Abstract
Keratitis is an inflammatory corneal condition responsible for 10% of visual impairment in low- and middleincome countries (LMICs), with bacteria, fungi, or amoeba as the most common infection etiologies. While an accurate and timely diagnosis is crucial for the selected treatment and the patients' sight outcomes, due to the high cost and limited availability of laboratory diagnostics in LMICs, diagnosis is often made by clinical observation alone, despite its lower accuracy. In this study, we investigate and compare different deep learning approaches to diagnose the source of infection: 1) three separate binary models for infection type predictions; 2) a multitask model with a shared backbone and three parallel classification layers (Multitask V1); and, 3) a multitask model with a shared backbone and a multi-head classification layer (Multitask V2). We used a private Brazilian cornea dataset to conduct the empirical evaluation. We achieved the best results with Multitask V2, with an area under the receiver operating characteristic curve (AUROC) confidence intervals of 0.7413-0.7740 (bacteria), 0.83950.8725 (fungi), and 0.9448-0.9616 (amoeba). A statistical analysis of the impact of patient features on models' performance revealed that sex significantly affects amoeba infection prediction, and age seems to affect fungi and bacteria predictions.

Abstract
Abstract Background. Breast cancer treatment has improved overall survival rates, with different locoregional approaches offering patients similar locoregional control but variable aesthetic outcomes that may lead to disappointment and poor quality of life (QoL). There are no standardized methods for informing patients of the different therapies prior to intervention, nor validated tools for evaluation of aesthetics and patients' expectations. The CINDERELLA Project is based on years of research and developments of new healthcare technologies by various partners, aimed to provide an artificial intelligence (AI) tool to aid shared decision-making by showing breast cancer patients the predicted aesthetic outcomes of their locoregional treatment. The clinical trial will evaluate the use of this tool within an AI cloud-based platform approach (CINDERELLA App) versus a standard approach. We anticipate that the CINDERELLA App will lead to improved satisfaction, psychosocial well-being and health-related QoL while maintaining the quality of care and providing environmental and economic benefits. Trial design. CINDERELLA is an international multicentric interventional randomized controlled open-label clinical trial. Using the CINDERELLA App, the AI and Digital Health arm will provide patients with complete information about the proposed types of locoregional treatments and photographs of similar patients previously treated with the same techniques. The Control arm will follow the standard approach of each clinical site. Randomization will be conducted online using the digital health platform CANKADO, ensuring a balanced distribution of participants between the two groups. CANKADO is the underlying platform through which physicians control the patients' app content and conduct all data collection. Privacy, data protection and ethical principles in AI usage were taken into account. Eligibility criteria. Patients diagnosed with primary breast cancer without evidence of systemic disease. All patients must sign an informed consent and be able to use a web-based app autonomously or with home-based support. Specific aims. Primary objective: to assess the levels of agreement among patients' expectations regarding the aesthetic outcome before and 12 months after locoregional treatment. The trial will also evaluate the aesthetic outcome level of agreement between the AI evaluation tool and self-evaluation. Secondary objectives: health-related QoL (EQ-5D-5L and BREAST-Q ICHOM questionnaires) and resource consumption (e.g., time spent in the hospital, out-of-pocket expenses). The questionnaires and photographs will be applied prior to any treatment, at wound healing, at 6 and 12 months following the completion of locoregional therapy. Statistical methods. Wilcoxon signed rank test will be used to assess the intervention's impact on the agreement level between expectations and obtained results. Weighted Cohen's kappa will be calculated to measure the improvement in classifying aesthetic results with intervention. Statistical tests and/or bootstrap techniques will compare results between arms. A similarity measure will be calculated between self-evaluation and outcome obtained with the AI tool for each participant, and a beta regression model will be used to analyze the intervention's effect. Secondary objectives will be evaluated by scoring questionnaires based on provided guidelines. Target accrual. The clinical trial, led by Champalimaud Clinical Centre, will enroll a minimum of 515 patients in each arm between July 2023 and January 2025. Recruitment is currently open at five study sites in Germany, Israel, Italy, Poland and Portugal. The clinical trial is still open for further international study sites. Funding. European Union grant HORIZON-HLTH-2021-DISEASE-04-04 Agreement No. 101057389. Citation Format: Eduard-Alexandru Bonci, Orit Kaidar-Person, Marília Antunes, Oriana Ciani, Helena Cruz, Rosa Di Micco, Oreste Davide Gentilini, Nicole Rotmensz, Pedro Gouveia, Jörg Heil, Pawel Kabata, Nuno Freitas, Tiago Gonçalves, Miguel Romariz, Helena Montenegro, Hélder P. Oliveira, Jaime S. Cardoso, Henrique Martins, Daniela Lopes, Marta Martinho, Ludovica Borsoi, Elisabetta Listorti, Carlos Mavioso, Martin Mika, André Pfob, Timo Schinköthe, Giovani Silva, Maria-Joao Cardoso. CINDERELLA Clinical Trial (NCT05196269): using artificial intelligence-driven healthcare to enhance breast cancer locoregional treatment decisions [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-11.

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Abstract
Breast cancer locoregional treatment causes alterations to the physical aspect of the breast, often negatively impacting the self-esteem of patients unaware of the possible aesthetic outcomes of those treatments. To improve patients' self-esteem and enable a more informed choice of treatment when multiple options are available, the possibility to predict how the patient might look like after surgery would be of invaluable help. However, no work has been proposed to predict the aesthetic outcomes of breast cancer treatment. As a first step, we compare traditional computer vision and deep learning approaches to reproduce asymmetries of post-operative patients on pre-operative breast images. The results suggest that the traditional approach is better at altering the contour of the breast. In contrast, the deep learning approach succeeds in realistically altering the position and direction of the nipple.

Abstract
In fields that rely on high-stakes decisions, such as medicine, interpretability plays a key role in promoting trust and facilitating the adoption of deep learning models by the clinical communities. In the medical image analysis domain, gradient-based class activation maps are the most widely used explanation methods and the field lacks a more in depth investigation into inherently interpretable models that focus on integrating knowledge that ensures the model is learning the correct rules. A new approach, B-cos networks, for increasing the interpretability of deep neural networks by inducing weight-input alignment during training showed promising results on natural image classification. In this work, we study the suitability of these B-cos networks to the medical domain by testing them on different use cases (skin lesions, diabetic retinopathy, cervical cytology, and chest X-rays) and conducting a thorough evaluation of several explanation quality assessment metrics. We find that, just like in natural image classification, B-cos explanations yield more localised maps, but it is not clear that they are better than other methods' explanations when considering more explanation properties.