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Imaging"],"abstract":"<jats:p>Domain shift poses a major challenge in many Machine Learning applications due to variations in data acquisition protocols, particularly in the medical field. Test-time augmentation (TTA) can solve the domain shift issue and improve robustness by aggregating predictions from multiple augmented versions of the same input. However, TTA may inadvertently generate unrealistic or Out-of-Distribution (OOD) samples that negatively affect prediction quality. In this work, we introduce a filtering procedure that removes from the TTA images all the OOD samples whose representations lie far from the training data distribution. Moreover, all the retained TTA images are weighted inversely to their distance from the training data. The final prediction is provided by a Self-Ensemble with Confidence, which is a lightweight ensemble strategy that fuses predictions from the original and retained TTA samples using a weighted soft voting scheme, without requiring multiple models or retraining. This method is model-agnostic and can be integrated with any deep learning architecture, making it broadly applicable across various domains. Experiments on cross-domain leukocyte classification benchmarks demonstrate that our method consistently improves over standard TTA and Baseline inference, particularly when strong domain shifts are present. Ablation studies and statistical tests confirm the effectiveness and significance of each component.<\/jats:p>","DOI":"10.3390\/jimaging11090295","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T10:29:18Z","timestamp":1756376958000},"page":"295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Test-Time Augmentation for Cross-Domain Leukocyte Classification via OOD Filtering and Self-Ensembling"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-8793","authenticated-orcid":false,"given":"Lorenzo","family":"Putzu","sequence":"first","affiliation":[{"name":"Department of Electrical and Electronic Engineering, University of Cagliari, 09123 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6571-3816","authenticated-orcid":false,"given":"Andrea","family":"Loddo","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Computer Science, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-0307","authenticated-orcid":false,"given":"Cecilia","family":"Di Ruberto","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Computer Science, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Burton, A.G., and Jandrey, K.E. 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