Mohammadsina Hassannia, Matthew A. Reyna, Reza Samenics.CL cs.IR
Electrocardiogram (ECG) interpretation requires knowledge of cardiology, electrophysiology, clinical diagnosis, ECG waveforms, signal acquisition, and instrumentation. Existing language-model benchmarks, however, primarily assess broad medical knowledge or interpretation of individual ECG signals and images rather than the broader contextual knowledge required for ECG interpretation. We developed ECGQuest, a literature-grounded resource for evaluating and fine-tuning ECG-specific language models. A GPT-4o-based pipeline generated questions from 23 ECG references and Computing in Cardiology proceedings from 2003-2025. The final dataset contains 10,904 unique True/False questions paired with their negated forms (21,808 Q&A pairs). We evaluated three commercial and 20 open-source language models on a held-out test set in a zero-shot setting. Five open-source models with 7-14B parameters were fine-tuned using Low-Rank Adaptation, with BERT and BiomedBERT included as supervised encoder baselines. Generalization was assessed on ECG-related subsets of MedMCQA and MedQA converted to binary True/False questions using official answer keys. Zero-shot accuracy on ECGQuest ranged from 49.5% to 74.4%, with GPT-5 performing best. General-purpose models outperformed medically specialized models, several models showed strong True/False bias, and encoder baselines performed near chance. Fine-tuning improved all open-source models by 6.5-14.1%. Fine-tuned DeepSeek-R1-Distill-Qwen-14B reached 76.3% accuracy, while a five-model voting ensemble reached 78.5%. On MedMCQA and MedQA, fine-tuning mainly benefited weaker or class-biased models and did not consistently improve strong base models. ECGQuest provides a reproducible benchmark for contextual ECG knowledge and shows that parameter-efficient fine-tuning can make smaller language models competitive with substantially larger commercial models.
Vasilis Dedousis, Lubnaa Abdur Rahman, Lorenzo Brigatο +8cs.CV
Accurate segmentation of interstitial lung disease (ILD) patterns is essential for quantitative disease assessment and longitudinal monitoring. However, existing approaches remain limited by relying on dense annotations and producing static predictions that cannot be refined, motivating interactive approaches. While promptable models show promise in interactive segmentation, their adaptation to ILDs remains largely unexplored. To address this gap, we investigate prompt-guided foundation models for ILD refinement and present, to the best of our knowledge, the first adaptation of MedSAM2 for interactive 3D ILD segmentation on thoracic CT. We investigate three fine-tuning strategies and multiple clinically motivated prompts: bounding-boxes (BBox), point, lasso, and scribble. On a dataset spanning seven ILD patterns and healthy lung tissue, full model fine-tuning performed best, improving the average Dice score by 4.7 percentage points over MedSAM2.While BBox prompts achieve the strongest performance, non-native MedSAM2 interactions such as lasso and scribble prompts also prove effective. Finally, we present and evaluate a proof-of-concept end-to-end workflow in which MedSAM2 is initialized from an automatic segmentation prior and subsequently refined using radiologist prompts. Model weights and plug-ins made available at: https://github.com/AIHNlab/ILD-SemiSegTool.
Clinical language models can achieve strong in-hospital accuracy yet fail under deployment shifts because they exploit note-specific artifacts (e.g., templates, separators, boilerplate) that do not reflect patient state. We propose CAST (Concept-guided Artifact Suppression Tuning), an SAE-based framework for auditable clinical text classification. CAST uses Sparse Autoencoders to expose sparse, human-auditable features from intermediate Transformer activations, labels SAE latents with an LLM-assisted interpretation pipeline and ICD-10 retrieval constraints, suppresses verified artifact latents via residual subtraction during fine-tuning, and provides post-hoc per-concept attributions for auditing model decisions. On MIMIC-IV discharge-note mortality prediction, CAST improves over its corresponding fine-tuned encoder baselines and remains competitive with strong LLM baselines, while producing a feature-level audit trail of the clinical concepts that support each prediction and the artifact concepts suppressed during training.
Biomedical knowledge graphs (KGs) offer structured medical knowledge that can ground large language model (LLM) reasoning in clinical diagnosis application, yet how KG signal should be integrated into LLMs remains an open question. We present a systematic study spanning five KG task formulations, three training paradigms, two KGs, and three base LLMs. At the task level, all paradigms improve over the non-finetuned baseline, but methods with comparable in-domain accuracy show substantially different knowledge transfer behavior. We introduce Gradient Intervention Density (GID) and Gradient Distortion (GD) to measure how broadly an optimizer modifies the pretrained model. GID and GD together reveal a clear divide: KG-judgment training under KL regularization produces sparse, localized updates (a regime we term as surgical alignment), while task-specific SFT produces dense ones. A controlled ablation shows that the objective and KL contribute to sparsity independently, and the paradigms that produce sparse updates also improve reasoning quality, even when their in-domain accuracy is lower than task-specific SFT. Assessing KG-LLM integration thus requires complementing accuracy with optimization-geometry diagnostics. Our implementation can be found at https://github.com/LARK-NLP-Lab/Surgical-Alignment.
Alexander J. Hish, Arjun Nagendran, Scott N. Comptoncs.AI
Background This study was designed to evaluate whether a domain-specific large language model (LLM) trained exclusively on patient education resources can answer questions about psychiatric medications, in a manner superior to LLM chatbots. We developed an LLM ("MIND") fine-tuned for clinical fidelity, trained on patient education resources from authoritative medical organizations. Methods We compared the responses of MIND, ChatGPT, and OpenEvidence to patient questions about escitalopram, using two methods: (1) computer analysis according to a rubric measuring accuracy, clarity, completeness, nuance, safety, and referral appropriateness; (2) ratings from N=10 board-licensed psychiatrists on similar metrics. Results When rated by rubric, MIND was rated highest in all domains (p<0.001). When rated by psychiatrists, ChatGPT was rated accurate more often than MIND with a negligible effect size (p=0.021, r=0.073); MIND was rated complete more often than ChatGPT with a small effect size (p<0.001, r=0.160); and MIND and ChatGPT were rated safe with the same frequency (p=0.955, r=0.002). The majority of psychiatrists preferred the responses generated by ChatGPT (57.6%) compared to MIND (42.4%, p=0.003). Conclusions MIND was able to answer many questions about escitalopram in a manner deemed accurate, complete, and safe by psychiatrists the majority of the time. However, despite MIND's ability to provide more complete responses, psychiatrists preferred ChatGPT's responses. MIND represents a step towards building safe LLM systems to enhance patient education in psychiatry.
Miguel Contreras, Scott Siegel, Subhash Nerella +30cs.CL cs.AI
Clinical decision-making relies on identifying relevant patient information to guide diagnosis and treatment, a challenge that is especially difficult in the data-dense and rapidly changing intensive care unit (ICU). Large language models (LLMs) could support this task. However, existing applications and datasets mostly emphasize surface-level retrieval or factual recall rather than the inductive and deductive reasoning clinicians practice to select and reason over decision-relevant evidence. We hypothesized that training LLMs on expert ICU reasoning could yield clinical reasoning skills that generalize beyond critical care. Here we introduce ICU-REACT, a reasoning dataset developed with 19 clinicians through a clinician-in-the-loop framework to teach LLMs to perform information retrieval and context-aware clinical reasoning in the ICU. Using ICU-REACT, we fine-tuned Clin-REACT models spanning 8B-70B parameters and three model families. Across five clinical reasoning benchmarks, Clin-REACT consistently outperformed its backbone models and open-source general-purpose and medical LLMs. Gains extended to different tasks including script concordance tests, and downstream diagnosis and treatment tasks. These findings suggest that expert reasoning supervision in critical care can improve broader clinical reasoning, although prospective evaluation is needed before real-world clinical use.
Marko Haralović, Sounic Akkaraju, Carlo Baretta +2cs.CV
Foundation models for medical image segmentation, like prompt-based MedSAM, generalize well across domains and modalities, often in zero or few-shot setups. However, their performance depends on the quality of prompts and the adaptation of the models to custom datasets. This work systematically examines how MedSAM generalizes across diverse medical imaging benchmarks, with six adaptation strategies: full-model and encoder-only LoRA, shallow and deep visual prompt tuning (VPT), and decoder-only and full fine-tuning. Models are trained on the International Skin Imaging Collaboration Challenge (ISIC 2018) dataset and evaluated under clean and increasingly noisy prompts on IN and Out-of-Distribution (OOD) datasets: close-OOD PH2 (dermoscopy), far-OOD BUSI (Breast Ultrasound Images Dataset) and CBIS-DDSM (Curated Breast Imaging Subset of the Digital Database for Screening Mammography). We show that adaptation improves performance on IN and close-OOD data but often reduces performance on far-OOD data. Full fine-tuning provides the best tradeoff, while encoder-only LoRA is the strongest parameter-efficient alternative, outperforming standard LoRA and VPT under far-OOD shifts. Using Centered Kernel Alignment (CKA), we show that far-OOD degradation is strongly associated with drift in decoder representations, whereas encoder similarity alone does not explain robustness. This suggests encoder-only LoRA provides stronger robustness than standard LoRA by adapting the encoder to distribution shift in visual features, while preserving the decoder pathway. We further show that random 0-100 pixel jitter on prompts produces more robust and better performing models. We thus conclude that robust MedSAM adaptation requires the combined consideration of prompt noise exposure, domain shift, and representation preservation. We release our code: https://github.com/ImSounic/medsam-vpt
Marvellous O. Ajala, Zainab Ashimiyu-Abdusalam, Comfort Adesinaq-bio.QM cs.AI cs.LG
We introduce Malaria-Instruct, a curated instruction-following dataset derived from the ChEMBL Legacy Malaria corpus for Malaria virtual screening, and conduct a systematic evaluation of five open-source LLMs; Gemma-2 2B/9B, TxGemma-2B/9B, and LlaSMol-Mistral-7B, on a rigorous out-of-distribution data split. Performance was benchmarked against classical ML models (Random Forest, XGBoost) and frontier proprietary models (Gemini 2.5, OpenAI o3) under few-shot conditions. Fine-tuned LLMs substantially outperformed all baselines: TxGemma-9B achieved the highest ROC-AUC ($0.731 \pm 0.005$) and LlaSMol-Mistral-7B the best enrichment factor (EF@1\% $\approx$ 4.99). Domain-specific fine-tuning proved categorically indispensable with TxGemma-9B collapsing from ROC-AUC 0.731 to 0.499, under its best few-shot condition, and neither Gemini 2.5 (ROC-AUC $\approx$ 0.53) nor o3 (ROC-AUC $\approx$ 0.59) achieved reliable discrimination without fine-tuning. Biomedical pretraining conferred a measurable advantage at equivalent scale, while chemistry-aware pretraining yielded superior prospective enrichment. Fine-tuned open-source LLMs represent a compelling, resource-efficient paradigm for antimalarial VS, outperforming both classical pipelines and proprietary reasoning models under structurally challenging conditions.
Deploying large language models (LLMs) for decision support in emergency departments (EDs) faces two major challenges: privacy risks of transmitting patient data to closed-source commercial LLMs and the lack of systematic evaluation of fine-tuning strategies for locally deployable open-source small language models (SLMs). We benchmarked eight open-source SLMs using zero-shot prompting, prefix tuning, Low-Rank Adaptation (LoRA), and full fine-tuning on three ED tasks: triage level prediction, specialist referral recommendation, and diagnosis prediction. Using 2,083 MIMIC-IV-ED cases and Claude Haiku 4.5 and Claude Sonnet 4.5 as baselines, we found that LoRA fine-tuned open-source SLMs outperform commercial baselines on triage level prediction and specialist referral recommendation, while diagnosis prediction remains challenging for open-source SLMs. Confusion matrix analysis further shows that fine-tuned open-source SLMs can detect highest-severity patients missed by the commercial baselines. These results demonstrate that locally deployable SLMs can achieve clinically competitive performance for ED decision support.
Hongxiang Gao, He-yang Xu, Yuwen Li +6eess.SP cs.CV cs.LG
Cardiologists interpret electrocardiograms by localizing waveform components, measuring rhythm and interval patterns, and translating these structured observations into diagnostic evidence. Whether this expert reading process can serve as an effective prior for ECG agents remains unclear. To address this question, we introduce LuminaECG, a clinically structured ECG reasoning framework that reformulates ECG interpretation as measurement-grounded visual reading. ECG signals are rendered on standard electrocardiographic grid paper to preserve the spatial and scale cues used in clinical reading. P-wave, QRS-complex, and T-wave boundaries are explicitly delineated, and color-coded segmentation decomposes the waveform into discrete visual measurement primitives. A general 2B vision-language backbone is then trained with low-rank supervised fine-tuning to associate these primitives with diagnostic reasoning, without architectural modification. Across open, proprietary, and ECG-specialist zero-shot baselines, LuminaECG improves both waveform measurement and diagnostic recovery. It reaches a clinically meaningful reader tier on the CODE-test benchmark, transfers across geographically diverse ECG datasets without retraining, and generates reports whose structure contains an emergent prognostic signal. These findings suggest that effective ECG agents require not only larger models, but supervision that preserves the alignment between measurable waveform evidence and clinical knowledge.
Bernes Lorier Atabonfack, Zion Kongbi Nfo, Ahmed Tahiru Issah +9cs.AI
Imaging device downtime is a major barrier to healthcare delivery in low- and middle-income countries (LMICs), often driven by limited access to specialized biomedical engineering support. We present a multi-modality medical equipment maintenance question-answering (QA) framework and demonstrate the fine-tuning of a medical foundation model for specialized technical troubleshooting tasks. Guided by a multi-country survey across nine LMICs, we curated technical manuals from MRI and ultrasound systems to generate the INGENZI_DatasetV1, containing 10,294 high-quality, filtered QA-context pairs. Using QLoRA-based parameter-efficient fine-tuning, we adapted the MedGemma-4b-it model to interpret system error logs and generate step-by-step equipment repair instructions. Compared to the baseline model, the fine-tuned system achieved substantial improvements across metrics, including F1 score (0.22 to 0.38), ROUGE-2 (0.18 to 0.41), and BERTScore F1 (0.86 to 0.91). These metric gains demonstrate that the model generates significantly more precise and procedurally accurate technical responses to new troubleshooting queries. This work establishes a reliable foundation for AI-assisted diagnostic and maintenance tools in resource-constrained settings.
To address this gap, we introduce TomaMMU, a large-scale Tomato leaf disease MultiModal Understanding dataset, alongside TomaBench, a benchmark for evaluating VLMs on tomato disease understanding. TomaMMU comprises 28,808 high-quality images spanning 15 categories and 213,119 human-annotated visual question-answer pairs, generated through a three-stage pipeline comprising Data Collection, Human Annotation, and Question-Answer Generation. Building on this foundation, TomaBench organizes seven agricultural tasks into a hierarchical three-level taxonomy spanning Basic Perception, Pathology Understanding, and Expert Diagnosis, which together enable systematic evaluation from low-level visual recognition to high-level diagnostic reasoning. The tasks assess visual symptom recognition, taxonomic relationships, and diagnostic reasoning, offering a comprehensive view of how well models grasp plant pathology. Our results pronounced gaps in fine-grained recognition and factually grounded reasoning with 14 state-of-the-art VLMs, consistently underperforming on both challenging MCQs and open-ended questions. These results suggest that current VLMs struggle to translate visual perception into reliable diagnostic knowledge, motivating the need for targeted domain adaptation. Simple fine-tuning on TomaMMU substantially narrows this gap, boosting accuracy on challenging MCQs to 96.09%, outperforming recent VLMs, and pointing toward promising directions for future work. All data and code is available in https://huggingface.co/datasets/enalis/TomaMMU.
Sina Amirrajab, Cian M Scannell, Volker Vehof +2cs.CV
Foundation models have shown strong transferability in cardiac MRI (CMR), but their effectiveness for heterogeneous multi-view and multi-sequence CMR analysis remains unclear. In this work, we explore the effectiveness of fine-tuning and combining different CMR foundation models for the Universal Multi-Sequence, Multi-Center and Multi-View CMR Segmentation (CMR-Multi) Challenge. CineMA was fine-tuned for cine and late gadolinium enhancement (LGE) segmentation across short-axis and long-axis views. For direct left-ventricular ejection fraction (LVEF) estimation, we used two recent frozen CMR foundation models to extract embedding vectors that were then combined using attention-based multiple-instance learning for LVEF regression. In the challenge validation set, cine segmentation achieved Dice scores of 0.862, 0.883, and 0.902 for short-axis, two-chamber and four-chamber cine MRI, respectively. LGE segmentation achieved Dice scores between 0.621 and 0.846 across views. The direct LVEF regression model achieved an MAE of 4.96 percentage points and a Pearson correlation of 0.91. These results indicate that foundation models can be effectively adapted and combined for multi-view CMR analysis, while accurate LGE scar segmentation remains a challenging task.
Scaling supervision for multi-turn medical agents is difficult because expert dialogue annotation is costly and clinical conversations are privacy-restricted. We introduce Guideline-as-Oracle (GAO), which compiles American Academy of Ophthalmology guidance into a 70-row operational rule table and uses it as the sole source of instance-level supervision for 3,000 training dialogues, reserving human labeling for evaluation. Because converting rules into dialogues is itself a design problem, we catalog eight construction strategies, including cited-row tier assignment, one-fact boundary pairs, metadata-only repair, and label repair, and characterize the evidential status of each: labeling mechanism, null, confounded, or evaluated only as a package. Fine-tuning a 9B backbone on this corpus yields GAO-Triage, improving agreement with a 201-case operational reference from 61.7% to 74.1% (exact McNemar p=0.0046) and emergent-case recall from 9.5% to 69.0%; the gains persist across a second seed and patient simulator. None of the seven general-purpose systems we test dominates GAO-Triage on both metrics, and GAO-Triage requires no frontier model at inference time. Permuting label-dialogue assignments collapses the model to a constant-routine predictor, indicating that the signal lies in guideline-derived assignment rather than dialogue surface form. Label repair coincides with the disappearance of a late-training safety degradation.
Medical visual grounding connects free-form clinical queries to spatial evidence in medical images and is an important component of interpretable medical artificial intelligence. However, general-purpose grounding models are predominantly trained on natural images, while existing medical localization resources remain fragmented across imaging modalities, datasets, and task formulations. To address this gap, we construct LocAnyMed-200K, a multimodal medical visual grounding dataset containing approximately 200K image-query-answer examples across computed tomography, optical medical imaging, ultrasound, and X-ray. We harmonize heterogeneous detection and localization resources into a unified free-form instruction format that supports one or multiple bounding boxes, point coordinates, and no-target outputs for negative queries. Full-parameter fine-tuning of LocateAnything-3B on LocAnyMed-200K improves F1@IoU 0.50 from 10.64 to 85.59 on a held-out evaluation split, demonstrating that large-scale domain-specific supervision can equip a general grounding model with effective medical localization capabilities. Beyond spatial coordinates, a clinically interpretable grounding system should also communicate the evidence supporting its prediction. We therefore derive LocAnyMed-CoT-20K, a rationale-augmented subset that connects anatomical context, visual observations, and spatial conclusions through structured reasoning and further improves cross-source generalization through fine-tuning. Together, these resources provide a unified foundation for studying both localization accuracy and rationale quality across heterogeneous medical imaging modalities. The code is publicly available at https://github.com/MiliLab/LocAnyMed.
Standard masked-language-model fine-tuning applies a uniform masking probability across every token position, assuming reconstruction difficulty is position-agnostic. When the degradation process is characterised and concentrated at predictable positions, this assumption fails: at peak damage sites the model can underperform a frequency-matched random predictor. We introduce VESTIGE, a parameter-free, drop-in replacement for the standard MLM collator that aligns the masking distribution with an empirically measured per-position corruption profile. We apply it to ancient DNA (aDNA) reconstruction, where cytosine deamination produces a position-dependent C-to-T / G-to-A gradient quantified per-position by mapDamage2. Rescaling so the mean C/G masking rate equals 15% - identical to standard MLM - isolates spatial redistribution as the sole variable, with model, data, seed, and hyperparameters held fixed across both DNABERT-2 runs on a mammoth CDS corpus (two specimens, seven genes). Across six terminal-zone widths and 626 paired windows, VESTIGE leads standard MLM at every width (Delta = +4.18 to +10.35 pp, all p < 10^-8), cuts validation cross-entropy by 13% (3.274 vs. 3.757), and yields ESMFold reconstructions with TM-score > 0.95 across all six reconstructions (three genes) even under damage amplified 10-30x beyond authentic PMD rates. A 1D CNN biosecurity classifier returns AUC = 0.935 and clears 98.2% of reconstructed windows, the 1.76% remainder attributable to reference-genome features, not reconstruction artefacts. The principle is domain-agnostic: any measurable position- or context-specific corruption profile - FFPE, bisulfite, metagenomic, or nanopore - substitutes directly for the PMD array, making VESTIGE a knowledge-guided training routine for intelligent systems operating on degraded or noisy sequence inputs.
Cognitive distortion amplifies negative emotions and contributes to mental health disorders. Cognitive Behavioral Therapy (CBT) is an effective way to address cognitive distortions, but its large-scale application is limited by the shortage of professional therapists. Although large language models (LLMs) have recently been explored for mental health applications, existing methods still suffer from limited domain specificity, overly flattering responses, and the absence of well-defined annotations for cognitive distortions. This paper proposes Cognivia, an evidence-based artificial intelligence therapist that integrates automatic cognitive distortion identification and rational response generation. Our framework is built on authoritative CBT texts widely regarded as core paradigms and standard references. It is further augmented with mental health question-answer (Q and A) data, and employs multi-stage prompting and structured generation strategies under the supervision of behavioral science experts. Then we fine-tune a lightweight LLM on this augmented CBT dataset to obtain Cognivia. In addition, we propose the first hierarchical quality evaluation framework for assessing LLM-generated rational responses, developed through collaboration between AI researchers and behavioral science experts. Cognivia is evaluated using lexical metrics, LLM-based Judges with two complementary criteria, and human evaluation by 10 behavioral science experts. It consistently outperforms the baseline methods in cognitive distortion recognition and rational response generation, demonstrating its effectiveness. Our code is available at https://github.com/SNOWTEAM2023/Cognivia.
Alexandre Filiot, Oskar Thaeter, Benoit Schmauch +1cs.CV cs.AI
Pathology foundation models (FMs) produce powerful tile-level representations which remain sensitive to scanner and staining variability, undermining deployment across laboratories. We develop a novel fine-tuning recipe that improves the robustness of pathology FMs to acquisition factors. Applied to ten different FMs, our fine-tuning strategy consistently improves robustness for every model as well as downstream performance, with no observed trade-off. On average, it raises the PathoROB robustness index by 23% (from 0.72 to 0.87) and increases the overall cross-benchmark performance by 43% on Patho-Bench, HEST and THUNDER combined, with individual gains reaching up to 72% in robustness (Phikon-v2) and 76% in performance (Midnight-12k). We publicly release the fine-tuned versions of Phikon-v2 (Phaet) and Midnight-12k (Mascaret) at https://huggingface.co/wearewaiv/models.
Large Language Models (LLMs) show promise for medical education, but most existing systems focus on localized interactions such as question answering or single-turn feedback, rather than organizing an entire clinical case into a decision-centered learning trajectory. We introduce \textit{MedGame}, a framework that transforms static clinical cases into structured, executable storytelling games. MedGame uses a dual-engine design: a Medical Narrative Designer synthesizes case-grounded clinical storylines with states and decision nodes, while a Story Director converts them into dependency-aware multimodal orchestration plans rendered by our released interactive platform. We construct MedGame Bench, a 5,000-case benchmark and evaluation protocol for Medical Narrative Generation and Story Direction. Experiments show that task-specific fine-tuning substantially improves open-source LLMs on MedGame Bench and narrows the gap with commercial models. A pilot student study further shows that learners perceive MedGame as more engaging and useful than text-only alternatives.
Tanay Aggarwal, Angelo Salatino, Francesco Osborne +1cs.DL cs.CL
Knowledge Organization Systems like Ontologies and taxonomies are fundamental for structuring scientific knowledge, yet their manual curation presents a persistent bottleneck in knowledge management. While Large Language Models (LLMs) offer a scalable mechanism for automated ontology generation, their capacity to classify complex, domain-specific semantics requires systematic evaluation. In this paper, we assess the performance of five small, open-source LLMs (up to 9 billion parameters) in identifying semantic relationships between biomedical concepts. To support this evaluation, we introduce MeSH-Rel-4K, a dataset comprising 4K semantic relationships extracted from the Medical Subject Headings (MeSH). We analyse three adaptation strategies: standard prompting, Chain-of-Thought prompting, and fine-tuning. While parameter-constrained models traditionally struggle with the nuances of in-context logic, our results reveal that targeted fine-tuning increases the average F1-score by 34.1 percentage points. These results confirm that direct fine-tuning effectively exceeds the reasoning bottlenecks of smaller LLMs, providing an accurate, automated methodology for the construction and evolution of specialised biomedical ontologies.
Electronic health records combine free-text clinical narratives with structured measurements such as vital signs, laboratory values, and comorbidities. Yet most clinical prediction systems still rely on task-specific fusion architectures, pairing dedicated encoders for each modality with learned combination mechanisms that must be re-engineered for every new task and clinical setting. We propose a simpler alternative: convert all patient data, regardless of modality, into a single natural language sequence and fine-tune a pretrained language model end-to-end, with no architectural modification for fusion. We evaluate this approach across three clinically distinct prediction tasks: in-hospital mortality on MIMIC-III, graft failure prediction using longitudinal data from a German transplant center, and emergency triage classification from ambulance records - comparing encoder-based (ModernBERT) and decoder-based (Llama 3.1, Gemma, DeepSeek-R1-Qwen, Qwen3) fine-tuning against established multimodal baselines and, for graft failure, a gradient boosting model currently used in clinical practice for post-transplant patient management. Across all three tasks, unified textual serialization matches or exceeds task-specific multimodal baselines, and outperforms the clinically deployed gradient boosting system on graft failure prediction. These results indicate that a single serialization-based paradigm, without bespoke fusion architectures, is sufficient for multimodal clinical prediction - substantially reducing system complexity while matching or exceeding specialized designs.
Chemical language models (CLMs) are trained with linearized representations such as SMILES, yet it remains unclear which chemically meaningful substructures they encode. To foster a better understanding of CLMs, we conduct a systematic study and probe for 78 molecular substructures across eight pre-trained and six randomly initialized models. We furthermore study how fine-tuning on chemical downstream tasks affects the learned representations of molecular substructures. Our results show that pre-training generally improves molecular structure awareness of CLMs, particularly in the upper layers. Moreover, randomly initialized models already encode ring structures well in the first layer. Our analysis on two chemical downstream tasks further reveals that, interestingly, fine-tuning affects task-relevant molecular substructures more than others, indicating that the changes in the representations follow chemical theory.
Violeta Basten-Romero, Rubén Muñoz-Tafalla, Anna María Díaz-Rovira +3cs.LG cs.AI q-bio.BM q-bio.GN
Protein language models are standard priors for biological sequence generation, but steering them toward explicit distributional design targets remains largely unexplored. We study a constrained protein generation problem in which sequences must match a desired amino-acid (AA) composition profile while preserving plausible sequence statistics and diversity. The motivating application is synthetic feed protein design, where the AA composition of dietary proteins directly determines their nutritional value. We propose a two-stage pipeline in which domain-adaptive fine-tuning (FT) on an in-domain protein dataset is followed by iterative reward-weighted FT via reinforcement learning (RL) anchored against the FT model as a frozen reference. We evaluate the pipeline on two AA compositions and find that FT brings the average composition close to the target, while the subsequent RL enforces specific sequence constraints that FT alone cannot satisfy. We additionally evaluate the design choices of the proposed composition reward term against two baselines and an ablated variant, isolate the contribution of each training stage, and verify that AA composition alignment is achieved without degrading sequence quality.
Depression is the leading cause of disability worldwide, and early detection of symptom change is essential for timely intervention. Validated instruments such as the Patient Health Questionnaire-9 (PHQ-9) support symptom monitoring at scale, but real-world completion rates are low, introducing response bias and systematic missingness. Passive approaches that infer severity from routinely generated data could close this gap. We address this by predicting PHQ-9 total scores directly from transcripts of conversations between users and an AI mental health application, requiring only conversation text and no additional clinical data. We fine-tune a Qwen3.5-27B backbone with a regression head, augment 3,111 ground-truth labels with pseudolabels generated by a reasoning model (Claude Opus) and iteratively trained intermediate models, for a combined dataset of 6,283 users. On a held-out test set of 842 users, our best model achieves MAE = 2.6, RMSE = 4.0, Pearson r = 0.80, and AUC = 0.91 at the PHQ-9 >= 10 clinical threshold. We also find AUC > 0.87 at every severity threshold from PHQ-9 >= 3 to PHQ-9 >= 24, demonstrating that the model captures depression severity across the full clinical spectrum. This work opens the door to passive, continuous symptom monitoring in AI mental health platforms, without requiring users to complete self-report measures.
Building trustworthy medical multimodal large language models (MLLMs) is critical for reliable clinical decision support. Existing medical hallucination benchmarks mainly focus on data collection, but often ignore where hallucinations originate within the reasoning process. We find that hallucination sources vary across samples: errors may arise from visual misrecognition, incorrect medical knowledge recall, or flawed reasoning integration. To enable source-level hallucination diagnosis, we introduce ClinHallu, a benchmark for stage-wise hallucination diagnosis in medical MLLM reasoning. ClinHallu contains 7,031 validated instances, where each instance is augmented with a structured reasoning trace decomposed into Visual Recognition, Knowledge Recall, and Reasoning Integration. We also use stage-replacement interventions to measure how correcting specific stages affects the final answer. Beyond evaluation, we show that trace-supervised fine-tuning reduces stage-wise hallucinations. ClinHallu provides a fine-grained hallucination testbed for diagnosing and mitigating reasoning failures in medical MLLMs. The benchmark is publicly available at https://github.com/alibaba-damo-academy/ClinHallu.
Melanoma is the most dangerous form of skin cancer with five-year survival rates exceeding 99% when detected early but falling sharply once the disease spreads. This paper proposes and evaluates a two-stage fine-tuning approach for ResNet50 applied to binary melanoma classification on dermoscopic images. The core challenges addressed are class imbalance and suboptimal transfer learning from single-stage fine-tuning. After stratified train/validation/test splitting, random oversampling was applied exclusively to the training set to achieve a 1:1 class balance. Stage 1 trained only the classification head with the ResNet50 base frozen, while Stage 2 fine-tuned all layers jointly at a low learning rate of 1e-5 to prevent catastrophic forgetting of learned visual features. On an independent test set of 3,826 images, the model achieved an AUC-ROC of 0.9559, accuracy of 88.34%, sensitivity of 87.56%, specificity of 89.13%, and F1-score of 88.29%. An ablation study confirms the two-stage protocol significantly outperforms single-stage fine-tuning, with sensitivity gains of over 4%. Grad-CAM visualizations demonstrate correct lesion localization. A fully deployable Streamlit detection application is provided alongside all training code.
Large Language Models such as GPT-4o and GPT-5 achieve strong zero-shot performance on biomedical claim verification, but cost and opacity limit scalable use. We fine-tune three small LLMs: Phi-3-mini (3.8B), Qwen2.5-3B, and Mistral-7B, via QLoRA on SciFact and HealthVer, providing the first study of QLoRA models against GPT-4o and fine-tuned BioLinkBERT encoders. Mistral-7B QLoRA surpasses both GPT-4o and GPT-5 (up to 12% F1 gain) at a fractional cost using just 1,008 training examples. We conduct extensive in-domain and cross-domain evaluation: models trained on SciFact tested on HealthVer and vice versa, at matched sizes to isolate dataset structure from data quantity. We identify a previously unreported structural artifact in SciFact that inflates in-domain scores, and show through bidirectional out-of-domain evaluation that training on structurally sound data enables robust cross-domain transfer. We plan to release all code and adapter checkpoints.
Buxin Su, Bingxuan Li, Cheng Qian +3cs.AI cs.CL cs.LG
Supervised fine-tuning with synthetic rationale data is widely assumed to improve language model performance on clinical prediction tasks by teaching models not just what to predict but why. We test this assumption on five-year Alzheimer's disease and related dementias (ADRD) prediction from longitudinal health histories. Across a large-scale controlled experiment of 504 configurations, we find that rationale-based SFT consistently and substantially hurts prediction performance relative to label-only fine-tuning. The degradation persists across model families and data scales, and is not resolved by using a reasoning-oriented base model. Crucially, the failure is not explained by poor rationale quality: human expert annotation confirms that the generated rationales are medically accurate and faithfully grounded in patient-specific evidence, and few-shot experiments show that the same rationales improve performance when used as inference-time demonstrations rather than training targets. We identify the root cause as a structural conflict between narrative plausibility and discriminative optimization. We hope our work paves the path toward a more precise understanding of when and how rationale-based supervision helps and when it does not, guiding the responsible development of language models for high-stakes clinical prediction.
Sotirios Vavaroutas, Yu Yvonne Wu, Ali Etemad +1cs.LG cs.AI
Data samples used for training often differ from those encountered during fine-tuning and deployment, and while ML models show promise, their performance remains limited when only small annotated datasets are available. Performance often degrades under distribution shifts caused by diverse sensors, populations, and application settings. Although pre-training helps, models frequently encounter out-of-distribution (OOD) data in real-world settings, leading to reduced robustness. Existing adaptation methods usually assume fixed distribution shifts and struggle when multiple types or severities occur. In particular, they overlook shift severity, for example treating adaptation to a large familiar dataset the same as adaptation to a small dataset with a new task, which limits generalisation. To address this, we propose ADAPTOOD, a novel framework that leverages data uncertainty to quantify distribution shift severity and guide fine-tuning for time series. This uncertainty measures how strongly samples from the target deployment distribution deviate from the pre-training distribution, providing a direct signal of OOD severity. Our framework combines this uncertainty with low-rank model updates and adaptive hyperparameter optimisation to improve adaptation. We show that ADAPTOOD achieves up to 7% higher accuracy and 12.9% higher precision than existing methods in OOD tasks, maintaining strong performance as distribution shift severity increases.
Baris Karacan, Vaibhav Bhargava, Barbara Di Eugenio +21cs.CL
Effective "all-team" summarization in high-complexity settings like the Neonatal Intensive Care Unit (NICU) requires aggregating insights from diverse disciplines (physicians, nurses, therapists) spread across hundreds of clinical free-text notes. Simply pooling heterogeneous text often leads to incoherent outputs. Structured summarization therefore first requires accurate categorization of sentence-level provenance across multi-source notes. This pilot study introduces a clinical provenance categorization pipeline using supervised fine-tuning (SFT) of large language models (LLMs). We adapted two Llama-3 models (8B and 70B) to MedSecId, a corpus of 2,002 MIMIC-III (Adult ICU) notes annotated with clinical provenance headers, achieving in-domain Macro F1 scores above 92% for both models. To evaluate cross-domain generalization, we assessed model capacity (8B vs. 70B) and quantization on a gold-standard dataset of 227 sentence-level spans derived from three multi-disciplinary NICU summaries. Experimental results demonstrate a scale-dependent transfer effect: while SFT produced only marginal changes for the 8B model, it substantially improved the 70B model, increasing Macro F1 by 7%. Notably, the quantized fine-tuned 70B model outperformed its full-precision baseline while substantially reducing computational requirements. These findings suggest that sufficient model capacity is critical for preserving semantic flexibility during cross-domain clinical transfer and that efficient quantized adaptation can enable structured provenance modeling for downstream summarization.