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Insulin resistance (IR), marked by reduced cellular responsiveness to insulin, and obesity, defined by the excessive accumulation of adipose tissue, are two intertwined conditions that significantly contribute to the global burden of cardiometabolic diseases. Adipose tissue, beyond merely storing triglycerides, acts as an active producer of biomolecules. In obesity, as adipose tissue undergoes hypertrophy, it becomes dysfunctional, altering the release of adipocyte-derived factors, known as adipokines. This dysfunction promotes low-grade chronic inflammation, exacerbates IR, and creates a hyperglycemic, proatherogenic, and prothrombotic environment. However, the fundamental cause of these phenomena remains unclear. This narrative review points to hypoxia as a critical trigger for the molecular changes associated with fat accumulation, particularly within visceral adipose tissue (VAT). The activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates homeostatic responses to low oxygen levels, initiates a series of molecular events in VAT, leading to the aberrant release of adipokines, many of which are still unexplored, and potentially affecting peripheral insulin sensitivity. Recent discoveries have highlighted the role of hypoxia and miRNA-128 in regulating the insulin receptor in visceral adipocytes, contributing to their dysfunctional behavior, including impaired glucose uptake. Understanding the complex interplay between adipose tissue hypoxia, dysfunction, inflammation, and IR in obesity is essential for developing innovative, targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Women who experience gestational diabetes mellitus (GDM) during their first pregnancy are at a high risk of developing GDM again in subsequent pregnancies. Even mothers with no previous history of GDM may develop the condition in a new pregnancy. Methods: In this retrospective cross-sectional observational study, 759 multiparous women tested for GDM in two successive pregnancies using the 75 g OGTT (IADPSG criteria) were enrolled. The OGTT was performed at 24–28 weeks' gestation or earlier if there was a history of GDM. Participants were categorized into four groups: women with normal glucose tolerance (NGT) in both pregnancies (n = 493), women with a first occurrence of GDM in their second pregnancy (n = 74), women with non-recurrent GDM in their second pregnancy (n = 92), and women with recurrent GDM in their second pregnancy (n = 100). Results: Intergroup comparisons revealed clinical predictors of GDM in the first pregnancy (family history of type 2 diabetes, PCOS, advanced maternal age, pregravid obesity) and in the second pregnancy (interpregnancy BMI gain), as well as predictors of recurrent GDM (pregravid obesity, PCOS). A positive correlation was observed between the OGTT glucose levels of consecutive pregnancies. Adjusted logistic regression indicated that a higher 1-h post-load glucose level (≥130 mg/dL) during the first pregnancy significantly increased the likelihood of new-onset GDM in the second pregnancy (OR: 2.496), whereas a higher 2-h post-load glucose level (≥153 mg/dL) at the first diagnostic OGTT increased the likelihood of recurrent GDM (OR: 2.214). Conclusions: Clinical risk factors and post-load glucose levels during the first gestational 75 g OGTT can help predict new-onset or recurrent GDM in multiparous women. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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

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

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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

This scientific research article titled "NLRP3 inflammasome activation and cell death" explores the activation of the NLRP3 inflammasome, a protein complex involved in the immune response, and its role in cell death. The authors discuss the mechanisms and signaling pathways associated with NLRP3 inflammasome activation and its implications in various diseases. This article provides valuable insights for researchers studying inflammation and cell death processes. [Extracted from the article]

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 6men) with an average education level of 14.9 ± 3.2 years. There were no significant differences in gender (X² = 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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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. [ABSTRACT FROM AUTHOR]

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

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m2) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m2) were recruited in the Endocrinology Unit ("Mater-Domini") of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p < 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals. [ABSTRACT FROM AUTHOR]

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 formacro- and micronutrients, and the accuracy was evaluated based on true positives and true negatives versus the total (97.15%). Then, ANNwas 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the last 10 years, the demand for robot-based depalletization systems has constantly increased due to the growth of sectors such as logistics, storage, and supply chains. Since the scenarios are becoming more and more unstructured, characterized by unknown pallet layouts and stock-keeping unit shapes, the classical depalletization systems based on the knowledge of predefined positions within the pallet frame are going to be substituted by innovative and robust solutions based on 2D/3D vision and Deep Learning (DL) methods. In particular, the Convolutional Neural Networks (CNNs) are deep networks that have proven to be effective in processing 2D/3D images, for example in the automatic object detection task, and robust to the possible variability among the data. However, deep neural networks need a big amount of data to be trained. In this context, whenever deep networks are involved in object detection for supporting depalletization systems, the dataset collection represents one of the main bottlenecks during the commissioning phase. The present work aims at comparing different training strategies to customize an object detection model aiming at minimizing the number of images required for model fitting, while ensuring reliable and robust performances. Different approaches based on a CNN for object detection are proposed, evaluated, and compared in terms of the F1-score. The study was conducted considering different starting conditions in terms of the neural network's weights, the datasets, and the training set sizes. The proposed approaches were evaluated on the detection of different kinds of paper boxes placed on an industrial pallet. The outcome of the work validates that the best strategy is based on fine-tuning of a CNN-based model already trained on the detection of paper boxes, with a median F1-score greater than 85.0 % . [ABSTRACT FROM AUTHOR]

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

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

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. [ABSTRACT FROM AUTHOR]

The non-destructive testing methods offer great benefit in detecting and classifying the weld defects. Among these, infrared (IR) thermography stands out in the inspection, characterization, and analysis of the defects from the camera image sequences, particularly with the recent advent of deep learning. However, in IR, the defect classification becomes a cumbersome task because of the exposure to the inconsistent and unbalanced heat source, which requires additional supervision. In light of this, authors present a fully automated system capable of detecting defective welds according to the electrical resistance properties in the inline mode. The welding process is captured by an IR camera that generates a video sequence. A set of features extracted by such video feeds supervised machine learning and deep learning algorithms in order to build an industrial diagnostic framework for weld defect detection. The experimental study validates the aptitude of a customized convolutional neural network architecture to classify the malfunctioning weld joints with mean accuracy of 99% and median f1 score of 73% across five-fold cross validation on our locally acquired real world dataset. The outcome encourages the integration of thermographic-based quality control frameworks in all applications where fast and accurate recognition and safety assurance are crucial industrial requirements across the production line. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Computer-aided diagnosis (CAD) systems can help radiologists in numerous medical tasks including classification and staging of the various diseases. The 3D tomosynthesis imaging technique adds value to the CAD systems in diagnosis and classification of the breast lesions. Several convolutional neural network (CNN) architectures have been proposed to classify the lesion shapes to the respective classes using a similar imaging method. However, not only is the black box nature of these CNN models questionable in the healthcare domain, but so is the morphological-based cancer classification, concerning the clinicians. As a result, this study proposes both a mathematically and visually explainable deep-learning-driven multiclass shape-based classification framework for the tomosynthesis breast lesion images. In this study, authors exploit eight pretrained CNN architectures for the classification task on the previously extracted regions of interests images containing the lesions. Additionally, the study also unleashes the black box nature of the deep learning models using two well-known perceptive explainable artificial intelligence (XAI) algorithms including Grad-CAM and LIME. Moreover, two mathematical-structure-based interpretability techniques, i.e., t-SNE and UMAP, are employed to investigate the pretrained models' behavior towards multiclass feature clustering. The experimental results of the classification task validate the applicability of the proposed framework by yielding the mean area under the curve of 98.2%. The explanability study validates the applicability of all employed methods, mainly emphasizing the pros and cons of both Grad-CAM and LIME methods that can provide useful insights towards explainable CAD systems. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the deadliest diseases worldwide. Computed Tomography (CT) images are a powerful tool for investigating the structure and texture of lung nodules. For a long time, trained radiologists have performed the grading and staging of cancer severity by relying on radiographic images. Recently, radiomics has been changing the traditional workflow for lung cancer staging by providing the technical and methodological means to analytically quantify lesions so that more accurate predictions could be performed while reducing the time required from each specialist to perform such tasks. In this work, we implemented a pipeline for identifying a radiomic signature composed of a reduced number of features to discriminate between adenocarcinomas and other cancer types. In addition, we also investigated the reproducibility of this radiomic study analysing the performances of the classification models on external validation data. In detail, we first considered two publicly available datasets, namely D1 and D2, composed of n = 262 and n = 89 samples, respectively. Ten significant features, according to univariate AUC evaluated on D1, were retained. Mann–Whitney U tests recognised three of these features to have a statistically different distribution, with a p-value < 0.05. Then, we collected n = 51 CT images from patients with lung nodules at the Azienda Ospedaliero—Universitaria "Policlinico Riuniti" in Foggia. Resident radiologists manually annotated the lung lesions in images to allow the subsequent analysis of the malignancy regions. We designed a pipeline for feature extraction from the Volumes of Interest in order to generate a third dataset, i.e., D3. Several experiments have been performed showing that the selected radiomic signature not only allowed the discrimination of lung adenocarcinoma from other cancer types independently from the input dataset used for training the models, but also allowed reaching good classification performances also on external validation data; in fact, the radiomic signature computed on D1 and evaluated on the local cohort allowed reaching an AUC of 0.70 ( p < 0.001 ) for the task of predicting the histological subtype. [ABSTRACT FROM AUTHOR]

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

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 p21Cip/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Liver segmentation is a crucial step in surgical planning from computed tomography scans. The possibility to obtain a precise delineation of the liver boundaries with the exploitation of automatic techniques can help the radiologists, reducing the annotation time and providing more objective and repeatable results. Subsequent phases typically involve liver vessels' segmentation and liver segments' classification. It is especially important to recognize different segments, since each has its own vascularization, and so, hepatic segmentectomies can be performed during surgery, avoiding the unnecessary removal of healthy liver parenchyma. In this work, we focused on the liver segments' classification task. We exploited a 2.5D Convolutional Neural Network (CNN), namely V-Net, trained with the multi-class focal Dice loss. The idea of focal loss was originally thought as the cross-entropy loss function, aiming at focusing on "hard" samples, avoiding the gradient being overwhelmed by a large number of falsenegatives. In this paper, we introduce two novel focal Dice formulations, one based on the concept of individual voxel's probability and another related to the Dice formulation for sets. By applying multi-class focal Dice loss to the aforementioned task, we were able to obtain respectable results, with an average Dice coefficient among classes of 82.91%. Moreover, the knowledge of anatomic segments' configurations allowed the application of a set of rules during the post-processing phase, slightly improving the final segmentation results, obtaining an average Dice coefficient of 83.38%. The average accuracy was close to 99%. The best model turned out to be the one with the focal Dice formulation based on sets. We conducted the Wilcoxon signed-rank test to check if these results were statistically significant, confirming their relevance. [ABSTRACT FROM AUTHOR]

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

A by‐product of energy‐dispersive X‐ray fluorescence (EDXRF)‐analysis consists of using the ratios of selected X‐ray peaks to determine the thickness of multilayered objects. Three different methods were developed in the past, all because the two main K or L X‐lines from an EDXRF spectrum emitted by a chemical element have a distinct energy and are differently attenuated by an overlying layer. This specific subject has many papers dedicated, but only a few considerations were devoted to the limits of these methods, that is, the range, for example, of gold thickness that can be usefully determined by each method. This paper defines these limits in the specific case of thin gilding (with d < 1 μm). Three typical situations were considered, and the following artefacts were studied: two artefacts on gilded lead, where the gold leaf is superimposed to a white lead pigment, both in the painting "La Fornarina" of Raphael, dated 1520 AD, and in the imperial carriage of Dom Pedro II emperor of Brazil. In this last case, the white lead pigment was painted over the wood structure of the carriage; four artefacts on gilded copper, three crowns and a pendant, from the tomb of the Lady of Cao, from the Moche civilization of the North of Peru, dated around 350 AD; finally, an artefact on gilded silver, a vase from the Chavín civilization of the North of Peru, dated around 1000‐200 BC. [ABSTRACT FROM AUTHOR]

Smart industrial workstations for the training and evaluation of workers are an innovative approach to face the problems of manufacturing quality assessment and fast training. However, such products do not implement algorithms that are able to accurately track the pose of a hand tool that might also be partially occluded by the operator's hands. In the best case, the already proposed systems roughly track the position of the operator's hand center assuming that a certain task has been performed if the hand center position is close enough to a specified area. The problem of the pose estimation of 3D objects, including the hand tool, is an open and debated problem. The methods that lead to high accuracies are time consuming and require a 3D model of the object to detect, which is why they cannot be adopted for a real-time training system. The rise in deep learning has stimulated the search for better-performing vision-based solutions. Nevertheless, the problem of hand tool pose estimation for assembly and training procedures appears to not have been extensively investigated. In this study, four different vision-based methods based, respectively, on ArUco markers, OpenPose, Azure Kinect Body Tracking and the YOLO network have been proposed in order to estimate the position of a specific point of interest of the tool that has to be tracked in real-time during an assembly or maintenance procedure. The proposed approaches have been tested on a real scenario with four users handling a power drill simulating three different conditions during an assembly procedure. The performance of the methods has been evaluated and compared with the HTC Vive tracking system as a benchmark. Then, the advantages and drawbacks in terms of the accuracy and invasiveness of the method have been discussed. The authors can state that OpenPose is the most robust proposal arising from the study. The authors will investigate the OpenPose performance in more depth in further studies. The framework appears to be very interesting regarding its integration into a smart workstation for quality assessment and training. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]