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Nuclear-derived morphological features and biomarkers provide relevant insights regarding the tumour microenvironment, while also allowing diagnosis and prognosis in specific cancer types. However, manually annotating nuclei from the gigapixel Haematoxylin and Eosin (H&E)-stained Whole Slide Images (WSIs) is a laborious and costly task, meaning automated algorithms for cell nuclei instance segmentation and classification could alleviate the workload of pathologists and clinical researchers and at the same time facilitate the automatic extraction of clinically interpretable features for artificial intelligence (AI) tools. But due to high intra- and inter-class variability of nuclei morphological and chromatic features, as well as H&Estains susceptibility to artefacts, state-of-the-art algorithms cannot correctly detect and classify instances with the necessary performance. In this work, we hypothesize context and attention inductive biases in artificial neural networks (ANNs) could increase the performance and generalization of algorithms for cell nuclei instance segmentation and classification. To understand the advantages, use-cases, and limitations of context and attention-based mechanisms in instance segmentation and classification, we start by reviewing works in computer vision and medical imaging. We then conduct a thorough survey on context and attention methods for cell nuclei instance segmentation and classification from H&E-stained microscopy imaging, while providing a comprehensive discussion of the challenges being tackled with context and attention. Besides, we illustrate some limitations of current approaches and present ideas for future research. As a case study, we extend both a general (Mask-RCNN) and a customized (HoVer-Net) instance segmentation and classification methods with context- and attention-based mechanisms and perform a comparative analysis on a multicentre dataset for colon nuclei identification and counting. Although pathologists rely on context at multiple levels while paying attention to specific Regions of Interest (RoIs) when analysing and annotating WSIs, our findings suggest translating that domain knowledge into algorithm design is no trivial task, but to fully exploit these mechanisms in ANNs, the scientific understanding of these methods should first be addressed.

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Abstract The increasing popularity of attention mechanisms in deep learning algorithms for computer vision and natural language processing made these models attractive to other research domains. In healthcare, there is a strong need for tools that may improve the routines of the clinicians and the patients. Naturally, the use of attention-based algorithms for medical applications occurred smoothly. However, being healthcare a domain that depends on high-stake decisions, the scientific community must ponder if these high-performing algorithms fit the needs of medical applications. With this motto, this paper extensively reviews the use of attention mechanisms in machine learning (including Transformers) for several medical applications. This work distinguishes itself from its predecessors by proposing a critical analysis of the claims and potentialities of attention mechanisms presented in the literature through an experimental case study on medical image classification with three different use cases. These experiments focus on the integrating process of attention mechanisms into established deep learning architectures, the analysis of their predictive power, and a visual assessment of their saliency maps generated by post-hoc explanation methods. This paper concludes with a critical analysis of the claims and potentialities presented in the literature about attention mechanisms and proposes future research lines in medical applications that may benefit from these frameworks.

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Algorithmic bias in healthcare mirrors existing data biases. However, the factors driving unfairness are not always known. Medical devices capture significant amounts of data but are prone to errors; for instance, pulse oximeters overestimate the arterial oxygen saturation of darker-skinned individuals, leading to worse outcomes. The impact of this bias in machine learning (ML) models remains unclear. This study addresses the technical challenges of quantifying the impact of medical device bias in downstream ML. Our experiments compare a “perfect world”, without pulse oximetry bias, using SaO2 (blood-gas), to the “actual world”, with biased measurements, using SpO2 (pulse oximetry). Under this counterfactual design, two models are trained with identical data, features, and settings, except for the method of measuring oxygen saturation: models using SaO2 are a “control” and models using SpO2 a “treatment”. The blood-gas oximetry linked dataset was a suitable test-bed, containing 163,396 nearly-simultaneous SpO2 - SaO2 paired measurements, aligned with a wide array of clinical features and outcomes. We studied three classification tasks: in-hospital mortality, respiratory SOFA score in the next 24 h, and SOFA score increase by two points. Models using SaO2 instead of SpO2 generally showed better performance. Patients with overestimation of O2 by pulse oximetry of = 3% had significant decreases in mortality prediction recall, from 0.63 to 0.59, P < 0.001. This mirrors clinical processes where biased pulse oximetry readings provide clinicians with false reassurance of patients’ oxygen levels. A similar degradation happened in ML models, with pulse oximetry biases leading to more false negatives in predicting adverse outcomes. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.

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