impact, and consistency of CoT reasoning in medical image understanding. M3CoTBench features 1) a diverse, multi-level difficulty dataset covering 24 examination types, 2) 13 varying-difficulty tasks, 3) a suite of CoT-specific evaluation metrics (correctness, efficiency, impact, and consistency) tailored to clinical reasoning, and 4) a performance analysis of multiple MLLMs. M3CoTBench systematically evaluates CoT reasoning across diverse medical imaging tasks, revealing current limitations of MLLMs in generating reliable and clinically interpretable reasoning, and aims to foster the development of transparent, trustworthy, and diagnostically accurate AI systems for healthcare. Project page at https://juntaojianggavin.github.io/projects/M3CoTBench/.

Large-scale multi-modal deep learning models have revolutionized domains such as healthcare, highlighting the importance of computational power. However, in resource-constrained regions like Low and Middle-Income Countries (LMICs), limited access to GPUs and data poses significant challenges, often leaving CPUs as the sole resource. To address this, we advocate for leveraging vector embeddings to enable flexible and efficient computational methodologies, democratizing multimodal deep learning across diverse contexts. Our paper investigates the efficiency and effectiveness of using vector embeddings from single-modal foundation models and multi-modal Vision-Language Models (VLMs) for multimodal deep learning in low-resource environments, particularly in healthcare. Additionally, we propose a simple yet effective inference-time method to enhance performance by aligning image-text embeddings. Comparing these approaches with traditional methods, we assess their impact on computational efficiency and model performance using metrics like accuracy, F1-score, inference time, training time, and memory usage across three medical modalities: BRSET (ophthalmology), HAM10000 (dermatology), and SatelliteBench (public health). Our findings show that embeddings reduce computational demands without compromising model performance. Furthermore, our alignment method improves performance in medical tasks. This research promotes sustainable AI practices by optimizing resources in constrained environments, highlighting the potential of embedding-based approaches for efficient multimodal learning. Vector embeddings democratize multimodal deep learning in LMICs, particularly in healthcare, enhancing AI adaptability in varied use cases.

Combining pretrained models is a common strategy for building AI systems, whether by aligning a vision encoder with a language model or merging fine-tuned checkpoints. However, finding compatible pairs typically requires costly empirical search, as compatibility is known only after alignment or merging. We propose COMPASS (COMPatibility ASsessment Score), a theoretically motivated diagnostic that estimates whether a model pair will be compatible prior to alignment or merging. Building on the observation that representational convergence is most robust at the level of local neighborhoods, COMPASS decomposes model compatibility into two cheap-to-compute axes: a pair-specific ease, defined as the k-NN overlap between the two encoders, and a paradigm-level ceiling, capturing the maximum overlap their training paradigms allow. Together, these two axes provide a ranking of candidate model pairs and prescribe how to act on each pair: (i) prioritize pairs that already agree and whose paradigms are compatible, (ii) invest additional compute on pairs with compatible paradigms but low initial agreement, (iii) switch the pretraining paradigm when it cannot support sufficient agreement, or (iv) deprioritize pairs that score poorly on both axes. We apply COMPASS to 72 cross-modal alignment experiments and 392 task-arithmetic model merges and show that compatibility estimates by COMPASS strongly correlate with downstream success, achieving average Pearson correlation of 0.91 on cross-modal alignment tasks and 0.70 on model merging.

Mental disorders are highly prevalent worldwide, but the shortage of psychiatrists and the inherent subjectivity of interview-based diagnosis create substantial barriers to timely and consistent mental-health assessment. Progress in AI-assisted psychiatric diagnosis is constrained by the absence of benchmarks that simultaneously provide realistic patient simulation, clinician-verified diagnostic labels, and support for dynamic multi-turn consultation. We present LingxiDiagBench, a large-scale multi-agent benchmark that evaluates LLMs on both static diagnostic inference and dynamic multi-turn psychiatric consultation in Chinese. At its core is LingxiDiag-16K, a dataset of 16,000 EMR-aligned synthetic consultation dialogues designed to reproduce real clinical demographic and diagnostic distributions across 12 ICD-10 psychiatric categories. Through extensive experiments across state-of-the-art LLMs, we establish key findings: (1) although LLMs achieve high accuracy on binary depression--anxiety classification (up to 92.3%), performance deteriorates substantially for depression--anxiety comorbidity recognition (43.0%) and 12-way differential diagnosis (28.5%); (2) dynamic consultation often underperforms static evaluation, indicating that ineffective information-gathering strategies significantly impair downstream diagnostic reasoning; (3) consultation quality assessed by LLM-as-a-Judge shows only moderate correlation with diagnostic accuracy, suggesting that well-structured questioning alone does not ensure correct diagnostic decisions. We release LingxiDiag-16K and the full evaluation framework to support reproducible research at https://github.com/Lingxi-mental-health/LingxiDiagBench.

Visual Language Models (VLMs) have demonstrated impressive capabilities in visual grounding tasks. However, their effectiveness in the medical domain, particularly for abnormality detection and localization within medical images, remains underexplored. A major challenge is the complex and abstract nature of medical terminology, which makes it difficult to directly associate pathological anomaly terms with their corresponding visual features. In this work, we introduce a novel approach to enhance VLM performance in medical abnormality detection and localization by leveraging decomposed medical knowledge. Instead of directly prompting models to recognize specific abnormalities, we focus on breaking down medical concepts into fundamental attributes and common visual patterns. This strategy promotes a stronger alignment between textual descriptions and visual features, improving both the recognition and localization of abnormalities in medical images.We evaluate our method on the 0.23B Florence-2 base model and demonstrate that it achieves comparable performance in abnormality grounding to significantly larger 7B LLaVA-based medical VLMs, despite being trained on only 1.5% of the data used for such models. Experimental results also demonstrate the effectiveness of our approach in both known and previously unseen abnormalities, suggesting its strong generalization capabilities.

Recent advancements in general-purpose AI have highlighted the importance of guiding AI systems towards the intended goals, ethical principles, and values of individuals and groups, a concept broadly recognized as alignment. However, the lack of clarified definitions and scopes of human-AI alignment poses a significant obstacle, hampering collaborative efforts across research domains to achieve this alignment. In particular, ML- and philosophy-oriented alignment research often views AI alignment as a static, unidirectional process (i.e., aiming to ensure that AI systems' objectives match humans) rather than an ongoing, mutual alignment problem [429]. This perspective largely neglects the long-term interaction and dynamic changes of alignment. To understand these gaps, we introduce a systematic review of over 400 papers published between 2019 and January 2024, spanning multiple domains such as Human-Computer Interaction (HCI), Natural Language Processing (NLP), Machine Learning (ML), and others. We characterize, define and scope human-AI alignment. From this, we present a conceptual framework of "Bidirectional Human-AI Alignment" to organize the literature from a human-centered perspective. This framework encompasses both 1) conventional studies of aligning AI to humans that ensures AI produces the intended outcomes determined by humans, and 2) a proposed concept of aligning humans to AI, which aims to help individuals and society adjust to AI advancements both cognitively and behaviorally. Additionally, we articulate the key findings derived from literature analysis, including discussions about human values, interaction techniques, and evaluations. To pave the way for future studies, we envision three key challenges for future directions and propose examples of potential future solutions.

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

Medical image segmentation exhibits intra- and inter-annotator variability due to ambiguous object boundaries, annotator preferences, expertise, and tools, among other factors. Lesions with ambiguous boundaries, e.g., spiculated or infiltrative nodules, or irregular borders per the ABCD rule, are particularly prone to disagreement and are often associated with malignancy. In this work, we curate IMA++, the largest multi-annotator skin lesion segmentation dataset, on which we conduct an in-depth study of variability due to annotator, malignancy, tool, and skill factors. We find a statistically significant (p<0.001) association between inter-annotator agreement (IAA), measured using Dice, and the malignancy of skin lesions. We further show that IAA can be accurately predicted directly from dermoscopic images, achieving a mean absolute error of 0.108. Finally, we leverage this association by utilizing IAA as a "soft" clinical feature within a multi-task learning objective, yielding a 4.2% improvement in balanced accuracy averaged across multiple model architectures and across IMA++ and four public dermoscopic datasets. The code is available at https://github.com/sfu-mial/skin-IAV.

Geometric alignment appears in a variety of applications, ranging from domain adaptation, optimal transport, and normalizing flows in machine learning; optical flow and learned augmentation in computer vision and deformable registration within biomedical imaging. A recurring challenge is the alignment of domains whose topology is not the same; a problem that is routinely ignored, potentially introducing bias in downstream analysis. As a first step towards solving such alignment problems, we propose an unsupervised algorithm for the detection of changes in image topology. The model is based on a conditional variational auto-encoder and detects topological changes between two images during the registration step. We account for both topological changes in the image under spatial variation and unexpected transformations. Our approach is validated on two tasks and datasets: detection of topological changes in microscopy images of cells, and unsupervised anomaly detection brain imaging.

Vision-grounded medical report generation aims to produce clinically accurate descriptions of medical images, anchored in explicit visual evidence to improve interpretability and facilitate integration into clinical workflows. However, existing methods often rely on separately trained detection modules that require extensive expert annotations, introducing high labeling costs and limiting generalizability due to pathology distribution bias across datasets. To address these challenges, we propose Self-Supervised Anatomical Consistency Learning (SS-ACL) -- a novel and annotation-free framework that aligns generated reports with corresponding anatomical regions using simple textual prompts. SS-ACL constructs a hierarchical anatomical graph inspired by the invariant top-down inclusion structure of human anatomy, organizing entities by spatial location. It recursively reconstructs fine-grained anatomical regions to enforce intra-sample spatial alignment, inherently guiding attention maps toward visually relevant areas prompted by text. To further enhance inter-sample semantic alignment for abnormality recognition, SS-ACL introduces a region-level contrastive learning based on anatomical consistency. These aligned embeddings serve as priors for report generation, enabling attention maps to provide interpretable visual evidence. Extensive experiments demonstrate that SS-ACL, without relying on expert annotations, (i) generates accurate and visually grounded reports -- outperforming state-of-the-art methods by 10\% in lexical accuracy and 25\% in clinical efficacy, and (ii) achieves competitive performance on various downstream visual tasks, surpassing current leading visual foundation models by 8\% in zero-shot visual grounding.

AI alignment refers to models acting towards human-intended goals, preferences, or ethical principles. Given that most large-scale deep learning models act as black boxes and cannot be manually controlled, analyzing the similarity between models and humans can be a proxy measure for ensuring AI safety. In this paper, we focus on the models' visual perception alignment with humans, further referred to as AI-human visual alignment. Specifically, we propose a new dataset for measuring AI-human visual alignment in terms of image classification, a fundamental task in machine perception. In order to evaluate AI-human visual alignment, a dataset should encompass samples with various scenarios that may arise in the real world and have gold human perception labels. Our dataset consists of three groups of samples, namely Must-Act (i.e., Must-Classify), Must-Abstain, and Uncertain, based on the quantity and clarity of visual information in an image and further divided into eight categories. All samples have a gold human perception label; even Uncertain (severely blurry) sample labels were obtained via crowd-sourcing. The validity of our dataset is verified by sampling theory, statistical theories related to survey design, and experts in the related fields. Using our dataset, we analyze the visual alignment and reliability of five popular visual perception models and seven abstention methods. Our code and data is available at https://github.com/jiyounglee-0523/VisAlign.

Diagnostic consultation is an online sequential decision-making process in which clinicians gather evidence through patient interaction until a diagnosis is sufficiently supported. Automating this process requires adaptive inquiry and interpretable decisions. Bayesian networks offer a natural foundation by updating diagnostic posteriors as evidence accumulates, but their use in open-ended consultation raises two challenges: linking diagnostic hypotheses to potential inquiries and translating evolving posteriors into consultation decisions. We introduce AutoDisym, an automated pipeline that integrates diagnostic knowledge with heterogeneous diagnosis-labeled clinical narratives to construct a Disorder--Symptom Bayesian Network (DSBN). Building on the DSBN, we propose ConsultMind, an uncertainty-aware framework that updates disorder posteriors after each response and uses posterior uncertainty to guide inquiry and diagnosis. We evaluate both methods across psychiatry, respiratory medicine, fever clinics, and three public datasets. The results show that AutoDisym can automatically construct high-quality DSBNs and that ConsultMind consistently improves diagnostic performance and explanation soundness. For example, AutoDisym achieves macro-averaged F1 scores of 81.37 for canonical symptoms and 72.19 for manifestations using GPT-5.6-Sol. ConsultMind improves Top-1 and Top-3 diagnostic accuracy by up to 22.15 and 37.89 percentage points, respectively. Physician evaluation further shows that ConsultMind improves the quality of ranking explanations, differential diagnoses, and diagnosis rationales across LLMs of different scales. This work offers a promising approach to automatic diagnostic consultation.

The guiding principle of AI alignment is to train large language models (LLMs) to be harmless, helpful, and honest (HHH). At the same time, there are mounting concerns that LLMs exhibit a left-wing political bias. Yet, the commitment to AI alignment cannot be harmonized with the latter critique. In this article, I argue that intelligent systems that are trained to be harmless and honest must necessarily exhibit left-wing political bias. Normative assumptions underlying alignment objectives inherently concur with progressive moral frameworks and left-wing principles, emphasizing harm avoidance, inclusivity, fairness, and empirical truthfulness. Conversely, right-wing ideologies often conflict with alignment guidelines. Yet, research on political bias in LLMs is consistently framing its insights about left-leaning tendencies as a risk, as problematic, or concerning. This way, researchers are actively arguing against AI alignment, tacitly fostering the violation of HHH principles.

Fine-tuning large language models (LLMs) on narrowly misaligned data generalizes to broadly misaligned behavior, a phenomenon termed emergent misalignment (EM). While prior work has found a correlation between harmful behavior and self-assessment in emergently misaligned models, it remains unclear how consistent this correspondence is across tasks and whether it varies across fine-tuning domains. We characterize the consistency of the EM persona by fine-tuning Qwen 2.5 32B Instruct on six narrowly misaligned domains (e.g., insecure code, risky financial advice, bad medical advice) and administering experiments including harmfulness evaluation, self-assessment, choosing between two descriptions of AI systems, output recognition, and score prediction. Our results reveal two distinct patterns: coherent-persona models, in which harmful behavior and self-reported misalignment are coupled, and inverted-persona models, which produce harmful outputs while identifying as aligned AI systems. These findings reveal a more fine-grained picture of the effects of emergent misalignment, calling into question the consistency of the EM persona.

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.

Large language models (LLMs) have shown substantial progress in natural language understanding and generation, proving valuable especially in the medical field. Despite advancements, challenges persist due to the complexity and diversity inherent in medical tasks, which can be categorized as knowledge-intensive tasks and alignment-required tasks. Previous approaches either ignore the latter task or focus on a minority of tasks and hence lose generalization. To address these drawbacks, we propose a progressive fine-tuning pipeline. This pipeline employs a Knowledge Aggregator and a Noise aggregator to encode diverse knowledge in the first stage and filter out detrimental information. In the second stage, we drop the Noise Aggregator to avoid the interference of suboptimal representation and leverage an additional alignment module optimized towards an orthogonal direction to the knowledge space to mitigate knowledge forgetting. Based on this two-stage paradigm, we proposed a Medical LLM through decoupling Clinical Alignment and Knowledge Aggregation (MedCare), which is designed to achieve state-of-the-art (SOTA) performance on over 20 medical tasks, as well as SOTA results on specific medical alignment tasks. Various model sizes of MedCare (1.8B, 7B, 14B) all demonstrate significant improvements over existing models with similar model sizes.

Medical imaging artificial intelligence has achieved strong performance in isolated image interpretation, but remains poorly aligned with radiological practice, where diagnosis and follow-up rely on comparison across prior studies and analogous reference cases. Here we formulate radiological comparison as an entity-aware cross-image reasoning problem and introduce a framework that supports both reference-case retrieval and temporal comparative interpretation. We construct MedReCo-DB, a large-scale comparative imaging resource derived from routine image-report pairs, comprising more than 690,000 images from over 160,000 patients across eight institutions, four countries and seven imaging modalities. Reports are decomposed into anatomical structures, abnormal findings and pathological conditions to provide supervision for entity-conditioned retrieval and comparative visual question answering. Using this resource, we develop MedReCo, an entity-aware visual encoder for controllable retrieval of clinically analogous cases, and MedReCo-VLM, a vision--language extension for generative interpretation of interval change. Across internal, external and cross-center evaluations, MedReCo achieved the highest Recall@1 in all 12 internal retrieval settings and improved external retrieval by a mean of 6.0 percentage points. In clinically confusable differential groups, it consistently outperformed the strongest baselines. MedReCo-VLM achieved the best performance across all comparative generation evaluations and improved longitudinal follow-up accuracy by 14.5-46.5 percentage points on chest radiographs and 13.0-27.9 percentage points on CT. These findings suggest that entity-aware comparative reasoning can be learned from routine clinical data at scale and may provide a more clinically aligned foundation for medical imaging AI.