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Abstract: Primary cutaneous spindle B-cell lymphoma is an uncommon subtype of cutaneous lymphoma characterized by a distinct spindled cytology of neoplastic B cells. Despite sharing clinical, histopathological, and phenotypical similarities with primary cutaneous follicle center lymphoma, an indolent form of B-cell lymphoma, it also exhibits certain features akin to primary cutaneous diffuse large B-cell lymphoma. Notably, in rare instances, a more aggressive clinical course has been observed. This report details a rare case of primary cutaneous spindle cell B-cell follicle center lymphoma, manifested as a prolonged solitary plaque of cicatricial alopecia. In addition, we provide a comprehensive review of existing cases documented in the literature., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024 the International Society of Dermatology.)

Background: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA., Methods: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients., Results: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life., Conclusions: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

The identification of EEG biomarkers to discriminate Subjective Cognitive Decline (SCD) from Mild Cognitive Impairment (MCI) conditions is a complex task which requires great clinical effort and expertise. We exploit the self-attention component of the Transformer architecture to obtain physiological explanations of the model's decisions in the discrimination of 56 SCD and 45 MCI patients using resting-state EEG. Specifically, an interpretability workflow leveraging attention scores and time-frequency analysis of EEG epochs through Continuous Wavelet Transform is proposed. In the classification framework, models are trained and validated with 5-fold cross-validation and evaluated on a test set obtained by selecting 20% of the total subjects. Ablation studies and hyperparameter tuning tests are conducted to identify the optimal model configuration. Results show that the best performing model, which achieves acceptable results both on epochs' and patients' classification, is capable of finding specific EEG patterns that highlight changes in the brain activity between the two conditions. We demonstrate the potential of attention weights as tools to guide experts in understanding which disease-relevant EEG features could be discriminative of SCD and MCI.

Purpose: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy., Methods: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC., Results: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC., Conclusions: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases., (© 2024. The Author(s).)

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.

Total, whole-atom, individual and integrated Compton scattering cross sections and Compton energy absorption scattering cross sections are evaluated for light elements, such as, H, C, N, O, P, and Ca, with relativistic impulse approximation methods. Most of the phantom materials composed of these elements, which are the basic constituents of biological soft-tissue and attenuation through them, provides potential source of information. Compton scattering cross-sections for few biological materials, such as, H 2 O, C 2 H 4 , C 8 H 8 , C 5 H 8 O 2 , C 6 H 11 NO, C 16 H 14 O 3 , C 55 H 102 O 6 , [Ca 3 (PO 4 )] 3 Ca (OH) 2 of medical interest, have been evaluated with the use of double differential scattering cross-section based on impulse approximation. Utilized these values to evaluate the Compton energy absorption cross sections and Compton component of mass energy absorption coefficients (cm 2 /g) in the energy region from 0.005 to 10 MeV. The derived results are compared with the theoretical tabulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus formation by inhibiting some factors involved in the coagulation cascade. In this study, four acidic glycan fractions from the marine sponge Sarcotragus spinosulus were purified by anion-exchange chromatography, and their anticoagulant properties were investigated through APTT and PT assays and compared with both standard glycosaminoglycans and holothurian sulphated polysaccharides. Moreover, their topographic localization was assessed through histological analysis, and their cytocompatibility was tested on a human fibroblast cell line. A positive correlation between the amount of acid glycans and the inhibitory effect towards both the intrinsic and extrinsic coagulation pathways was observed. The most effective anticoagulant activity was shown by a highly charged fraction, which accounted for almost half (about 40%) of the total hexuronate-containing polysaccharides. Its preliminary structural characterization, performed through infrared spectroscopy and nuclear magnetic resonance, suggested that it may consist of a fucosylated chondroitin sulphate, whose unique structure may be responsible for the anticoagulant activity reported herein for the first time.

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.

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.

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.

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.

Introduction: Subtle cognitive dysfunction and mental fatigue are frequent after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, characterizing the so-called long COVID-19 syndrome. This study aimed to correlate cognitive, neurophysiological, and olfactory function in a group of subjects who experienced acute SARS-CoV-2 infection with persistent hyposmia at least 12 weeks before the observation., Methods: For each participant (32 post-COVID-19 patients and 16 controls), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) data were acquired using an integrated EEG-fNIRS system during the execution of a P300 odd-ball task and a Stroop test. The Sniffin' Sticks test was conducted to assess subjects' olfactory performance. The Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB) were also administered., Results: The post-COVID-19 group consisted of 32 individuals (20 women and 12 men) with an average education level of 12.9 ± 3.12 years, while the control group consisted of 16 individuals (10 women and 6 men) with an average education level of 14.9 ± 3.2 years. There were no significant differences in gender ( X 2 = 0, p = 1) or age between the two groups (age 44.81 ± 13.9 vs. 36.62 ± 11.4, p = 0.058). We identified a lower concentration of oxyhemoglobin ( p < 0.05) at the prefrontal cortical level in post-COVID-19 subjects during the execution of the Stroop task, as well as a reduction in the amplitude of the P3a response. Moreover, we found that post-COVID-19 subjects performed worst at the MoCA screening test ( p = 0.001), Sniffin's Sticks test ( p < 0.001), and Stroop task response latency test ( p < 0.001)., Conclusions: This study showed that post-COVID-19 patients with persistent hyposmia present mild deficits in prefrontal function, even 4 months after the end of the infection. These deficits, although subtle, could have long-term implications for quality of life and cognitive wellbeing. It is essential to continue monitoring and evaluating these patients to better understand the extent and duration of cognitive impairments associated with long COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Clemente, La Rocca, Quaranta, Iannuzzi, Vecchio, Brunetti, Gentile, Dibattista, Lobasso, Bevilacqua, Stramaglia and de Tommaso.)

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.

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., (© 2023. Springer Nature Limited.)

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.

The complex pathobiology of lung cancer, and its spread worldwide, has prompted research studies that combine radiomic and genomic approaches. Indeed, the early identification of genetic alterations and driver mutations affecting the tumor is fundamental for correctly formulating the prognosis and therapeutic response. In this work, we propose a radiogenomic workflow to detect the presence of KRAS and EGFR mutations using radiomic features extracted from computed tomography images of patients affected by lung adenocarcinoma. To this aim, we investigated several feature selection algorithms to identify the most significant and uncorrelated sets of radiomic features and different classification models to reveal the mutational status. Then, we employed the SHAP (SHapley Additive exPlanations) technique to increase the understanding of the contribution given by specific radiomic features to the identification of the investigated mutations. Two cohorts of patients with lung adenocarcinoma were used for the study. The first one, obtained from the Cancer Imaging Archive (TCIA), consisted of 60 cases (25% EGFR, 23% KRAS); the second one, provided by the Azienda Ospedaliero-Universitaria 'Ospedali Riuniti' of Foggia, was composed of 55 cases (16% EGFR, 28% KRAS). The best-performing models proposed in our study achieved an AUC of 0.69 and 0.82 on the validation set for predicting the mutational status of EGFR and KRAS, respectively. The Multi-layer Perceptron model emerged as the top-performing model for both oncogenes, in some cases outperforming the state of the art. This study showed that radiomic features can be associated with EGFR and KRAS mutational status in patients with lung adenocarcinoma.

Background: Histological assessment of colorectal cancer (CRC) tissue is a crucial and demanding task for pathologists. Unfortunately, manual annotation by trained specialists is a burdensome operation, which suffers from problems like intra- and inter-pathologist variability. Computational models are revolutionizing the Digital Pathology field, offering reliable and fast approaches for challenges like tissue segmentation and classification. With this respect, an important obstacle to overcome consists in stain color variations among different laboratories, which can decrease the performance of classifiers. In this work, we investigated the role of Unpaired Image-to-Image Translation (UI2IT) models for stain color normalization in CRC histology and compared to classical normalization techniques for Hematoxylin-Eosin (H&E) images., Methods: Five Deep Learning normalization models based on Generative Adversarial Networks (GANs) belonging to the UI2IT paradigm have been thoroughly compared to realize a robust stain color normalization pipeline. To avoid the need for training a style transfer GAN between each pair of data domains, in this paper we introduce the concept of training by exploiting a meta-domain, which contains data coming from a wide variety of laboratories. The proposed framework enables a huge saving in terms of training time, by allowing to train a single image normalization model for a target laboratory. To prove the applicability of the proposed workflow in the clinical practice, we conceived a novel perceptive quality measure, which we defined as Pathologist Perceptive Quality (PPQ). The second stage involved the classification of tissue types in CRC histology, where deep features extracted from Convolutional Neural Networks have been exploited to realize a Computer-Aided Diagnosis system based on a Support Vector Machine (SVM). To prove the reliability of the system on new data, an external validation set composed of N = 15,857 tiles has been collected at IRCCS Istituto Tumori "Giovanni Paolo II"., Results: The exploitation of a meta-domain consented to train normalization models that allowed achieving better classification results than normalization models explicitly trained on the source domain. PPQ metric has been found correlated to quality of distributions (Fréchet Inception Distance - FID) and to similarity of the transformed image to the original one (Learned Perceptual Image Patch Similarity - LPIPS), thus showing that GAN quality measures introduced in natural image processing tasks can be linked to pathologist evaluation of H&E images. Furthermore, FID has been found correlated to accuracies of the downstream classifiers. The SVM trained on DenseNet201 features allowed to obtain the highest classification results in all configurations. The normalization method based on the fast variant of CUT (Contrastive Unpaired Translation), FastCUT, trained with the meta-domain paradigm, allowed to achieve the best classification result for the downstream task and, correspondingly, showed the highest FID on the classification dataset., Conclusions: Stain color normalization is a difficult but fundamental problem in the histopathological setting. Several measures should be considered for properly assessing normalization methods, so that they can be introduced in the clinical practice. UI2IT frameworks offer a powerful and effective way to perform the normalization process, providing realistic images with proper colorization, unlike traditional normalization methods that introduce color artifacts. By adopting the proposed meta-domain framework, the training time can be reduced, and the accuracy of downstream classifiers can be increased., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

Background: Artificial neural networks (ANNs) and logistic regression (LR) are the models of chosen in many medical data classification tasks. Several published articles were based on summarizing the differences and similarities of these models from a technical point of view and critically assessing the quality of the models. The aim of this study was to compare ANN and LR the statistical techniques to predict gastrointestinal cancer in an elderly cohort in Southern Italy (ONCONUT study)., Method: In 1992, ONCONUT was started with the aim of evaluating the relationship between diet and cancer development in a Southern Italian elderly population. Patients with gastrointestinal cancer (ICD-10 from 150.0 to 159.9) were included in the study ( n = 3,545)., Results: This cohort was used to train and test the ANN and LR. LR was evaluated separately for macro- and micronutrients, and the accuracy was evaluated based on true positives and true negatives versus the total (97.15%). Then, ANN was trained and the accuracy was evaluated (96.61% for macronutrients and 97.06% for micronutrients). To further investigate the classification capabilities of ANN, k-fold cross-validation and genetic algorithm (GA) were used after balancing the dataset among classes., Conclusions: Both LR and ANN had high accuracy and similar performance. Both models had the potential to be used as decision clinical support integrated into clinical practice, because in many circumstances, the use of a simple LR model was likely to be adequate for real-world needs, but in others in which there were large amounts of data, the application of advanced analytic tools such as ANNs could be indicated, and the GA optimizer needed to optimize the accuracy of ANN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Donghia, Guerra, Misciagna, Loiacono, Brunetti and Bevilacqua.)

Introduction-The purpose of this study was to determine the relative impact of modifiable and non-modifiable risk factors in the development of gestational diabetes mellitus (GDM), with a particular focus on maternal preconception body mass index (BMI) and age, two important determinants of insulin resistance. Understanding the factors that contribute most to the current escalation of GDM rates in pregnant women could help to inform prevention and intervention strategies, particularly in areas where this female endocrine disorder has an elevated prevalence. Methods-A retrospective, contemporary, large population of singleton pregnant women from southern Italy who underwent 75 g OGTT for GDM screening was enrolled at the Endocrinology Unit, "Pugliese Ciaccio" Hospital, Catanzaro. Relevant clinical data were collected, and the characteristics of women diagnosed with GDM or with normal glucose tolerance were compared. The effect estimates of maternal preconception BMI and age as risk factors for GDM development were calculated through correlation and logistic regression analysis by adjusting for potential confounders. Results-Out of the 3856 women enrolled, 885 (23.0%) were diagnosed with GDM as per IADPSG criteria. Advanced maternal age (≥35 years), gravidity, reproductive history of spontaneous abortion(s), previous GDM, and thyroid and thrombophilic diseases, all emerged as non-modifiable risk factors of GDM, whereas preconception overweight or obesity was the sole potentially modifiable risk factor among those investigated. Maternal preconception BMI, but not age, had a moderate positive association with fasting glucose levels at the time of 75 g OGTT (Pearson coefficient: 0.245, p < 0.001). Abnormalities in fasting glucose drove the majority (60%) of the GDM diagnoses in this study. Maternal preconception obesity almost tripled the risk of developing GDM, but even being overweight resulted in a more pronounced increased risk of developing GDM than advanced maternal age (adjusted OR for preconception overweight: 1.63, 95% CI 1.320-2.019; adjusted OR for advanced maternal age: 1.45, 95% CI 1.184-1.776). Conclusions-Excess body weight prior to conception leads to more detrimental metabolic effects than advanced maternal age in pregnant women with GDM. Thus, in areas in which GDM is particularly common, such as southern Italy, measures aiming to counteracting maternal preconception overweight and obesity may be efficient in reducing GDM prevalence.

Objective . This study aims to design and implement the first deep learning (DL) model to classify subjects in the prodromic states of Alzheimer's disease (AD) based on resting-state electroencephalographic (EEG) signals. Approach . EEG recordings of 17 healthy controls (HCs), 56 subjective cognitive decline (SCD) and 45 mild cognitive impairment (MCI) subjects were acquired at resting state. After preprocessing, we selected sections corresponding to eyes-closed condition. Five different datasets were created by extracting delta, theta, alpha, beta and delta-to-theta frequency bands using bandpass filters. To classify SCD vs MCI and HC vs SCD vs MCI, we propose a framework based on the transformer architecture, which uses multi-head attention to focus on the most relevant parts of the input signals. We trained and validated the model on each dataset with a leave-one-subject-out cross-validation approach, splitting the signals into 10 s epochs. Subjects were assigned to the same class as the majority of their epochs. Classification performances of the transformer were assessed for both epochs and subjects and compared with other DL models. Main results . Results showed that the delta dataset allowed our model to achieve the best performances for the discrimination of SCD and MCI, reaching an Area Under the ROC Curve (AUC) of 0.807, while the highest results for the HC vs SCD vs MCI classification were obtained on alpha and theta with a micro-AUC higher than 0.74. Significance . We demonstrated that DL approaches can support the adoption of non-invasive and economic techniques as EEG to stratify patients in the clinical population at risk for AD. This result was achieved since the attention mechanism was able to learn temporal dependencies of the signal, focusing on the most discriminative patterns, achieving state-of-the-art results by using a deep model of reduced complexity. Our results were consistent with clinical evidence that changes in brain activity are progressive when considering early stages of AD., (Creative Commons Attribution license.)

Background: Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, putting them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite the fact that an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodeling and worse CV outcomes, scarce evidence exists on their role in this setting., Methods: We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectively followed (median 22 months). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events., Results: Circulating levels of all miRNAs were lower in HD patients as compared with healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint ( P  < .001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox regression analyses [hazard ratio (HR) ranging from 0.943 to 0.995; P  = .05 to .02] while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal receiver operating characteristic-derived cut-off value ( P ranging from .001 to <.0001; crude HRs 7.95 to 8.61)., Conclusions: Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short mid-term. Future studies on larger HD populations are needed to generalize these findings., Competing Interests: The authors declare no conflict of interest with respect to the present work. The results presented in this paper have not been published previously in whole or part, except in abstract format., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Nesfatin-1 is a new anorexigenic neuropeptide involved in the regulation of hunger/satiety, eating, and affective disorders. We aimed to investigate nesfatin-1 secretion in vitro, in murine adipose cells, and in human adipose fat samples, as well as to assess the link between circulating nesfatin-1 levels, NUCB2 and Fat Mass and Obesity Gene ( FTO ) polymorphisms, BMI, Eating Disorders (EDs), and pathological behaviors. Nesfatin-1 secretion was evaluated both in normoxic fully differentiated 3T3-L1 mouse adipocytes and after incubation under hypoxic conditions for 24 h. Omental Visceral Adipose tissue (VAT) specimens of 11 obese subjects, and nesfatin-1 serum levels' evaluation, eating behaviors, NUCB2 rs757081, and FTO rs9939609 polymorphisms of 71 outpatients seeking treatment for EDs with different Body Mass Index (BMI) were studied. Significantly higher levels of nesfatin-1 were detected in hypoxic 3T3-L1 cultured adipocytes compared to normoxic ones. Nesfatin-1 was highly detectable in the VAT of obese compared to normal-weight subjects. Nesfatin-1 serum levels did not vary according to BMI, sex, and EDs diagnosis, but correlations with grazing; emotional, sweet, and binge eating; hyperphagia; social eating; childhood obesity were evident. Obese subjects with CG genotype NUCB2 rs757081 and AT genotype FTO rs9939609 polymorphisms had higher nesfatin-1 levels. It could represent a new biomarker of EDs comorbidity among obese patients.

Ionizing radiation (IR) can induce some associated pathological conditions due to numerous cell damages. The influence of sex is scarcely known, and even less known is whether the effect of antioxidants is sex-dependent. Given the increased use of IR, we investigated whether male human umbilical vein endothelial cells (MHUVECs) and female human umbilical vein endothelial cells (FHUVECs) respond differently to IR exposure and whether the antioxidants 10 mM taurine (TAU) and 5 mM N-acetylcysteine (NAC) can prevent IR-induced damage in a sex-dependent way. In untreated cells, sex differences were observed only during autophagy, which was higher in FHUVECs. In non-irradiated cells, preincubation with TAU and NAC did not modify viability, lactate dehydrogenase (LDH) release, migration, or autophagy, whereas only NAC increased malondialdehyde (MDA) levels in FHUVECs. X-ray irradiation increased LDH release and reduced viability and migration in a sex-independent manner. TAU and NAC did not affect viability while reduced LDH release in irradiated cells: they have the same protective effect in FHUVECs, while, TAU was more protective than NAC in male cells.. Moreover, TAU and NAC significantly promoted the closure of wounds in both sexes in irradiated cells, but NAC was more effective at doing this in FHUVECs. In irradiated cells, TAU did not change autophagy, while NAC attenuated the differences between the sexes. Finally, NAC significantly decreased MDA in MHUVECs and increased MDA in FHUVECs. In conclusion, FHUVECs appear to be more susceptible to IR damage, and the effects of the two antioxidants present some sex differences, suggesting the need to study the influence of sex in radiation mitigators., Competing Interests: The authors declare no conflict of interest

Background: Achieving optimal glycemic targets is the main therapeutic goal in patients with type 2 diabetes (T2D) mellitus. HbA1c is the reference biomarker for monitoring glycemic control; however, in specific conditions affecting erythrocyte turnover or in patients on multiple daily injection (MDI) insulin regimens, the determination of glycated albumin (GA) may be preferable. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel class of antidiabetic drugs that lower plasma glucose concentrations quickly, with insulin-independent mechanisms. Herein, we explored the role of GA in predicting the short-term response to SGLT-2 inhibitors as add-on to MDI insulin., Methods: Sixteen patients with long-standing, poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor were subjected to plasma GA and HbA1c measurements at 30 days intervals for up to 3 months in order to examine the temporal changes of these glycemic biomarkers., Results: At the end of the study, grossly coincident with the life span of erythrocytes, a significant decrease in median HbA1c was observed, (from 8.7 [range: 8.2-9.3%] at baseline to 7.2 [range: 7.0-7.9%]), with the advantage of less insulin dose requirements. However, significant, and incremental reductions in median GA determinations could be already evident after 30 days (-3.5 [range: -7.5, -2.5%]) and 60 days (-6.4 [range: -10.5, -4.7%]) from the start of SGLT-2 inhibitor treatment and persisted for up to 3 months (-8.6 [range: -12.1, 6.1%]). The decrements of HbA1c observed at the 3-month visit were highly correlated with the concurrent absolute reductions of plasma GA (ρ=0.550, P=0.027), whereas a borderline significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days., Conclusions: Although limited by the small number of participants, these preliminary findings suggest that GA, rather than HbA1c, could represent a useful and reliable biomarker in T2D to monitor the early glucose-lowering effects of antidiabetic drugs with rapid onset of action, such as SGLT-2 inhibitors and MDI insulin.

Introduction: Germ cell tumors (GCTs) are the most common type of cancer in young men. These tumors usually originate from the testis, but they can occasionally develop from extragonadal sites probably due to primordial germ cells (PGCs) migration errors. Cisplatin-based chemotherapy is usually effective for male GCTs, but the risk of toxicity is high and new therapeutic strategies are needed. Although Metformin (Met) has been widely studied as a potential cancer treatment over the past decades, there is limited evidence to support its use in treating male GCTs. Additionally, the mechanism by which it acts on tumor cells is still not entirely understood., Methods: SEM-1 cells, a newly established human cell line of extragonadal origin, were treated with Met. Cell viability was studied by MTT assay, while cell migration and invasion were studied by the wound healing assay and the transwell assay, respectively. The effect of Met on 3D spheroid formation was determined by seeding SEM-1 cells in appropriate cell suspension culture conditions, and cell cycle was characterized by flow cytometry. Factors involved in PGCs migration and GCT invasion, such as IGFBP1, IGF1R, MMP-11 and c-Kit, together with cyclin D1 (a key regulator of cell cycle progression), and the upstream factor, HMGA1, were determined by immunoblots., Results: Treatment of SEM-1 cells with Met resulted in a potent and dose-dependent reduction of cell proliferation, as evidenced by decreased nuclear abundance of cyclin D1 and cell cycle arrest in G1 phase. Also, Met prevented the formation of 3D spheroids, and blocked cell migration and invasion by reducing the expression of IGFBP1, IGF1R and MMP-11. Both, IGFBP1 and MMP-11 are under control of HMGA1, a chromatin-associated protein that is involved in the regulation of important oncogenic, metabolic and embryological processes. Intriguingly, an early reduction in the nuclear abundance of HMGA1 occurred in SEM-1 cells treated with Met., Conclusions: Our results document the antiproliferative and antimigratory effects of Met in SEM-1 cells, providing new insights into the potential treatments for male GCTs. The anticancer properties of Met in SEM-1 cells are likely related to its ability to interfere with HMGA1 and downstream targets, including cyclin D1, the IGFs system, and MMP-11., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salatino, Mirabelli, Chiefari, Greco, Di Vito, Bonapace, Brunetti, Crocerossa, Epstein, Foti and Brunetti.)

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.

Previous studies have shown that olfactory function plays an essential role in the bonding of a romantic relationship. Body odors, in particular, seem involved in both mate choices and other intimate behaviors. Our sense of smell is also crucial to detect possible pathogen threats, by activating a suitable disgust reaction. Previous studies have shown that disgust sensitivity is negatively related to sociosexuality, and disgust generally inhibits our sexual drive. In the present study, we explored the possible relation between olfactory function, pathogen disgust sensitivity, sociosexuality, sexual well-being, and infidelity through a web survey. Our exploratory analyses found that, in a large Italian sample (N = 1107), among those in a stable relationship, self-reported olfactory function predicted sexual well-being (p < .05) and negatively predicted infidelity (p < .05) when controlling for other relevant sociodemographics variables. Moreover, the relation between self-reported olfactory function and sexual well-being was mediated by pathogen disgust sensitivity. Although significant, these results must be interpreted with caution, because the effect sizes were small., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Background and Objectives: Thyroid dysfunction is associated with non-alcoholic fatty liver disease, but its role in the progression of liver damage in obese patients remains unclear. In addition, several case reports have suggested the existence of a levothyroxine-induced liver injury, which has been poorly investigated. Our aim was to verify whether a difference in the prevalence of liver fibrosis exists in a population of obese individuals taking Levothyroxine. Materials and Methods: We conducted a cross-sectional study on a population of 137 obese individuals, of which 49 were on replacement therapy with Levothyroxine. We excluded those who had hypertriglyceridemia and diabetes mellitus. All participants underwent a liver stiffness assessment by transient elastography as well as biochemical measurements. In subjects with liver fibrosis, other cause of liver fibrosis were ruled out. Results: Participants taking Levothyroxine had a higher prevalence of liver fibrosis than those not taking Levothyroxine (30.6% vs. 2.3%; p < 0.001), and these results were obtained after we made an adjustment for age (Exp(B) = 18.9; 95% CI = 4.1−87.4; p < 0.001). The liver stiffness value differed significantly between groups (6.0 ± 3.6 and 5.1 ± 1.2, p = 0.033). Of those subjects taking Levothyroxine, there were no significant differences in the dose of medication (1.21 ± 0.36 vs. 1.07 ± 0.42; p = 0.240) and treatment duration (13.7 ± 7.43 vs. 11.13 ± 6.23; p = 0.380) between those with and without liver fibrosis. Conclusions: We found, for the first time, a greater prevalence of liver fibrosis in obese individuals taking Levothyroxine than in those not taking this medication. This finding needs to be confirmed by longitudinal population studies as well as by cellular studies.

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.

Vaginal infections affect millions of women annually worldwide. Therapeutic options are limited, moreover drug-resistance increases the need to find novel antimicrobials for health promotion. Recently phytochemicals were re-discovered for medical treatment. Myrtle ( Myrtus communis L.) plant extracts showed in vitro antioxidant, antiseptic and anti-inflammatory properties thanks to their bioactive compounds. The aim of the present study was to create novel nanodevices to deliver three natural extracts from leaves, seeds and fruit of myrtle, in vaginal milieu. We explored their effect on human cells ( HeLa , Human Foreskin Fibroblast-1 line, and stem cells isolated from skin), resident microflora ( Lactobacillus acidophilus ) and on several vaginal pathogens ( Trichomonas vaginalis , Escherichia coli , Staphylococcus aureus , Candida albicans , Candida kefyr , Candida glabrata , Candida parapsilosis , Candida krusei ). Polycaprolactone-Gelatin nanofibers encapsulated with leaves extract and soaked with seed extracts exhibited a different capability in regard to counteracting microbial proliferation. Moreover, these nanodevices do not affect human cells and resident microflora viability. Results reveal that some of the tested nanofibers are interesting candidates for future vaginal infection treatments.

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.

Recent and growing literature has reported that oleuropein (OLE), the main polyphenol in olive leaf extract, inhibits tumor cell proliferation and reduces the invasiveness properties of cancer cells; therefore, OLE may play a significant role in the development of new drugs for cancer treatment. These antineoplastic properties have been reported in many experimental cancer models, but the effect of OLE on seminoma cells is yet to be evaluated. In the present study, we demonstrate, for the first time, that OLE reduces cell viability in both intra- and extragonadal TCAM-2 and SEM-1 seminoma cells, respectively, in a dose-dependent manner. As shown by Western-blot analysis, OLE exposure reduced cyclin-D1 expression and upregulated p21 Cip/WAF1 , concomitantly affecting the upstream pathway of NF-κB, leading to the reduction of its nuclear content, thereby suggesting that OLE could modulate cell-cycle regulators by inhibiting NF-κB. Moreover, Annexin V staining revealed that OLE induced apoptosis in cancer cells and upregulated the pro-apoptotic factor BAX. Through wound-healing scratch and transmigration assays, we also demonstrated that OLE significantly reduced the migration and motility of TCAM-2 and SEM-1 cells, and downregulated the expression of TGFβ-1, which is known to be the main pro-fibrotic factor involved in the acquisition of the migratory and invasive properties of cancer cells. Collectively, our results indicate that OLE reduces seminoma cell proliferation, promotes apoptosis, and counteracts cell migration and motility. Further studies are needed to explore the molecular mechanisms underlying these observed effects.

From the availability of metals to the technology and tools needed to transform them, roughly every civilization in the Mediterranean basin has a metalsmith story. Many of the objects produced by them share a few peculiar characteristics, usages, or even shapes. In this scenario, a class of objects that can be clustered by their usage, i.e., working tools, stands out from the crowd. For this study, a set of working tools from the Nuragic civilization (Sardinia, Italy) was researched with a non-destructive technique: X-ray Fluorescence (XRF). A quantification of the chemical species present in their alloy was obtained with the use of Monte Carlo simulations. The XRMC package, used for the simulations, managed for the first time to reproduce very complex corrosion layers and to thoroughly characterize them from a chemical perspective. The obtained results were discussed and compared to other results reported in the literature.

Background: Advanced stages of different renal diseases feature glomerular sclerosis at a histological level which is observed by light microscopy on tissue samples obtained by performing a kidney biopsy. Computer-aided diagnosis (CAD) systems leverage the potential of artificial intelligence (AI) in healthcare to support physicians in the diagnostic process., Methods: We propose a novel CAD system that processes histological images and discriminates between sclerotic and non-sclerotic glomeruli. To this goal, we designed, tested, and compared two artificial neural network (ANN) classifiers. The former implements a shallow ANN classifying hand-crafted features extracted from Regions of Interest (ROIs) by means of image-processing procedures. The latter, instead, employs the IBM Watson Visual Recognition System, which uses a deep artificial neural network making decisions taking the images as input, without the need to design any procedure for describing images with features. The input dataset consisted of 428 sclerotic glomeruli and 2344 non-sclerotic glomeruli derived from images of kidney biopsies scanned by the Aperio ScanScope System., Results: Both AI approaches allowed to very accurately distinguish (mean MCC 0.95 and mean Accuracy 0.99) between sclerotic and non-sclerotic glomeruli. Although the systems may seem interchangeable, the approach based on feature extraction and classification would allow clinicians to gain information on the most discriminating features. In fact, further procedures could explain the classifier's decision by analysing which subset of features impacted the most on the final decision., Conclusions: We developed a customizable support system that can facilitate the work of renal pathologists both in clinical and research settings., (© 2021. Italian Society of Nephrology.)

This is the first study on the bony labyrinth of Cynotherium sardous , an intriguing extinct canid that inhabited Sardinia in the late Middle and Late Pleistocene. The morphological features of the cochlea indicate that C. sardous had a lower number of cochlear turns (2.25) than all extant canids. This feature, as well as the reduced length of the spiral canal, the cochlear curvature rate, and the narrow basal membrane, indicates that C. sardous had poor hearing abilities limited to high-frequency sounds with a low limit of 250 Hz and poor echolocalization skills. From the data available, it is not possible to infer whether C. sardous was unable to echolocalize its prey and relied on other senses (e.g., smell and sight) to locate them or whether the acoustic range of C. sardous was specialized for identifying the sounds produced by its most common prey to transmit signals for predator warnings or group communication. All things considered, the results obtained confirm the utility of cochlea morphological studies in reconstructing the hearing abilities of this species and in providing some suggestions about its ethology, but they fall short of providing any new sound evidence regarding the ecological role of C. sardous in the Late Pleistocene Sardinian ecosystem.

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., (© 2022. The Author(s).)

The Sardinian protohistoric civilisation (Final Bronze Age and the Early Iron Age) has greatly contributed to the development of metallurgy in the Mediterranean area by producing a large number of bronze artefacts. Among them, small boat models (so-called "navicelle") represent one of the most characteristic objects from the Sardinian Protohistoric civilisation. This work is an attempt to classify these boats on the basis of their alloy composition, provenience, and morphology. Due to the impossibility of removing the boats from the museum, alloys were characterised using energy-dispersive X-ray fluorescence spectrometry and Monte Carlo simulations. Fifteen boats were analyzed. Obtained results were compared to other performed analyses in the last few decades with different techniques and reported in the literature. Analyses allow for characterising both the bulk composition of ternary alloy Cu-Sn-Pb and patina thickness, offering useful information about their conservation status and the technological achievements of Sardinian craftsmen, while also providing information on smelting temperatures and casting techniques.

This paper describes a case study of a linen yarn found inside a spiral bronze necklace fragment during an excavation campaign in la Prisgiona, a Nuragic settlement, near Arzachena, in north-east Sardinia. The site is one of the most interesting settlements of the Nuragic period. Abandoned after a fire, it was no longer inhabited, thus allowing the preservation of the Nuragic stratigraphy. The necklace fragments are part of a votive burial and the yarn is the only known textile material belonging to the Bronze Age period from Sardinia. The uniqueness of the finding, in the rare corpus of prehistoric textile materials, and the small amount of it available do not allow conventional analyses and requires a non-invasive/micro-invasive method. The protocol established to preserve as much as possible the entirety of the object, involving polarize light microscopy, portable ATR-FTIR, SEM-EDS, micro X-ray Computer Tomography and XRD, was successfully used to extend knowledge about the materials and techniques of this civilisation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)