Rising adoption of artificial intelligence in scientific publishing: evaluating the role, risks, and ethical implications in paper drafting and review process.

BACKGROUND: In the rapid evolving landscape of artificial intelligence (AI), scientific publishing is experiencing significant transformations. AI tools, while offering unparalleled efficiencies in paper drafting and peer review, also introduce notable ethical concerns. CONTENT: This study delineates AI's dual role in scientific publishing: as a co-creator in the writing and review of scientific papers and as an ethical challenge. We first explore the potential of AI as an enhancer of efficiency, efficacy, and quality in creating scientific papers. A critical assessment follows, evaluating the risks vs. rewards for researchers, especially those early in their careers, emphasizing the need to maintain a balance between AI's capabilities and fostering independent reasoning and creativity. Subsequently, we delve into the ethical dilemmas of AI's involvement, particularly concerning originality, plagiarism, and preserving the genuine essence of scientific discourse. The evolving dynamics further highlight an overlooked aspect: the inadequate recognition of human reviewers in the academic community. With the increasing volume of scientific literature, tangible metrics and incentives for reviewers are proposed as essential to ensure a balanced academic environment. SUMMARY: AI's incorporation in scientific publishing is promising yet comes with significant ethical and operational challenges. The role of human reviewers is accentuated, ensuring authenticity in an AI-influenced environment. OUTLOOK: As the scientific community treads the path of AI integration, a balanced symbiosis between AI's efficiency and human discernment is pivotal. Emphasizing human expertise, while exploit artificial intelligence responsibly, will determine the trajectory of an ethically sound and efficient AI-augmented future in scientific publishing.

Second opinion machine learning for fast-track pathway assignment in hip and knee replacement surgery: the use of patient-reported outcome measures.

BACKGROUND: The frequency of hip and knee arthroplasty surgeries has been rising steadily in recent decades. This trend is attributed to an aging population, leading to increased demands on healthcare systems. Fast Track (FT) surgical protocols, perioperative procedures designed to expedite patient recovery and early mobilization, have demonstrated efficacy in reducing hospital stays, convalescence periods, and associated costs. However, the criteria for selecting patients for FT procedures have not fully capitalized on the available patient data, including patient-reported outcome measures (PROMs). METHODS: Our study focused on developing machine learning (ML) models to support decision making in assigning patients to FT procedures, utilizing data from patients' self-reported health status. These models are specifically designed to predict the potential health status improvement in patients initially selected for FT. Our approach focused on techniques inspired by the concept of controllable AI. This includes eXplainable AI (XAI), which aims to make the model's recommendations comprehensible to clinicians, and cautious prediction, a method used to alert clinicians about potential control losses, thereby enhancing the models' trustworthiness and reliability. RESULTS: Our models were trained and tested using a dataset comprising 899 records from individual patients admitted to the FT program at IRCCS Ospedale Galeazzi-Sant'Ambrogio. After training and selecting hyper-parameters, the models were assessed using a separate internal test set. The interpretable models demonstrated performance on par or even better than the most effective 'black-box' model (Random Forest). These models achieved sensitivity, specificity, and positive predictive value (PPV) exceeding 70%, with an area under the curve (AUC) greater than 80%. The cautious prediction models exhibited enhanced performance while maintaining satisfactory coverage (over 50%). Further, when externally validated on a separate cohort from the same hospital-comprising patients from a subsequent time period-the models showed no pragmatically notable decline in performance. CONCLUSIONS: Our results demonstrate the effectiveness of utilizing PROMs as basis to develop ML models for planning assignments to FT procedures. Notably, the application of controllable AI techniques, particularly those based on XAI and cautious prediction, emerges as a promising approach. These techniques provide reliable and interpretable support, essential for informed decision-making in clinical processes.

Where is laboratory medicine headed in the next decade? Partnership model for efficient integration and adoption of artificial intelligence into medical laboratories.

OBJECTIVES: The field of artificial intelligence (AI) has grown in the past 10 years. Despite the crucial role of laboratory diagnostics in clinical decision-making, we found that the majority of AI studies focus on surgery, radiology, and oncology, and there is little attention given to AI integration into laboratory medicine. METHODS: We dedicated a session at the 3rd annual European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) strategic conference in 2022 to the topic of AI in the laboratory of the future. The speakers collaborated on generating a concise summary of the content that is presented in this paper. RESULTS: The five key messages are (1) Laboratory specialists and technicians will continue to improve the analytical portfolio, diagnostic quality and laboratory turnaround times; (2) The modularized nature of laboratory processes is amenable to AI solutions; (3) Laboratory sub-specialization continues and from test selection to interpretation, tasks increase in complexity; (4) Expertise in AI implementation and partnerships with industry will emerge as a professional competency and require novel educational strategies for broad implementation; and (5) regulatory frameworks and guidances have to be adopted to new computational paradigms. CONCLUSIONS: In summary, the speakers opine that the ability to convert the value-proposition of AI in the laboratory will rely heavily on hands-on expertise and well designed quality improvement initiative from within laboratory for improved patient care.

Potentials and pitfalls of ChatGPT and natural-language artificial intelligence models for the understanding of laboratory medicine test results. An assessment by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Artificial Intelligence (WG-AI).

OBJECTIVES: ChatGPT, a tool based on natural language processing (NLP), is on everyone's mind, and several potential applications in healthcare have been already proposed. However, since the ability of this tool to interpret laboratory test results has not yet been tested, the EFLM Working group on Artificial Intelligence (WG-AI) has set itself the task of closing this gap with a systematic approach. METHODS: WG-AI members generated 10 simulated laboratory reports of common parameters, which were then passed to ChatGPT for interpretation, according to reference intervals (RI) and units, using an optimized prompt. The results were subsequently evaluated independently by all WG-AI members with respect to relevance, correctness, helpfulness and safety. RESULTS: ChatGPT recognized all laboratory tests, it could detect if they deviated from the RI and gave a test-by-test as well as an overall interpretation. The interpretations were rather superficial, not always correct, and, only in some cases, judged coherently. The magnitude of the deviation from the RI seldom plays a role in the interpretation of laboratory tests, and artificial intelligence (AI) did not make any meaningful suggestion regarding follow-up diagnostics or further procedures in general. CONCLUSIONS: ChatGPT in its current form, being not specifically trained on medical data or laboratory data in particular, may only be considered a tool capable of interpreting a laboratory report on a test-by-test basis at best, but not on the interpretation of an overall diagnostic picture. Future generations of similar AIs with medical ground truth training data might surely revolutionize current processes in healthcare, despite this implementation is not ready yet.

Accuracy of automated 3D cephalometric landmarks by deep learning algorithms: systematic review and meta-analysis.

OBJECTIVES: The aim of the present systematic review and meta-analysis is to assess the accuracy of automated landmarking using deep learning in comparison with manual tracing for cephalometric analysis of 3D medical images. METHODS: PubMed/Medline, IEEE Xplore, Scopus and ArXiv electronic databases were searched. Selection criteria were: ex vivo and in vivo volumetric data images suitable for 3D landmarking (Problem), a minimum of five automated landmarking performed by deep learning method (Intervention), manual landmarking (Comparison), and mean accuracy, in mm, between manual and automated landmarking (Outcome). QUADAS-2 was adapted for quality analysis. Meta-analysis was performed on studies that reported as outcome mean values and standard deviation of the difference (error) between manual and automated landmarking. Linear regression plots were used to analyze correlations between mean accuracy and year of publication. RESULTS: The initial electronic screening yielded 252 papers published between 2020 and 2022. A total of 15 studies were included for the qualitative synthesis, whereas 11 studies were used for the meta-analysis. Overall random effect model revealed a mean value of 2.44 mm, with a high heterogeneity (I2 = 98.13%, τ2 = 1.018, p-value < 0.001); risk of bias was high due to the presence of issues for several domains per study. Meta-regression indicated a significant relation between mean error and year of publication (p value = 0.012). CONCLUSION: Deep learning algorithms showed an excellent accuracy for automated 3D cephalometric landmarking. In the last two years promising algorithms have been developed and improvements in landmarks annotation accuracy have been done.

The Effect of Holographic Heart Models and Mixed Reality for Anatomy Learning in Congenital Heart Disease: An Exploratory Study.

In this paper, we present an exploratory study on the potential impact of holographic heart models and mixed reality technology on medical training, and in particular in teaching complex Congenital Heart Diseases (CHD) to medical students. Fifty-nine medical students were randomly allocated into three groups. Each participant in each group received a 30-minute lecture on a CHD condition interpretation and transcatheter treatment with different instructional tools. The participants of the first group attended a lecture in which traditional slides were projected onto a flat screen (group "regular slideware", RS). The second group was shown slides incorporating videos of holographic anatomical models (group "holographic videos", HV). Finally, those in the third group wore immersive, head-mounted devices (HMD) to interact directly with holographic anatomical models (group "mixed reality", MR). At the end of the lecture, the members of each group were asked to fill in a multiple-choice questionnaire aimed at evaluating their topic proficiency, as a proxy to evaluate the effectiveness of the training session (in terms of acquired notions); participants from group MR were also asked to fill in a questionnaire regarding the recommendability and usability of the MS Hololens HMDs, as a proxy of satisfaction regarding its use experience (UX). The findings show promising results for usability and user acceptance.

How is test laboratory data used and characterised by machine learning models? A systematic review of diagnostic and prognostic models developed for COVID-19 patients using only laboratory data.

The current gold standard for COVID-19 diagnosis, the rRT-PCR test, is hampered by long turnaround times, probable reagent shortages, high false-negative rates and high prices. As a result, machine learning (ML) methods have recently piqued interest, particularly when applied to digital imagery (X-rays and CT scans). In this review, the literature on ML-based diagnostic and prognostic studies grounded on hematochemical parameters has been considered. By doing so, a gap in the current literature was addressed concerning the application of machine learning to laboratory medicine. Sixty-eight articles have been included that were extracted from the Scopus and PubMed indexes. These studies were marked by a great deal of heterogeneity in terms of the examined laboratory test and clinical parameters, sample size, reference populations, ML algorithms, and validation approaches. The majority of research was found to be hampered by reporting and replicability issues: only four of the surveyed studies provided complete information on analytic procedures (units of measure, analyzing equipment), while 29 provided no information at all. Only 16 studies included independent external validation. In light of these findings, we discuss the importance of closer collaboration between data scientists and medical laboratory professionals in order to correctly characterise the relevant population, select the most appropriate statistical and analytical methods, ensure reproducibility, enable the proper interpretation of the results, and gain actual utility by using machine learning methods in clinical practice.

The multicenter European Biological Variation Study (EuBIVAS): a new glance provided by the Principal Component Analysis (PCA), a machine learning unsupervised algorithms, based on the basic metabolic panel linked measurands.

OBJECTIVES: The European Biological Variation Study (EuBIVAS), which includes 91 healthy volunteers from five European countries, estimated high-quality biological variation (BV) data for several measurands. Previous EuBIVAS papers reported no significant differences among laboratories/population; however, they were focused on specific set of measurands, without a comprehensive general look. The aim of this paper is to evaluate the homogeneity of EuBIVAS data considering multivariate information applying the Principal Component Analysis (PCA), a machine learning unsupervised algorithm. METHODS: The EuBIVAS data for 13 basic metabolic panel linked measurands (glucose, albumin, total protein, electrolytes, urea, total bilirubin, creatinine, phosphatase alkaline, aminotransferases), age, sex, menopause, body mass index (BMI), country, alcohol, smoking habits, and physical activity, have been used to generate three databases developed using the traditional univariate and the multivariate Elliptic Envelope approaches to detect outliers, and different missing-value imputations. Two matrix of data for each database, reporting both mean values, and "within-person BV" (CVP) values for any measurand/subject, were analyzed using PCA. RESULTS: A clear clustering between males and females mean values has been identified, where the menopausal females are closer to the males. Data interpretations for the three databases are similar. No significant differences for both mean and CVPs values, for countries, alcohol, smoking habits, BMI and physical activity, have been found. CONCLUSIONS: The absence of meaningful differences among countries confirms the EuBIVAS sample homogeneity and that the obtained data are widely applicable to deliver APS. Our data suggest that the use of PCA and the multivariate approach may be used to detect outliers, although further studies are required.

Comparing Handcrafted Features and Deep Neural Representations for Domain Generalization in Human Activity Recognition.

Human Activity Recognition (HAR) has been studied extensively, yet current approaches are not capable of generalizing across different domains (i.e., subjects, devices, or datasets) with acceptable performance. This lack of generalization hinders the applicability of these models in real-world environments. As deep neural networks are becoming increasingly popular in recent work, there is a need for an explicit comparison between handcrafted and deep representations in Out-of-Distribution (OOD) settings. This paper compares both approaches in multiple domains using homogenized public datasets. First, we compare several metrics to validate three different OOD settings. In our main experiments, we then verify that even though deep learning initially outperforms models with handcrafted features, the situation is reversed as the distance from the training distribution increases. These findings support the hypothesis that handcrafted features may generalize better across specific domains.

Machine Learning for Health: Algorithm Auditing & Quality Control.

Developers proposing new machine learning for health (ML4H) tools often pledge to match or even surpass the performance of existing tools, yet the reality is usually more complicated. Reliable deployment of ML4H to the real world is challenging as examples from diabetic retinopathy or Covid-19 screening show. We envision an integrated framework of algorithm auditing and quality control that provides a path towards the effective and reliable application of ML systems in healthcare. In this editorial, we give a summary of ongoing work towards that vision and announce a call for participation to the special issue  Machine Learning for Health: Algorithm Auditing & Quality Control in this journal to advance the practice of ML4H auditing.

Development, evaluation, and validation of machine learning models for COVID-19 detection based on routine blood tests.

Objectives: The rRT-PCR test, the current gold standard for the detection of coronavirus disease (COVID-19), presents with known shortcomings, such as long turnaround time, potential shortage of reagents, false-negative rates around 15-20%, and expensive equipment. The hematochemical values of routine blood exams could represent a faster and less expensive alternative. Methods: Three different training data set of hematochemical values from 1,624 patients (52% COVID-19 positive), admitted at San Raphael Hospital (OSR) from February to May 2020, were used for developing machine learning (ML) models: the complete OSR dataset (72 features: complete blood count (CBC), biochemical, coagulation, hemogasanalysis and CO-Oxymetry values, age, sex and specific symptoms at triage) and two sub-datasets (COVID-specific and CBC dataset, 32 and 21 features respectively). 58 cases (50% COVID-19 positive) from another hospital, and 54 negative patients collected in 2018 at OSR, were used for internal-external and external validation. Results: We developed five ML models: for the complete OSR dataset, the area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.83 to 0.90; for the COVID-specific dataset from 0.83 to 0.87; and for the CBC dataset from 0.74 to 0.86. The validations also achieved good results: respectively, AUC from 0.75 to 0.78; and specificity from 0.92 to 0.96. Conclusions: ML can be applied to blood tests as both an adjunct and alternative method to rRT-PCR for the fast and cost-effective identification of COVID-19-positive patients. This is especially useful in developing countries, or in countries facing an increase in contagions.

As if sand were stone. New concepts and metrics to probe the ground on which to build trustable AI.

BACKGROUND: We focus on the importance of interpreting the quality of the labeling used as the input of predictive models to understand the reliability of their output in support of human decision-making, especially in critical domains, such as medicine. METHODS: Accordingly, we propose a framework distinguishing the reference labeling (or Gold Standard) from the set of annotations from which it is usually derived (the Diamond Standard). We define a set of quality dimensions and related metrics: representativeness (are the available data representative of its reference population?); reliability (do the raters agree with each other in their ratings?); and accuracy (are the raters' annotations a true representation?). The metrics for these dimensions are, respectively, the degree of correspondence, Ψ, the degree of weighted concordance ϱ, and the degree of fineness, Φ. We apply and evaluate these metrics in a diagnostic user study involving 13 radiologists. RESULTS: We evaluate Ψ against hypothesis-testing techniques, highlighting that our metrics can better evaluate distribution similarity in high-dimensional spaces. We discuss how Ψ could be used to assess the reliability of new predictions or for train-test selection. We report the value of ϱ for our case study and compare it with traditional reliability metrics, highlighting both their theoretical properties and the reasons that they differ. Then, we report the degree of fineness as an estimate of the accuracy of the collected annotations and discuss the relationship between this latter degree and the degree of weighted concordance, which we find to be moderately but significantly correlated. Finally, we discuss the implications of the proposed dimensions and metrics with respect to the context of Explainable Artificial Intelligence (XAI). CONCLUSION: We propose different dimensions and related metrics to assess the quality of the datasets used to build predictive models and Medical Artificial Intelligence (MAI). We argue that the proposed metrics are feasible for application in real-world settings for the continuous development of trustable and interpretable MAI systems.

Ordinal labels in machine learning: a user-centered approach to improve data validity in medical settings.

BACKGROUND: Despite the vagueness and uncertainty that is intrinsic in any medical act, interpretation and decision (including acts of data reporting and representation of relevant medical conditions), still little research has focused on how to explicitly take this uncertainty into account. In this paper, we focus on the representation of a general and wide-spread medical terminology, which is grounded on a traditional and well-established convention, to represent severity of health conditions (for instance, pain, visible signs), ranging from Absent to Extreme. Specifically, we will study how both potential patients and doctors perceive the different levels of the terminology in both quantitative and qualitative terms, and if the embedded user knowledge could improve the representation of ordinal values in the construction of machine learning models. METHODS: To this aim, we conducted a questionnaire-based research study involving a relatively large sample of 1,152 potential patients and 31 clinicians to represent numerically the perceived meaning of standard and widely-applied labels to describe health conditions. Using these collected values, we then present and discuss different possible fuzzy-set based representations that address the vagueness of medical interpretation by taking into account the perceptions of domain experts. We also apply the findings of this user study to evaluate the impact of different encodings on the predictive performance of common machine learning models in regard to a real-world medical prognostic task. RESULTS: We found significant differences in the perception of pain levels between the two user groups. We also show that the proposed encodings can improve the performances of specific classes of models, and discuss when this is the case. CONCLUSIONS: In perspective, our hope is that the proposed techniques for ordinal scale representation and ordinal encoding may be useful to the research community, and also that our methodology will be applied to other widely used ordinal scales for improving validity of datasets and bettering the results of machine learning tasks.

Detection of COVID-19 Infection from Routine Blood Exams with Machine Learning: A Feasibility Study.

The COVID-19 pandemia due to the SARS-CoV-2 coronavirus, in its first 4 months since its outbreak, has to date reached more than 200 countries worldwide with more than 2 million confirmed cases (probably a much higher number of infected), and almost 200,000 deaths. Amplification of viral RNA by (real time) reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard test for confirmation of infection, although it presents known shortcomings: long turnaround times (3-4 hours to generate results), potential shortage of reagents, false-negative rates as large as 15-20%, the need for certified laboratories, expensive equipment and trained personnel. Thus there is a need for alternative, faster, less expensive and more accessible tests. We developed two machine learning classification models using hematochemical values from routine blood exams (namely: white blood cells counts, and the platelets, CRP, AST, ALT, GGT, ALP, LDH plasma levels) drawn from 279 patients who, after being admitted to the San Raffaele Hospital (Milan, Italy) emergency-room with COVID-19 symptoms, were screened with the rRT-PCR test performed on respiratory tract specimens. Of these patients, 177 resulted positive, whereas 102 received a negative response. We have developed two machine learning models, to discriminate between patients who are either positive or negative to the SARS-CoV-2: their accuracy ranges between 82% and 86%, and sensitivity between 92% e 95%, so comparably well with respect to the gold standard. We also developed an interpretable Decision Tree model as a simple decision aid for clinician interpreting blood tests (even off-line) for COVID-19 suspect cases. This study demonstrated the feasibility and clinical soundness of using blood tests analysis and machine learning as an alternative to rRT-PCR for identifying COVID-19 positive patients. This is especially useful in those countries, like developing ones, suffering from shortages of rRT-PCR reagents and specialized laboratories. We made available a Web-based tool for clinical reference and evaluation (This tool is available at https://covid19-blood-ml.herokuapp.com/ ).

Machine learning in laboratory medicine: waiting for the flood?

This review focuses on machine learning and on how methods and models combining data analytics and artificial intelligence have been applied to laboratory medicine so far. Although still in its infancy, the potential for applying machine learning to laboratory data for both diagnostic and prognostic purposes deserves more attention by the readership of this journal, as well as by physician-scientists who will want to take advantage of this new computer-based support in pathology and laboratory medicine.

Morphological and molecular characterization of human hamstrings shows that tendon features are not influenced by donor age.

PURPOSE: Age-related modifications of tendons, such as reduced tenocyte proliferation and modified extracellular matrix (ECM) turnover, have been previously described, but results are often incomplete and discordant. The aim of this study was to investigate, using morphological and molecular methods, the effect of ageing on human tendons and tenocytes, especially focusing on the collagen turnover pathways, in order to understand how the ageing process could influence tendon biology and structure. METHODS: Morphological analysis was performed on fragments from human semitendinosus and gracilis tendons harvested from 10 adult (mean age 41.8 ± 13.3 years) and 6 aged healthy patients (mean age 72.7 ± 7.0 years) by haematoxylin and eosin, Sirius red and Alcian blue staining. The expression of genes and proteins involved in collagen turnover and focal adhesions was assessed by real-time PCR, slot blot and zymography in cultured tenocytes. Cytoskeleton arrangement was studied by immunofluorescence and cell migration by wound healing assay. RESULTS: The structure and composition of ECM in ageing tendons are preserved as well as the expression of genes and proteins involved in collagen turnover pathways. Although morphological analysis revealed that ageing tenocytes tended to an impaired migration potential and that actin filaments are occasionally shorter and randomly distributed, the expression of proteins involved in focal adhesion formation is preserved. CONCLUSION: Results of this study suggest that the structure of ageing tendons is preserved and that ageing tenocytes maintain their ability for ECM remodelling, supporting the hypothesis that ageing tendons maintain their biomechanical properties. The biological reliability of aged tendons has a clinical relevance, supporting the use of tendon autografts also in the elderly patients. Since the common and successful orthopaedic procedure of anterior cruciate ligament reconstruction using either autografts or allografts is becoming more common in older age groups, these findings suggest that the donor age would not significantly influence the clinical outcome.

Never tell me the odds: Investigating pro-hoc explanations in medical decision making.

This paper examines a kind of explainable AI, centered around what we term pro-hoc explanations, that is a form of support that consists of offering alternative explanations (one for each possible outcome) instead of a specific post-hoc explanation following specific advice. Specifically, our support mechanism utilizes explanations by examples, featuring analogous cases for each category in a binary setting. Pro-hoc explanations are an instance of what we called frictional AI, a general class of decision support aimed at achieving a useful compromise between the increase of decision effectiveness and the mitigation of cognitive risks, such as over-reliance, automation bias and deskilling. To illustrate an instance of frictional AI, we conducted an empirical user study to investigate its impact on the task of radiological detection of vertebral fractures in x-rays. Our study engaged 16 orthopedists in a 'human-first, second-opinion' interaction protocol. In this protocol, clinicians first made initial assessments of the x-rays without AI assistance and then provided their final diagnosis after considering the pro-hoc explanations. Our findings indicate that physicians, particularly those with less experience, perceived pro-hoc XAI support as significantly beneficial, even though it did not notably enhance their diagnostic accuracy. However, their increased confidence in final diagnoses suggests a positive overall impact. Given the promisingly high effect size observed, our results advocate for further research into pro-hoc explanations specifically, and into the broader concept of frictional AI.

Ensemble Predictors: Possibilistic Combination of Conformal Predictors for Multivariate Time Series Classification.

In this article we propose a conceptual framework to study ensembles of conformal predictors (CP), that we call Ensemble Predictors (EP). Our approach is inspired by the application of imprecise probabilities in information fusion. Based on the proposed framework, we study, for the first time in the literature, the theoretical properties of CP ensembles in a general setting, by focusing on simple and commonly used possibilistic combination rules. We also illustrate the applicability of the proposed methods in the setting of multivariate time-series classification, showing that these methods provide better performance (in terms of both robustness, conservativeness, accuracy and running time) than both standard classification algorithms and other combination rules proposed in the literature, on a large set of benchmarks from the UCR time series archive.

Evidence-based XAI: An empirical approach to design more effective and explainable decision support systems.

This paper proposes a user study aimed at evaluating the impact of Class Activation Maps (CAMs) as an eXplainable AI (XAI) method in a radiological diagnostic task, the detection of thoracolumbar (TL) fractures from vertebral X-rays. In particular, we focus on two oft-neglected features of CAMs, that is granularity and coloring, in terms of what features, lower-level vs higher-level, should the maps highlight and adopting which coloring scheme, to bring better impact to the decision-making process, both in terms of diagnostic accuracy (that is effectiveness) and of user-centered dimensions, such as perceived confidence and utility (that is satisfaction), depending on case complexity, AI accuracy, and user expertise. Our findings show that lower-level features CAMs, which highlight more focused anatomical landmarks, are associated with higher diagnostic accuracy than higher-level features CAMs, particularly among experienced physicians. Moreover, despite the intuitive appeal of semantic CAMs, traditionally colored CAMs consistently yielded higher diagnostic accuracy across all groups. Our results challenge some prevalent assumptions in the XAI field and emphasize the importance of adopting an evidence-based and human-centered approach to design and evaluate AI- and XAI-assisted diagnostic tools. To this aim, the paper also proposes a hierarchy of evidence framework to help designers and practitioners choose the XAI solutions that optimize performance and satisfaction on the basis of the strongest evidence available or to focus on the gaps in the literature that need to be filled to move from opinionated and eminence-based research to one more based on empirical evidence and end-user work and preferences.