Data Science for Health Image Alignment: A User-Friendly Open-Source ImageJ/Fiji Plugin for Aligning Multimodality/Immunohistochemistry/Immunofluorescence 2D Microscopy Images.

Most of the time, the deep analysis of a biological sample requires the acquisition of images at different time points, using different modalities and/or different stainings. This information gives morphological, functional, and physiological insights, but the acquired images must be aligned to be able to proceed with the co-localisation analysis. Practically speaking, according to Aristotle's principle, "The whole is greater than the sum of its parts", multi-modal image registration is a challenging task that involves fusing complementary signals. In the past few years, several methods for image registration have been described in the literature, but unfortunately, there is not one method that works for all applications. In addition, there is currently no user-friendly solution for aligning images that does not require any computer skills. In this work, DS4H Image Alignment (DS4H-IA), an open-source ImageJ/Fiji plugin for aligning multimodality, immunohistochemistry (IHC), and/or immunofluorescence (IF) 2D microscopy images, designed with the goal of being extremely easy to use, is described. All of the available solutions for aligning 2D microscopy images have also been revised. The DS4H-IA source code; standalone applications for MAC, Linux, and Windows; video tutorials; manual documentation; and sample datasets are publicly available.

Supporting Smart Home Scenarios Using OWL and SWRL Rules.

Despite the pervasiveness of IoT domotic devices in the home automation landscape, their potential is still quite under-exploited due to the high heterogeneity and the scarce expressivity of the most commonly adopted scenario programming paradigms. The aim of this study is to show that Semantic Web technologies constitute a viable solution to tackle not only the interoperability issues, but also the overall programming complexity of modern IoT home automation scenarios. For this purpose, we developed a knowledge-based home automation system in which scenarios are the result of logical inferences over the IoT sensors data combined with formalised knowledge. In particular, we describe how the SWRL language can be employed to overcome the limitations of the well-known trigger-action paradigm. Through various experiments in three distinct scenarios, we demonstrated the feasibility of the proposed approach and its applicability in a standardised and validated context such as SAREF.

Reliability of Body Temperature Measurements Obtained with Contactless Infrared Point Thermometers Commonly Used during the COVID-19 Pandemic.

During the COVID-19 pandemic, there has been a significant increase in the use of non-contact infrared devices for screening the body temperatures of people at the entrances of hospitals, airports, train stations, churches, schools, shops, sports centres, offices, and public places in general. The strong correlation between a high body temperature and SARS-CoV-2 infection has motivated the governments of several countries to restrict access to public indoor places simply based on a person's body temperature. Negating/allowing entrance to a public place can have a strong impact on people. For example, a cancer patient could be refused access to a cancer centre because of an incorrect high temperature measurement. On the other hand, underestimating an individual's body temperature may allow infected patients to enter indoor public places where it is much easier for the virus to spread to other people. Accordingly, during the COVID-19 pandemic, the reliability of body temperature measurements has become fundamental. In particular, a debated issue is the reliability of remote temperature measurements, especially when these are aimed at identifying in a quick and reliable way infected subjects. Working distance, body-device angle, and light conditions and many other metrological and subjective issues significantly affect the data acquired via common contactless infrared point thermometers, making the acquisition of reliable measurements at the entrance to public places a challenging task. The main objective of this work is to sensitize the community to the typical incorrect uses of infrared point thermometers, as well as the resulting drifts in measurements of body temperature. Using several commercial contactless infrared point thermometers, we performed four different experiments to simulate common scenarios in a triage emergency room. In the first experiment, we acquired several measurements for each thermometer without measuring the working distance or angle of inclination to show that, for some instruments, the values obtained can differ by 1 °C. In the second and third experiments, we analysed the impacts of the working distance and angle of inclination of the thermometers, respectively, to prove that only a few cm/degrees can cause drifts higher than 1 °C. Finally, in the fourth experiment, we showed that the light in the environment can also cause changes in temperature up to 0.5 °C. Ultimately, in this study, we quantitatively demonstrated that the working distance, angle of inclination, and light conditions can strongly impact temperature measurements, which could invalidate the screening results.

Unsupervised Event Graph Representation and Similarity Learning on Biomedical Literature.

The automatic extraction of biomedical events from the scientific literature has drawn keen interest in the last several years, recognizing complex and semantically rich graphical interactions otherwise buried in texts. However, very few works revolve around learning embeddings or similarity metrics for event graphs. This gap leaves biological relations unlinked and prevents the application of machine learning techniques to promote discoveries. Taking advantage of recent deep graph kernel solutions and pre-trained language models, we propose Deep Divergence Event Graph Kernels (DDEGK), an unsupervised inductive method to map events into low-dimensional vectors, preserving their structural and semantic similarities. Unlike most other systems, DDEGK operates at a graph level and does not require task-specific labels, feature engineering, or known correspondences between nodes. To this end, our solution compares events against a small set of anchor ones, trains cross-graph attention networks for drawing pairwise alignments (bolstering interpretability), and employs transformer-based models to encode continuous attributes. Extensive experiments have been done on nine biomedical datasets. We show that our learned event representations can be effectively employed in tasks such as graph classification, clustering, and visualization, also facilitating downstream semantic textual similarity. Empirical results demonstrate that DDEGK significantly outperforms other state-of-the-art methods.

Accuracy of Mobile Applications versus Wearable Devices in Long-Term Step Measurements.

Fitness sensors and health systems are paving the way toward improving the quality of medical care by exploiting the benefits of new technology. For example, the great amount of patient-generated health data available today gives new opportunities to measure life parameters in real time and create a revolution in communication for professionals and patients. In this work, we concentrated on the basic parameter typically measured by fitness applications and devices-the number of steps taken daily. In particular, the main goal of this study was to compare the accuracy and precision of smartphone applications versus those of wearable devices to give users an idea about what can be expected regarding the relative difference in measurements achieved using different system typologies. In particular, the data obtained showed a difference of approximately 30%, proving that smartphone applications provide inaccurate measurements in long-term analysis, while wearable devices are precise and accurate. Accordingly, we challenge the reliability of previous studies reporting data collected with phone-based applications, and besides discussing the current limitations, we support the use of wearable devices for mHealth.

Corrigendum: CONNECTED: leveraging digital twins and personal knowledge graphs in healthcare digitalization.

[This corrects the article DOI: 10.3389/fdgth.2023.1322428.].

Two-dimensional segmentation fusion tool: an extensible, free-to-use, user-friendly tool for combining different bidimensional segmentations.

Introduction: In several fields, the process of fusing multiple two-dimensional (2D) closed lines is an important step. For instance, this is fundamental in histology and oncology in general. The treatment of a tumor consists of numerous steps and activities. Among them, segmenting the cancer area, that is, the correct identification of its spatial location by the segmentation technique, is one of the most important and at the same time complex and delicate steps. The difficulty in deriving reliable segmentations stems from the lack of a standard for identifying the edges and surrounding tissues of the tumor area. For this reason, the entire process is affected by considerable subjectivity. Given a tumor image, different practitioners can associate different segmentations with it, and the diagnoses produced may differ. Moreover, experimental data show that the analysis of the same area by the same physician at two separate timepoints may result in different lines being produced. Accordingly, it is challenging to establish which contour line is the ground truth. Methods: Starting from multiple segmentations related to the same tumor, statistical metrics and computational procedures could be exploited to combine them for determining the most reliable contour line. In particular, numerous algorithms have been developed over time for this procedure, but none of them is validated yet. Accordingly, in this field, there is no ground truth, and research is still active. Results: In this work, we developed the Two-Dimensional Segmentation Fusion Tool (TDSFT), a user-friendly tool distributed as a free-to-use standalone application for MAC, Linux, and Windows, which offers a simple and extensible interface where numerous algorithms are proposed to "compute the mean" (i.e., the process to fuse, combine, and "average") multiple 2D lines. Conclusions: The TDSFT can support medical specialists, but it can also be used in other fields where it is required to combine 2D close lines. In addition, the TDSFT is designed to be easily extended with new algorithms thanks to a dedicated graphical interface for configuring new parameters. The TDSFT can be downloaded from the following link: https://sourceforge.net/p/tdsft.

CONNECTED: leveraging digital twins and personal knowledge graphs in healthcare digitalization.

Healthcare has always been a strategic domain in which innovative technologies can be applied to increase the effectiveness of services and patient care quality. Recent advancements have been made in the adoption of Digital Twins (DTs) and Personal Knowledge Graphs (PKGs) in this field. Despite this, their introduction has been hindered by the complex nature of the context itself which leads to many challenges both technical and organizational. In this article, we reviewed the literature about these technologies and their integrations, identifying the most critical requirements for clinical platforms. These latter have been used to design CONNECTED (COmpreheNsive and staNdardized hEalth-Care plaTforms to collEct and harmonize clinical Data), a conceptual framework aimed at defining guidelines to overcome the crucial issues related to the development of healthcare applications. It is structured in a multi-layer shape, in which heterogeneous data sources are first integrated, then standardized, and finally used to realize general-purpose DTs of patients backed by PKGs and accessible through dedicated APIs. These DTs will be the foundation on which smart applications can be built.

CometAnalyser: A user-friendly, open-source deep-learning microscopy tool for quantitative comet assay analysis.

Comet assay provides an easy solution to estimate DNA damage in single cells through microscopy assessment. It is widely used in the analysis of genotoxic damages induced by radiotherapy or chemotherapeutic agents. DNA damage is quantified at the single-cell level by computing the displacement between the genetic material within the nucleus, typically called "comet head", and the genetic material in the surrounding part of the cell, considered as the "comet tail". Today, the number of works based on Comet Assay analyses is really impressive. In this work, besides revising the solutions available to obtain reproducible and reliable quantitative data, we developed an easy-to-use tool named CometAnalyser. It is designed for the analysis of both fluorescent and silver-stained wide-field microscopy images and allows to automatically segment and classify the comets, besides extracting Tail Moment and several other intensity/morphological features for performing statistical analysis. CometAnalyser is an open-source deep-learning tool. It works with Windows, Macintosh, and UNIX-based systems. Source code, standalone versions, user manual, sample images, video tutorial and further documentation are freely available at: https://sourceforge.net/p/cometanalyser.

Software tools for 3D nuclei segmentation and quantitative analysis in multicellular aggregates.

Today, we are fully immersed into the era of 3D biology. It has been extensively demonstrated that 3D models: (a) better mimic the physiology of human tissues; (b) can effectively replace animal models; (c) often provide more reliable results than 2D ones. Accordingly, anti-cancer drug screenings and toxicology studies based on multicellular 3D biological models, the so-called "-oids" (e.g. spheroids, tumoroids, organoids), are blooming in the literature. However, the complex nature of these systems limit the manual quantitative analyses of single cells' behaviour in the culture. Accordingly, the demand for advanced software tools that are able to perform phenotypic analysis is fundamental. In this work, we describe the freely accessible tools that are currently available for biologists and researchers interested in analysing the effects of drugs/treatments on 3D multicellular -oids at a single-cell resolution level. In addition, using publicly available nuclear stained datasets we quantitatively compare the segmentation performance of 9 specific tools.

Dendritic Cell Vaccination in Metastatic Melanoma Turns "Non-T Cell Inflamed" Into "T-Cell Inflamed" Tumors.

Dendritic cell (DC)-based vaccination effectively induces anti-tumor immunity, although in the majority of cases this does not translate into a durable clinical response. However, DC vaccination is characterized by a robust safety profile, making this treatment a potential candidate for effective combination cancer immunotherapy. To explore this possibility, understanding changes occurring in the tumor microenvironment (TME) upon DC vaccination is required. In this line, quantitative and qualitative changes in tumor-infiltrating T lymphocytes (TILs) induced by vaccination with autologous tumor lysate/homogenate loaded DCs were investigated in a series of 16 patients with metastatic melanoma. Immunohistochemistry for CD4, CD8, Foxp3, Granzyme B (GZMB), PDL1, and HLA class I was performed in tumor biopsies collected before and after DC vaccination. The density of each marker was quantified by automated digital pathology analysis on whole slide images. Co-expression of markers defining functional phenotypes, i.e., Foxp3+ regulatory CD4+ T cells (Treg) and GZMB+ cytotoxic CD8+ T cells, was assessed with sequential immunohistochemistry. A significant increase of CD8+ TILs was found in post-vaccine biopsies of patients who were not previously treated with immune-modulating cytokines or Ipilimumab. Interestingly, along with a maintained tumoral HLA class I expression, after DC vaccination we observed a significant increase of PDL1+ tumor cells, which significantly correlated with intratumoral CD8+ T cell density. This observation might explain the lack of a significant concurrent cytotoxic reactivation of CD8+ T cell, as measured by the numbers of GZMB+ T cells. Altogether these findings indicate that DC vaccination exerts an important role in sustaining or de novo inducing a T cell inflamed TME. However, the strength of the intratumoral T cell activation detected in post-DC therapy lesions is lessened by an occurring phenomenon of adaptive immune resistance, yet the concomitant PDL1 up-regulation. Overall, this study sheds light on DC immunotherapy-induced TME changes, lending the rationale for the design of smarter immune-combination therapies.