Comparison of current methods for anti-dsDNA antibody detection and reshaping diagnostic strategies.

Anti-double-stranded DNA antibodies (anti-dsDNA) are considered a specific marker for systemic lupus erythematosus (SLE). Though the Farr technique was once the reference method for their detection, it has been almost entirely replaced by more recently developed assays. However, there is still no solid evidence of the commutability of these methods in terms of diagnostic accuracy and their correlation with the Crithidia luciliae immunofluorescence test (CLIFT). Anti-dsDNA antibody levels were measured in 80 subjects: 24 patients with SLE, 36 disease controls drawn from different autoimmune rheumatic diseases (14 systemic sclerosis, 10 Sjögren's syndrome, nine autoimmune myositis, three mixed connective tissue disease), 10 inflammatory arthritis and 10 apparently healthy blood donors by eight different methods: fluorescence enzyme immunoassay, microdot array, chemiluminescent immunoassay (two assays), multiplex flow immunoassay, particle multi-analyte technology immunoassay and two CLIFT. At the recommended manufacturer cut-off, the sensitivity varied from 67% to 92%, while the specificity ranged from 84% to 98%. Positive agreement among CLIFT and the other assays was higher than negative agreement. Mean agreement among methods assessed by the Cohen's kappa was 0.715, ranging from moderate (0.588) to almost perfect (0.888). Evaluation of the concordance among quantitative values by regression analysis showed a poor correlation index (mean r2, 0.66). The present study shows that current technologies for anti-dsDNA antibody detection are not fully comparable. In particular, their different correlation with CLIFT influences their positioning in the diagnostic algorithm for SLE (either in association or sequentially). Considering the high intermethod variability, harmonization and commutability of anti-dsDNA antibody testing remains an unachieved goal.

Pareto optimization of deep networks for COVID-19 diagnosis from chest X-rays.

The year 2020 was characterized by the COVID-19 pandemic that has caused, by the end of March 2021, more than 2.5 million deaths worldwide. Since the beginning, besides the laboratory test, used as the gold standard, many applications have been applying deep learning algorithms to chest X-ray images to recognize COVID-19 infected patients. In this context, we found out that convolutional neural networks perform well on a single dataset but struggle to generalize to other data sources. To overcome this limitation, we propose a late fusion approach where we combine the outputs of several state-of-the-art CNNs, introducing a novel method that allows us to construct an optimum ensemble determining which and how many base learners should be aggregated. This choice is driven by a two-objective function that maximizes, on a validation set, the accuracy and the diversity of the ensemble itself. A wide set of experiments on several publicly available datasets, accounting for more than 92,000 images, shows that the proposed approach provides average recognition rates up to 93.54% when tested on external datasets.

Visual4DTracker: a tool to interact with 3D + t image stacks.

BACKGROUND: Biological phenomena usually evolves over time and recent advances in high-throughput microscopy have made possible to collect multiple 3D images over time, generating [Formula: see text] (or 4D) datasets. To extract useful information there is the need to extract spatial and temporal data on the particles that are in the images, but particle tracking and feature extraction need some kind of assistance. RESULTS: This manuscript introduces our new freely downloadable toolbox, the Visual4DTracker. It is a MATLAB package implementing several useful functionalities to navigate, analyse and proof-read the track of each particle detected in any [Formula: see text] stack. Furthermore, it allows users to proof-read and to evaluate the traces with respect to a given gold standard. The Visual4DTracker toolbox permits the users to visualize and save all the generated results through a user-friendly graphical user interface. This tool has been successfully used in three applicative examples. The first processes synthetic data to show all the software functionalities. The second shows how to process a 4D image stack showing the time-lapse growth of Drosophila cells in an embryo. The third example presents the quantitative analysis of insulin granules in living beta-cells, showing that such particles have two main dynamics that coexist inside the cells. CONCLUSIONS: Visual4DTracker is a software package for MATLAB to visualize, handle and manually track [Formula: see text] stacks of microscopy images containing objects such cells, granules, etc.. With its unique set of functions, it remarkably permits the user to analyze and proof-read 4D data in a friendly 3D fashion. The tool is freely available at https://drive.google.com/drive/folders/19AEn0TqP-2B8Z10kOavEAopTUxsKUV73?usp=sharing.

AI-based applications in hybrid imaging: how to build smart and truly multi-parametric decision models for radiomics.

INTRODUCTION: The quantitative imaging features (radiomics) that can be obtained from the different modalities of current-generation hybrid imaging can give complementary information with regard to the tumour environment, as they measure different morphologic and functional imaging properties. These multi-parametric image descriptors can be combined with artificial intelligence applications into predictive models. It is now the time for hybrid PET/CT and PET/MRI to take the advantage offered by radiomics to assess the added clinical benefit of using multi-parametric models for the personalized diagnosis and prognosis of different disease phenotypes. OBJECTIVE: The aim of the paper is to provide an overview of current challenges and available solutions to translate radiomics into hybrid PET-CT and PET-MRI imaging for a smart and truly multi-parametric decision model.

Large-scale automated identification of mouse brain cells in confocal light sheet microscopy images.

MOTIVATION: Recently, confocal light sheet microscopy has enabled high-throughput acquisition of whole mouse brain 3D images at the micron scale resolution. This poses the unprecedented challenge of creating accurate digital maps of the whole set of cells in a brain. RESULTS: We introduce a fast and scalable algorithm for fully automated cell identification. We obtained the whole digital map of Purkinje cells in mouse cerebellum consisting of a set of 3D cell center coordinates. The method is accurate and we estimated an F1 measure of 0.96 using 56 representative volumes, totaling 1.09 GVoxel and containing 4138 manually annotated soma centers. AVAILABILITY AND IMPLEMENTATION: Source code and its documentation are available at http://bcfind.dinfo.unifi.it/. The whole pipeline of methods is implemented in Python and makes use of Pylearn2 and modified parts of Scikit-learn. Brain images are available on request. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A deep learning approach for overall survival prediction in lung cancer with missing values.

BACKGROUND AND OBJECTIVE: In the field of lung cancer research, particularly in the analysis of overall survival (OS), artificial intelligence (AI) serves crucial roles with specific aims. Given the prevalent issue of missing data in the medical domain, our primary objective is to develop an AI model capable of dynamically handling this missing data. Additionally, we aim to leverage all accessible data, effectively analyzing both uncensored patients who have experienced the event of interest and censored patients who have not, by embedding a specialized technique within our AI model, not commonly utilized in other AI tasks. Through the realization of these objectives, our model aims to provide precise OS predictions for non-small cell lung cancer (NSCLC) patients, thus overcoming these significant challenges. METHODS: We present a novel approach to survival analysis with missing values in the context of NSCLC, which exploits the strengths of the transformer architecture to account only for available features without requiring any imputation strategy. More specifically, this model tailors the transformer architecture to tabular data by adapting its feature embedding and masked self-attention to mask missing data and fully exploit the available ones. By making use of ad-hoc designed losses for OS, it is able to account for both censored and uncensored patients, as well as changes in risks over time. RESULTS: We compared our method with state-of-the-art models for survival analysis coupled with different imputation strategies. We evaluated the results obtained over a period of 6 years using different time granularities obtaining a Ct-index, a time-dependent variant of the C-index, of 71.97, 77.58 and 80.72 for time units of 1 month, 1 year and 2 years, respectively, outperforming all state-of-the-art methods regardless of the imputation method used. CONCLUSIONS: The results show that our model not only outperforms the state-of-the-art's performance but also simplifies the analysis in the presence of missing data, by effectively eliminating the need to identify the most appropriate imputation strategy for predicting OS in NSCLC patients.

AI-based methodologies for exoskeleton-assisted rehabilitation of the lower limb: a review.

Over the past few years, there has been a noticeable surge in efforts to design novel tools and approaches that incorporate Artificial Intelligence (AI) into rehabilitation of persons with lower-limb impairments, using robotic exoskeletons. The potential benefits include the ability to implement personalized rehabilitation therapies by leveraging AI for robot control and data analysis, facilitating personalized feedback and guidance. Despite this, there is a current lack of literature review specifically focusing on AI applications in lower-limb rehabilitative robotics. To address this gap, our work aims at performing a review of 37 peer-reviewed papers. This review categorizes selected papers based on robotic application scenarios or AI methodologies. Additionally, it uniquely contributes by providing a detailed summary of input features, AI model performance, enrolled populations, exoskeletal systems used in the validation process, and specific tasks for each paper. The innovative aspect lies in offering a clear understanding of the suitability of different algorithms for specific tasks, intending to guide future developments and support informed decision-making in the realm of lower-limb exoskeleton and AI applications.

Multi input-Multi output 3D CNN for dementia severity assessment with incomplete multimodal data.

Alzheimer's Disease is the most common cause of dementia, whose progression spans in different stages, from very mild cognitive impairment to mild and severe conditions. In clinical trials, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) are mostly used for the early diagnosis of neurodegenerative disorders since they provide volumetric and metabolic function information of the brain, respectively. In recent years, Deep Learning (DL) has been employed in medical imaging with promising results. Moreover, the use of the deep neural networks, especially Convolutional Neural Networks (CNNs), has also enabled the development of DL-based solutions in domains characterized by the need of leveraging information coming from multiple data sources, raising the Multimodal Deep Learning (MDL). In this paper, we conduct a systematic analysis of MDL approaches for dementia severity assessment exploiting MRI and PET scans. We propose a Multi Input-Multi Output 3D CNN whose training iterations change according to the characteristic of the input as it is able to handle incomplete acquisitions, in which one image modality is missed. Experiments performed on OASIS-3 dataset show the satisfactory results of the implemented network, which outperforms approaches exploiting both single image modality and different MDL fusion techniques.

A deep learning approach for virtual contrast enhancement in Contrast Enhanced Spectral Mammography.

Contrast Enhanced Spectral Mammography (CESM) is a dual-energy mammographic imaging technique that first requires intravenously administering an iodinated contrast medium. Then, it collects both a low-energy image, comparable to standard mammography, and a high-energy image. The two scans are combined to get a recombined image showing contrast enhancement. Despite CESM diagnostic advantages for breast cancer diagnosis, the use of contrast medium can cause side effects, and CESM also beams patients with a higher radiation dose compared to standard mammography. To address these limitations, this work proposes using deep generative models for virtual contrast enhancement on CESM, aiming to make CESM contrast-free and reduce the radiation dose. Our deep networks, consisting of an autoencoder and two Generative Adversarial Networks, the Pix2Pix, and the CycleGAN, generate synthetic recombined images solely from low-energy images. We perform an extensive quantitative and qualitative analysis of the model's performance, also exploiting radiologists' assessments, on a novel CESM dataset that includes 1138 images. As a further contribution to this work, we make the dataset publicly available. The results show that CycleGAN is the most promising deep network to generate synthetic recombined images, highlighting the potential of artificial intelligence techniques for virtual contrast enhancement in this field.

Exploring Negated Entites for Named Entity Recognition in Italian Lung Cancer Clinical Reports.

This paper explores the potential of leveraging electronic health records (EHRs) for personalized health research through the application of artificial intelligence (AI) techniques, specifically Named Entity Recognition (NER). By extracting crucial patient information from clinical texts, including diagnoses, medications, symptoms, and lab tests, AI facilitates the rapid identification of relevant data, paving the way for future care paradigms. The study focuses on Non-small cell lung cancer (NSCLC) in Italian clinical notes, introducing a novel set of 29 clinical entities that include both presence or absence (negation) of relevant information associated with NSCLC. Using a state-of-the-art model pretrained on Italian biomedical texts, we achieve promising results (average F1-score of 80.8%), demonstrating the feasibility of employing AI for extracting biomedical information in the Italian language.

Emerging Microorganisms and Infectious Diseases: One Health Approach for Health Shared Vision.

Emerging infectious diseases (EIDs) are newly emerging and reemerging infectious diseases. The National Institute of Allergy and Infectious Diseases identifies the following as emerging infectious diseases: SARS, MERS, COVID-19, influenza, fungal diseases, plague, schistosomiasis, smallpox, tick-borne diseases, and West Nile fever. The factors that should be taken into consideration are the genetic adaptation of microbial agents and the characteristics of the human host or environment. The new approach to identifying new possible pathogens will have to go through the One Health approach and omics integration data, which are capable of identifying high-priority microorganisms in a short period of time. New bioinformatics technologies enable global integration and sharing of surveillance data for rapid public health decision-making to detect and prevent epidemics and pandemics, ensuring timely response and effective prevention measures. Machine learning tools are being more frequently utilized in the realm of infectious diseases to predict sepsis in patients, diagnose infectious diseases early, and forecast the effectiveness of treatment or the appropriate choice of antibiotic regimen based on clinical data. We will discuss emerging microorganisms, omics techniques applied to infectious diseases, new computational solutions to evaluate biomarkers, and innovative tools that are useful for integrating omics data and electronic medical records data for the clinical management of emerging infectious diseases.

Multi-objective optimization determines when, which and how to fuse deep networks: An application to predict COVID-19 outcomes.

The COVID-19 pandemic has caused millions of cases and deaths and the AI-related scientific community, after being involved with detecting COVID-19 signs in medical images, has been now directing the efforts towards the development of methods that can predict the progression of the disease. This task is multimodal by its very nature and, recently, baseline results achieved on the publicly available AIforCOVID dataset have shown that chest X-ray scans and clinical information are useful to identify patients at risk of severe outcomes. While deep learning has shown superior performance in several medical fields, in most of the cases it considers unimodal data only. In this respect, when, which and how to fuse the different modalities is an open challenge in multimodal deep learning. To cope with these three questions here we present a novel approach optimizing the setup of a multimodal end-to-end model. It exploits Pareto multi-objective optimization working with a performance metric and the diversity score of multiple candidate unimodal neural networks to be fused. We test our method on the AIforCOVID dataset, attaining state-of-the-art results, not only outperforming the baseline performance but also being robust to external validation. Moreover, exploiting XAI algorithms we figure out a hierarchy among the modalities and we extract the features' intra-modality importance, enriching the trust on the predictions made by the model.

Radiomic Machine-Learning Analysis of Multiparametric Magnetic Resonance Imaging in the Diagnosis of Clinically Significant Prostate Cancer: New Combination of Textural and Clinical Features.

BACKGROUND: The aim of our study was to develop a radiomic tool for the prediction of clinically significant prostate cancer. METHODS: From September 2020 to December 2021, 91 patients who underwent magnetic resonance imaging prostate fusion biopsy at our institution were selected. Prostate cancer aggressiveness was assessed by combining the three orthogonal planes-Llocal binary pattern the 3Dgray level co-occurrence matrix, and other first order statistical features with clinical (semantic) features. The 487 features were used to predict whether the Gleason score was clinically significant (≥7) in the final pathology. A feature selection algorithm was used to determine the most predictive features, and at the end of the process, nine features were chosen through a 10-fold cross validation. RESULTS: The feature analysis revealed a detection accuracy of 83.5%, with a clinically significant precision of 84.4% and a clinically significant sensitivity of 91.5%. The resulting area under the curve was 80.4%. CONCLUSIONS: Radiomic analysis allowed us to develop a tool that was able to predict a Gleason score of ≥7. This new tool may improve the detection rate of clinically significant prostate cancer and overcome the limitations of the subjective interpretation of magnetic resonance imaging, reducing the number of useless biopsies.

Deep pathomics: A new image-based tool for predicting response to treatment in stage III non-small cell lung cancer.

Despite the advantages offered by personalized treatments, there is presently no way to predict response to chemoradiotherapy in patients with non-small cell lung cancer (NSCLC). In this exploratory study, we investigated the application of deep learning techniques to histological tissue slides (deep pathomics), with the aim of predicting the response to therapy in stage III NSCLC. We evaluated 35 digitalized tissue slides (biopsies or surgical specimens) obtained from patients with stage IIIA or IIIB NSCLC. Patients were classified as responders (12/35, 34.7%) or non-responders (23/35, 65.7%) based on the target volume reduction shown on weekly CT scans performed during chemoradiation treatment. Digital tissue slides were tested by five pre-trained convolutional neural networks (CNNs)-AlexNet, VGG, MobileNet, GoogLeNet, and ResNet-using a leave-two patient-out cross validation approach, and we evaluated the networks' performances. GoogLeNet was globally found to be the best CNN, correctly classifying 8/12 responders and 10/11 non-responders. Moreover, Deep-Pathomics was found to be highly specific (TNr: 90.1) and quite sensitive (TPr: 0.75). Our data showed that AI could surpass the capabilities of all presently available diagnostic systems, supplying additional information beyond that currently obtainable in clinical practice. The ability to predict a patient's response to treatment could guide the development of new and more effective therapeutic AI-based approaches and could therefore be considered an effective and innovative step forward in personalised medicine.

CNN-Based Approaches with Different Tumor Bounding Options for Lymph Node Status Prediction in Breast DCE-MRI.

BACKGROUND: The axillary lymph node status (ALNS) is one of the most important prognostic factors in breast cancer (BC) patients, and it is currently evaluated by invasive procedures. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), highlights the physiological and morphological characteristics of primary tumor tissue. Deep learning approaches (DL), such as convolutional neural networks (CNNs), are able to autonomously learn the set of features directly from images for a specific task. MATERIALS AND METHODS: A total of 155 malignant BC lesions evaluated via DCE-MRI were included in the study. For each patient's clinical data, the tumor histological and MRI characteristics and axillary lymph node status (ALNS) were assessed. LNS was considered to be the final label and dichotomized (LN+ (27 patients) vs. LN- (128 patients)). Based on the concept that peritumoral tissue contains valuable information about tumor aggressiveness, in this work, we analyze the contributions of six different tumor bounding options to predict the LNS using a CNN. These bounding boxes include a single fixed-size box (SFB), a single variable-size box (SVB), a single isotropic-size box (SIB), a single lesion variable-size box (SLVB), a single lesion isotropic-size box (SLIB), and a two-dimensional slice (2DS) option. According to the characteristics of the volumes considered as inputs, three different CNNs were investigated: the SFB-NET (for the SFB), the VB-NET (for the SVB, SIB, SLVB, and SLIB), and the 2DS-NET (for the 2DS). All the experiments were run in 10-fold cross-validation. The performance of each CNN was evaluated in terms of accuracy, sensitivity, specificity, the area under the ROC curve (AUC), and Cohen's kappa coefficient (K). RESULTS: The best accuracy and AUC are obtained by the 2DS-NET (78.63% and 77.86%, respectively). The 2DS-NET also showed the highest specificity, whilst the highest sensibility was attained by the VB-NET based on the SVB and SIB as bounding options. CONCLUSION: We have demonstrated that a selective inclusion of the DCE-MRI's peritumoral tissue increases accuracy in the lymph node status prediction in BC patients using CNNs as a DL approach.

Artificial Intelligence in Bone Metastases: An MRI and CT Imaging Review.

(1) Background: The purpose of this review is to study the role of radiomics as a supporting tool in predicting bone disease status, differentiating benign from malignant bone lesions, and characterizing malignant bone lesions. (2) Methods: Two reviewers conducted the literature search independently. Thirteen articles on radiomics as a decision support tool for bone lesions were selected. The quality of the methodology was evaluated according to the radiomics quality score (RQS). (3) Results: All studies were published between 2018 and 2021 and were retrospective in design. Eleven (85%) studies were MRI-based, and two (15%) were CT-based. The sample size was <200 patients for all studies. There is significant heterogeneity in the literature, as evidenced by the relatively low RQS value (average score = 22.6%). There is not a homogeneous protocol used for MRI sequences among the different studies, although the highest predictive ability was always obtained in T2W-FS. Six articles (46%) reported on the potential application of the model in a clinical setting with a decision curve analysis (DCA). (4) Conclusions: Despite the variability in the radiomics method application, the similarity of results and conclusions observed is encouraging. Substantial limits were found; prospective and multicentric studies are needed to affirm the role of radiomics as a supporting tool.

Quantib Prostate Compared to an Expert Radiologist for the Diagnosis of Prostate Cancer on mpMRI: A Single-Center Preliminary Study.

Background: To evaluate the clinical utility of an Artificial Intelligence (AI) radiology solution, Quantib Prostate, for prostate cancer (PCa) lesions detection on multiparametric Magnetic Resonance Images (mpMRI). Methods: Prostate mpMRI exams of 108 patients were retrospectively studied. The diagnostic performance of an expert radiologist (>8 years of experience) and of an inexperienced radiologist aided by Quantib software were compared. Three groups of patients were assessed: patients with positive mpMRI, positive target biopsy, and/or at least one positive random biopsy (group A, 73 patients); patients with positive mpMRI and a negative biopsy (group B, 14 patients), and patients with negative mpMRI who did not undergo biopsy (group-C, 21 patients). Results: In group A, the AI-assisted radiologist found new lesions with positive biopsy correlation, increasing the diagnostic PCa performance when compared with the expert radiologist, reaching an SE of 92.3% and a PPV of 90.1% (vs. 71.7% and 84.4%). In group A, the expert radiologist found 96 lesions on 73 mpMRI exams (17.7% PIRADS3, 56.3% PIRADS4, and 26% PIRADS5). The AI-assisted radiologist found 121 lesions (0.8% PIRADS3, 53.7% PIRADS4, and 45.5% PIRADS5). At biopsy, 33.9% of the lesions were ISUP1, 31.4% were ISUP2, 22% were ISUP3, 10.2% were ISUP4, and 2.5% were ISUP5. In group B, where biopsies were negative, the AI-assisted radiologist excluded three lesions but confirmed all the others. In group-C, the AI-assisted radiologist found 37 new lesions, most of them PIRADS 3, with 32.4% localized in the peripherical zone and 67.6% in the transition zone. Conclusions: Quantib software is a very sensitive tool to use specifically in high-risk patients (high PIRADS and high Gleason score).

A Multimodal Ensemble Driven by Multiobjective Optimisation to Predict Overall Survival in Non-Small-Cell Lung Cancer.

Lung cancer accounts for more deaths worldwide than any other cancer disease. In order to provide patients with the most effective treatment for these aggressive tumours, multimodal learning is emerging as a new and promising field of research that aims to extract complementary information from the data of different modalities for prognostic and predictive purposes. This knowledge could be used to optimise current treatments and maximise their effectiveness. To predict overall survival, in this work, we investigate the use of multimodal learning on the CLARO dataset, which includes CT images and clinical data collected from a cohort of non-small-cell lung cancer patients. Our method allows the identification of the optimal set of classifiers to be included in the ensemble in a late fusion approach. Specifically, after training unimodal models on each modality, it selects the best ensemble by solving a multiobjective optimisation problem that maximises both the recognition performance and the diversity of the predictions. In the ensemble, the labels of each sample are assigned using the majority voting rule. As further validation, we show that the proposed ensemble outperforms the models learning a single modality, obtaining state-of-the-art results on the task at hand.