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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.

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

Il diabete mellito gestazionale (DMG), è il disordine endocrino-metabolico a maggiore prevalenza nelle donne in gravidanza e si associa a un alto rischio di complicanze materno-fetali. L’eziologia di tale condizione è complessa e multifattoriale, con fattori di rischio e meccanismi patogenetici in gran parte comuni a quelli del diabete mellito di tipo 2 (DMT2), il quale spesso compare nelle donne che hanno una storia di DMG anche a soli pochi anni di distanza dal parto. Tuttavia, mentre per la prevenzione del DMT2 gli interventi multimodali di modifica dello stile di vita, comprendenti programmi di attività fisica o esercizio fisico, uniti a cambiamenti nutrizionali e comportamentali, sono associati a benefici certi, lo stesso non vale per il DMG, per cui esistono evidenze scientifiche di natura osservazionale e sperimentale a volte contrastanti. Dall’analisi della letteratura più recente, riassunta in questa rassegna, emerge la necessità di spostare l’attenzione della ricerca sugli effetti di una prevenzione di precisione, che adatti il timingdi inizio, la tipologia e l’intensità del programma di esercizio fisico per la prevenzione del DMG alle caratteristiche fisiologiche delle singole gestanti. Si ravvisa, inoltre, il bisogno di estendere la “finestra d’intervento” al periodo preconcezionale per massimizzare le possibilità di successo, soprattutto nelle donne ad alto rischio.

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

•Chemical and microstructural analyses identified chalcopyrite as the mineral used for Cu extraction, associated with arsenopyrite and galena.•Lead Isotope Analysis showed that the copper used to make the artefact exhibits a Pb isotope composition compatible with the groups of ore deposits from Iglesiente/Sulcis, in Sardinia.•The data obtained in this work support the hypothesis of the existence of contacts between Sardinia and Middle Tyrrhenian Italy during the Iron Age.•The statuette may represent the first object of Sardinian origin found in a residential context.•The non-destructive EDXRF-MCS method, used to characterize the alloy in terms of composition and structure, once again proved its effectiveness, achieving results similar to those achieved with micro-invasive techniques.

The forkhead transcription factor (FoxO1) is a master transcriptional regulator of fundamental cellular processes ranging from cell proliferation and differentiation to inflammation and metabolism. However, despite its relevance, the mechanism(s) underlying FoxO1gene regulation are largely unknown. We have previously shown that the chromatin factor high-mobility group A1 (HMGA1) plays a key role in the transcriptional regulation of glucose-responsive genes, including some that are involved in FoxO1-mediated glucose metabolism. Here we investigated the impact of HMGA1 on FoxO1gene expression. FoxO1 protein and gene expression studies were performed by Western blot analysis combined with qRT-PCR of material from human cultured cells and EBV-transformed lymphoblasts, and from primary cultured hepatocytes from wild-type and Hmga1–/–mice. Reporter gene assays and chromatin immunoprecipitation for binding of HMGA1 to the endogenous FoxoO1locus were performed in cells overexpressing HMGA1 and in cells pretreated with siRNA targeting HMGA1. HMGA1 increased FoxO1 mRNA and protein expression in vitro, in cultured HepG2 and HEK-293 cells by binding FoxO1gene promoter, thereby activating FoxO1gene transcription. Forced expression of HMGA1 in primary cultured hepatocytes from Hmga1–/–mice and in EBV-transformed lymphoblasts from subjects with reduced expression of endogenous HMGA1 increased FoxO1 mRNA and protein levels. These findings may contribute to the understanding of FoxO1gene regulation and its role in metabolism.

The prevalence of type 2 diabetes mellitus has increased worldwide over the past three decades, as a consequence of the more westernized lifestyle, which is responsible for the increasing obesity rate in the modern adult’s life. Concomitant with this increase there has been a gradual rise in the overall prevalence of gestational diabetes mellitus, a condition that strongly predisposes to overt diabetes later in life. Many women with previous gestational diabetes mellitus show glucose intolerance in the early postpartum period. Although the best screening strategy for postpartum glucose intolerance is still debated, numerous evidences indicate that identification of these women at this time is of critical importance, as efforts to initiate early intensive lifestyle modification, including hypocaloric diet and physical activity, and to ameliorate the metabolic profile of these high-risk subjects can prevent or delay the onset of type 2 diabetes mellitus. Nevertheless, less than one fifth of women attend the scheduled postpartum screening following gestational diabetes mellitus and they are at increased risk to develop type 2 diabetes mellitus later in their lives. Unsatisfying results have also come from early intervention strategies and tools that have been developed during the last few years to help improving the rate of adherence to postpartum glycemic testing, thereby indicating that more effective strategies are needed to improve women’s participation in postpartum screening.

In the last few years, bone has been recognized as an endocrine organ that modulates glucose metabolism by secretion of osteocalcin, an osteoblast-specific hormone, that influences fat deposition and blood sugar levels. To date, however, very few in vitro models have been developed to investigate, at the molecular levels, the relationship between glucose, insulin and osteocalcin. This study aims at covering this gap. We studied osteogenic differentiation, osteocalcingene expression, and osteblast-mediated insulin secretion, using cultured MG-63 human osteoblast-like cells that underwent glucotoxicity and insulin resistance. In addition, we investigated whether a correlation existed between hyperglycemia and/or insulin resistance and total osteocalcin serum concentrations in patients. While insulin and low glucose increased osteocalcingene expression, disruption of insulin signaling in MG-63 osteoblasts and high glucose concentration in cell culture medium decreased osteocalcingene transcription and reduced osteogenic differentiation. Concomitantly, insulin secretion was significantly impaired in rat INS-1 β-cells treated with conditioned medium from insulin resistant MG-63 cells or cells exposed to high glucose concentrations. Also, chronic hyperglycemia, but not insulin resistance, inversely correlated with circulating osteocalcin levels in patients. Our results further support the existence of an endocrine axis between bone, where osteocalcin is produced, and pancreatic β-cells, and add new insights into the molecular details of this relationship. These findings may contribute to the understanding of osteocalcin regulation and its role in metabolism.

Introduction and objective: Computer Aided Decision (CAD) systems based on Medical Imaging could support radiologists in grading Hepatocellular carcinoma (HCC) by means of Computed Tomography (CT) images, thus avoiding medical invasive procedures such as biopsies. The identification and characterization of Regions of Interest (ROIs) containing lesions is an important phase allowing an easier classification in two classes of HCCs. Two steps are needed for the detection of lesioned ROIs: a liver isolation in each CT slice and a lesion segmentation. Materials and methods: Materials consist in abdominal CT hepatic lesion from 18 patients subjected to liver transplant, partial hepatectomy, or US-guided needle biopsy. Several approaches are implemented to segment the region of liver and, then, detect the lesion ROI. Results: A Deep Learning approach using Convolutional Neural Network is followed for HCC grading. The obtained good results confirm the robustness of the segmentation algorithms leading to a more accurate classification.

Thyroid dysfunction induces several renal derangements involving all nephron portions. Furthermore, dysthyroidism is a recognized risk factor associated with the development of chronic kidney disease. Current data, in fact, demonstrate that either subclinical or overt thyroid disease is associated with significant changes in creatinine, estimated glomerular filtration rate, measured glomerular filtration rate and Cystatin C. Herein, we systematically reviewed several relevant studies aiming at the identification of the most sensitive and specific parameter for the correct renal function evaluation in patients with thyroid dysfunction, that are usually treated as outpatients. Our systematic review indicates that estimated glomerular filtration rate, preferably with CKD-EPI equation, appears to be the most reliable and wieldy renal function parameter. Instead, Cystatin C should be better used in the grading of thyroid dysfunction severity.

Synchrotron-based planar diffraction-enhanced imaging system (Sy-DEI) and the combined system in tomography mode (Sy-DEI-CT) has been used to acquire the images of the walnut at 20 keV. Sy-DEI and Sy-DEI-CT systems utilize the refraction properties of the X-rays, when X-rays traversing the sample. These are identified as phase-sensitive X-ray imaging systems, which uses the phase shift rather than the absorption contrast as the imaging signal and substantially increase the image contrast. Walnut seeds are high density source of nutrients, particularly proteins and essential fatty acids. Recently, scientific evidence shows that, it offers health benefits, when used as a source of food material. Knowing the internal features by non-destructive methods are useful compared to conventional methods. Systems based on refraction properties are reliable for contrast enhancement and visibility. At 20 keV, the changes in the hard part and certain features of internal parts are clearly visible.

Polymeric products are largely used for consolidation of stone in the field of cultural heritage. Nevertheless, the main problem of polymeric compounds is related to their macromolecular nature, it being difficult for a polymer to penetrate inside the pores which may have a very small diameter. These considerations are the starting points for in situpolymerization. According to this technique, not the pre‐formed polymer, but the monomer is introduced into the stone and it is polymerized in situin a subsequent step.

Compton tomography generally makes use of the same scanning techniques (rotations and translations) as transmission tomography but modifies the reconstruction software. However, it is also possible to use an x–y scanning technique, i.e. two independent sets of linear translations of the source and of the detector. The x–y technique allows one to scan only a limited zone of the sample, whereas the rotation–translations method needs to scan the whole sample. x–y scanning has a serious drawback: it is more sensitive than the translation–rotation technique to self-absorption phenomena in the matrix. In this paper a new algorithm for x–y scanning reconstruction is described. This algorithm considers and corrects self-absorption effects without requiring a priori knowledge about the chemical composition. Copyright © 2002 John Wiley & Sons, Ltd.

Compton, Rayleigh and fluorescence cross-sections for low, medium and high Z atoms are measured at low photon energies (<100 keV) using an X-ray tube with secondary target. A new approach is developed to estimate the solid angle approximation and geometrical efficiency for a system with experimental arrangement using X-ray tube and secondary target as excitation source. Using this arrangement basic interaction cross-section measurements are performed in vacuum and reasonable monochromacy is achieved. Our motivation is mainly based on fundamental radiation interactions and radiology in mind. The present X-ray system considering the geometrical effects of the measuring system is more advantageous as far as the reduction of incoherently scattered background and improvement of monochroamcy is concerned. The variation of the solid angle is studied by changing the radius and length of the collimators towards and away from the source and sample. From these values the variation of the solid angle and geometrical efficiency is deduced and the optimum value is used for the experimental work. The experimental system is very simple in design, compact and economical. Experimental results based on these systems are compared with theoretical estimates and good agreement is observed in between them.

We have previously identified two closely related nuclear binding proteins that specifically interact with two unique functional AT‐rich sequences of the 5′ regulatory region of the human insulin receptor gene. Expression of these nuclear binding proteins increases during myocyte and adipocyte differentiation, and in other tissues appears to correlate with insulin receptor content. We have hypothesized, therefore, that insulin receptor expression in the insulin target tissues is regulated at least in part by these nuclear proteins. Here we show data on purification and biochemical characterization of these DNA binding proteins. Using a conventional chromatographic purification procedure combined with electrophoresis mobility shift assay and immunoblot analyses, a unique ~15 kDa protein, either identical to or highly related to the architectural transcription factor HMGI(Y), has now been identified, suggesting an essential role for HMGI(Y) in regulating insulin receptor gene transcription. Direct evidence of HMGI(Y) insulin receptor promoter interactions is provided by functional analysis with the CAT reporter gene and by hormone binding studies in cells expressing HMGI(Y) antisense RNA. In these experiments, antisense HMGI(Y) specifically inhibits insulin receptor promoter function and insulin receptor protein expression, indicating that HMGI(Y) is required for proper transcription of insulin receptor gene. Moreover, our data consistently support the hypothesis that a putative defect in this nuclear binding protein may cause insulin receptor dysfunction with subsequent impairment of insulin signaling and action.—Brunetti, A., Manfioletti, G., Chiefari, E., Goldfine, I. D., Foti, D. Transcriptional regulation of human insulin receptor gene by the high‐mobility group protein HMGI(Y). FASEB J.15, 492‐500 (2001)

In energy-dispersive x-ray fluorescence analysis, the estimation of the net area of the peaks is a primary requirement. This task requires a non-linear fitting of the peaks. The most common procedures are based on the Marquardt– Levenberg technique. This technique generally works well only when the spectrum is perfectly known, i.e. all the peaks are recognized. Moreover, it is sometimes difficult to introduce constraints on the fit due to peak shape or other physical properties. In this paper a new technique is proposed, based on a set of genetic operators. It works well even when the knowledge of the peaks is incomplete and it also allows one easily to introduce constraints. The results obtained with this algorithm are generally superior with respect to a standard implementation of a Marquardt– Levenberg procedure. The only drawback is the speed of convergence, that is slower than in the Marquardt– Levenberg technique. Copyright © 2001 John Wiley & Sons, Ltd.

•A peculiar funeral rite was found in the necropolis of Monte Sirai (Italy).•The tomb T310 presents a female individual together with a perinatal individual.•Perinatal remains were deposited in a cooking pot accompanied by avifaunal remains.•XRD/FT-IR analysis showed that the infant remains underwent intense heat treatment.•This burial has close analogies with practices in tophetsanctuaries.

Recent evidence suggests that insulin signaling through the insulin receptor A type (Ex11−), regulates insulin gene transcription. Because chronic hyperglycemia negatively affects insulin receptor function and regulates alternative splicing of the insulin receptor, we inquired whether chronic exposure of pancreatic β‐cells to high glucose results in alterations in insulin signaling due to changes in insulin receptor expression and relative abundance of its spliced isoforms. Our results demonstrate that the insulin receptor is localized in insulin secretory vescicles in human pancreatic β‐cells. Furthermore, we find that alterations in insulin expression and secretion caused by chronic exposure to high glucose are paralleled by decreased insulin receptor expression and increased relative abundance of the Ex11+ isoform in both human islets and RIN β‐cells. PDX‐1 and HMGI(Y) transcription factors are down‐regulated by high glucose. These changes are associated with defects in insulin signaling involving insulin receptor‐associated PI 3‐kinase/Akt/PHAS‐I pathway in RIN β‐cells. Re‐expression in RIN β‐cells chronically exposed to high glucose of the Ex11−, but not the Ex11+, isoform restored insulin mRNA expression. These data suggest that changes in early steps of insulin receptor signaling may play a role in determining β‐cell dysfunction caused by chronic hyperglycemia.

Correction to: Endocrinehttps://doi.org/10.1007/s12020-017-1396-0 The article Insulin and osteocalcin: further evidence for a mutual cross-talk, written by Francesco L. Bilotta, Biagio Arcidiacono, Sebastiano Messineo, Marta Greco, Eusebio Chiefari, Domenico Britti, Tomoko Nakanishi, Daniela P. Foti, Antonio Brunetti, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 2 September 2017 without open access.

Insulin-like growth factor I (IGF-I) regulates articular cartilage homeostasis. During osteoarthritis (OA), the anabolic responses of chondrocytes to IGF-I are likely to be prevented by the enhanced production of IGF-binding proteins (IGFBPs), especially IGFBP-3. The aim of this study is to evaluate whether the architectural transcription factor high mobility group A1 (HMGA1) influences IGFBP-3 overexpression in vitro, in cultured chondrocytic cell lines, and ex vivo, in human osteoarthritic cartilage compared to healthy human cartilage controls.

Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D), in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance) and the increase in bioavailable insulin-like growth factor I (IGF-I) appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG), whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS) that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

This work presents the recent developments of xraylib, an ANSI C library designed to provide convenient access to a large number of X-ray related databases, with a focus on quantitative XRF applications. The discussed enhancements include improved XRF production cross sections that take into account cascade effects and M-lines, as well as revised line energies, atomic level widths, Compton broadening profiles etc. A full overview is presented of the complete API.