ToxLens: A Reproducible Graph-Learning Framework for Leakage-Aware, Uncertainty-Calibrated Molecular Toxicity Prediction

Molecular toxicity prediction is increasingly used to prioritise compounds before experimental testing, but conventional benchmark performance can overstate practical utility when structurally related molecules occur across training and test folds. We introduce ToxLens, a reproducible multi-task graph-learning framework for 11 toxicity endpoints spanning Ames mutagenicity, acute oral toxicity, hERG inhibition, and Tox21 nuclear-receptor and stress-response assays. The workflow combines conservative chemical curation, sphere-exclusion filtering, a leakage-aware UMAP-HDBSCAN split, parallel graph and global-feature encoders joined by late concatenation, temperature-scaled Monte Carlo dropout with conformal-style prediction sets, applicability-domain analysis, and SHAP-guided toxicophore discovery with occlusion controls. On the leakage-controlled test fold, a five-seed soft-voting ensemble achieved a Matthews correlation coefficient score of 0.44, an area under the receiver operating characteristic curve score of 0.83, and an area under the precision-recall curve score of 0.58. It exceeded four ECFP4-based shallow baselines on all 11 endpoints under the same split and validation-based threshold-selection protocol. Controlled ablations showed that the global pathway was important, whereas late concatenation outperformed the tested gated and feature-wise linear modulation fusion variants. Conformal-style prediction sets revealed substantial endpoint-specific variation in set efficiency, and discrimination and calibration improved with similarity to the training domain. Retraining on fixed published Tox21 Challenge and TDA folds produced competitive, but not uniformly state-of-the-art, performance. SHAP-guided occlusion and consensus subgraph mining yielded model-derived structural hypotheses, 44 of which contained at least one occurrence that passed the predefined counterfactual criteria.

Parameter-Efficient pretrained-CT-to-MRI Transfer for Rectal Cancer Segmentation: Performance-Calibration Trade-offs

Accurate rectal cancer segmentation from magnetic resonance imaging (MRI) is essential for adaptive radiotherapy and tumor response assessment, but deployment also requires computational efficiency and informative, calibrated uncertainty estimates. We therefore introduce SWIFT, a SWin pretrained model wIth parameter-eFficient and Tumor-aware fine-tuning for rectal cancer segmentation. A Swin V2 encoder pretrained on 10,444 public 3D CT volumes using a DINOv2-style objective was adapted to T2-weighted MRI through four cumulative configurations: full fine-tuning (SWIFT), decoder compression (SWIFTe), low-rank adaptation (SWIFTe-LoRA), and a four-member LoRA-decoder ensemble (SWIFTe-LDE4). Geometric accuracy, tumor detection, radiomic agreement, and probability calibration were evaluated on a held-out 247-case test set from a single-institution cohort acquired using 1.5 or 3 Tesla GE scanners. Compared with SWIFT, SWIFTe reduced total parameters by 70.1% (from 72.8M to 21.8M) and increased tumor detection rate from 89.9% to 93.9%, while achieving a slightly lower median surface DSC (0.61 versus 0.62) and improved radiomic agreement. In a separate SWIFTe ablation, removing tumor-aware augmentation reduced detection from 93.9% to 89.9% but increased surface DSC from 0.61 to 0.64, demonstrating a detection-boundary-agreement trade-off. SWIFTe-LoRA used 14.6% of SWIFTe's trainable parameters while retaining similar segmentation performance. SWIFTe-LDE4 achieved the lowest calibration errors among the four configurations after temperature scaling (expected calibration error, 0.217; Brier score, 0.222), although the absolute expected calibration error indicates residual miscalibration. Similar efficiency-calibration patterns were observed using the public VoCo checkpoint, supporting robustness across pretrained initializations rather than external clinical generalizability.

Evaluating and Calibrating Diffusion Model-derived Uncertainty for Quantitative MRI Mapping

Quantitative MRI (qMRI) provides standardised tissue parameter maps, but the reliability of deep learning-based qMRI mapping methods is often not explicitly characterised. In this work we systematically evaluate uncertainty maps for quantitative MRI derived from multiple inferences of a data-consistent diffusion model-based qMRI framework. Evaluation on synthetic test data assessed error-awareness, high-error detection, selective prediction, and Gaussian interval calibration. Diffusion model-derived uncertainty was positively associated with the mapping error, while risk-coverage analysis showed that excluding high-uncertainty voxels reduced the retained error. However, the raw uncertainty was poorly calibrated for quantitative interval interpretation. Calibration was substantially improved using a post-hoc procedure combining prediction-value-dependent bias correction with scalar uncertainty scaling. Qualitative evaluation on a healthy volunteer showed spatially meaningful uncertainty patterns. These results indicate that diffusion model-derived uncertainty is informative for reliability assessment and selective prediction, but requires calibration for quantitative interval interpretation.

When Confidence Fails: Overconfidence in LLMs under Uncertainty and Missing Clinical Information

Large Language Models (LLMs) have achieved strong performance in medical question answering and clinical reasoning tasks. However, their reliability under uncertainty remains poorly understood which raises critical concerns for deployment in high-stakes clinical settings. In such environments, incorrect predictions are inherently risky, but confident incorrect predictions can be particularly harmful as they may mislead clinical decision-making. In this paper, we conduct a systematic behavioral analysis of LLMs under clinical information uncertainty. We propose an evaluation framework based on the MedMCQA dataset consisting of two complementary uncertainty settings. First, we introduce linguistic uncertainty cues through prompt modifications to simulate ambiguous clinical contexts. Second, we construct an answer removal setting, wherein the correct option is deliberately excluded mandating the model to recognize insufficient information and abstain. We analyze both model accuracy and confidence behavior using multiple calibration metrics including calibration gap, Expected Calibration Error (ECE), and Unsafe Confident Error Rate (UCER) across 500 medical questions. Our results reveal a consistent failure mode, i.e., although accuracy degrades under increasing uncertainty, model confidence remains misaligned with accuracy. This leads to a substantial increase in unsafe confident errors, indicating that model confidence remains largely insensitive to clinically meaningful information loss. Furthermore, we observe significant variation across models in their ability to abstain when the correct answer is unavailable, with some models persistently producing high confidence hallucinated answers. These findings expose critical limitations in the epistemic reliability of current LLMs and highlight the need for uncertainty aware evaluation methods prior to their deployment in clinical workflows.

On-Device Multi-Species Malaria Detection with Uncertainty-Calibrated Slide-Level Aggregation

Malaria remains a leading cause of mortality in resource-limited settings, where expert microscopists are scarce. Automated diagnosis based on microscopy images thus has strong potential to improve care delivery. But for an algorithm to deploy, a necessary requirement is that it meet a suite of non-obvious (from a machine learning (ML) perspective) clinical constraints. Therefore, in close consultation with a national health center we developed a malaria diagnosis pipeline which addresses key requirements listed by the health care center but typically ignored in the ML malaria literature. In particular, it includes: (i) stopping criteria (to reduce image acquisition and time-to-result); (ii) human-in-the-loop functionality (for review and accountability); (iii) multi-species discrimination (since treatment varies by species); (iv) thick film detection (standard for microscopy); (v) computationally-efficient uncertainty calculations (to aid clinician review); and (vi) an edge device platform (since internet can be spotty in this catchment area). The mobile system performs all inference on-device using YOLOv13n deployed via TensorFlow Lite. It detects four species and white blood cells from Giemsa-stained thick blood smear images, aggregating per-image detections into slide-level parasitemia with World Health Organization (WHO)-standard quantification. This paper highlights these various clinical constraints and offers methods to address them. Evaluated on 2,739 annotated images across all four species, the system achieves mAP@0.5 of 0.863, per-image parasite count correlation of r = 0.812, slide-level r = 0.951 (soft counting, 10 images/slide), and runs entirely offline with a pipeline time of 10.27 +- 1.65 s per image.

Exact and Calibrated Diffusion Reconstruction for Digital Breast Tomosynthesis

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.

Interpretable Probabilistic Medical Image Segmentation via Gaussian Process with Explicit Modelling of Annotation Bias and Variability

Deep learning-based medical image segmentation models are trained using annotations that exhibit systematic bias and variability across raters. While probabilistic multi-rater approaches can emulate annotator-specific delineations, annotator characteristics are typically encoded implicitly in deep latent feature space, making direct analysis of their influence on predictive distributions less straightforward. We propose a logit-space probabilistic segmentation framework based on stochastic variational Gaussian Process that explicitly decomposes predictions into an image-dependent reference logit distribution and annotator specific perturbations parameterised by bias and variance. This formulation enables more explicit analysis on how intra- and inter-rater variability propagate to predictive distributions. We evaluate the method on a multi-annotator medical image dataset, which shows that explicitly modelling annotator specific perturbations improves uncertainty calibration while maintaining comparable segmentation accuracy, compared with state-of-the-art multi-rater probabilistic segmentation method. The learned bias and variance parameters quantitatively reflect annotator-specific behaviour. Furthermore, controlled perturbation experiments over bias and variance demonstrate how changes in annotator parameters systematically influence predictive performance. The code used in this paper is made publicly available at https://github.com/QiLi111/GPS-Var.