Non-Small Cell Lung Cancer

While a centralized approach involving patient consent to collect and analyze data centrally would theoretically offer the best data quality and predictive performance, it is not always feasible in practice. Federated Learning (FL) architectures have shown to be a very promising approach to use and access distributed disease related resources within the GDPR boundaries. In a previous case report, we described the preconditions at the participating sites and necessary administrative and process related steps to prepare data, people and infrastructure for improving subtype identification and assessing treatment options in pancreatic cancer. We update this report sharing our experience in tackling the challenges and show preliminary results of the actual federated learning AI pipelines. At the participating sites, we have to identify and annotate the data being accessible after extraction and transformation in a local FL hub - in our case a centrally developed and distributively deployed Docker container. This container comprises the FL scripts generating local models. We apply a newly developed FL algorithm considering all local features, including partial overlapping features specific to the local sites. Theoretically, an annotation in a cancer setting should succeed using the German oncology core data set (oBDS), which is already utilized for mandatory reporting to cancer registries, and can be sustained in the FL setting. The FL algorithms deal robustly with partially overlapping features as we showed with public data sets. Major roadblocks including straightening operational concepts for the infrastructures, ethics approval for such novel architectures and support for every site have been addressed. However, scaling up this approach in the future faces hurdles; while including broader multi-modal data sets should be feasible, large-scale deployment to more sites remains challenging.

Breast histopathology analysis increasingly relies on distributed learning because direct data pooling across institutions is often restricted by privacy, governance, and communication constraints. This study compares server-based Federated Averaging (FedAvg), fully decentralized gossip learning, and Hybrid Gossip-FedAvg for invasive ductal carcinoma (IDC) patch classification. Experiments used 277,524 color image patches with patient-disjoint training, validation, and test partitions and a workload-balanced, Dirichlet-guided allocation across six nodes. Ring, random degree-3, and fully connected gossip topologies were evaluated together with sensitivity analyses for statistical heterogeneity, mixing coefficient, learning rate, model drift, prediction disagreement, calibration, clinically motivated operating points, communication payload, and patient-level IDC burden, together with auxiliary backbone robustness analyses. In the principal alpha=0.3 experiment, Hybrid Gossip-FedAvg achieved a test area under the receiver operating characteristic curve (ROC-AUC) of 0.8811, closely followed by FedAvg at 0.8801 and fully connected gossip at 0.8751. Across three independent patient-level repetitions, FedAvg and Hybrid Gossip-FedAvg obtained the same mean ROC-AUC of 0.9082, with standard deviations of 0.0037 and 0.0043, respectively. Hybrid achieved the highest mean area under the precision-recall curve of 0.8240, whereas FedAvg produced the lowest mean Brier score of 0.1335. Denser gossip graphs improved discrimination but increased theoretical model payload, while ring gossip remained sensitive to learning rate and mixing strength. Overall, FedAvg provided the most consistently reliable server-based baseline, topology-aware gossip offered a viable decentralized alternative, and Hybrid Gossip-FedAvg provided a balanced compromise between peer-to-peer diffusion and periodic global coordination.

Cervical cancer is a major global health challenge, with disease burden falling disproportionately on low- and middle-income countries (LMICs) due to a shortage of trained specialists and the subjective nature of colposcopy-based screening. To address this challenge, we propose a novel deep learning framework for the automated grading of Cervical Intraepithelial Neoplasia (CIN) and the prediction of clinical Swede scores. We also introduce the BUET Multi-Center Colposcopy Dataset, a novel, multi-center cohort designed and annotated for Swede score prediction and CIN grading. Our proposed dual-stream cross-attention architecture mimics the visual reasoning of an expert colposcopist by explicitly fusing paired multimodal cervigrams to evaluate comparative tissue responses. Furthermore, we introduce a custom composite loss function to address severe class imbalances and scoring inconsistencies across the five Swede score components. The proposed framework achieved 71.85% accuracy and an 86.23% AUC-ROC for three-class CIN grading, outperforming existing methods. For Swede score component prediction, the architecture achieved AUC-ROC values ranging from 75.7% to 88.4%, with the composite loss function yielding consistent F1-score improvements. Finally, the total predicted Swede Score, which ranges between 0 and 10, shows a Mean Absolute Error (MAE) of 1.489. The results show that the proposed method can pave the way towards developing AI-assisted colposcopy screening tools to support risk-based triage in resource-limited healthcare settings. The dataset and source code are publicly available(url: https://github.com/mHealthBuet/BUET-colposcopy)

Brain metastases exhibit high inter-lesion variability in size, enhancement pattern, and post-treatment appearance, making volumetric segmentation of both pre- and post-treatment cases the central challenge of the BraTS 2026 Task 1 (Brain Metastases). We build a pragmatic pipeline on a 5-fold nnU-Net ResEnc-L ensemble, in which each fold is trained independently for 1,000 epochs with the standard Dice + cross-entropy loss on 1,296 four-modality training cases. This ensemble is followed by a rule-based post-processing cascade tuned for the lesion-wise Dice similarity coefficient (LW-DSC), a detection-oriented metric that behaves very differently from the traditional global Dice. The final pipeline reaches an LW-DSC of 0.733 / 0.751 / 0.713 / 0.549 on the enhancing tumour (ET), tumour core (TC), whole tumour (WT), and resection cavity (RC) sub-regions on the official validation leaderboard. Rather than trusting these leaderboard gains, we audit every post-processing stage with a five-fold out-of-fold (OOF) analysis with no model-training leakage over all 1,296 training cases, scored with the official BraTS evaluation code (BraTS_evaluation): it confirms two stages as robust, per-fold-consistent improvements while the third improves only the leaderboard and does not reproduce out-of-fold. We further provide a mechanistic analysis of the LW-DSC metric that explains why recall-recovering post-processing carries low risk whereas component deletion does not, and we report thirteen negative results spanning loss engineering, alternative backbones, and inference-time settings, several of which run counter to widely held intuitions. Source code is released under Apache-2.0 at https://github.com/hornbeamliu/brats2026-met.

Lung cancer is one of the leading causes of death worldwide, and its early diagnosis is crucial to improving patients prognosis and quality of life. However, the process of interpreting medical images for the detection of lung cancer is complex and requires trained experts. In this context, artificial intelligence (AI) and deep learning (DL) emerge as potential tools to automate and optimize image analysis. The objective of this work is to review the most recent and relevant applications of AI and DL in the field of radiology for the detection of lung cancer. To this end, an exhaustive search was carried out in scientific databases such as PubMed,IEEEXPLORE, Scopus and Web of Science, and 96 articles published from 2015 to the present addressing the use of AI and DL in biomedical engineering were selected. Emphasis is placed on the use of convolutional neural networks (CNN) with transfer learning and Data Augmentation as promising techniques to improve the accuracy and efficiency of the image interpretation process. The results show that the use of AI and DL can offer an effective alternative for the early diagnosis of lung cancer, with high sensitivity and specificity. However, current limitations and challenges that must be addressed to guarantee its responsible and safe application in clinical practice are also identified, such as the lack of standardized data, the ex plainability of the models, patient privacy, and the ethical and social implications. It is concluded that the use of AI and DL can have a positive impact on the care of patients with lung cancer, but further research and regulation are required to ensure its quality and reliability.

High classification accuracy alone is insufficient for clinical image analysis, where calibrated confidence and reliable uncertainty estimates are essential. This study proposes a reliability-aware Hybrid-K ensemble selection framework for multiclass cervical cytology classification using the SIPaKMeD dataset. Nine deep learning architectures were evaluated using a fixed stratified five-fold partition and three training seeds. After post-hoc temperature scaling, models were assessed using macro-F1, accuracy, AUROC, expected calibration error (ECE), worst-class ECE (WC-ECE), area under the risk-coverage curve (AURC), Brier score, and negative log-likelihood (NLL). Models were ranked using an equal-weight composite score, and Hybrid-K ensembles were formed from the top-ranked models using soft voting. Robustness was examined using 5,000 Dirichlet-sampled metric-weight vectors, leave-one-metric-out analysis, and corrected paired testing across 15 fold-by-seed evaluations. The final Hybrid-2 ensemble, comprising Swin-Tiny and TinyViT-5M, reduced AURC by 43%, NLL by 17%, and WC-ECE by 36% relative to the best individual model. It was selected in 96.8% of random weighting scenarios, remained unchanged across all leave-one-metric-out analyses, and improved the full composite score. However, per-metric gains were not statistically significant after Holm-Bonferroni correction (all adjusted p >= 0.168). Because post-hoc calibration did not use a fully independent calibration set, calibration-dependent results should be interpreted as exploratory internal estimates. Overall, the framework identified a compact ensemble robust to alternative metric weightings and improved reliability point estimates under internal validation on a single dataset.

High-risk non-muscle-invasive bladder cancer (HR-NMIBC) carries substantial risks of recurrence and progression, while current clinical risk stratification remains limited. CHIMERA was established as a multimodal AI challenge to benchmark prediction in HR-NMIBC under standardized evaluation. Task BRS predicts RNA-seq-defined BCG Response Subtypes from histopathology and structured clinicopathological data, whereas Task Progression models time-to-progression using histopathology, structured data, and RNA sequencing. A multimodal dataset of 368 patients was divided into public training and hidden validation and test sets. In total, 159 submissions were made, and 13 top-performing models were selected for benchmarking. The best models achieved a weighted F1 score of 0.73 for Task BRS and a C-index of 0.68 for Task Progression. Post-challenge analyses revealed task-dependent modality contributions, cohort-dependent performance degradation, and sensitivity to missing structured data. In Task BRS, histopathology partly compensated for pathology-derived structured variables, whereas progression models showed greater dependence on complementary inputs. Cross-model error analysis further identified patients that were consistently difficult across different architectures, with T1 substage associated with prediction difficulty. These findings highlight barriers to transportability and the importance of missingness-aware modeling and independent multi-institutional validation. CHIMERA provides a standardized multimodal benchmark for bladder cancer and a framework for studying not only model performance, but also robustness, information sufficiency, and patient-level prediction failure.

Organoids are three-dimensional tissue models whose morphology provides important insights into tumor development, disease progression, and drug testing. Extracting these morphological features relies heavily on manual segmentation, which is time-consuming and labor-intensive. Furthermore, performing quantitative statistical analysis typically requires custom coding skills and a mathematical background, presenting a major barrier for experimental biologists. To address these challenges, we introduce MorphoOrgaAgent, a multi-agent framework that achieves zero-shot organoid segmentation, automated data analysis, and report generation based on natural language input. The framework consists mainly of three core components: a TaskUnderstandingAgent that identifies requested measurements and visualization types; a hybrid segmentation module that combines Cellpose-derived geometric prompts with text prompts to guide SAM3 for zero-shot organoid instance segmentation; and a ReportAgent that computes quantitative metrics and compiles them alongside generated visualizations into a structured report. We further introduce MorphoOrgaVQA, a benchmark designed for quantitative evaluation of agent systems in organoid morphology analysis. Experimental results demonstrate that MorphoOrgaAgent handles both explicit and descriptive user requests, produces measurements closely matching ground truth, and generates complete analysis reports without requiring manual programming. The complete source code and MorphoOrgaVQA benchmark are publicly available at https://github.com/peng-lab/MorphoOrgaAgent.

Background: Large language models (LLMs) show promise for extracting information from clinical free-text documents, but their outputs are often unstructured and lack traceability, complicating validation and adoption in clinical workflows. In this work we introduce SIFTING, an LLM-based framework designed to address these shortcomings. Methods: SIFTING combines the language comprehension capabilities of LLMs with segment-level processing and structured prompts with strict output control, linking findings to the source text to enable both accurate and transparent information extraction. To demonstrate its capabilities, we applied the framework to the task of extracting tumor T-stage information from 130 lung cancer radiology reports (SIFTING-T-stage). A compact 4-bit quantized version of the open-source LLM Llama-3.3-70B (35 GB) was used in a fully self-hosted setup, providing full control over data and model. Performance was evaluated against a reference standard created by four clinical experts and compared with a range of LLMs as used in a conventional single-prompt approach, using bootstrap resampling to estimate confidence intervals. Results: SIFTING-T-stage achieved an accuracy of 90% (95% CI: 84-95) against the reference standard. We found its performance to be comparable to even the largest state-of-the-art LLMs with reasoning capabilities and to be interchangeable with clinical experts (p < 0.001), while at the same time offering full traceability through source text references. Conclusion: SIFTING enables accurate, structured, and traceable information extraction from clinical free-text documents. It ensures data control, reproducibility, and verifiable outputs that can support clinical validation and workflow integration.

Clear cell renal cell carcinoma (CCRCC) grading is essential for treatment planning, yet existing approaches either analyze patch-level images directly or focus solely on nuclei-level classification, without linking to final tumor grading. We propose a semantic-guided multimodal preprocessing method that integrates nuclei classification maps from existing pre-trained models with RGB histopathology images for Vision Transformer (ViT)-based CCRCC grading. Our approach employs classification map channel concatenation and multiplicative modulation, with optimized overlays to leverage nuclei grading information, while preserving RGB textural features. Evaluation of multiple preprocessing strategies demonstrates that semantic-guided enhancement achieves 0.916 balanced accuracy, outperforming RGB-only baseline (0.707) and max-voting aggregation from prior studies (0.427). Sensitivity analysis reveals that this 21 percentage point improvement over baseline persists even under simulated perturbation at rates matching current state-of-the-art nuclei classification model error thresholds, suggesting both effective semantic utilization and practical robustness. These findings show that preprocessing-based multimodal fusion can leverage the diagnostic potential of existing imperfect nuclei classifiers, effectively bridging previously isolated fine-grained nuclear-level analysis with coarse-grained ViT-based patch classification. Per-class recall was consistent across grades (0.93, 0.91, 0.91), indicating that gains are not concentrated in the majority class. Because the sensitivity analysis perturbs ground-truth maps rather than predictions from an actual nuclei model, this result characterizes robustness under simulated error rather than deployment with a real upstream model, which remains for future work.

Reducing the review of clearly cancer-negative screening mammograms could lower radiologist workload without compromising cancer detection. We propose a closed-loop threshold-aware training strategy in which the dismissal threshold is recalculated during training and used to penalize cancer-positive images that approach the dismissal region. We evaluated the method on NLBS and RSNA using five controlled training configurations, with case-level assessment based on a one-sided 99% Clopper--Pearson upper bound for cancer prevalence among dismissed cases. The proposed model achieved the highest case-level dismissal rates at both 98% and 95% recall targets. On NLBS, dismissal reached 19.74% and 21.70%, while the cross-entropy baseline did not meet either recall target. On RSNA, dismissal improved from 7.04% to 14.31% and from 13.49% to 19.69%. In external RSNA$\to$NLBS evaluation, the proposed model achieved dismissal rates of 12.95% and 19.87% at the 98% and 95% recall targets, respectively. These results support closed-loop threshold-aware training for high-recall selective dismissal.

Clinically relevant oncology information is distributed across heterogeneous, longitudinal documentation, creating substantial abstraction burden and requiring accurate attribution across specimens, tumors, biomarkers, and time points, while manual cancer-registry abstraction can require 27.2 minutes per case, highlighting the need for scalable methods that preserve clinical context while converting documentation into structured data. We evaluate an oncology information-extraction workflow in which OncoLens supplies multi-source, oncology-aware document selection, aggregation, and normalization from integrated EHRs, while the NimbleMind Multi-Agent System (nMAS) is a configurable oncology information-extraction workflow that extracts clinically relevant structured fields from fragmented oncology documentation. The extraction task uses a clinician-informed schema of 328 attributes spanning report metadata, diagnosis, staging, and cancer-type-specific information. nMAS separates clinician-defined field specifications from model execution and combines complexity-aware extraction, report-level consolidation, and source-grounded validation. The retrospective evaluation included 230 de-identified oncology documents from 40 patients and 418 clinician-reviewed document-field pairs containing 1,126 non-empty reference values. Evaluation focused on fields identified by clinicians as present in the source documents rather than exhaustively annotating all 328 schema fields. nMAS achieved a rank-weighted value-level precision of 82.6%, recall of 87.5%, and F1 of 85.0%, compared with an F1 of 66.4% for an independently implemented UMA-style MiniMax M2.5 comparator. These findings support the feasibility of using a configurable, source-grounded extraction workflow to convert fragmented oncology documentation into reusable structured data.

Breast Cancer Multidisciplinary Team (MDT) meetings manage increasingly complex cases under considerable time pressure, and documentation requirements can reduce clinical efficiency and decision quality. Existing AI based MDT workflows rely on cloud-based processing, limiting their use because patient discussions contain identifiable information. We developed a fully on-device AI pipeline using open-source Automatic Speech Recognition (ASR) and Large Language Models (LLMs) that transcribes breast cancer MDT discussions, structures clinical information, and generates treatment recommendations using retrieval-augmented generation (RAG) grounded in National Institute for Health and Care Excellence (NICE) guidance. The pipeline runs on a single NVIDIA Jetson AGX Orin, ensuring that patient audio, transcripts, and outputs remain within institutional infrastructure. Evaluation included two recorded simulated MDT discussions, ten clinically validated synthetic discussions, and 1,270 acoustically augmented recordings. Optimisation of Whisper large-v3 reduced word error rate by 20.7% and 24.4% on the recorded discussions and achieved performance within 0.58% WER and 1.58% word information lost of a commercial clinical ASR benchmark on augmented audio. MedGemma-RAG identified 2.3 times more MDT-concordant interventions than a proprietary cloud comparator (p = 0.020), with no significant difference in overall accuracy. Stakeholders identified automated documentation, treatment recommendation support, and case triage as the most credible near-term applications while highlighting workflow integration, governance, and clinician trust as key implementation challenges. These findings demonstrate the feasibility of privacy-preserving, fully on-device AI for MDT documentation and guideline-informed decision support, providing a foundation for prospective clinical evaluation.

Pancreatic cancer is among the most lethal malignancies; risk stratification of intraductal papillary mucinous neoplasms (IPMNs) offers a crucial opportunity for early intervention but typically requires invasive tissue biopsy. Dominant vision-based approaches, including radiomics and deep learning, provide promising but initially separate discrimination opportunities. Similarly, multisequence MRI (T1W/T2W) and anatomically decomposed (head, body and tail) analysis of the pancreas provide additional and potentially complementary signals. Effective fusion of this information is crucial in ordinal IPMN dysplasia risk prediction and can be accomplished via a meticulously regularized and calibrated ensemble stacking combiner. We present cUPMI, a class-conditional Gaussian augmentation of a combiner's log-probability meta-features, and test it on various prediction paradigms. In our multi-center analysis, we find cUPMI adds limited value to properly regularized L2-logistic binary classification stacks, but consistently regularizes higher-capacity tree combiners in the binary and radiomics-only setting (RF +0.015 and XGBoost +0.024 binary AUC, positive in all seeds). Its cleanest ordinal benefit appears for XGBoost on an 8-stream radiomics task (3-class no < low < high, +0.022 QWK in all seeds). Separately, fold-locked fusion of radiomics and 2.5D CNN streams yields the strongest overall model, an RF stack reaching QWK 0.595 (95% CI [0.54, 0.64]) and binary AUC 0.839, surpassing radiomics, 2.5D ResNet, and 3D DenseNet-121 baselines.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, predominantly arising from precancerous polyps. Accurate detection, segmentation, and endoscopic and histological classification of colorectal polyps are crucial for timely clinical intervention. In this study, we present PolypVision, a three-stage hierarchical deep learning framework that sequentially performs: (Stage 1) binary classification of polyps as adenomatous or hyperplastic, with simultaneous Paris and JNet classification, using EfficientNetV2-M with Focal Loss; (Stage 2) polyp segmentation with recommended resection method using a UNet++ decoder with the Stage 1 backbone as encoder, optimized with Dice and BCE losses; and (Stage 3) adenoma subtype classification (tubular, tubulovillous, villous) using EfficientNetV2-M with transfer learning from Stage 2. Evaluated on three public datasets -- PolypGen, Kvasir-SEG, and CVC-ClinicDB -- PolypVision achieves an AUC of approximately 0.99 for frame classification and a detection mAP@50 of 94.4% on Kvasir-SEG, outperforming or matching state-of-the-art methods. Gradient-weighted Class Activation Maps (Grad-CAM) confirm that the model attends to clinically relevant lesion features. The framework is device-independent, operating across diverse endoscopic imaging systems without hardware-specific adaptation. These results demonstrate that a hierarchical, transfer-learning-driven pipeline with task-specific loss functions offers a robust, device-independent, and clinically meaningful approach to automated colorectal polyp analysis. PolypVision is freely available as a web application at https://polypvision.com, a DataBioX initiative, with a free usage tier open to all users.

Lung cancer remains one of the leading causes of cancer- related mortality worldwide. Although targeted therapies have improved outcomes for patients with non-small cell lung cancer (NSCLC), they rely on mutation profiling through tissue biopsy, an invasive procedure with several limitations. This study investigates PET/CT-based radio- genomic prediction of epidermal growth factor receptor (EGFR), tumour protein 53 (TP53), and Kirsten rat sarcoma viral oncogene (KRAS) mutations using deep learning. We further evaluate whether pairwise multi-label learning improves mutation prediction compared with conventional single-gene classification. To the best of our knowledge, this is among the first studies to systematically investigate multi-label learning for PET/CT radiogenomic mutation prediction in NSCLC. Experiments were conducted on a novel UK-based radiogenomics cohort. Joint pre- diction of KRAS and TP53 improved AUC from 0.58 to 0.64 for KRAS and from 0.69 to 0.71 for TP53. For the EGFR/KRAS pair, only EGFR benefited from joint learning, while no improvement was observed for the EGFR/TP53 pair. These findings demonstrate that the effectiveness of multi-label learning depends on the specific combination of gene mutations being modelled, suggesting that mutation-specific modelling strategies may be preferable for PET/CT radiogenomic prediction.

Foundation models provide transferable CT representations, but predictions based directly on these embeddings are difficult to interpret. We developed concept bottleneck models that map two frozen CT foundation-model representations to eight radiologist-defined pulmonary-nodule attributes and predict malignancy from the estimated concepts and nodule size. The models included CT-FM, a whole-CT self-supervised encoder using a 96^3-voxel nodule-centered patch, and FMCIB, a nodule-focused contrastive encoder using a 50-mm crop. Eight ridge-regression concept heads were trained on 2,610 LIDC-IDRI nodules. Malignancy models were trained on LUNA25 and evaluated on a held-out internal test set and the external DLCS cohort. Concept fidelity was assessed using five-fold cross-validated R^2, and malignancy discrimination was assessed using AUROC with 95% confidence intervals estimated by patient-grouped bootstrap resampling. Concept fidelity was modest but higher for FMCIB than CT-FM for subtlety (R2, 0.24 vs. 0.11), spiculation (0.17 vs. 0.08), texture (0.17 vs. 0.07), and lobulation (0.15 vs. 0.05). Internally, the CT-FM and FMCIB concept+size models achieved AUROCs of 0.86 (95% CI, 0.80-0.92) and 0.86 (0.79-0.92), respectively. Externally, AUROCs were 0.72 (0.68-0.75) and 0.73 (0.70-0.76), compared with 0.73 for nodule size alone and 0.60 and 0.67 for the corresponding embedding only probes. Additive predictions could be decomposed into feature-level contributions and modified through controlled concept interventions. Concept bottlenecks provided transparent malignancy predictions with discrimination similar to nodule size alone, while differences in concept fidelity suggest that concept recovery depends on the underlying foundation-model representation.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is central to breast cancer imaging, but gadolinium administration increases scan burden and motivates contrast-reduced alternatives, including synthetic contrast generation. We propose a latent bridge matching (LBM) framework for synthesizing peak-enhanced breast DCE-MRI from pre-contrast images in the MAMA-SYNTH challenge setting. Instead of starting from Gaussian noise as in conventional latent diffusion models (LDMs), the proposed model learns a conditional bridge between paired pre-contrast and peak-enhanced VAE latents. A latent UNet predicts the remaining correction from intermediate bridge states to the peak-enhanced latent, enabling iterative refinement while keeping the trajectory anchored to patient-specific anatomy. We evaluated two LBM conditioning variants on 91 DUKE validation cases. For the tumor-conditioned variant, tumor masks were used as conditioning inputs. Tumor-conditioning improved performance compared with pre-contrast conditioning, reducing MSE from 1.023 to 0.940 and FRD from 7.523 to 4.716, while increasing tumor SSIM from 0.355 to 0.429. The tumor-conditioned LBM also outperformed the evaluated LDM baseline on this validation cohort. These results suggest that latent bridge matching is a promising pre-contrast-anchored formulation for virtual contrast enhancement, while further work is needed to validate generalization and remove dependence on ground-truth tumor masks at inference.

Recent advances in machine learning have greatly improved breast cancer detection, enabling more accurate and timely diagnosis. Deep learning (DL) models show strong potential for medical image analysis; however, as their architectural complexity increases, their environmental impacts are becoming a growing concern. In this paper, we present a comparative analysis of seven DL models for breast cancer detection on two medical datasets: Breast Ultrasound and BreakHis 400X. The evaluated architectures range from Convolutional Neural Networks (CNNs) and transformers to hybrid models. In addition to performance metrics, we assess CO2 emissions during both training and inference. Our results show that EfficientNet and ResNet consistently deliver strong performance, although with higher CO2 emissions. The selected transformers, such as DeiT-Tiny, perform competitively on both datasets, whereas DenseNet121 achieves lower accuracy. On the Breast Ultrasound Dataset, DeiT provides the most favourable balance between accuracy and energy consumption, whereas on the BreakHis dataset, the ViT and Swin models achieve the best results. Overall, our findings indicate that no single architecture category from the evaluated ones consistently dominates across the two selected datasets. Our results highlight the importance of jointly considering performance, emissions, and dataset characteristics when selecting models for medical applications.

Pathologic complete response (pCR) is an important endpoint in neoadjuvant chemotherapy (NAC) for breast cancer, and predicting pCR from imaging during treatment could support treatment response assessment. Many existing imaging-based approaches rely on a single static timepoint, which fails to capture changes that occur during treatment. In this work, we present a longitudinal framework that combines a frozen 3D foundation encoder (Pillar-0) with our Temporal Dynamics Network (TDN) to predict treatment response from serial Dynamic Contrast-Enhanced (DCE) MRI acquired across four clinical timepoints from pre-treatment to pre-surgery. The TDN combines time-aware volumetric embeddings with clinical and treatment data to predict pCR. Evaluated on 982 patients from the combined I-SPY2 and ACRIN-6698 cohort, the proposed model achieves strong performance across all reported metrics when longitudinal 3D imaging is fused with clinical data (test AUROC: 73.6%, balanced accuracy: 69.1%). While clinical variables provide the strongest individual predictive signal, longitudinal 3D imaging contributes complementary information when fused with clinical data, improving pCR prediction. Our source code is available at: https://github.com/omarftt/longitudinal_temporal_pillar.

Survival analysis is an established framework for analyzing time-to-event data, yet many clinical machine learning studies still binarize the outcome before model training. This practice excludes censored patients, collapses temporal information into a single threshold, and can affect which features are selected as prognostically relevant. We examine the cost of this binarization in the context of Bayesian network (BN) feature selection, using two recent publications as case studies: one that applies BN-based feature selection to a head-and-neck cancer cohort and a second surgical cohort study that, while not BN-based, likewise binarizes its survival endpoint. We replace the binary scoring function with the Cox partial log-likelihood for feature-to-outcome edges, a modification we call the Survival-Aware Bayesian network, and recover prognostic features that binarization misses. Our ablation experiment confirms that the improvement is driven by the time-to-event scoring formulation rather than by retaining more patients. The results generalize across five endpoint-cohort combinations in head-and-neck cancer and extend to three further cancer types (breast, colorectal, and kidney). We propose that clinical studies with survival outcomes should use time-to-event methods by default, as binarization discards the prognostic signal retained by survival analysis.

Neuro-oncology decisions require coordinated interpretation of serial MRI, pathology, molecular markers, treatment history, performance status, and evolving guidelines. We present TumorBoard, a multi-agent decision-support system built around a shared longitudinal case state and an auditable claim-evidence ledger. Specialist agents for radiology, neuropathology, molecular diagnosis, guidelines, and therapy planning produce atomic claims with provenance. An adversarial critic exposes contradictions, and a safety governor releases, qualifies, or defers recommendations according to evidence sufficiency and temporal validity. On a 360-case hidden benchmark at a matched token budget, TumorBoard achieved an action F1 of 0.772 and evidence entailment of 0.914. It exceeded the strongest typed-council baseline by 3.1 percentage points (95% CI: 1.6 to 4.7, adjusted p = 0.0012), while recommendation-to-evidence coverage reached 0.927. Under evidence deletion, the system deferred 84.2% of unsafe cases and limited harmful recommendations to 5.8%. The safety governor reduced harmful release by 7.8 percentage points at a false-deferral cost of 4.3 percentage points. Ablation studies of the ledger, critic, and governor produced the predicted failure patterns, establishing structured coordination as the source of the measured multi-agent advantage.

Deep learning models can predict cancer recurrence from H&E stained slides, but the localized molecular states underlying these predictions remain largely obscured. Here, we developed an outcome informed spatial pathology framework in TNBC that integrates AI generated recurrence risk heatmaps with mass spectrometry based spatial proteomics. In a cohort of 156 patients, distribution based aggregation of high scoring patches achieved an AUC of 0.77 and a C-index of 0.77 in an independent test cohort. Bulk proteomics associated high image derived risk with cell cycle and genome maintenance programs and low risk with immune activation. High and low risk patches coexisted within the same tumor compartment and displayed distinct nuclear and architectural features, revealing intratumoral heterogeneity beyond tissue compartment identity. We then used the heatmaps as coordinate level guides to physically isolate and profile 46 AI defined tumor regions from two recurrence patients. Spatial proteomic profiling revealed a concordant molecular contrast across both patients: mitotic programs were enriched in high risk regions and immune and antigen presentation programs in low risk regions. A 13 protein composite derived from these spatial contrasts showed a trend toward poorer recurrence-free survival with increasing scores in an expanded cohort, while the corresponding transcript based composite stratified recurrence free survival in the independent METABRIC TNBC cohort. Integrating the protein composite with the H&E derived risk score improved the out of bag C-index from 0.679 to 0.739 and enhanced time dependent discrimination at 3 and 5 years. Together, these findings define a new role for outcome trained AI models as spatially explicit experimental guides that connect prognostic morphology with localized molecular states and advance biologically grounded, multiscale biomarker discovery in TNBC.

Lung cancer results in roughly 1.8 million fatalities annually worldwide, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Despite advancements in treatment, survival stratification remains challenging due to intratumoral heterogeneity inadequately captured by conventional descriptors. Standard radiomic and deep learning techniques regard imaging features as independent quantities, overlooking structured interactions between tumor characteristics. We evaluate whether structured proxy features can enhance multimodal NSCLC survival prediction by augmenting pretreatment computed tomography (CT) representations, radiomics, and clinical variables with six simulation-derived features designed to capture interactions between heterogeneity and morphology. A radiomic-parameterized cellular automaton generates growth-rate and necrosis-ratio proxy features from baseline CT by using entropy and sphericity to compute low-dimensional proxy parameters. The imaging backbone is a Transformer-based Masked Autoencoder (TMAE), which was chosen after a systematic evaluation with alternative encoders within the same pipeline and provides attention-based visualizations that highlight tumor regions receiving higher model attention. On the public Lung1 cohort (n = 390), the primary four-modality fusion attained a C-index of 0.641 (iAUC 0.731, log-rank p < 0.001). The primary result compares favorably with prior multimodal results on Lung1 (C-index 0.631; iAUC 0.592 [15]) under a comparable evaluation protocol, while a separate exploratory coefficient-optimization analysis achieved a best observed C-index of 0.662 (iAUC 0.748). These results indicate that, in addition to conventional radiomic, deep, and clinical representations within the Lung1 benchmark, simulation-derived proxy features may provide complementary predictive information within this fixed Lung1 benchmark.

Breast DCE-MRI AI is increasingly being explored for breast-level classification of no-lesion, benign, and malignant findings, beyond conventional lesion-centered diagnosis. Within this broader diagnostic scope, however, patient-specific background variability remains a major source of imaging confounding across classification tasks. Existing approaches predominantly focus on unilateral or lesion-centric analysis, whereas bilateral methods offer limited explicit modeling of spatially adaptive cross-breast correspondence. We propose PRISM-Net, a registration-free bilateral framework that leverages contralateral breast features as patient-specific references for background-aware representation learning. PRISM-Net integrates bilateral feature matching and asymmetry-aware attention to establish adaptive inter-breast correspondence and enhance representations of discriminative asymmetric patterns. On ODELIA, Macro AUC, Micro AUC, and quadratic weighted kappa were $84.11 \pm 2.33$, $90.64 \pm 1.61$, and $60.94 \pm 5.64$ on the in-distribution test set, and $68.51 \pm 4.54$, $80.74 \pm 2.68$, and $43.45 \pm 7.10$ on the held-out institution, respectively, outperforming the evaluated baseline methods across the primary evaluation metrics. PRISM-Net further demonstrated performance on independent institutional and background-complexity evaluations. Ablation experiments revealed that both bilateral relation modeling and asymmetry-aware reweighting contributed to improved classification performance. These findings highlight patient-specific bilateral reference modeling as a clinically grounded strategy for DCE-MRI interpretation, improving asymmetric pattern discrimination through explicit modeling of background complexity.

Background: Early prediction of distant metastasis (DM) risk in head and neck cancer (HNC) can enable timely interventions that may improve treatment outcomes. Many current machine learning methods rely on prior knowledge of the region of interest such as tumor segmentations, which require expert knowledge, is time-consuming and introduces user-dependent variability. Medical image-based foundation models have recently been developed for specific imaging modalities to streamline down-stream prediction tasks by extracting modality-relevant features. Purpose: In this study, we evaluate the effectiveness of using a foundation model as the feature extractor to predict DM risk in HNC patients and compare its performance with traditional approaches that require prior knowledge on the regions of interest. Methods: Preoperative CT images of 2327 patients from the RADCURE dataset were used. Three features-sets were created including radiomics, deep-learning based features, and CT Foundation derived features. The feature-sets were used individually in a multi-layer perceptron (MLP) to predict DM risk. Results: The model using CT Foundation embeddings outperformed the radiomics and deep learning-based models, achieving a Receiver Operating Characteristic Area Under the Curve (AUC) of 0.791, compared to AUC values of 0.772 and 0.753 for the radiomics and deep learning-based models, respectively. The CT Foundation based model had similar performance to a model that combined the use of radiomics and deep learning-based features that achieved an AUC of 0.794. Conclusions: Features based on foundation models offer a promising alternative to traditional radiomics while reducing the need for domain expertise and extensively annotated datasets. Their minimal preprocessing requirements also make them a more accessible and scalable option.

Enhancing classification performance in mammography remains a persistent challenge across both small curated datasets and large-scale clinical cohorts. Conventional transfer learning approaches often neglect dataset-specific characteristics, while recent neighborhood-informed methods have been restricted to narrow tasks with rigid formulations, limiting their scalability to population-level datasets. To address these challenges, we propose the Dataset-Informed Transfer Learning (DITL) framework, which integrates dataset-derived difficulty signals with neighborhood-based triplet supervision in a unified objective. DITL introduces two adaptive components: (i) Adaptive Difficulty-Weighted Cross-Entropy (A-DWCE), which assigns per-sample weights based on k-nearest neighbor label purity in a self-supervised feature space, and (ii) Adaptive Neighborhood Representation Triplet (A-NR-Triplet), which enforces intra-class compactness and inter-class separation using a learnable margin. Unlike focal loss, DITL requires no hyperparameter tuning, removes heuristic weighting and fixed margins, and incurs negligible computational overhead, yielding a robust and scalable optimization strategy. On the large-scale VinDR-Mammo dataset, DITL achieves state-of-the-art performance for whole-image breast density classification, with significant improvements across accuracy, F1-score, and AUC (p < 0.0001). Beyond large cohorts, DITL also delivers consistent, statistically significant gains on small ROI datasets (p < 0.0001). By bridging small-scale lesion analysis with large-scale density estimation, DITL establishes a clinically relevant, scalable, and generalizable framework for mammography classification, spanning the full breast cancer screening-to-diagnosis spectrum.

Dysphagia is a debilitating late effect of head and neck cancer (HNC) treatment, yet timely identification of at-risk patients remains challenging in survivorship care. Definitive assessment relies on videofluoroscopic imaging, as captured by the Dynamic Imaging Grade of Swallowing Toxicity (CTCAE-DIGEST), which, while validated, requires specialized equipment, trained personnel, and significant patient burden, limiting its routine use in surveillance. Patient-reported outcomes (PROs), by contrast, are low-cost, scalable, and easily collected at any clinical encounter, making them an attractive alternative signal for identifying patients who may warrant further evaluation. However, a clear clinical framework for translating PRO responses into actionable interventions is still evolving. In particular, uncertainty remains regarding when a patient's self-reported symptom burden should prompt escalation of care. This study addresses this gap by formulating a single-visit PRO-clinical prediction framework and introducing a clinically interpretable two-stage stacking model to predict swallowing impairment risk using PRO responses and structured clinical variables, without requiring videofluoroscopic imaging. The proposed framework quantifies the independent contributions of patient-reported symptoms and clinical factors within a unified and interpretable risk assessment model. Our findings demonstrate that individual MDADI responses contain predictive information beyond that captured by composite or global summary scores, while interpretability analyses reveal symptom patterns and clinical risk factors associated with swallowing impairment. Together, these results support the use of structured PRO-clinical integration as a practical, imaging-free approach for dysphagia risk stratification in HNC survivorship.

18F-FDG PET/CT plays a central role in staging, treatment planning, and response assessment for head and neck cancer by providing functional information that complements anatomical CT imaging. However, PET acquisition requires radiotracer administration, specialized infrastructure, and additional cost, limiting its availability for repeated imaging. We present a proof of concept deep learning framework for synthesizing PET like images directly from routine CT scans with the goal of providing complementary metabolic information that may support imaging triage and clinical decision support rather than replace diagnostic PET. Forty-four patients from the publicly available QIN-HEADNECK dataset were retrospectively analyzed using five fold cross-validation. We propose a fully three dimensional dual path architecture consisting of (i) a regression U-Net optimized for voxel-wise quantitative SUV estimation and (ii) a conditional generative adversarial network optimized for realistic PET texture. Their outputs are integrated using hotspot guided Laplacian pyramid blending, allowing quantitative information from the regression pathway to be preserved within metabolically active regions while leveraging adversarial texture synthesis elsewhere. The proposed framework achieved a mean absolute error of 0.00395, PSNR of 39.19 dB, and SSIM of 0.9634 on reconstructed three dimensional PET volumes. Qualitative evaluation demonstrated accurate localization of many FDG-avid lesions while producing anatomically realistic background texture. Consistent with previous CT to PET synthesis studies, the principal limitation was systematic underestimation of SUV within highly metabolically active tumor regions.

Whole-slide survival models commonly provide risk rankings without calibrated statements about individual event times. We evaluate fixed-cutoff drcosarc, a post-hoc conformal wrapper for discrete-time multiple-instance learning survival heads using frozen UNI2-h representations, in an internal 18-configuration sweep across five TCGA cohorts and an external five-configuration evaluation across three CPTAC cohorts. We distinguish configuration--fold--split summaries of the inverse-probability-of-censoring-weighted (IPCW) estimate and median lower predictive bound (LPB) from a hierarchy-aware patient-ensemble estimand of the mean drcosarc--naive LPB difference. At $α=0.1$, the drcosarc IPCW estimate was nearest 0.90 in KIRC, LUAD, and STAD. Patient-ensemble drcosarc--naive intervals excluded zero in KIRC, KIRP, STAD, UCEC, and CPTAC-CCRCC, but included zero in internal LUAD, CPTAC-LUAD, CPTAC-UCEC, and the internal LUSC extension. In a 20-replicate low-censoring semi-synthetic setting with known event times, drcosarc empirical coverage was 0.9129 [0.9053, 0.9207]. An exploratory analysis supported a head-error-by-censoring interaction within that data-generating process. In a two-cohort ABMIL sensitivity analysis, increasing the hazard grid to $K=16$ raised localized marginal IPCW estimates above the prespecified 0.87 threshold and yielded positive paired LPB differences, although worst-group estimates remained below 0.87. Overall, performance was cohort dependent, and its interpretation changed with the patient-level unit, estimand, and censoring assumptions.

The function of many genes is still unknown, and conventional driver-discovery methods, which rely on how frequently a gene is mutated, cannot assess genes that are only rarely affected. Here we pair Evo2-based genome analysis with routine clinical imaging to identify gene--phenotype associations at genome-wide scale. For every somatic mutation across three TCGA cohorts (cRCC=clear cell renal cell carcinoma, HCC=hepatocellular carcinoma, and BC=breast cancer; $n = 340$ total), Evo2 predicts a severity score, with no task-specific training. Per-gene severity summaries are then correlated with radiomic features extracted from paired tumor segmentations, controlling for total mutation burden. In TCGA-cRCC ($n = 162$), this sweep recovers established renal-cancer drivers and identifies 46 additional genes reaching false discovery rate (FDR) significance absent from curated cancer-gene panels, several of which are Mendelian ciliopathy and cytoskeletal-disease genes. These results demonstrate that pairing a genomic language model with widely available clinical imaging can serve as a hypothesis-free discovery tool for gene--imaging associations invisible to conventional approaches.

Federated learning has emerged as a potential solution to privacy concerns associated with using sensitive health data for training predictive models, particularly in personalised cancer care. This research investigates whether federated learning can support the development of robust models for predicting tumour progression in breast cancer patients while addressing four critical deployment pillars: transparency, scalability, security, and fairness. This study evaluates a federated learning framework using multimodal data, including clinical information, tumour characteristics, biomarker data, and patient demographics, alongside medical imaging data such as MRI scans, to model changes in tumour characteristics over time. The performance of the federated approach was compared with that of a centralised model trained on aggregated data. The report then further examines strategies to enhance secure model updates, maintain performance across patient subgroups, and support scalability across institutions. The findings assess whether federated learning can achieve predictive performance comparable to centralised learning while preserving data locality. These results contribute to understanding the feasibility of privacy-preserving, multimodal predictive modelling and support future applications such as digital twins to assist clinicians and patients in personalised treatment planning.

Breast cancer is one of the most widespread types of cancer, affecting approximately 8 million women worldwide. Electronic health records of patients diagnosed with this disease can serve as valuable datasets for computational analyses, enabling the discovery of new insights about the pathology. Unsupervised clustering, in particular, can identify groups of patients with medically significant features, revealing data trends that might otherwise go unnoticed by medical doctors. In this study, we first applied the DBSCAN density-based clustering method to three independent datasets derived from electronic medical records of patients with mammary carcinoma. Subsequently, to enhance our results, we preceded the DBSCAN application with a dimensionality reduction phase using UMAP. We evaluated our clustering outcomes using three statistical indices (DBCV, DCSI, and DISCO). Our results confirm the effectiveness of combining UMAP with DBSCAN for clustering data derived from electronic health records, paving the way for the medical interpretation of the patient groups identified by our approach.

Early and timely screening of laryngeal cancer is crucial for improving clinical outcomes. In recent years, NBI endoscopy has become a standard diagnostic tool for the detection of laryngeal lesions. However, its effective use requires well-trained clinicians and the procedure is time-consuming and subject to interobserver variability. In this context, the application of artificial intelligence (AI) offers a promising solution to support clinical decision-making. In this work, we proposed applying transformer and attention mechanism for analyzing the narrow band imaging and distinguish benign and malignant lesions. Results show it has good classification performance with F1 (82.72%), accuracy(82.33%). In addition, the result of laryngeal cancer screening is explainable for clinicians. The explainability is utilizing the state of art segmentation method (MedSAM) to provide the useful pathological information area for clinicians. The proposed methodology fusing classification and segmentation provides a translating on laryngeal cancer screening.

Ovarian cancer is the deadliest gynecological malignancy; accurate and objective segmentation of adnexal masses and functional ovaries in ultrasound (US) remains challenging due to operator variability and morphological complexity. We present OvAi Focus (SynDiag s.r.l., Italy), a stand-alone AI software medical device that performs multi-class semantic segmentation of functional ovaries and adnexal masses, distinguishing cystic from solid components. The system was trained and independently validated on a multicenter dataset of 1,081 adult women from 6 centers across Italy and Israel. Segmentation achieved DICE scores of 0.87 (complete lesion), 0.85 (cystic), 0.68 (solid), and 0.62 (functional ovary), in line with or superior to state-of-the-art approaches across heterogeneous acquisition settings.

Accurate determination of pancreatic ductal adenocarcinoma (PDAC) resectability relies on evaluating how the tumor interacts with major peripancreatic vessels on CT imaging, yet expert assessment often shows substantial variability. We introduce a fully automated multimodal deep learning framework that jointly analyzes 3D contrast enhanced CT and structured clinical information to classify patients into the three National Comprehensive Cancer Network (NCCN) resectability categories (upfront resectable, borderline resectable, locally advanced). The approach uses a Swin-UNETR backbone to obtain anatomy aware image representations through auxiliary segmentation of pancreas, tumor, and vascular structures. These features are fused with a compact clinical embedding derived from 17 routinely collected variables and processed by a lightweight classification head. Model training is guided by a dynamic multitask objective that adapts the balance between segmentation and classification based on current tumor Dice performance, promoting feature representations that remain both anatomically informed and discriminative.

Accurate dermatological diagnosis naturally necessitates equitable performance across diverse populations, yet a systematic lack of expertly annotated images, especially for underrepresented skin tones and rare diseases, impedes progress toward measurably fair methods. We introduce cgDDI (Controllable Generation of Diverse Dermatological Imagery), a hybrid framework that (1) synthesizes realistic healthy skin samples without disturbing other input properties, (2) maps single-sample rare lesions onto novel skin-tones and locations non-parametrically, and (3) allows for efficient parametric generation with as few as 10 training samples. The framework supports both human and automated segmentation masking, enabling scalability to datasets without pre-made lesion masks. We grow a 656-image dataset by more than 400x and validate across two datasets: biopsy-confirmed Diverse Dermatology Images (DDI) and expert-verified Fitzpatrick17k (F17k). On the DDI benchmark, we achieve malignancy classification accuracy of 86.4% under synthetic-only training and 90.9% state-of-the-art performance with real data fine-tuning, alongside leading fairness metrics. Cross-dataset experiments show +13.9% accuracy improvements on unseen F17k data despite minimal disease overlap. We openly release 266k+ synthetic images, code, and generative models to further support fairness research at https://github.com/hectorcarrion/ControllableGenDDI.

Limited-angle digital breast tomosynthesis (DBT) reconstructs a volume from a few low-dose projections over a narrow arc. At a representative nine-view, $25^{\circ}$ protocol more than 98% of image space is unmeasured, so a learned prior must supply structure in the missing wedge. Conditional diffusion priors achieve strong perceptual quality here but leave three clinical obstacles: inexact data consistency, unlocalized hallucination, and uncalibrated uncertainty. We enforce measurements exactly by replacing the per-step proximal update of a conditional diffusion sampler with exact Euclidean projection onto the data-consistent set, computed via an $m$-dimensional dual system with a one-time Gram matrix $AA^{\top}$ factorization. This projection costs 4.5 ms per step (a $248\times$ speedup) and drives the data residual to the double-precision floor ($2.4\times10^{-13}$). We prove it is the $ρ\to0$ limit of the proximal step, provide a no-harm theorem, and show that exactly consistent sample ensembles have variance supported on null($A$). Thus, the mean's entire error lies in the unmeasured subspace covered by the uncertainty map. On patient-derived breast phantoms, this improves fidelity at no depth-resolution cost. Conversely, a proximal step applied post-update degrades quality, isolating the consistency step's placement as decisive. Isotonic recalibration brings the ensemble spread to a calibrated error scale (expected calibration error $0.029\to0.008$; standardized error $4.7\to0.96$), ranking errors better than the pure prior. We also repair a 20.3% adjoint mismatch in a deployed projector via a materialized operator of record. This is the first data-consistent, uncertainty-calibrated learned reconstruction for limited-angle DBT. The solver naturally relaxes to discrepancy-ball and maximum-a-posteriori modes for noisy measurements.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths globally, with approximately 1,926,425 new cases and 904,019 deaths reported in 2022. Accurate histologic grading plays a critical role in prognosis and treatment planning for colorectal adenocarcinoma. In recent years, artificial intelligence and its subcategories, including machine learning and deep learning, have been increasingly employed for automated cancer detection and classification. An appropriate and well-organized dataset is the essential first step to achieve this goal. This paper introduces CRC-HGD, a histopathological microscopy image dataset of 1,914 images obtained from 214 colorectal adenocarcinoma patients (Grade I: 106, Grade II: 75, Grade III: 33). The specimens are H&E-stained colorectal tissue sections acquired at the Poursina Hakim Research Center of Isfahan University of Medical Sciences, Iran, diagnosed between 2014 and 2019, and graded according to the World Health Organization (WHO) criteria into three grades: well-differentiated (Grade I), moderately differentiated (Grade II), and poorly differentiated (Grade III). For each specimen, four magnification levels are provided: 4x, 10x, 20x, and 40x. The dataset is accessible via Mendeley Data (https://doi.org/10.17632/yfp5sfj47m.4) and at http://databiox.com, where the latest version is also available. The distinctive feature of this dataset is the provision of labeled specimens across all three differentiation grades at multiple magnification levels, enabling comprehensive computational analysis of colorectal cancer grading.

Background: Deep learning models can classify thyroid nodules on ultrasound, but reliable clinical decision support also requires calibrated probabilities, uncertainty estimation, and selective referral, particularly under dataset shift. Methods: We developed a calibrated deterministic five-member deep ensemble for ROI-based thyroid nodule classification and selective image-based triage. TN5000 was used for model development, five-fold cross-validation, member-wise vector-scaling calibration, and fold-specific threshold selection. TN3K served as an independent external dataset-shift evaluation. The framework used ConvNeXt-Tiny with squeeze-and-excitation attention, ensemble-mean malignancy probability, and mutual information (MI) as an ensemble-disagreement score. A three-tier policy assigned images to No-FNA suggestion, FNA recommendation, or radiologist review. Results: On pooled out-of-fold TN5000 predictions, the ensemble achieved AUC-ROC 0.9395, AP 0.9715, ECE 0.0088, and Brier score 0.0813. At 50% nominal MI retention, 7.2% of cases received a No-FNA suggestion, 39.9% an FNA recommendation, and 52.9% radiologist review, with 98.3% No-FNA NPV and 99.83% malignancy capture. On TN3K, AUC-ROC decreased to 0.7870, AP to 0.7254, ECE increased to 0.1899, and Brier score to 0.2281. The frozen TN5000 policy assigned 83.7% to review, 1.0% to No-FNA, and 15.3% to FNA recommendation. No malignant image entered the No-FNA pathway, but FNA-recommendation PPV fell to 76.6%. Conclusion: The framework showed strong internal discrimination and calibration, but limited external threshold transportability. Selective prediction may help identify images unsuitable for automated triage, but local recalibration, threshold validation, and prospective clinical evaluation are required before deployment.

Accurate cervical cytology image classification is a key component of automated cervical cancer screening, where reliable recognition of normal, precancerous, and cancer-associated cellular patterns from Pap smear images can improve screening efficiency and diagnostic consistency. However, this task remains challenging because cervical cells exhibit complex morphology, subtle intra-class variations, and strong inter-class similarities. Existing convolution-based models capture local texture well but have limited ability to model long-range relationships, whereas attention-based models provide broader context but often lack explicit structural guidance. To address these limitations, we propose a geometry-aware classification framework for cervical cancer screening-oriented cytology image analysis, incorporating semantic abstraction and structural priors learned from pre-trained vision-language features. The method uses Gaussian expert modules to generate axis-wise priors from global semantic information, capturing structural regularities such as nuclear alignment and cellular spatial organization. These priors are embedded into an axial self-attention module to modulate similarity computation along horizontal and vertical directions, improving long-range dependency modeling and structure-sensitive feature interaction. Experiments on the Mendeley liquid-based cytology and SIPaKMeD datasets show that the proposed method achieves 99.48% accuracy on the former and 96.08% on the latter, with balanced gains in recall, precision, and overall classification performance. Visual analysis further shows that the learned priors highlight diagnostically relevant cellular regions, demonstrating the potential of the proposed framework as a screening-oriented decision-support tool for cervical cytology.

Breast cancer remains the most commonly diagnosed malignancy among women worldwide, yet accurate detection and characterization of breast masses in mammography remain challenging due to subtle intensity variations, heterogeneous tissue densities, and indistinct lesion boundaries that complicate radiological interpretation. To address these limitations, we propose BiLoG-Net, a deep learning framework that jointly performs breast mass segmentation and malignancy classification through bi-context location-aware feature modeling and segmentation-guided attention mechanisms. Our architecture integrates a novel encoder-decoder paradigm with Fire-based feature extraction, lightweight global and local feature enhancement modules, and adaptive location-aware gating to simultaneously capture long-range contextual dependencies and fine-grained boundary-sensitive details. Unlike conventional multi-stage pipelines, our tightly coupled multi-task design enables mutual reinforcement between pixel-level localization and image-level diagnosis, reducing error propagation while producing spatially grounded malignancy predictions. Evaluated on CBIS-DDSM and INBreast benchmarks, BiLoG-Net achieves state-of-the-art performance with Dice scores of 94.20% and 93.10%, classification accuracies of 95.20% and 93.60%, and AUC values of 97.10% and 96.00%, respectively, substantially outperforming existing CNN and transformer-based baselines. By combining precise boundary delineation with reliable malignancy assessment in a single end-to-end model, this work holds strong potential for clinical computer-aided detection systems, helping radiologists prioritize suspicious cases and improve screening efficiency in busy clinical settings.

Cervical cytology classification models are typically evaluated on curated, class-balanced benchmarks, but real-world liquid-based cytology (LBC) collections are often small and class-imbalanced. This paper presents a class-imbalance-aware and calibration-aware ensemble classification study on the Mendeley LBC dataset, using its native four-class Bethesda taxonomy (NILM, LSIL, HSIL, SCC) rather than a collapsed binary formulation. Three lightweight architectures (Swin-Tiny, TinyViT-5M, DenseNet121) are trained directly on Mendeley LBC using weighted random sampling to counteract class imbalance, and compared against two soft-voting ensembles (Hybrid-2, Hybrid-3). Post-hoc temperature scaling is fit on a held-out calibration subset carved out of the training portion of each cross-validation fold, distinct from both the training data used to fit model weights and the evaluation fold used for final metrics, avoiding the optimistic calibration estimates that result when the same data is used for both purposes. Calibration substantially reduces expected calibration error, Brier score, and negative log-likelihood for every model and ensemble configuration tested, while discrimination metrics (accuracy, macro-F1, macro-AUROC) remain essentially unchanged. Ensemble size shows no consistent additional reliability benefit over the best individual model once all configurations are properly calibrated. Confusion matrices show that all classification errors, across every configuration, are confined to the boundary between high-grade lesions (HSIL) and carcinoma (SCC); no errors involve the negative (NILM) or low-grade (LSIL) categories. These results suggest that, for this dataset, calibration is the dominant lever for reliability, not ensemble size, though this conclusion should be read in light of the dataset's modest size.

Hepatocellular carcinoma (HCC) is a common malignancy and a leading cause of cancer-related mortality. Current guidelines and staging systems provide coarse categories, but often miss within-stage heterogeneity and the clinical context in electronic medical records (EMRs). We present HCC-STAR (Hepatocellular Carcinoma Staging, Treatment And pRognosis), a clinically aligned large language model that reads routine EMR narratives and jointly outputs risk score-based staging, ranked guideline-consistent treatments with evidence-based rationales, and individualized survival estimates. We curated about 30,000 HCC cases from SEER and expanded them into EMR-style narrative training data using a clinician-validated, prompt-based augmentation workflow. On this corpus, we developed a knowledge-aligned reasoning framework optimized with a step-verifiable composite reward, moving beyond text-level memorization of clinical guidelines. In a multi-center cohort of 6,668 patients from 12 hospitals in China, HCC-STAR achieved state-of-the-art performance in treatment recommendation and risk stratification compared with clinical guidelines and competitive models, including GPT-5 and Gemini-2.5 Pro. Hypothetical overall-survival analysis showed a median survival of 51 months under adherence to HCC-STAR recommendations, compared with 29 and 32 months under BCLC and CNLC. In clinician-centric evaluations, blinded hepatobiliary specialists rated HCC-STAR's reasoning and evidence-based justifications as trustworthy. The model surpassed resident and attending physicians in treatment accuracy and helped physicians make more accurate decisions faster when used as an assistant. These findings support HCC-STAR as a reliable and verifiable decision-support system for risk stratification and precision therapy in HCC.

Accurate prognosis prediction is important for treatment planning in lung cancer, but deep learning-driven survival modelling is often limited by the scarcity of curated imaging cohorts with reliable outcome data. This study evaluates whether representations from a domain-specific foundation model can be used for multimodal survival prediction in data-constrained clinical settings. We assess the foundation model CT-CLIP as a feature extractor for pretreatment computed tomography images and clinical variables from 242 diagnosed lung cancer patients. The evaluation includes adaptation strategies based on frozen encoders, full fine-tuning, and low-rank adaptation, together with modality ablations and comparisons with clinical and multimodal baselines. The results show that a frozen CT-CLIP model combined with a trainable lightweight survival head outperforms the clinical baseline and achieves comparable or improved performance relative to other multimodal approaches, and separates patients into clinically meaningful high- and low-risk groups.

Whole-body fluorodeoxyglucose positron emission tomography combined with computed tomography is widely used in cancer care, but manual lesion delineation is slow, subjective, and difficult to scale. We present GLOW-FDG, an open-source artificial intelligence model for whole-body cancer lesion segmentation in fluorodeoxyglucose positron emission tomography and computed tomography. The model was trained on 1,563 scans spanning multiple cancer types and evaluated on 185 external scans from independent institutions. Across breast cancer, nonmetastatic and oligometastatic lung cancer, head and neck cancer, and metastatic melanoma, GLOW-FDG consistently outperformed publicly available benchmark models in lesion detection, while reducing false positives and maintaining strong segmentation accuracy. Quantification of total tumor burden and total lesion glycolysis was robust across cohorts, and performance approached the variability observed between expert radiation oncologists. These results support GLOW-FDG as a generalizable tool for automated cancer segmentation and quantitative imaging biomarker extraction in whole-body imaging.

Sparse feature selection is critical for high-dimensional machine learning, yet traditional $\ell_1$-regularized methods are often brittle under observational noise and spurious correlations, leading to unstable feature supports and degraded generalization. Although adversarial training has been widely used to improve model robustness, its interaction with hierarchical sparse feature selection remains underexplored. In this work, we propose Adversarial LassoNet (AdLNet), a stability-driven sparse feature selection framework that integrates input-space adversarial perturbations with the hierarchical sparsity mechanism of LassoNet. We derive a tractable first-order adversarial approximation under local smoothness assumptions and provide an NTK-inspired spectral analysis to characterize how perturbation-driven training can reduce gradient concentration. Experiments on high-dimensional SERS data, six public benchmark datasets, and ColoredMNIST show that AdLNet maintains competitive sparse-selection performance while improving out-of-distribution robustness by 4.4% and feature support reproducibility by 6.3% under nearly matched support sparsity on ColoredMNIST. On the high-dimensional lung cancer screening dataset, AdLNet achieves a 5.3% test accuracy gain and a 6.0% AUC improvement over vanilla LassoNet. Code and dataset are available at https://github.com/719573/Adversarial-LassoNet.

This study aims to predict Tumor, Node, and Metastasis (TNM) stage labels independently, with the Cancer Genome Atlas (TCGA) pathology report as the sixth shared task of SMM4H-HeaRD 2026. The problem is framed as three multi-label classification tasks. We explore both classical and deep learning approaches using Term Frequency-Inverse Document Frequency (TF-IDF) features and embeddings from ClinicalBERT, BioBERT, and PubMedBERT. These representations are used with Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), Feed-Forward Neural Networks (FFNN), and Wide Residual Networks (WRN). Our results show that individual embeddings perform similarly to the TNM label classification, while their combination improves its predictive ability. WRN achieves AUROC scores of 0.839 (T), 0.8502 (N), and 0.803 (M) with F1-scores of 0.622, 0.702, and 0.9337, respectively, for the training phase. LightGBM with TF-IDF performs best with AUROC scores of 0.9368 (T), 0.9524 (N), and 0.8311 (M) and F1-scores of 0.7559 (T), 0.7384 (N), and 0.7017 (M) during the training phase. Furthermore, the result of the Codabench for the test sets indicates a Macro-F1 score of 0.978, 0.957, and 0.879 for the T, N, and M categories respectively for test set 1; while test set 2 records a Macro-F1 score for T, N, and M is 0.807, 0.767, 1.0 respectively. However, performance declined during the evaluation phase of the test sets, a drop from 0.938 to 0.858 of test set 1 to 2, for the Macro-F1 score across all stages; suggesting limitations in model generalizability, sensitivity to class imbalance, and challenges in processing lengthy clinical documents. Although this study provides an efficient baseline model and a reproducible pipeline, further optimization and validation are required before it can be considered suitable for use in a real-world clinical setting.

Breast fibroadenoma (FA) and phyllodes tumor (PT) are fibroepithelial breast lesions with highly overlapping appearances on B-mode ultrasound, making benign and borderline PT prone to being misclassified as FA and complicating preoperative decision-making. Existing computer-aided diagnosis methods commonly rely on single-modal imaging features and insufficiently exploit complementary clinical and textual information. To address this limitation, we construct the FAPT-M Dataset, a pathology-confirmed multimodal dataset comprising 910 patients with strictly reviewed ultrasound images, structured clinical attributes, and ultrasound diagnostic descriptions. Based on this dataset, we propose a clinically guided multimodal framework that integrates DenseNet-based visual encoding, CLIP-inspired text encoding, and lightweight clinical encoding, and further introduces clinical-conditioned adaptive modulation, cross-modal Transformer fusion, and dual-path representation learning to improve feature alignment and multimodal interaction. Under patient-level five-fold cross-validation, the proposed method achieves an accuracy of 77.64%, F1-score of 73.38%, and AUC of 89.74%, outperforming representative CNN-, Transformer-, and vision-language-based baselines. Ablation studies and class-balanced evaluations further confirm the contribution of three-modality fusion and the key architectural components. Overall, this work provides an effective multimodal approach for fine-grained FA-PT classification and establishes a high-quality benchmark for multimodal breast ultrasound analysis.

NA methylation profiling has become a powerful approach for central nervous system (CNS) tumor classification, yet important challenges remain regarding cross-cohort transferability, methodological correctness, and robust multiclass evaluation. In this work, we propose a novel and methodologically rigorous machine-learning approach for methylation-based CNS tumor classification that combines Sparse Random Projection for dimensionality reduction with multinomial logistic regression for classification. We evaluate the proposed approach in the same general experimental setting established by a widely used reference classifier. On the 2,801-sample reference cohort, our method achieves a mean accuracy of 96% under stratified 3-fold cross-validation. On the independent 1,104-sample clinical evaluation cohort, it reaches 86% accuracy at the 91-class level and 93% when predictions are evaluated at the methylation class family level. These results improve upon the corresponding state-of-the-art reference figures of 82% class-level concordance and 88% family-level concordance, yielding absolute gains of approximately 4 and 5 percentage points, respectively. This improvement is clinically relevant: in a diagnostic setting, a 5-point increase in correct tumor classification can directly affect cancer subtype assignment and, in turn, influence treatment selection and downstream clinical decision-making. Our results show that the proposed model, grounded in stronger methodological practice in machine learning, consistently outperforms the previous state of the art across evaluation settings and can materially improve the reliability of CNS tumor classification.

Radiomics is the established approach for CT-based lung cancer phenotyping, yet comparisons with foundation models rarely isolate contributions of feature extractor, classification head, and segmentation choice, or test cross-cohort robustness. We benchmark five feature extractors (Curia, Curia-2, DINOv3, Radiomics2D, Radiomics3D), seven classification heads (TabPFN, TabICL, XGBoost, CatBoost, Random Forest, logistic regression, Ridge), and three segmentation regimes on five tasks: tumor volume and stage classification, 2-year survival prediction, histology classification, and age prediction. Models are trained on LUNG1 (n=338) and evaluated on an internal test set (n=84) and the external LUNG2 cohort (n=211), with worst-case cross-cohort performance as the primary metric. The dominant design factor is task-dependent: segmentation drives volume and stage classification, while classifier choice drives survival, histology, and age prediction. Radiomics is competitive for tumor volume, tumor stage and survival (partly due to label-derivation effects for the former); Curia variants reach comparable peak scores for survival; DINOv3 falls slightly short across tasks. Patch and slice aggregation have negligible impact. We recommend Curia with tumor segmentation and a CatBoost head as a safe default, achieving the best mean rank across the three primary clinical tasks, though task-specific selection consistently outperforms any cross-task default. When tumor delineations are unavailable, Curia-2 with lung segmentation and logistic regression offers a competitive alternative. All pipelines use a two-stage design suited to small cohort sizes where end-to-end fine-tuning would risk overfitting.

We present a multi center breast fine needle aspiration cytology (FNAC) dataset designed for patch wise classification using C1 to C5 reporting labels. The prospective dataset includes 321 patients and 470 whole-slide images (WSIs) collected from participating tertiary medical centers in India between May 2023 and March 2026. Slides were stained using Papanicolaou (190 WSIs) or MayGrunwald Giemsa (280 WSIs), scanned on a Hamamatsu NanoZoomer S360 at 40X magnification and 0.25 microns per pixel, and stored directly in NDPI format. Across the 470 WSIs, 446 WSIs contain annotated patch regions, yielding 7,398 PNG image patches with expert-verified C1 to C5 labels. The release includes NDPI WSIs, WSI-level GeoJSON annotation files, extracted patch images, deidentified metadata, a data dictionary, a validation summary, a manifest linking WSIs to Zenodo records, and code for dataset inspection and reuse. The complete dataset is approximately 950 GB and is available through Zenodo.

H&E-stained whole-slide images offer cohort-scale availability and rich spatial context but lack molecular specificity, whereas bulk RNA-seq provides transcriptome-wide resolution at high cost with limited archival availability. We show that training a lightweight alignment module atop frozen histopathology and RNA-Seq foundation models enables open-vocabulary molecular prompting -- querying H&E slides with gene-set signatures to predict pathway activity without sequencing or end-to-end retraining. Using contrastive learning on a multi-cancer cohort (N=1,720), we achieve a 25-fold improvement in retrieval over baseline methods. Systematic analysis reveals a graduated predictability spectrum: morphologically grounded programs (cell-cycle programs, immune-related) are most reliably predicted (R^2>0.5), while predicting pathways with no morphological footprint remains challenging as expected. We validate clinical utility on the POSEIDON clinical trial: H&E-predicted squamous cell carcinoma scores recapitulate NSCLC subtype identity and predicted IFN-gamma mirror PD-L1 tumor-cell expression groups. Furthermore, genesets describing immune activation and fibrosis predict known tumor microenvironment archetypes from histology alone. We further validate generalization of our approach across unseen cohorts and demonstrate data-efficient domain adaptation, establishing a slide-native framework for molecular analysis on H&E images.

Multimodal Large Models have significantly advanced automated breast ultrasound diagnosis. However, most existing frameworks utilize opaque, end-to-end paradigms prioritizing global statistical correlations over structured clinical reasoning. Consequently, these models remain susceptible to shortcut learning amid extreme real-world epidemiological imbalances, often bypassing rare but decisive malignant indicators for dominant benign patterns. To address this disconnect, we propose Latent-CURE, a novel diagnostic framework driven by asymmetric weighted chain-of-thought methodology grounded in latent space reasoning. Unlike traditional approaches, our framework constructs an implicit reasoning trajectory forcing the model to sequentially infer standardized BI-RADS morphological descriptors before converging on a final diagnosis. Furthermore, to combat the extreme scarcity of critical malignant features, we couple this architecture with a dual-asymmetric optimization strategy. By dynamically adjusting margins and weights, this strategy safeguards high-specificity malignant descriptors from being overshadowed by common benign priors. Comprehensive evaluations demonstrate that our knowledge-injected approach provides transparent clinical evidence while achieving robust, accurate diagnostic performance in imbalanced medical cohorts.

Ovarian cancer is frequently diagnosed at an advanced stage, making preoperative contrast-enhanced computed tomography (CT) central to staging and surgical planning; yet the scarcity of annotated imaging data, compounded by privacy regulations, limits the development of generalizable computational models in this domain. Text-conditioned 3D CT synthesis has shown promise, but existing pipelines depend on paired radiology reports and have been evaluated only on chest CT. We propose OvESyn (Ovarian Evidence-based Synthesis), a framework that constructs standardized Findings and Impression sections directly from CT-derived imaging descriptors and routine clinical metadata, without any original radiology report, and uses them to condition a latent diffusion model adapted to 493 high-grade serous ovarian carcinoma patients. This is the first text-conditioned 3D CT synthesis framework adapted to an abdomino-pelvic oncologic setting. A systematic ablation over two adaptation axes, vision-language encoder alignment and generator fine-tuning, identifies generator domain adaptation as the operative mechanism for crossing the domain gap and establishing the target anatomy: without it, synthesis remains anchored to the thoracic pretraining domain, with Precision and Recall collapsing to zero and FID2.5D exceeding 140, regardless of encoder alignment. Encoder alignment instead refines intensity and fine detail. The full OvESyn attains the best distributional and intensity fidelity (FID2.5D 29.35, Precision 0.671, Wasserstein-1 0.044), while the generator-only variant maximizes coverage (Recall 0.645), reflecting a fidelity/coverage trade-off governed by encoder adaptation. Requiring only automatic segmentations and routine preoperative metadata, OvESyn supports transferability to report-scarce settings and provides a foundation for synthetic cohort generation in abdomino-pelvic oncologic imaging.

Predicting distant metastasis from the digital H & E slides of the primary tumor is a critical yet challenging task in computational pathology. Multiple Instance Learning (MIL) approaches can attend to subdomains in whole slide images (WSIs) that harbor features of pre-metastatic cancer regions. However, conventional MIL models largely treat tissue patches as unordered bags, discarding the spatial layout that defines how these regions are arranged and interact across the tissue. We propose that metastatic risk is shaped not only by local patch appearance, but also by the geometric organization of patches in the WSI and the interaction between the tissue compartments. To this end, we introduce Distance-aware Tissue Modeling for Multiple Instance Learning (DTMF-MIL), a spatial MIL framework that reinforces feature embeddings with explicit distance priors. By computing signed distance functions (SDFs) to capture regions with similar features, and representing each patch with radial-basis distance responses and local SDF statistics, DTMF-MIL learns positions of patches with respect to regional interiors and boundaries. The interactions between similar patches are contextualized across local tissue neighborhoods and used to guide slide-level attention while pooling patch feature evidence for metastasis prediction. We evaluate DTMF-MIL for prediction of distant prostate cancer metastasis in an internal prostate needle-biopsy cohort (IPC) from a large hospital system and on public TCGA-COAD and TCGA-KIRC datasets across multiple pathology foundation-model backbones. Across most dataset, backbone, and metric combinations, DTMF-MIL achieves the strongest results consistently.

Early detection of oral cancer markedly improves clinical outcomes, yet specialized diagnostic tools remain scarce in low-resource settings. Smartphone-based screening is a scalable alternative but needs lightweight models that run within edge-hardware constraints. Hybrid classical-quantum architectures are emerging candidates for parameter-efficient learning, yet most rely on qubit hardware that needs cryogenic operation, unsuitable for edge deployment. Continuous-variable (CV) photonic quantum computing, which operates at room temperature, offers a complementary route. We investigate a hybrid classical-CV quantum classifier for oral cancer detection from smartphone images. The pipeline combines a MobileNetV1 feature extractor, principal component analysis to 16 dimensions, and a parameterized CV-QNN of displacement, interferometric, and Kerr gates on a photonic backend. We propose a simplified $Φ\circ D \circ U_1$ CV-QNN architecture that cuts trainable parameters 40-45% relative to the standard CV-QNN layer of Killoran et al. (2019a), and identify dimensionality-reduction and encoding-restriction strategies that mitigate barren plateaus, raising loss-gradient variance by roughly 58 orders of magnitude. Whether the simplified layer beats the full layer is width-dependent: the full layer holds a small but significant edge at two qumodes, whereas the simplified layer is significantly better at four qumodes using 44% fewer parameters. The strongest model, a four-qumode simplified CV-QNN with only 18 parameters, attains the highest validation AUC of all models, exceeds a 55-parameter classical baseline using 67% fewer parameters, and reaches 100% calibrated test accuracy across all seeds. These results support CV photonic quantum machine learning for parameter-efficient, room-temperature medical image classification and motivate progress toward edge quantum AI.

Cross-domain diagnosis remains a major challenge in cervical cell pathology due to pronounced domain shifts across institutions and the subtle visual differences among disease stages, which jointly impair model generalization. To address these issues, this paper proposes a two-stage framework for cross-domain cervical cell detection. In the first stage, we propose the Spatially-Continuous Unpaired Neural Schrödinger Bridge (SC-UNSB), which constructs a synthetic intermediate domain to mitigate cross-domain distribution shifts by modeling image translation as an entropy-regularized optimal transport process. In the second stage, we propose a dual-level feature alignment strategy within a knowledge distillation, which progressively aligns shallow structural features and deep semantic representations to facilitate the transfer of domain-invariant knowledge from the source to the target model. Experimental results demonstrate that the proposed method effectively mitigates domain shift and category ambiguity, improving the cross-domain detection performance.

Accurate assessment of tumor proportion score (TPS) in non-small cell lung cancer (NSCLC) is critical for treatment planning and prognosis. Key challenges include the tedious manual work required to annotate each slide, combined with the limited number of experts certified for this task. Multiple instance learning (MIL) has proven to be an effective approach for predicting TPS scores at the slide level; however, existing methods struggle with non-expressive (zero class) images. Our approach involves two models: (1) an embedding-extraction and multiclass-classification network that captures the histopathological features of individual patches, and (2) a MIL model that aggregates these embeddings to predict zero-inflated beta (ZIBeta) parameters representing the overall TPS probability distribution for the entire slide. Using only slide-level TPS scores as labels, we demonstrate how this end-to-end framework can leverage a novel distribution-based architecture to improve prediction accuracy and explainability. ZIBeta modeling significantly outperforms baseline linear and ridge regression while capturing expected accuracy through distribution concentration.

Single-cell studies require analysts to convert raw measurements into specific biological claims through multi-step workflows and integration of metadata, assay context, and auxiliary evidence. Existing AI-biology benchmarks largely measure broad knowledge, executable workflows, or local analysis steps. We introduce scBench-Long, a benchmark for long-horizon single-cell biology in which agents must recover scientific conclusions from raw or near-raw data without prescribed methods. The benchmark contains 21 evaluations spanning melanoma CD8 T-cell reactivity, CD8 RNA+ATAC regulatory inference, human--monkey chimera development, KRAS-driven lung tumor aging, and lethal COVID-19 lung pathology. Tasks cover paired scRNA/TCR sequencing, RNA and chromatin profiling, cross-species transcriptomics, combinatorial scRNA-seq, single-nucleus RNA-seq, immune repertoires, ortholog maps, ligand--receptor resources, and validation evidence. Candidate claims are reproduced, reviewed, and converted into controlled answer vocabularies with deterministic grading and trajectory rubrics. Across 1,068 completed trajectories, the strongest model--harness pair passes 16/63 runs (25.4%). scBench-Long evaluates whether agents can move beyond local analysis steps and make complex scientific claims that are supported by single-cell data.