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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.

According to the scientific literature, climate change, due to human activities, can damage the environment, with psycho-physical consequences for humans. The scientific literature has highlighted how severe weather events can cause fear, stress, concern for the future, and eco-anxiety. In light of this information, this study aims to explore the concept of eco-anxiety. However, climate change is still perceived as a secondary problem. It would also be worth investigating the real importance that people attach to environmental issues compared to other circumstances, such as wars or pandemics.

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.

Formalised elicitation of expert judgements has been used to help tackle several problematic societal issues, including volcanic crises and pandemic threats. We present an expert elicitation exercise for Piton de la Fournaise volcano, La Réunion island, held remotely in April 2021. This involved 28 experts from nine countries who considered a hypothetical effusive eruption crisis involving a new vent opening in a high-risk area. The tele-elicitation presented several challenges, but is a promising and workable option for application to future volcanic crises. Our exercise considered an “uncommon” eruptive scenario with a vent outside the present caldera and within inhabited areas, and provided uncertainty ranges for several hazard-related questions for such a scenario (e.g. probability of eruption within a defined timeframe; elapsed time until lava flow reaches a critical location, and other hazard management issues). Our exercise indicated that such a scenario would probably present very different characteristics compared to recent eruptions, and that it is fundamental to include well-prepared expert elicitations in updated civil protection evacuation plans to improve disaster response procedures.

BackgroundArtificial 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).MethodIn 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).ResultsThis 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.ConclusionsBoth 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.

Background and study aims—Albuminuria, defined as an enhanced urine albumin/creatinine ratio (ACR) on a spot sample, is a validated biomarker of glomerular damage. However, it cannot always detect early renal failures in patients with type 2 diabetes (T2D), thus prompting the search for more sensitive and specific parameters. Herein, we investigated the differential role of plasma and urine neutrophil-gelatinase-associated lipocalin (NGALp,—NGALu) for the detection of diabetic kidney disease (DKD). Methods—Traditional glomerular (serum creatinine, cystatin C, ACR) damage biomarkers were evaluated in 84 patients with T2D and in 21 metabolically healthy controls. Diabetic patients were stratified into four groups based on T2D duration (less or more than 5 years) and presence and severity of DKD (early- or advanced-stage), as defined by the ACR and estimated glomerular filtration rate (eGFR). NGALp and NGALu were determined by ELISA methodology and compared among groups. Results—There was no difference in NGALp and NGALu levels between the metabolically healthy individuals and the age-matched, newly diagnosed diabetic patients in the absence of DKD. However, in contrast to NGALu, NGALp was found to be substantially increased in patients with long-standing diabetes without biochemical evidence of DKD, closely mirroring the modest, but still accelerated, decline in the eGFR typical of this chronic dysmetabolic condition, and remained overexpressed throughout the stages of DKD progression. Increased NGALu levels were, instead, rather specific in patients with biochemical evidence of DKD (i.e., marked by increased albuminuria), regardless of T2D duration. Spearman’s correlation and regression analyses showed that patient age and T2D duration could exert a strong positive impact exclusively on NGALp concentrations (ρ = 0.419, p < 0.001 for age; ρ = 0.581, p < 0.001 for T2D), and none on NGALu. Furthermore, receiver operating characteristic (ROC) analysis showed the best performance of NGALp compared to NGALu for the detection of DKD (AUC = 0.817 for NGALp, AUC = 0.711 for NGALu). Conclusions—Our data suggest a different pathophysiological and predictive role for urine and plasma NGAL in the context of T2D and DKD.

Background. Cyberchondria is a term used to refer to excessive surfing the web looking for health care information, excessive checking behavior being related to health-related anxiety. This period of quarantine for the Covid-19 pandemic is increasing the pathological use of the internet, and the excessive surfing the web looking for health care information. Another dimension related to the Covid-19 outbreak refers to uncertainty intolerance, for this reason being necessary for the healthcare professionals to provide clear and linear information. Aim. The aim of this review is to identify the psychological correlations connected to cyberchondria in the quarantine period. Methods. Following the PRISMA guidelines, we carried out a systematic review of the literature on PubMed. The terms used for the search were “Cyberchondria” OR “Anxiety” AND “Quarantine”. Results. As resulting from the reviewed literature, there is a relationship between anxiety for one’s own state of health and cyberchondria, with negative psychological effects of quarantine, including post-traumatic stress symptoms, depression, anxiety, low mood, irritability, insomnia, uncertainty, emotional exhaustion, this condition being associated with hypervigilance, and catastrophic misinterpretation of bodily signs. Conclusion. In the light of this and according to the literature, it would be desirable that research can further explore the factors influencing the increase in cyberchondria in the future.

Abstract 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.

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 recent advancements in the surging field of Deep Learning (DL) have revolutionized every sphere of life, and the healthcare domain is no exception. The enormous success of DL models, particularly with image data, has led to the development of image-guided Robot Assisted Surgery (RAS) systems. By and large, the number of studies concerning image-driven computer assisted surgical systems using DL has increased exponentially. Additionally, the contemporary availability of surgical datasets has also boosted the DL applications in RAS. Inspired by the latest trends and contributions in surgery, this literature survey presents a summarized analysis of recent innovations of DL in image-guided RAS systems. After a thorough review, a sum of 184 articles are selected and grouped into four categories, based on the literature and the relevancy of the task in the articles, comprising 1) Surgical Tools, 2) Surgical Processes, 3) Surgical Surveillance, and 4) Surgical Performance. The survey also discusses publicly available surgical datasets and highlights the basics of the DL models. Furthermore, the legal, ethical, and technological challenges together with the intuitive predictions and recommendations related to the autonomous RAS systems are also presented. The study reveals that Convolutional Neural Network (CNN) is most widely adopted architecture, whereas, the JIGSAWS is most employed dataset in RAS. The study suggests fusing kinematic data along with image data, which produces better accuracy and precision, particularly in gesture and trajectory segmentation tasks. Additionally, CNN and long short term memory networks have shown remarkable performance, however, authors recommend employing these gigantic architectures only when simpler models have failed to produce satisfactory results. The simpler models, despite their limitations, are time and cost effective and yield considerable outcomes even on the smaller datasets.

Abstract Background To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. Methods This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. Results The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58–79 vs 51 years, IQR 41–60; p

Abstract Background Computer-aided diagnosis (CAD) systems based on medical images could support physicians in the decision-making process. During the last decades, researchers have proposed CAD systems in several medical domains achieving promising results. CAD systems play an important role in digital pathology supporting pathologists in analyzing biopsy slides by means of standardized and objective workflows. In the proposed work, we designed and tested a novel CAD system module based on image processing techniques and machine learning, whose objective was to classify the condition affecting renal corpuscles (glomeruli) between sclerotic and non-sclerotic. Such discrimination is useful for the biopsy slides evaluation performed by pathologists. Results We collected 26 digital slides taken from the kidneys of 19 donors with Periodic Acid-Schiff staining. Expert pathologists have conducted the slides preparation, digital acquisition and glomeruli annotations. Before setting the classifiers, we evaluated several feature extraction techniques from the annotated regions. Then, a feature reduction procedure followed by a shallow artificial neural network allowed discriminating between the glomeruli classes. We evaluated the workflow considering an independent dataset (i.e., processing images not used in the training procedure). Ten independent runs of the training algorithm, and evaluation, allowed achieving MCC and Accuracy of 0.95 (± 0.01) and 0.99 (standard deviation

Background: according to the DSM-5, somatic symptom disorder (SSD) is characterized by physical symptoms that cause a disruption in patient functioning and by excessive preoccupation about symptoms. There is a high prevalence of SSD in the general population, with a range going from 5 to 7% and with a relevant cost burden for healthcare system. So, it appears useful to know what the state of art regarding this significant problem is. Methods: the aim of this work is to review studies published in the last twenty years, using Pubmed, Scopus, Cochrane and PsichInfo, as search engines and the following terms: “somatic symptom disorder”, “somatization”, “somatoform disorder”, “medically unexplained symptoms”, “bodily distress syndrome” and “psychosomatic medicine”, linked by the Boolean operator “OR”. Exclusion criteria are studies in languages other than English and French, studies about pediatric population and animals, type of publication other than journal articles. Results: etiology of SSD is multifactorial, involving internal and external factors. Neuroanatomical studies show the presence of abnormalities in CNS of SSD patients. Assessment still results a problematic field, due to uncertainty of nosography. The therapeutic approach toward SSD can be pharmacological, but also the psychotherapy in its different approaches. Conclusions: the issue of SSD is complex and needs further investigations. To correctly analyze this phenomenon, it is necessary to consider both psychological and organic factors, being on the base of this disorder. It is worth to develop this research because an improvement of the state of art about this matter could lead to improve the approach to SSD, resulting in better quality of patients’ life.

Objective The aim of this work is to explore patient’ unmet needs of rare and complex rheumatic tissue diseases (rCTDs) patients during pregnancy and its planning by means of the narrative-based medicine (NBM) approach.Methods A panel of nine rCTDs patients’ representatives was identified to codesign a survey aimed at collecting the stories of rCTD patients who had one or more pregnancies/miscarriages. The results of the survey and the stories collected were analysed and discussed with a panel of patients’ representatives to identify unmet needs, challenges and possible strategies to improve the care of rCTD patients.Results 129 replies were collected, and 112 stories were analysed. Several unmet needs in the management of pregnancy in rCTDs were identified, such as fragmentation of care among different centres, lack of education and awareness on rCTD pregnancies among midwifes, obstetricians and gynaecologists. The lack of receiving appropriate information and education on rCTDs pregnancy was also highlighted by patients and their families. The need for a holistic approach and the availability specialised pregnancy clinics with a multidisciplinary organisation as well as the provision of psychological support during all the phases around pregnancy was considered also a priority.Conclusion The adoption of the NBM approach enabled a direct identification of unmet needs, and a list of possible actions was elaborated to improve the care of rCTD patients and their families in future initiatives.

IntroductionGerm 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.MethodsSEM-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.ResultsTreatment 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.ConclusionsOur 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.

The outdoor sculpture of the first Portuguese king, D. Afonso Henriques (c. 1109–1185 AD), placed in Guimarães (North Portugal), is one of the most emblematic national sculptures. Created in 1887 by António Soares dos Reis, it possesses a remarkable symbolic value in the presumed birthplace of the king. In addition to the artistic and heritage importance of the monument, it is one of the few sculptures cast by a Portuguese industrial foundry in the 19th century. This study obtained data on the sculpture’s elemental composition and corrosion products, gathering important historical and technical information. For this purpose, a multi-analytical approach consisting of X-ray fluorescence (XRF), X-ray diffraction (XRD), optical microscopy (OM) and scanning electron microscopy (SEM-EDS) was carried out to characterise the bulk metal and corrosion layers. The data revealed a ternary alloy of Cu, Sn and Zn, with Pb, Fe, As, Bi and Mn as minor elements. The alloy matches that of other sculptures cast in that period. In terms of corrosion, it is characterised by the presence of oxides. These results represent the first step for applying an appropriate conservation strategy for bronze sculptures with similar characteristics.

Introduction: The prevention of occupational accidents in the sphere of occupational health and safety is an important issue in the Italian work setting; health workers, and especially nurses, are continually exposed to the risk of work-related accidents, which can affect the quality of care provided. Aim: The aim of this review is to investigate the nurse's perceived level of preparedness with regard to occupational safety. Methods: A narrative review of the literature was conducted using some of the main databases such as PubMed, CINAHL and Cochrane. Results: The studies analysed show that Italian nurses have little knowledge about occupational health and safety legislation. Conclusions: Establishing specific postgraduate training events and identifying specific legislation for healthcare personnel could represent essential steps towards implementing this specific knowledge.

Miniaturized bronze flasks represent a small portion of a wide metallurgical production that flourished in Sardinia (Italy) between the Final Bronze Age (FBA) and the Early Iron Age (EIA). They replicate a well-known and symbolic type of object, the pilgrims’ flask, common in all Europe and Mediterranean basin, and have but few archaeological parallels. For these reasons, their characterization can be considered important from an archaeological perspective. Three flasks, preserved at the Antiquarium Arborense museum (Oristano), were analyzed by X-Ray Fluorescence Spectroscopy (XRF) and Raman spectroscopy, integrated by multispectral images. The samples, coming from illegal excavations, posed two problems: establishing their authenticity and investigating the alloy composition of such particular objects. All specimens presented a widespread degradation in the outer surface: XRF and Raman spectroscopy indicated the presence of copper oxides, calcium and copper carbonates deposits. The abscence of Zn, a clear marker of forgeries, was not detected by XRF. In two of the flasks, an unusual Sn content above 20%, was detected. For FBA and EIA, especially regarding southern Europe, Sn was extremely rare, and was possibly used with caution. Further results are presented herein.

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.

Background: Elevated levels of specific proinflammatory molecules in the cerebrospinal fluid (CSF) have been associated with disability progression, enhanced neurodegeneration and higher incidence of mood disorders in people with multiple sclerosis (MS). Studies in animal models of MS suggest that preventive exercise may play an immunomodulatory activity, with beneficial effects on both motor deficits and behavioral alterations. Here we explored the impact of lifestyle physical activity on clinical presentation and associated central inflammation in a large group of newly diagnosed patients with MS. Furthermore, we addressed the causal link between exercise-mediated immunomodulation and mood symptoms in the animal setting. Methods: A cross-sectional study was conducted on 235 relapsing-remitting MS patients at the time of the diagnosis. Patients were divided into 3 groups (“sedentary”, “lifestyle physical activity” and “exercise”) according to the level of physical activity in the six months preceding the evaluation. Patients underwent clinical, neuropsychological and psychiatric evaluation, magnetic resonance imaging and lumbar puncture for diagnostic purposes. The CSF levels of proinflammatory and anti-inflammatory cytokines were analyzed and compared with a group of 80 individuals with non-inflammatory and non-degenerative diseases. Behavioral and electrophysiological studies were carried out in control mice receiving intracerebral injection of IL-2 or vehicle. Behavior was also assessed in mice with experimental autoimmune encephalomyelitis (EAE), animal model of MS, reared in standard (sedentary group) or running wheel-equipped (exercise group) cages. Results: In exercising MS patients, depression and anxiety were reduced compared to sedentary patients. The CSF levels of the interleukin-2 and 6 (IL-2, IL-6) were increased in MS patients compared with control individuals. In MS subjects exercise was associated with normalized CSF levels of IL-2. In EAE mice exercise started before disease onset reduced both behavioral alterations and striatal IL-2 expression. Notably, a causal role of IL-2 in mood disorders was shown. IL-2 administration in control healthy mice induced anxious- and depressive-like behaviors and impaired type-1 cannabinoid (CB1) receptor-mediated neurotransmission at GABAergic synapses, mimicking EAE-induced synaptic dysfunction. Conclusions: Our results indicate an immunomodulatory effect of exercise in MS patients, associated with reduced CSF expression of IL-2, which might result in reduced mood disorders. These data suggest that exercise in the early stages may act as a disease-modifying therapy in MS although further longitudinal studies are needed to clarify this issue.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health‐related quality of life. RHAPSODY (rilonacept inhibition of interleukin‐1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL‐1α and ‐β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient‐reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient‐reported outcome (PRO) questionnaires assessing pericarditis pain, health‐related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run‐in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run‐in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run‐in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health‐related quality of life. All PRO scores significantly improved (P

Introdução: O câncer renal corresponde a 13a neoplasia mais incidente no mundo, sendo o terceiro tipo de câncer geniturinário mais comum. A maioria dos pacientes e assintomática, ocorrendo o diagnóstico de maneira incidental durante a realização de exames de imagem. O tratamento padrão-ouro e o cirúrgico. Objetivo: Correlacionar os parâmetros clínicos e patológicos com a sobrevida livre de doença em pacientes com câncer renal submetidos à nefrectomia. Método: Estudo retrospectivo com 99 pacientes submetidos a tratamento cirúrgico do câncer renal no período de 2010 a 2020. Foram comparados os parâmetros clínicos e patológicos com o desfecho clinico oncológico após nefrectomia. Resultados: Os 99 pacientes tiveram seguimento pós-operatório médio de 26,9 meses, sendo a sobrevida livre de doença (media) de 61,9%. A análise univariada demonstrou que as variáveis tamanho de tumor >7 cm e graus de Fuhrman III e IV estiveram relacionadas a progressão de doença após a nefrectomia (p=0,046 e IC=1,017-7,083; p=0,005 e IC=1,725-23,004, respectivamente). Na análise multivariada, o tamanho do tumor >7 cm (p=0,014 e IC=1,290-9,326) e os graus de Fuhrman III e IV (p=0,028 e IC=1,174-16,616) foram identificados como fatores preditores a progressão. Conclusão: O tamanho tumoral >7 cm e/ou os graus III ou IV de Fuhrman são fatores de risco para recorrência tumoral após o tratamento cirúrgico do câncer renal.

Introdução: O câncer de próstata e a neoplasia maligna mais incidente em homens, representando 29% dos diagnósticos da doença no Brasil, segundo o Instituto Nacional de câncer Jose Alencar Gomes da Silva (INCA). Esse câncer e suspeito em alterações do toque retal e/ou do nível sérico do antígeno prostático especifico (PSA) total, sendo o diagnóstico definitivo feito por estudo histopatológico. Objetivo: Verificar a associação entre parâmetros clínicos e anatomopatológicos após prostatectómica radical com recidiva bioquímica ao longo do seguimento. Método: Estudo retrospectivo observacional dos parâmetros clínicos (idade, PSA inicial, toque retal, classificação histopatológica da International Society of Urological Pathology (ISUP), escala de D’Amico e estádio clínico) e anatomopatológicos (grau ISUP da peça cirúrgica, margens cirúrgicas, extensão extracapsular tumoral e presença de linfonodos acometidos), de 177 pacientes submetidos a prostatectomia radical em serviço de uro-oncologia de junho/2010-maio/2018. Resultados: A recidiva bioquímica ocorreu em 44,1% dos casos no tempo de seguimento médio de 34,9 meses. A análise univariada demonstrou PSA inicial >9 ng/mL, toque retal alterado, classificação patológica ISUP 4 e 5, risco D’Amico alto e estagio clinico TNM T3 como fatores diretamente associados a recidiva bioquímica. As margens cirúrgicas foram positivas em 46,3%; em 47,7%, identificou-se extensão extraprostática tumoral. Linfonodos positivos em 10,9% e vesículas seminais comprometidas ocorreram em 21,8%. Conclusão: Fatores clinico-patológicos podem ser preditores de recidiva bioquímica. Nesses casos, foi identificado padrão clinico pré-tratamento supostamente mais agressivo em comparação a literatura em geral. Além disso, deve-se considerar a curva de aprendizado dos cirurgiões em formação no serviço, o que pode resultar em maiores taxas de margens cirúrgicas positivas.

Background and Objectives: This present study was aimed at exploring hyperarousal and aberrant salience in a sample of the Italian general population to understand their possible role in the acceptance of anti-COVID-19 vaccination. Materials and Methods: Sociodemographic data questions, the “Acceptance of Vaccination” measure, the Hyperarousal Scale (H-Scale), and the Aberrant Salience Inventory (ASI) were sent as an unpaid online survey to the general population (age range 18–80 years) within the Italian territory. Results: The enrolled subjects were divided into two subgroups: “Pro-vax” (n = 806; 87.4%) and “No-vax” (n = 116; 12.6%). Statistical analysis showed significant differences between groups in the “Education Level” (p = 0.001) category, higher in the “Pro-vax” group, and in the ASI “Senses Sharpening” (p = 0.007), “Heightened Emotionality” (p = 0.008), and “Heightened Cognition” (p = 0.002) subscales with the “Total Score” (p = 0.015), all higher in “No-vax” subjects. Furthermore, a linear regression model evidenced that only ”Education Level” (β = 0.143; p < 0.0001) and “Senses Sharpening” (β = −0.150; p = 0.006) were, respectively, direct and inverse predictors of “Acceptance of Vaccination”. Conclusions: Our results show that several subthreshold conditions, such as somatosensory amplification, anxiety traits, and panic experiences, should be taken into account by authoritative sources involved in health education, communication, and policy to alleviate public concerns about vaccine safety, for the present and also future pandemics, and to provide more inclusive, informed, and accurate public health preventive and treatment programs.

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 (

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.

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.

Plant–soil biota represent a unique living system crucial for improving crops’ adaptation to climate change. In vineyards, plant–soil relations are mediated by rootstock–scion interaction, with grafted vines being the main plant material employed in vineyard planting. The interaction between two deeply different biological systems such as Vitis vinifera sativa and the American Vitis species may modify vines’ adaptation to abiotic stress. The aim of this study was to investigate the physiological response (chlorophyll content—CHL; stomatal conductance—gs) of grafted and ungrafted vines and assess the involvement of Arbuscular Mycorrhizal Fungi (AMF) in this response. In two vineyards located in Central Italy, the presence of AMF was assessed in the roots of grafted and ungrafted cv ‘Aleatico’ vines. The morphological traits of AMF and root mycorrhizal colonization differed in the grafted and ungrafted vines. Under limited climate conditions, ungrafted vines showed better leaf resilience traits (high CHL and gs values) and larger AMF storage organs (vesicles). On the other hand, the grafted ones—which are more sensitive to climate conditions (lower gs and CHL)—involved AMF colonization strategies (greater abundance of arbuscoles and mycorrhizal colonization potential) linked to the improved uptake and transport of water from the bulk soil to the vine. Taken together, these findings highlight different mycorrhizal colonization strategies and storage behaviors in grafted and ungrafted vineyards and with respect to different physical and chemical soil traits.

A machine learning method for classifying lung ultrasound is proposed here to provide a point of care tool for supporting a safe, fast, and accurate diagnosis that can also be useful during a pandemic such as SARS-CoV-2. Given the advantages (e.g., safety, speed, portability, cost-effectiveness) provided by the ultrasound technology over other examinations (e.g., X-ray, computer tomography, magnetic resonance imaging), our method was validated on the largest public lung ultrasound dataset. Focusing on both accuracy and efficiency, our solution is based on an efficient adaptive ensembling of two EfficientNet-b0 models reaching 100% of accuracy, which, to our knowledge, outperforms the previous state-of-the-art models by at least 5%. The complexity is restrained by adopting specific design choices: ensembling with an adaptive combination layer, ensembling performed on the deep features, and minimal ensemble using two weak models only. In this way, the number of parameters has the same order of magnitude of a single EfficientNet-b0 and the computational cost (FLOPs) is reduced at least by 20%, doubled by parallelization. Moreover, a visual analysis of the saliency maps on sample images of all the classes of the dataset reveals where an inaccurate weak model focuses its attention versus an accurate one.

Abstract Newer biologic drugs and immunomodulatory agents, as well as more tolerated and effective radiation therapy schemes, have reduced treatment toxicity in oncology patients. However, although imaging assessment of tumor response is adapting to atypical responses like tumor flare, expected changes and complications of chemo/radiotherapy are still routinely encountered in post-treatment imaging examinations. Radiologists must be aware of old and newer therapeutic options and related side effects or complications to avoid a misinterpretation of imaging findings. Further, advancements in oncology research have increased life expectancy of patients as well as the frequency of long-term therapy-related side effects that once could not be observed. This pictorial will help radiologists tasked to detect therapy-related complications and to differentiate expected changes of normal tissues from tumor relapse.

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.

BackgroundNeuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil (BEO) is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor (BEO) on motor cortex using Transcranial magnetic stimulation (TMS).Materials and MethodsWe examined the primary motor cortex (M1) excitability during perception of a pleasant odor (BEO) or perception of odorless saline (experiment 1). Furthermore, we tested the effect of olfactory imagery (OI) of BEO on corticospinal excitability (experiment 2). The increase in motor evoked potential (MEP) amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability.ResultsThe results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor (BEO). The correlation analysis shows an association with neuroticism personality trait (experiment 1) and with general olfactory imagery ability (experiment 2).ConclusionBoth perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems.

Therapeutic monoclonal antibodies (mAbs), including immune checkpoint inhibitors (ICIs), are an important breakthrough for the treatment of cancer and have dramatically changed clinical outcomes in a wide variety of tumours. However, clinical response varies among patients receiving mAb-based treatment, so it is necessary to search for predictive biomarkers of response to identify the patients who will derive the greatest therapeutic benefit. The interaction of mAbs with Fc gamma receptors (FcγR) expressed by innate immune cells is essential for antibody-dependent cellular cytotoxicity (ADCC) and this binding is often critical for their in vivo efficacy. FcγRIIa (H131R) and FcγRIIIa (V158F) polymorphisms have been reported to correlate with response to therapeutic mAbs. These polymorphisms play a major role in the affinity of mAb receptors and, therefore, can exert a profound impact on antitumor response in these therapies. Furthermore, recent reports have revealed potential mechanisms of ICIs to modulate myeloid subset composition within the tumour microenvironment through FcγR-binding, optimizing their anti-tumour activity. The purpose of this review is to highlight the clinical contribution of FcγR polymorphisms to predict response to mAbs in cancer patients.

In the current literature, the utility of transient ischemic attack (TIA) diagnosis is under revision by the scientific community and experts. If initially this term was considered a valid diagnostic category, over the years the definition of TIA has been completely subverted, underlining the scientific lability of this nosological entity [...]