AURA: Active-Response Attribution under Treatment Ambiguity in Bacterial Cytological Profiling

When a bacterial sample is exposed to several antibiotics, not every applied drug necessarily acts: if the organism is resistant to one of them, that drug leaves no morphological trace. The clinically meaningful quantity is therefore not which antibiotics were applied, but which ones were active. We show that these two are sharply decoupled in real E. coli microscopy - naively assuming the applied combination equals the active one is correct only about 37% of the time - yet existing computational tools are ill-suited to recovering the active set. Forward perturbation models such as scGen, CPA, and IMPA are designed to predict appearance from treatment, not the reverse, and inverting them degrades sharply; discriminative image classifiers tend to memorise strain- and batch-specific texture and fail to transfer across experimental replicates. We introduce AURA, which reframes the task as constrained, energy-based inverse attribution. Its central inductive bias is that the active set must be a subset of the applied set; this collapses the candidate space and lets AURA infer the active subset of applied antibiotics by decomposing residual morphology into antibiotic response atoms and selecting the subset with the lowest reconstruction energy, using no strain label at test time. AURA-E adds evidence-aware abstention, withholding a prediction when candidate explanations remain near-equally plausible. On cross-replicate transfer in an E. coli cytological profiling dataset, AURA recovers the active antibiotic combination with 95.47% exact-match accuracy.

Physics-consistent deep learning for blind aberration recovery in mobile optics

Mobile photography is often limited by complex, lens-specific optical aberrations. While recent deep learning methods approach this as an end-to-end deblurring task, these "black-box" models lack explicit optical modeling and can hallucinate details. Conversely, classical blind deconvolution remains highly unstable. To bridge this gap, we present Lens2Zernike, a deep learning framework that blindly recovers physical optical parameters from a single blurred image. To the best of our knowledge, no prior work has simultaneously integrated supervision across three distinct optical domains. We introduce a novel physics-consistent strategy that explicitly minimizes errors via direct Zernike coefficient regression (z), differentiable physics constraints encompassing both wavefront and point spread function derivations (p), and auxiliary multi-task spatial map predictions (m). Through an ablation study on a ResNet-18 backbone, we demonstrate that our full multi-task framework (z+p+m) yields a 35% improvement over coefficient-only baselines. Crucially, comparative analysis reveals that our approach outperforms two established deep learning methods from previous literature, achieving significantly lower regression errors. Ultimately, we demonstrate that these recovered physical parameters enable stable non-blind deconvolution, providing substantial in-domain improvement on the patented Institute for Digital Molecular Analytics and Science (IDMxS) Mobile Camera Lens Database for restoring diffraction-limited details from severely aberrated mobile captures.

HD-TTA: Hypothesis-Driven Test-Time Adaptation for Safer Brain Tumor Segmentation

Standard Test-Time Adaptation (TTA) methods typically treat inference as a blind optimization task, applying generic objectives to all or filtered test samples. In safety-critical medical segmentation, this lack of selectivity often causes the tumor mask to spill into healthy brain tissue or degrades predictions that were already correct. We propose Hypothesis-Driven TTA, a novel framework that reformulates adaptation as a dynamic decision process. Rather than forcing a single optimization trajectory, our method generates intuitive competing geometric hypotheses: compaction (is the prediction noisy? trim artifacts) versus inflation (is the valid tumor under-segmented? safely inflate to recover). It then employs a representation-guided selector to autonomously identify the safest outcome based on intrinsic texture consistency. Additionally, a pre-screening Gatekeeper prevents negative transfer by skipping adaptation on confident cases. We validate this proof-of-concept on a cross-domain binary brain tumor segmentation task, applying a source model trained on adult BraTS gliomas to unseen pediatric and more challenging meningioma target domains. HD-TTA improves safety-oriented outcomes (Hausdorff Distance (HD95) and Precision) over several state-of-the-art representative baselines in the challenging safety regime, reducing the HD95 by approximately 6.4 mm and improving Precision by over 4%, while maintaining comparable Dice scores. These results demonstrate that resolving the safety-adaptation trade-off via explicit hypothesis selection is a viable, robust path for safe clinical model deployment. Code will be made publicly available upon acceptance.