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Melanotic cutaneous lupus erythematosus (LE) is a newly described clinical variant of chronic cutaneous LE, presenting with localized or diffuse brownish or grayish macular and reticulated pigmentation in the absence of erythema, scaling, atrophy, scarring, or telangiectasia. The diagnosis is based upon histopathology, which demonstrates the characteristic features of LE with an interface vacuolar dermatitis with melanophages, and a superficial and deep, perivascular and periadnexal lymphocytic infiltrate with mucin deposition. Herein, we describe a case of a 61‐year‐old White male presenting with melanotic cutaneous LE with a blaschkoid distribution on his face in which the histopathological phenomenon of "true melanocytic nests" in the setting of a lichenoid pattern was seen. We want to highlight how nests of cellular aggregates at the dermoepidermal junction labeling with melanocytic markers may occur in the setting of an interface tissue reaction. This benign reactional pattern may mimic atypical melanocytic proliferations, especially on sun‐damaged skin. Clinicopathological correlation and careful microscopic examination using a panel of multiple melanocytic markers is crucial for making an accurate final diagnosis. All the cases of melanotic cutaneous LE reported in the literature are also reviewed. [ABSTRACT FROM AUTHOR]

The observation of action seems to involve the generation of the internal representation of that same action in the observer, a process named motor resonance (MR). The objective of this study was to verify whether an experimental paradigm of action observation in a laboratory context could elicit cortical motor activation in 21 early Parkinson's disease (PD) patients compared to 22 controls. Participants were instructed to simply observe (observation-only session) or to respond (Time-to-contact detection session) at the instant the agent performed a grasping action toward a graspable or ungraspable object. We used functional near-infrared spectroscopy with 20 channels on the motor and premotor brain areas and event-related desynchronization of alpha-mu rhythm. In both groups, response times were more accurate in graspable than ungraspable object trials, suggesting that motor resonance is present in PD patients. In the Time-to-contact detection session, the oxyhemoglobin levels and alpha-mu desynchronization prevailed in the graspable object trials rather than in the ungraspable ones. This study demonstrates the preservation of MR mechanisms in early PD patients. The action observation finalized to a consequent movement can activate cortical networks in patients with early PD, suggesting early rehabilitation interventions taking into account specific observation paradigms preceding motor production. [ABSTRACT FROM AUTHOR]

Lichen Planus Pigmentosus (LPP) is an uncommon variant of lichen planus characterized by the development of dark greyish-brown macules and patches primarily affecting sun-exposed areas. Histologically, it presents with lichenoid interface dermatitis with many melanophages. In select cases, the presence of melanocytic nests or pseudomelanocytic nests within LPP lesions has been documented, posing a diagnostic challenge. We present a detailed case report of a 32-year-old Eritrean woman with a longstanding history of hyperpigmented macules, alongside an in-depth review of the existing literature on lichenoid dermatoses featuring melanocytic or pseudomelanocytic nests. This paper delves into the clinical presentation, histopathological features, differential diagnosis, and potential mechanisms underlying this intriguing phenomenon. [ABSTRACT FROM AUTHOR]

The study of visuomotor adaptation (VMA) capabilities has been encompassed in various experimental protocols aimed at investigating human motor control strategies and/or cognitive functions. VMA-oriented frameworks can have clinical applications, primarily in the investigation and assessment of neuromotor impairments caused by conditions such as Parkinson's disease or post-stroke, which affect the lives of tens of thousands of people worldwide. Therefore, they can enhance the understanding of the specific mechanisms of such neuromotor disorders, thus being a potential biomarker for recovery, with the aim of being integrated with conventional rehabilitative programs. Virtual Reality (VR) can be entailed in a framework targeting VMA since it allows the development of visual perturbations in a more customizable and realistic way. Moreover, as has been demonstrated in previous works, a serious game (SG) can further increase engagement thanks to the use of full-body embodied avatars. Most studies implementing VMA frameworks have focused on upper limb tasks and have utilized a cursor as visual feedback for the user. Hence, there is a paucity in the literature about VMA-oriented frameworks targeting locomotion tasks. In this article, the authors present the design, development, and testing of an SG-based framework that addresses VMA in a locomotion activity by controlling a full-body moving avatar in a custom VR environment. This workflow includes a set of metrics to quantitatively assess the participants' performance. Thirteen healthy children were recruited to evaluate the framework. Several quantitative comparisons and analyses were run to validate the different types of introduced visuomotor perturbations and to evaluate the ability of the proposed metrics to describe the difficulty caused by such perturbations. During the experimental sessions, it emerged that the system is safe, easy to use, and practical in a clinical setting. Despite the limited sample size, which represents the main limitation of the study and can be compensated for with future recruitment, the authors claim the potential of this framework as a useful instrument for quantitatively assessing either motor or cognitive impairments. The proposed feature-based approach gives several objective parameters as additional biomarkers that can integrate the conventional clinical scores. Future studies might investigate the relation between the proposed biomarkers and the clinical scores for specific disorders such as Parkinson's disease and cerebral palsy. [ABSTRACT FROM AUTHOR]

Nuclei identification is a fundamental task in many areas of biomedical image analysis related to computational pathology applications. Nowadays, deep learning is the primary approach by which to segment the nuclei, but accuracy is closely linked to the amount of histological ground truth data for training. In addition, it is known that most of the hematoxylin and eosin (H&E)-stained microscopy nuclei images contain complex and irregular visual characteristics. Moreover, conventional semantic segmentation architectures grounded on convolutional neural networks (CNNs) are unable to recognize distinct overlapping and clustered nuclei. To overcome these problems, we present an innovative method based on gradient-weighted class activation mapping (Grad-CAM) saliency maps for image segmentation. The proposed solution is comprised of two steps. The first is the semantic segmentation obtained by the use of a CNN; then, the detection step is based on the calculation of local maxima of the Grad-CAM analysis evaluated on the nucleus class, allowing us to determine the positions of the nuclei centroids. This approach, which we denote as NDG-CAM, has performance in line with state-of-the-art methods, especially in isolating the different nuclei instances, and can be generalized for different organs and tissues. Experimental results demonstrated a precision of 0.833, recall of 0.815 and a Dice coefficient of 0.824 on the publicly available validation set. When used in combined mode with instance segmentation architectures such as Mask R-CNN, the method manages to surpass state-of-the-art approaches, with precision of 0.838, recall of 0.934 and a Dice coefficient of 0.884. Furthermore, performance on the external, locally collected validation set, with a Dice coefficient of 0.914 for the combined model, shows the generalization capability of the implemented pipeline, which has the ability to detect nuclei not only related to tumor or normal epithelium but also to other cytotypes. [ABSTRACT FROM AUTHOR]

In prostate cancer, fusion biopsy, which couples magnetic resonance imaging (MRI) with transrectal ultrasound (TRUS), poses the basis for targeted biopsy by allowing the comparison of information coming from both imaging modalities at the same time. Compared with the standard clinical procedure, it provides a less invasive option for the patients and increases the likelihood of sampling cancerous tissue regions for the subsequent pathology analyses. As a prerequisite to image fusion, segmentation must be achieved from both MRI and TRUS domains. The automatic contour delineation of the prostate gland from TRUS images is a challenging task due to several factors including unclear boundaries, speckle noise, and the variety of prostate anatomical shapes. Automatic methodologies, such as those based on deep learning, require a huge quantity of training data to achieve satisfactory results. In this paper, the authors propose a novel optimization formulation to find the best superellipse, a deformable model that can accurately represent the prostate shape. The advantage of the proposed approach is that it does not require extensive annotations, and can be used independently of the specific transducer employed during prostate biopsies. Moreover, in order to show the clinical applicability of the method, this study also presents a module for the automatic segmentation of the prostate gland from MRI, exploiting the nnU-Net framework. Lastly, segmented contours from both imaging domains are fused with a customized registration algorithm in order to create a tool that can help the physician to perform a targeted prostate biopsy by interacting with the graphical user interface. [ABSTRACT FROM AUTHOR]

Depleted metals have been produced since many centuries ago. Probably the most famous examples from ancient times are the so-called Tumbaga gold artifacts, whose production was introduced by the pre-Colombian civilizations. Tumbaga-like structures have been identified also in modern nanotechnological materials. In both cases, but specially for the ancient Tumbaga, due to their preciousness, their characterization should be obtained by non-destructive analysis. Several analytical protocols have been developed, some of them non-destructive, such as those based on X-ray Fluorescence, but the results obtained do not always allow for a reliable identification of Tumbaga with respect to gilding or single alloy samples. Besides the capability to distinguish between different structures of the sample, it is also important to obtain a quantitative estimation of its composition. In order to meet this demand, a new approach based on X-ray Fluorescence coupled to Monte Carlo simulations is proposed. It allows one to distinguish easily between the three manufacturing techniques and to quantify the composition of the sample without any destructive sampling. It constitutes a new tool for the study of complex alloy structures. The protocol is applied here to some ancient Tumbaga gold samples and is described in detail, comparing the results to those obtained with other techniques. [ABSTRACT FROM AUTHOR]

The Nuragic civilization (Sardinia, Italy, XVIII–VIII B.C) developed a flourishing bronze metallurgy with strong connections with other civilizations from the Mediterranean basin. Within the large bronze production, there are some peculiar representations of human figures, known in the archaeological environment of Sardinia as bronzetti, depicting warriors, priests, and offerers. In this paper, an interesting couple of Nuragic statuettes representing offerers, one from the Pigorini Museum in Rome and another from the Musei Reali in Turin, were analyzed. They have been investigated with X-ray fluorescence integrated with Monte Carlo simulations (XRF-MC). The combined methodology provides more accurate results, ranging from the structural characterization to the identification of the corrosion layers to the estimation of the composition of the alloy of the artifact. One of the most striking results regards the heads of the offerers: both heads are covered with a thick iron-based layer, even though the whole artifacts are made of a copper alloy. To understand the reason behind this peculiar corrosion patina, several hypotheses have been considered, including the possibility that these iron mineralizations are the consequence of an ancient superficial treatment, intending to confer a chromatic effect on the figurine's head. [ABSTRACT FROM AUTHOR]

Scientific evidence points to a shared neural representation between performing and observing an action. The action observation notoriously determines a modulation of the observer's sensorimotor system, a phenomenon called Motor Resonance (MR). Fibromyalgia (FM) patients suffer from a condition characterized by generalized musculoskeletal pain in which even simple movement can exacerbate their symptoms. Maladaptive functioning of the primary motor cortex is a common finding in patients with chronic pain. Activation of the motor cortex is known to induce an analgesic effect in patients with chronic pain. In this exploratory study, we intend to verify if the mere observation of a movement could elicit activation of the motor cortical areas in patients with FM. Therefore, the purpose of this study was to examine the presence of MR in patients affected by fibromyalgia. We adopted a behavioral paradigm known for detecting the presence of MR and a neurophysiological experiment. Participants watched videos showing gripping movements towards a graspable or an ungraspable object, respectively, and were asked to press a button the instant the agent touched the object (Time-to-contact detection session). In a different experimental session, participants were only requested to observe and pay attention to the videos (Observation-only session). During each experimental session, the participants' cerebral hemodynamic activity was recorded using the functional Near-Infrared Spectroscopy method. The behavioral task analysis revealed the presence of MR in both FM patients and healthy controls. Moreover, neurophysiological findings suggested that the observation of movement during the Observation-only session provoked activation and modulation of the cortical motor networks of FM patients. These results could represent evidence of the possible beneficial effects of movement observation in restarting motor activation, notoriously reduced, in FM patients. [ABSTRACT FROM AUTHOR]

The high artistic and cultural relevance of particular objects, in this case from the Nuragic civilization, have stimulated the growth of a forgery industry, replicating small bronze boats (navicelle), statues (bronzetti), and other objects. It is often the case where the forgeries are of such quality that it becomes difficult to distinguish them from authentic artifacts without a proper chemical analysis. In this research, a Monte Carlo simulation algorithm for X-ray interactions with matter is used to obtain the chemical composition from the bulk of each object from a set of five. The method employed has the advantage of being completely nondestructive and relatively fast. The objects' chemical composition and morphology were compared with the data available from authentic artifacts so their authenticity could be inferred. Four of the five objects are likely to be authentic, where two of them could be associated with a Sardinian origin. [ABSTRACT FROM AUTHOR]

Background: Experimental and clinical studies suggested an analgesic effect on chronic pain by motor cortex activation. The present study explored the complex mechanisms of interaction between motor and pain during performing the slow and fast finger tapping task alone and in concomitant with nociceptive laser stimulation. Method: The participants were 38 patients with fibromyalgia (FM) and 21 healthy subjects. We used a simultaneous multimodal method of laser-evoked potentials and functional near-infrared spectroscopy to investigate metabolic and electrical changes during the finger tapping task and concomitant noxious laser stimulation. Functional near-infrared spectroscopy is a portable and optical method to detect cortical metabolic changes. Laser-evoked potentials are a suitable tool to study the nociceptive pathways function. Results: We found a reduced tone of cortical motor areas in patients with FM compared to controls, especially during the fast finger tapping task. FM patients presented a slow motor performance in all the experimental conditions, requesting rapid movements. The amplitude of laser evoked potentials was different between patients and controls, in each experimental condition, as patients showed smaller evoked responses compared to controls. Concurrent phasic pain stimulation had a low effect on motor cortex metabolism in both groups nor motor activity changed laser evoked responses in a relevant way. There were no correlations between Functional Near-Infrared Spectroscopy (FNIRS) and clinical features in FM patients. Conclusion: Our findings indicated that a low tone of motor cortex activation could be an intrinsic feature in FM and generate a scarce modulation on pain condition. A simple and repetitive movement such as that of the finger tapping task seems inefficacious in modulating cortical responses to pain both in patients and controls. The complex mechanisms of interaction between networks involved in pain control and motor function require further studies for the important role they play in structuring rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Background: The automatic segmentation of kidneys in medical images is not a trivial task when the subjects undergoing the medical examination are affected by Autosomal Dominant Polycystic Kidney Disease (ADPKD). Several works dealing with the segmentation of Computed Tomography images from pathological subjects were proposed, showing high invasiveness of the examination or requiring interaction by the user for performing the segmentation of the images. In this work, we propose a fully-automated approach for the segmentation of Magnetic Resonance images, both reducing the invasiveness of the acquisition device and not requiring any interaction by the users for the segmentation of the images.Methods: Two different approaches are proposed based on Deep Learning architectures using Convolutional Neural Networks (CNN) for the semantic segmentation of images, without needing to extract any hand-crafted features. In details, the first approach performs the automatic segmentation of images without any procedure for pre-processing the input. Conversely, the second approach performs a two-steps classification strategy: a first CNN automatically detects Regions Of Interest (ROIs); a subsequent classifier performs the semantic segmentation on the ROIs previously extracted.Results: Results show that even though the detection of ROIs shows an overall high number of false positives, the subsequent semantic segmentation on the extracted ROIs allows achieving high performance in terms of mean Accuracy. However, the segmentation of the entire images input to the network remains the most accurate and reliable approach showing better performance than the previous approach.Conclusion: The obtained results show that both the investigated approaches are reliable for the semantic segmentation of polycystic kidneys since both the strategies reach an Accuracy higher than 85%. Also, both the investigated methodologies show performances comparable and consistent with other approaches found in literature working on images from different sources, reducing both the invasiveness of the analyses and the interaction needed by the users for performing the segmentation task. [ABSTRACT FROM AUTHOR]

In this paper, we present the results of the archaeometric analysis performed on a nuragic bronze statuette, representing a boat model decorated with zoomorphic figurines, made in Sardinia during the early Iron Age. The bronze boat model was found in the Etruscan tomb of the Duce located in Vetulonia (Italy) and dated no later than the second half of the seventh century bc. The Vetulonia boat model represents an extraordinary example of this type of objects, exhibiting a high level of complexity from the manufacturing point of view and an unusual choice of the subjects represented by the figurines. The study was performed by means of Time of Flight Neutron Diffraction, a non-destructive method able to give us quantitative information on phase composition and microstructure. [ABSTRACT FROM AUTHOR]

Abstract Computer Aided Diagnosis (CAD) systems can support physicians in classifying different kinds of breast cancer, liver cancer and blood tumours also revealed by images acquired via Computer Tomography, Magnetic Resonance, and Blood Smear systems. In this regard, this survey focuses on papers dealing with the description of existing CAD frameworks for the classification of the three mentioned diseases, by detailing existing CAD workflows based on the same steps for supporting the diagnosis of these tumours. In detail, after an appropriate acquisition of the images, the fundamental steps carried out by a CAD framework can be identified as image segmentation, feature extraction and classification. In particular, in this work, specific CAD frameworks are considered, where the task of feature extraction is performed by using both traditional handcrafted strategies and Convolutional Neural Networks-based innovative methodologies, whereas the final supervised pattern classification is based on neural/non-neural machine learning methods. The cited methodology is focused on sharing and reviewing an amount of specific works. Then, the performance of three selected case studies are carefully reported, designed with the aim of showing how final outcomes can vary according to different choices in each step of the adopted workflow. More in detail, these case studies concern with breast images acquired by Tomosynthesis and Magnetic Resonance, hepatocellular carcinoma images acquired by Computed Tomography and enhanced by a triphasic protocol with a contrast medium, peripheral blood smear images for cellular blood tumours and are used to compare their performance. [ABSTRACT FROM AUTHOR]

Abstract Computer Aided Decision (CAD) systems, based on 3D tomosynthesis imaging, could support radiologists in classifying different kinds of breast lesions and then improve the diagnosis of breast cancer (BC) with a lower X-ray dose than in Computer Tomography (CT) systems. In previous work, several Convolutional Neural Network (CNN) architectures were evaluated to discriminate four different classes of lesions considering high-resolution images automatically segmented: (a) irregular opacity lesions, (b) regular opacity lesions, (c) stellar opacity lesions and (d) no-lesions. In this paper, instead, we use the same previously extracted relevant Regions of Interest (ROIs) containing the lesions, but we propose and evaluate two different approaches to better discriminate among the four classes. In this work, we evaluate and compare the performance of two different frameworks both considering supervised classifiers topologies. The first framework is feature-based, and consider morphological and textural hand-crafted features, extracted from each ROI, as input to optimised Artificial Neural Network (ANN) classifiers. The second framework, instead, considers non-neural classifiers based on automatically computed features evaluating the classification performance extracting several sets of features using different Convolutional Neural Network models. Final results show that the second framework, based on features computed automatically by CNN architectures performs better than the first approach, in terms of accuracy, specificity, and sensitivity. [ABSTRACT FROM AUTHOR]

In this study, Monte Carlo (MC) simulations combined with energy dispersive X-ray fluorescence (EDXRF) spectroscopy have been used to characterize non-destructively a collection of Cu-based artifacts recovered from two archeological sites in southern Portugal: (a) the Chalcolithic E.T.A.R. site of Vila Nova de Mil Fontes and (b) the Middle Bronze Age site of Quinta do Estácio 6. The metal artifacts show a multilayered structure made up of three distinct layers: (a) brownish carbonate soil-derived crust, (b) green oxidized corrosion patina, and (c) bulk metal. In order to assess the reliability of the EDXRF-based Monte Carlo simulations to reproduce the composition of the alloy substrate in archeological bronze artifacts without the need to previously remove the superficial corrosion and soil derived patinas, EDXRF analysis together with scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) was also performed on cleaned and patina-/crust-coated areas of the artifacts. Characterization of the mineralogical composition of the corrosion products in the surface patinas was further determined by means of X-ray diffraction (XRD). Results suggest that the adopted EDXRF/Monte Carlo protocol may represent a safe and fast analytical approach in the quantitative characterization of the bulk chemical composition of Cu-based metal artifacts even in the presence of fairly thick corrosion patinas and/or soil-derived encrustations at the surface of the archeological objects. [ABSTRACT FROM AUTHOR]

Abstract The Monte Sa Idda type swords belong to a well characterized typological class, whose origin has long been debated and seems to coincide with the Iberian Peninsula. The name comes from the site of the first discovery of a hoard containing this type of swords, among other bronze artefacts, namely Monte Sa Idda, Decimoputzu-Cagliari, Italy. The swords were produced through fusion inside a casting mould. Such kind of casting mould has not been found in Sardinia, and this may suggests that finished objects were either imported or made using clay or sand casting mould. Moreover, the discovery of these types of sword, in hoards and in votive deposits, raises the problem of their functional use. It is unknown if the blades were intended to be used as weapons, and therefore subjected to cold working necessary for thinning and sharpening of the blade, or as ceremonial objects. In order to answer to these questions, a neutron diffraction experiment was performed on three swords belonging to the Monte Sa Idda type. The results obtained are presented and discussed in the paper. Highlights • Determination of the manufacturing technique of some “Sa Idda” swords • New data on their provenience • Determination of: alloy composition, dendritic segregation, mineralization phase [ABSTRACT FROM AUTHOR]

Pedestrian detection and tracking have become an important field in the computer vision research area. This growing interest, started in the last decades, might be explained by the multitude of potential applications that could use the results of this research field, e.g. robotics, entertainment, surveillance, care for the elderly and disabled, and content-based indexing. In this survey paper, vision-based pedestrian detection systems are analysed based on their field of application, acquisition technology, computer vision techniques and classification strategies. Three main application fields have been individuated and discussed: video surveillance, human-machine interaction and analysis. Due to the large variety of acquisition technologies, this paper discusses both the differences between 2D and 3D vision systems, and indoor and outdoor systems. The authors reserved a dedicated section for the analysis of the Deep Learning methodologies, including the Convolutional Neural Networks in pedestrian detection and tracking, considering their recent exploding adoption for such a kind systems. Finally, focusing on the classification point of view, different Machine Learning techniques have been analysed, basing the discussion on the classification performances on different benchmark datasets. The reported results highlight the importance of testing pedestrian detection systems on different datasets to evaluate the robustness of the computed groups of features used as input to classifiers. [ABSTRACT FROM AUTHOR]

This work is part of a broader research line that aims to develop and implement a nondestructive methodology for the chemical characterization of archaeological metals based on a protocol that combines energy dispersive X-ray fluorescence spectrometry (ED-XRF) with a Monte Carlo (MC) simulation algorithm. In this paper, the ED-XRF-MC protocol has been applied to estimate the chemical composition of a selected group of 26 copper-based artifacts and fragments recovered at Perdigões, one of the larger Chalcolithic sites of southwest Iberia. All the analyzed artifacts have a multilayered structure composed of the alloy substrate and of a superficial layer common in each metal buried for hundreds of years and consisting of the patina mixed with soil. Due to the difficulty in determining the quantitative composition of these alloys in the presence of this complex patina/encrustation layer, the spectrometric protocol applied in this paper allows to simulate and to determine the composition of the bulk alloy without any prior removal of the overlying corrosion patina layer and soil-derived crust, even in the presence of rough and irregular surfaces, thus preserving the physical integrity of the artifacts. The overall results obtained with the ED-XRF-MC protocol indicates that the artifacts from Perdigões are almost pure coppers with a low amount of arsenic (<3.0 wt%) and reduced concentration of elements such as Pb, Bi, and Sb, in agreement with the third millennium metallurgy known in southwestern Iberia. Also based on previously theoretical–experimental studies, the data presented in this paper show how the applied analytical methodology can be a fast and completely nondestructive analytical tool reliable for routine and large-scale chemical analysis of archaeological metals, thus representing a major advance to be broadly applied within the field of cultural heritage studies. [ABSTRACT FROM AUTHOR]

The article focuses on investigating the effects of X-ray exposure and antioxidants on male and female HUVECs, finding that female cells are more affected by ionizing radiation damage, and the antioxidants taurine and N-acetylcysteine have varying protective effects based on sex.

The chemical composition of a unique bronze artifact known as the “ Cesta ” (“Basket”) belonging to the ancient Nuragic civilization of the Island of Sardinia, Italy has been analyzed by combining X-ray Fluorescence Spectroscopy (XRF) with Monte Carlo simulations using the XRMC code. The “ Cesta ” had been discovered probably in the XVIII century with the first graphic representation reported around 1761. In a later draft (dated 1764), the basket has been depicted as being carried upside-down on the shoulder of a large bronze warrior Barthélemy (1761), Pinza (1901), Winckelmann (1776) . The two pictorial representations differed only by the presence of handles in the most recent one. XRF measurements revealed that the handles of the object are composed by brass while the other parts are composed by bronze suggesting the handles as being a later addition to the original object. The artifact is covered at its surface by a fairly thick corrosion patina. In order to determine the bronze bulk composition without the need for removing the outer patina, the artifact has been modeled as a two layer object in Monte Carlo simulations. [ABSTRACT FROM AUTHOR]

The analytical study of Cultural Heritage objects often requires merely a qualitative determination of composition and manufacturing technology. However, sometimes a qualitative estimate is not sufficient, for example when dealing with multilayered metallic objects. Under such circumstances a quantitative estimate of the chemical contents of each layer is sometimes required in order to determine the technology that was used to produce the object. A quantitative analysis is often complicated by the surface state: roughness, corrosion, incrustations that remain even after restoration, due to efforts to preserve the patina. Furthermore, restorers will often add a protective layer on the surface. In all these cases standard quantitative methods such as the fundamental parameter based approaches are generally not applicable. An alternative approach is presented based on the use of Monte Carlo simulations for quantitative estimation. [ABSTRACT FROM AUTHOR]

X-ray fluorescence (XRF) is a well known nondestructive technique. It is also applied to multilayer characterization, due to its possibility of estimating both composition and thickness of the layers. Several kinds of cultural heritage samples can be considered as a complex multilayer, such as paintings or decorated objects or some types of metallic samples. Furthermore, they often have rough surfaces and this makes a precise determination of the structure and composition harder. The standard quantitative XRF approach does not take into account this aspect. In this paper, we propose a novel approach based on a combined use of X-ray measurements performed with a polychromatic beam and Monte Carlo simulations. All the information contained in an X-ray spectrum is used. This approach allows obtaining a very good estimation of the sample contents both in terms of chemical elements and material thickness, and in this sense, represents an improvement of the possibility of XRF measurements. Some examples will be examined and discussed. [ABSTRACT FROM AUTHOR]

We have addressed an X-ray fluorescence (XRF) and X-ray diffraction (XRD) on a collection of thirteen fossil bone belonging to the Molí del Baró 1 paleontological site located near Sant Romà d'Abella (Isona i Conca Dellà Municipality, Lleida Province, Spain, dated to about 66.5 Ma, to investigate the fossilization occurred in this site in terms of physico-chemical properties. As a general behaviour, the XRD patterns showed the bioapatite mineral at a varying level of percentage, and accordingly, the correspondent XRF spectra turned out to be mainly dominated by the presence of Ca, obviously accompanied by phosphorus. Simultaneously, other elements such as Sr, Fe, Ba and Zn were found at non-negligible concentration levels and helped to assign the phase components in the XRD spectra. In three specimens, it was observed by XRD the rather unusual case where the original bioapatite bone mineral was completely substituted for by other mineralogical phases. In addition to this, celestite was also found as an important phase in ten specimens out of the thirteen examined. The occurrence of celestite in the bone structure appears a rather unusual observation within the literature of bones diagenesis. Its provenance is generally ascribed to marine vertebrate organisms, but the presence in the fossil bones of this site, where no evidence of marine environment exists, can be reconciled with occurrence of refluxing processes involving diagenetically altered fluids which were discharged into beds containing strontium sulphate-rich waters. [ABSTRACT FROM AUTHOR]

Abstract: Generally, quantitative X-ray fluorescence (XRF) analysis estimates the content of chemical elements in a sample based on the areas of the fluorescence peaks in the energy spectrum. Besides the concentration of the elements, the peak areas depend also on the geometrical conditions. In fact, the estimate of the peak areas is simple if the sample surface is smooth and if the spectrum shows a good statistic (large-area peaks). For this reason often the sample is prepared as a pellet. However, this approach is not always feasible, for instance when cultural heritage or valuable samples must be analyzed. In this case, the sample surface cannot be smoothed. In order to address this problem, several works have been reported in the literature, based on experimental measurements on a few sets of specific samples or on Monte Carlo simulations. The results obtained with the first approach are limited by the specific class of samples analyzed, while the second approach cannot be applied to arbitrarily irregular surfaces. The present work describes a more general analysis tool based on a new fast Monte Carlo algorithm, which is virtually able to simulate any kind of surface. At the best of our knowledge, it is the first Monte Carlo code with this option. A study of the influence of surface irregularities on the measured spectrum is performed and some results reported. [Copyright &y& Elsevier]

We conducted an X-Ray Fluorescence investigation on bone fragments belonging to King Peter III of Aragon and Queen Blanche of Anjou. The spectroscopic analysis was carried out in selected points of the bone fragments. Several transitional elements normally unexpected in the bone composition have been found at varying level of concentration. The presence of these elements was interpreted in relation to chemical treatments for mummification of bodies as well as to dietary habits, including tools used for cooking and for the consumption of food. [ABSTRACT FROM AUTHOR]

A Roman bronze statuette from the 2nd Century BC was recovered from a nuragic sanctuary close to Florinas, in the north of Sardinia. The facial portion of the statuette is covered by a silver mask, partially gilded and attached to the bronze by tin-lead welding. The silver mask was carefully analyzed by portable energy-dispersive X-ray fluorescence (EDXRF), a non-destructive and non-invasive method. The aim of the analysis was to reconstruct the layered structure of the silver gilt mask, and to determine homogeneity and thickness of the gold, silver and lead–tin sheets. This is possible by using the internal ratio of the X-ray lines, i.e. starting from the surface, Au (L α/L β), Ag (K α/K β), Au-L α/Ag-K α and Pb (L α/L β).The results were compared with those obtained with simulated X-ray spectra, obtained both experimentally and by using the Monte Carlo simulation technique. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of millions of individuals and caused millions of deaths worldwide. Predicting the clinical course of the disease is of pivotal importance to manage patients. Several studies have found hematochemical alterations in COVID-19 patients, such as inflammatory markers. We retrospectively analyzed the anamnestic data and laboratory parameters of 303 patients diagnosed with COVID-19 who were admitted to the Polyclinic Hospital of Bari during the first phase of the COVID-19 global pandemic. After the pre-processing phase, we performed a survival analysis with Kaplan–Meier curves and Cox Regression, with the aim to discover the most unfavorable predictors. The target outcomes were mortality or admission to the intensive care unit (ICU). Different machine learning models were also compared to realize a robust classifier relying on a low number of strongly significant factors to estimate the risk of death or admission to ICU. From the survival analysis, it emerged that the most significant laboratory parameters for both outcomes was C-reactive protein min; H R = 17.963 (95% CI 6.548–49.277, p < 0.001) for death, H R = 1.789 (95% CI 1.000–3.200, p = 0.050) for admission to ICU. The second most important parameter was Erythrocytes max; H R = 1.765 (95% CI 1.141–2.729, p < 0.05) for death, H R = 1.481 (95% CI 0.895–2.452, p = 0.127) for admission to ICU. The best model for predicting the risk of death was the decision tree, which resulted in ROC-AUC of 89.66%, whereas the best model for predicting the admission to ICU was support vector machine, which had ROC-AUC of 95.07%. The hematochemical predictors identified in this study can be utilized as a strong prognostic signature to characterize the severity of the disease in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Abstract: This work presents the recent developments of xraylib, an ANSI C library that provides convenient access to a large number of X-ray related databases, with a focus on quantitative X-ray fluorescence applications. The enhancements include improved X-ray fluorescence production cross sections that take into account cascade effects and M-lines, as well as revised line energies, atomic level widths, Compton broadening profiles etc. A full overview of the complete application programming interface is presented. [Copyright &y& Elsevier]

A portable EDXRF equipment was employed to analyze pre-Columbian metals (gold, silver and copper objects) and to determine the thickness of gold in the case of gildings. To this aim, the EDXRF equipment was optimized to detect Cu, Au and Ag, and various methods were developed to determine from X-ray spectra (K-lines ratio) the thickness of the gildings. These methods were first tested to measure gilding compositions and thicknesses of pens and decorative objects. Then pre-Columbian metals were analyzed, such as gold, silver, copper, gilded copper and gilded silver objects from the Royal Tomb of Sipán and from the Museum of Sicán, in the north of Peru. [ABSTRACT FROM AUTHOR]

Estimate of sorption of liquid materials inside porous stones is an important parameter in industrial material testing and cultural heritage conservation. In the latter case, a suitable polymer can be used for both consolidation and conservation, it being applied either in the final form or as its parent monomer, which is subsequently allowed to polymerize in situ by the classical method or by frontal polymerization. However, the sorption of such materials through the stone is often difficult because of their viscosity and/or stone porosity. For this reason, the amount of monomer (or polymer) is a parameter of great interest in order to determine the extent of protection reachable by the treatment. In this paper a new methodology based on X-ray tomography is presented. The methodology makes use of a contrast agent added to the monomer that does not interact with its propagation inside the stone and allows to increase the absorption coefficient and so to observe the monomer inside the sample, which is finally frontally polymerized. [Copyright &y& Elsevier]

Compton tomography is a non-destructive technique that allows one to reconstruct the spatial distribution of the electronic density of the sample analyzed. This information is complementary to the absorption coefficient distribution at a given energy, which can be obtained by a more conventional transmission tomography. However, the reconstruction algorithms used in Compton tomography are different and more complex than those used in transmission tomography. This is mainly due to the absorption of the X-ray photons along the path from the source to the interaction point and from the interaction point to the detector. Only a few of the reconstruction algorithms reported in the literature take absorption corrections into account, and the problems of a quantitative reconstruction have seldom been discussed. In this paper a new kind of reconstruction algorithm is described and the first results are reported and discussed. [Copyright &y& Elsevier]

Background: Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression. Methods: To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients. Results: Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues. Conclusion: These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter. [ABSTRACT FROM AUTHOR]

Presents a study which examined the estimation and removal of the continuum on which the X-ray spectrum is superimposed, in energy dispersive X-ray fluorescence analysis. Comparison of continuum amplitude with peak amplitudes; Description of an approach to continuum removal based on mathematical morphology; Results of this study.

In the field of neuroscience, brain–computer interfaces (BCIs) are used to connect the human brain with external devices, providing insights into the neural mechanisms underlying cognitive processes, including aesthetic perception. Non-invasive BCIs, such as EEG and fNIRS, are critical for studying central nervous system activity and understanding how individuals with cognitive deficits process and respond to aesthetic stimuli. This study assessed twenty participants who were divided into control and impaired aging (AI) groups based on MMSE scores. EEG and fNIRS were used to measure their neurophysiological responses to aesthetic stimuli that varied in pleasantness and dynamism. Significant differences were identified between the groups in P300 amplitude and late positive potential (LPP), with controls showing greater reactivity. AI subjects showed an increase in oxyhemoglobin in response to pleasurable stimuli, suggesting hemodynamic compensation. This study highlights the effectiveness of multimodal BCIs in identifying the neural basis of aesthetic appreciation and impaired aging. Despite its limitations, such as sample size and the subjective nature of aesthetic appreciation, this research lays the groundwork for cognitive rehabilitation tailored to aesthetic perception, improving the comprehension of cognitive disorders through integrated BCI methodologies. [ABSTRACT FROM AUTHOR]

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non‐invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non‐invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring. [ABSTRACT FROM AUTHOR]

• Multianalytical study of a Moche funerary mask. • ED-XRF characterization of the metal alloy with Monte Carlo simulation. • Characterization of adhesive material and its components belonging to Moche culture. • Py-GC/MS and GC/MS were used for the chemical characterization of adhesive material. • SEM-EDS and ATR-FTIR were applied to characterize inorganic filler. The aim of this paper is to characterize materials belonging to one of the masks coming from the Lord of Ucupe's tomb in the region of Lambayeque in Peru. The mask belongs to the Moche culture which lived in the north of Peru since 100 CE. Along with the study of the extraordinary metal alloy technique using X-ray fluorescence (ED XRF) integrated with the Monte Carlo simulation, this paper investigates the blackish material used as an adhesive for its inlaid eyes. This material was analysed through the ATR FT-IR and characterized through Py-GC/MS and GC/MS for the organic components and SEM-EDS for the inorganic components. The chemical characterization of the adhesive material coming from this type of artefact, based on our knowledge of current literature, is the first on this material and allows us to take a further step into the understanding of the constituents used for this purpose. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship. [ABSTRACT FROM AUTHOR]

The painting studied, featuring the Virgin contemplating the sleeping Child, is a well-known composition in the religious context, especially popular since the 16th century. The technique, oil on copper plate, and materials were examined applying a multimethodological non-invasive approach. The main goal was to quantitatively characterize the layer composition and thickness. To obtain them, X-ray fluorescence spectroscopy coupled with Monte Carlo simulation was used for the first time, to the best of our knowledge, for this kind of object. This technique was also integrated with more conventional photographic and spectroscopic techniques such as multiband imaging (MBI), Raman spectroscopy, external reflection Fourier transform infrared spectroscopy (ER FT-IR), and optical microscopy. The obtained data showed the use of a background based on lead white, a wide palette, which includes azurite, vermilion, lead white, and some ochers, and documented the conservation status. Although the investigations contended with the object's complexity, the results demonstrate the efficacy of the XRF–Monte Carlo simulation approach in characterizing the materials constituting the artwork in a totally non-invasive way. [ABSTRACT FROM AUTHOR]

This paper describes the results obtained from an archaeometric study of a bronze Nuragic small boat model (Sardinia, Italy) dating from the Early Iron Age (presumably 9th–7th centuries BC). The artifact comes from an unknown location in Sardinia and is one of the objects that came to the Museum of Turin in the 19th century. This model is of particular interest as it is a unique Nuragic boat model containing a human figure among its decorations. The artifact is kept in the collection of the Royal Museum of Turin (Italy) and is a typical example of Sardinian manufacture from the Early Iron Age. This study was carried out using a combination of non-invasive techniques with energy dispersive X-ray fluorescence spectrometry (ED-XRF) integrated with Monte Carlo (MC) simulations and Raman spectroscopy, which allowed the characterization of the alloy of the artifact. [ABSTRACT FROM AUTHOR]

The Moche civilization in Peru developed marvelous metallurgy, primarily using alloys of gold, copper and silver, with the most famous of them called Tumbaga, which resembles pure gold after a depletion process on its surface. However, they also created objects with more standard single-layer alloys or gilding. To distinguish between these techniques in a non-destructive manner is essential. Here, we analyzed a thigh protector, composed of two parts, one seemingly in silver and the other seemingly in gold. The sample was analyzed using X-ray fluorescence measurements integrated with Monte Carlo simulation. The results show that the silver part is formed of a silver-based alloy covered in a corrosion layer, while the gold part is made of Tumbaga. Moreover, for the first time, the gold profiles of different Tumbaga gold objects, from the same burial, were compared, allowing us to obtain information about the standardization of their manufacture. [ABSTRACT FROM AUTHOR]

Background: Despite patients undergoing chronic hemodialysis (HD) being notoriously prone to adverse cardiovascular (CV) events, risk prediction in this population remains challenging. miRNA 122-5p, a short, non-coding RNA predominantly involved in lipid and carbohydrate metabolism, has recently been related to the onset and progression of CV disease. Methods: We run a pilot, multicenter, longitudinal, observational study to evaluate the clinical significance and prognostic usefulness of circulating miRNA 122-5p in a multicentric cohort of 74 individuals on maintenance HD. Results: Patients displayed lower circulating miRNA 122-5p as compared to healthy controls (p = 0.004). At correlation analyses, ALT (β = 0.333; p = 0.02), E/e' (β = 0.265; p = 0.02) and CRP (β = −0.219; p = 0.041) were independent predictors of miRNA 122-5p levels. During a median follow-up of 22 months (range of 1–24), 30 subjects (40.5%) experienced a composite endpoint of all-cause mortality and fatal/non-fatal CV events. Baseline circulating miRNA 122-5p was higher in these subjects (p = 0.01) and it predicted a significantly higher risk of endpoint occurrence (Kaplan–Meier crude HR 3.192; 95% CI 1.529–6.663; p = 0.002; Cox regression adjusted HR 1.115; 95% CI 1.009–1.232; p = 0.03). Conclusions: Altered miRNA 122-5p levels in HD patients may reflect hepatic and CV damage and may impart important prognostic information for improving CV risk prediction in this particular setting. [ABSTRACT FROM AUTHOR]

Digital Subtraction Angiography is commonly affected by artifacts due to the patient movements during the acquisition of the images without and with the contrast medium. This paper presents a preliminary study on an angiographic and angio-tomographic technique based on the quasi-simultaneous acquisition of two images, obtained using two different filters at the exit of an X-ray tube. One of the two filters (K-edge filter) contains the same chemical element used as a contrast agent (gadolinium in this study). This filter absorbs more radiation with energy just above the so called K-edge energy of gadolinium than the radiation with energy just below it. The other filter (an aluminium filter in this study) is simply used to suppress the low-energy contribution to the spectrum. Using proper calibration curves, the two images are combined to obtain an image of the contrast agent distribution. In the angio-tomographic application of the proposed technique two images, corresponding to the two filter types, are acquired for each viewing angle of the tomographic scan. From the two tomographic reconstructions, it is possible to obtain a three-dimensional map of the contrast agent distribution. The technique was tested on a sample consisting of a rat skull placed inside a container filled with water. Six small cylinders with 4.7 mm internal diameter containing the contrast medium at different concentrations were placed inside the skull. In the plain angiographic application of the technique, five out of six cylinders were visible, with gadolinium concentration down to 0.96%. In the angio-tomographic application, all six cylinders were visible, with gadolinium concentration down to 0.49%. This preliminary study shows that the proposed technique can provide images of the contrast medium at low concentration without most of the artifacts that are present in images produced by conventional techniques. The results encourage further investigation on the feasibility of a clinical implementation of the technique. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on elderly diabetic patients with heart failure. The study found that SGLT2i improved clinical symptoms, cognitive function, and physical performance in these patients. The research also revealed sex differences, with men experiencing greater improvements in cognitive function and functional abilities compared to women. Additionally, oxidative stress and platelet activation biomarkers improved after 6 months of SGLT2i treatment. The study suggests that adding SGLT2 inhibitors to medical therapy can lead to improvements in various outcomes for elderly patients with heart failure and type 2 diabetes. However, the study had limitations, including a small sample size and the absence of a control group. The findings also emphasize the importance of considering sex differences in heart failure management. [Extracted from the article]

Background: Handwriting represents one of the major symptom in Parkinson's Disease (PD) patients. The computer-aided analysis of the handwriting allows for the identification of promising patterns that might be useful in PD detection and rating. In this study, we propose an innovative set of features extracted by geometrical, dynamical and muscle activation signals acquired during handwriting tasks, and evaluate the contribution of such features in detecting and rating PD by means of artificial neural networks.Methods: Eleven healthy subjects and twenty-one PD patients were enrolled in this study. Each involved subject was asked to write three different patterns on a graphic tablet while wearing the Myo Armband used to collect the muscle activation signals of the main forearm muscles. We have then extracted several features related to the written pattern, the movement of the pen and the pressure exerted with the pen and the muscle activations. The computed features have been used to classify healthy subjects versus PD patients and to discriminate mild PD patients from moderate PD patients by using an artificial neural network (ANN).Results: After the training and evaluation of different ANN topologies, the obtained results showed that the proposed features have high relevance in PD detection and rating. In particular, we found that our approach both detect and rate (mild and moderate PD) with a classification accuracy higher than 90%.Conclusions: In this paper we have investigated the representativeness of a set of proposed features related to handwriting tasks in PD detection and rating. In particular, we used an ANN to classify healthy subjects and PD patients (PD detection), and to classify mild and moderate PD patients (PD rating). The implemented and tested methods showed promising results proven by the high level of accuracy, sensitivity and specificity. Such results suggest the usability of the proposed setup in clinical settings to support the medical decision about Parkinson's Disease. [ABSTRACT FROM AUTHOR]

In recent years, there has been a dramatic increase in the number of pregnancies complicated by gestational diabetes mellitus (GDM). GDM occurs when maternal insulin resistance develops and/or progresses during gestation, and it is not compensated by a rise in maternal insulin secretion. If not properly managed, this condition can cause serious short-term and long-term problems for both mother and child. Lifestyle changes are the first line of treatment for GDM, but if ineffective, insulin injections are the recommended pharmacological treatment choice. Some guidance authorities and scientific societies have proposed the use of metformin as an alternative pharmacological option for treating GDM, but there is not yet a unanimous consensus on this. Although the use of metformin appears to be safe for the mother, concerns remain about its long-term metabolic effects on the child that is exposed in utero to the drug, given that metformin, contrary to insulin, crosses the placenta. This review article describes the existing lines of evidence about the use of metformin in pregnancies complicated by GDM, in order to clarify its potential benefits and limits, and to help clinicians make decisions about who could benefit most from this drug treatment. [ABSTRACT FROM AUTHOR]

Highlights • Computer-assisted handwriting analysis applied in Parkinson's disease research. • Model-free technique for differentiating Parkinsonian patients from healthy subjects. • Finding most representative features and best writing patterns for Parkinson research. • Comparison of AI-based classification approaches for handwriting analysis. • Role of muscular activities on handwriting analysis applied to Parkinson research. Abstract Patients suffering from Parkinson's disease are characterized by an abnormal handwriting activity since they have difficulties in motor coordination and a decline in cognition. In this paper, we propose a model-free technique for differentiating Parkinson's disease patients from healthy subjects by using a handwriting analysis tool based on computer vision and surface ElectroMyoGraphy (sEMG) signal-processing techniques and an Artificial Intelligence-based classifier. Experimental tests have been conducted with both healthy and Parkinson's Disease patients using the proposed technique to address some specific research scientific questions regarding most representative features, best writing patterns, best AI-based classification approach between ANN optimal topology and SVM approaches in terms of both accuracy and repeatability of the results. Finally, the obtained results are reported and discussed to infer some important properties on writing patterns, classification approaches and the role of muscular activities on the handwriting analysis applied to neurodegenerative disease research. [ABSTRACT FROM AUTHOR]

Background and aim—Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods—Thirty subjects, aged 45–65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results—Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions—The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations. [ABSTRACT FROM AUTHOR]