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Background: Several US risk stratification score systems (RSSs) have been developed to standardize a thyroid nodule risk of malignancy. It is still a matter of debate which RSS is the most reliable. The purpose of this study is to evaluate: (1) the concordance between the American College of Radiology TI-RADS (ACR TI-RADS) and fine needle aspiration cytology (FNAC), (2) the cancer rate in the ACR TI-RADS categories, (3) the characteristics of nodules evaluated by FNAC even if not formally indicated according to ACR TI-RADS (‘not indicated FNACs”). Methods: From January 2021 to September 2022, patients attending the Endocrinology Unit of the CTO Hospital of Rome for evaluation of thyroid nodules were included. Results: 830 nodules had negative cytology, belonging to TIR2 and TIR1C. One hundred and thirteen nodules were determined to be suspicious for or consistent with malignancy belonging to TIR3B/TIR4/TIR5. Of this last group, 94% were classified as TR4/TR5 nodules. In total, 87/113 underwent surgery. Among these, 73 had histologically proven cancer, 14 turned out to be benign. “Not indicated FNACs” was 623. Among these, 42 cancers were present. Conclusions: This study confirmed the diagnostic power of ACR TI-RADS. In addition, these data suggest revising the ACR TI-RADS indication to FNAC, especially for TR4.

Attribution studies on recent global warming by Global Climate Model (GCM) ensembles converge in showing the fundamental role of anthropogenic forcings as primary drivers of temperature in the last half century. However, despite their differences, all these models pertain to the same dynamical approach and come from a common ancestor, so that their very similar results in attribution studies are not surprising and cannot be considered as a clear proof of robustness of the results themselves. Thus, here we adopt a completely different, non-dynamical, data-driven and fully nonlinear approach to the attribution problem. By means of neural network (NN) modelling, and analysing the last 160 years, we perform attribution experiments and find that the strong increase in global temperature of the last half century may be attributed basically to anthropogenic forcings (with details on their specific contributions), while the Sun considerably influences the period 1910–1975. Furthermore, the role of sulphate aerosols and Atlantic Multidecadal Oscillation for better catching interannual to decadal temperature variability is clarified. Sensitivity analyses to forcing changes are also performed. The NN outcomes both corroborate our previous knowledge from GCMs and give new insight into the relative contributions of external forcings and internal variability to climate.

A novel statistical downscaling system for seasonal predictions is presented, based on an ensemble of neural networks with Bayesian regularization. The system SIBILLA (Statistical Integrated Bayesian Information system for Large to Local area Analysis) is able to take multiple predictor fields and/or time series as inputs. Gridded fields are compressed using empirical orthogonal functions, and a canonical correlation analysis is performed between predictors and each predictand. The first canonical variates are used as effective predictors in a neural network ensemble system. Final outputs for each parameter are expressed as a probability distribution for each station/grid point in the space of observations, as a result of the convolution of Gaussian mixtures. A first example of application in the Italian area is presented. An overall increase in skill score performances with respect to European Centre for Medium-Range Weather Forecasts (ECMWF) System 4 direct model output for the period 1981–2010 was found, even if probably not as high as desirable in a fully operational system.

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In recent years, meteo-climatic changes contributed to the geographical expansion and modifications of habitat that become more suitable to phlebotomine vectors. Among these vectors, the role of Sergentomyia minuta in the circulation of mammalian leishmaniases has been recently discussed. Here we apply a neural network model (specifically developed for modelling relationships among variables in small datasets) to estimate the population abundance of S. minuta starting from meteo-climatic variables only, during three capturing seasons (2014–2016) in an Italian site. The results show that we are able to explain a wide majority of the variance in the data of population density (R2 = 0.632). This is obtained through the application of a neural model driven in input by averaged mean temperature, relative humidity and temperature at 10 cm belowground during oviposition, larval and adult stages. A modelling pruning activity shows the major role of humidity in driving the number of captures, but also an important nonlinear role of temperature, which highlights the importance of possible heat waves on population density of S. minuta.

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In elderly subjects, renal insufficiency and osteoporosis often coexist with high risk of fracture and elevated socio-economic burden. Today a large number of effective anti-osteoporotic drugs are available but generally they are contraindicated in patients with chronic kidney disease (CKD) because of their progressive accumulation. Denosumab, instead, does not require dose adjustments for different degrees of renal impairment so it can be a valid treatment in osteoporotic patients with CKD. Limited data are available in the literature concerning the use of denosumab in hemodialysis (HD). The aim of our study was, therefore, to study the efficacy and tolerability of this drug in this particular subset of patients. We retrospectively reviewed the charts of 12 osteoporotic HD patients who received a single 60-mg subcutaneous dose of denosumab every 6 months for an observation period of 24 months. Serum electrolyte, markers of bone turnover and quantitative ultrasound (QUS) were evaluated. Over 24 months, we observed a gradual improvement of bone metabolism: β-CrossLaps from 2567.08 ± 1264 to 1492.5 ± 1182.5 pg/ml; bone alkaline phosphatase (BALP) from 33.5 ± 28.8 to 11.8 ± 3.7 mcg/l, and of QUS index (T-score from −5.33 ± 1.58 to −4.84 ± 1.2; risk of fracture from 13.9 ± 4.7 to 11.07 ± 5.3 %). Few cases of hypocalcemia were detected, more significant after the first and second injection, but with careful monitoring of serum calcium and rapid therapy adjustment we could easily manage serum Ca levels. Our pilot experience highlights the safety and efficacy of denosumab in the treatment of osteoporosis in HD patients, potentially supporting its use to reduce the burden of fractures in this patient population.

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The influence of climatic changes on migrations around the world is a topic widely discussed in the scientific literature, but investigations are often limited to particular regions. The possible causes of migration flows from Africa to Europe due to landings in Italy, a peninsula which can be considered as a 'bridge' between these two continents, have not been investigated in detail even if, at present, this problem is at the top of the political agenda in Europe. Here a simple linear model and a fully nonlinear one (neural networks—NNs) are applied to the study of possible climatic influences on migration flows from the Sahel to Italy during the period 1995–2009. The results show the ability of the NN model to explain the majority of the variance found in the data and permit the identification of the major climatic drivers affecting the amount of yields in Sahelian countries and the migrations flows from them to Italy. In particular, the use of a NN model fully identifies both linear and nonlinear influences. We can explain much of the variance in the migration data (R2 = 0.775). Agriculture (harvest yields) is shown to link climatic changes and migration, and poor yields can enhance this latter phenomenon. Heat waves (during the cereal growing season) have an important nonlinear role. The annual temperature, however, is most likely the dominant climatic factor influencing migrations in this region.

The use of galectin-3 ThyroTest in the preoperative evaluation of cytologically indeterminate (Thy-3) thyroid nodules has been largely validated by retrospective and prospective multicentre studies. Here we report the results of galectin-3 ThyroTest routinely applied in the management of Thy-3 nodules in combination with clinical and ultrasonography (US) examination, in which galectin-3 positive nodules were directly referred to surgery whereas galectin-3 negative lesions were considered for clinical and US long-term follow-up. A cohort of 331 patients, bearing 340 thyroid Thy-3 nodules, was enrolled and subjected to galectin-3 expression analysis. A total of 256 galectin-3 negative nodules were directed to periodical clinical and US examination, while 84 galectin-3 positive cases were referred to surgery. Excluding 63 dropout patients plus 15 patients that were operated because of clinical reasons the remaining 176 galectin-3 negative nodules were followed with clinical and US examination for an average period of 31 months. During the follow-up, the volume of galectin-3 negative nodules was unchanged in 85 cases (48 %), reduced in 47 (27 %), and increased in 44 (25 %). Based on combined clinical features and US follow-up results, a total of 36 out of 191 galectin-3 negative nodules (19 %) were referred to surgery, with a final histological finding of 28 benign lesions, three follicular tumor of uncertain malignant potential (FT-UMP), and five malignant lesions, corresponding to a 7 % false negative rate. In the group of 84 galectin-3 positive nodules, we detected 65 thyroid cancers with a prevalence of 77 %, 12 FT-UMPs, and 7 false positive lesions, corresponding to a 4 % false positive rate. A total of 150 patients were not operated and are still under clinical and US monitoring while surgery was performed in 118 patients with a final 70 thyroid cancers diagnosed, corresponding to a 59 % prevalence of malignancy detected at surgery and to a 26 % prevalence of malignancy among the entire Thy-3 nodule population. Galectin-3 ThyroTest is an easy and cheap diagnostic procedure that integrates conventional fine-needle-aspiration cytology, reduces the number of unnecessary thyroidectomies and increases the rate of malignancy at surgery. Clinical and US follow-up of galectin-3 negative lesions allows to further reduce false negative cases.

In thyroid nodule management, ultrasound (US) features, such as hypoechogenicity of the lesion, irregular margins, microcalcifications, and intralesional vascular signal, alone or combined, have to be considered as suggestive for malignancy. Because of the low prevalence of medullary thyroid cancer (MTC), a few papers analyzed US characteristics associated with this cancer in small series, with controversial results. Aim of this study was to evaluate in MTC the US risk factors of thyroid nodule. In this order, a series of nodules histologically proven as MTC and a group of nodules with histology of papillary cancer (PTC) were retrospectively compared with a control group of benign nodule. Fifty percent MTC were solid hypoechoic and 16% showed microcalcifications with significant difference with respect to the benign group (p

Core needle biopsy (CNB) has been recently described as an accurate second-line test in thyroid inconclusive cytology (FNA). Here we retrospectively investigated the potential improvement given by Galectin-3, Cytokeratin-19, and HBME-1 on the accuracy of CNB in thyroid nodules with prior indeterminate FNA report. The study included 74 nodules. At CNB diagnosis, 15 were cancers, 40 were benign, and 19 had uncertain/non-diagnostic CNB report. The above immunohistochemical (IHC) panel was analyzed in all cases. After surgery, 19 malignant and 55 benign lesions were found. All 15 cancers and all 40 benign nodules diagnosed at CNB were confirmed at final histology. Regarding the uncertain CNB group, 4 (21 %) were malignant and 15 (79 %) benign. When we considered all the series, the most accurate IHC combination was Galectin-3 plus HBME-1, while HBME-1 was the most sensitive marker in those nodules with uncertain CNB report. The combination of CNB plus IHC could indentify 19/19 cancers and 53/55 benign lesions. Sensitivity and specificity of CNB increased from 79 to 100 % and from 73 to 96 %, respectively, by adding IHC. CNB can diagnose the majority of thyroid nodules with previous indeterminate FNA cytology, while the accuracy of CNB is increased by adding Galectin-3, Cytokeratin-19, and HBME-1 panel. We suggest to adopt CNB as a second-line approach to indeterminate thyroid FNA, and apply IHC in those lesions with uncertain/non-diagnostic CNB report. This approach should improve the pre-surgical diagnosis of patients. These results should be confirmed in larger prospective series.

Starting from Humanism this paper retraces the exegetical history of ser. num. 548B7-C4 and examines the semantic problems of the text. The main issue is the meaning of the verb μύνασθαι, whose semantic value is determined by the anecdote, just-mentioned by Timon, about the Spartan king Brasidas.

Aim of the study was to evaluate the elastographic appearance of medullary thyroid carcinoma (MTC) by a retrospective evaluation of 18 nodules histologically proven as MTC. Free-hand qualitative elastography was performed using Hitachi Logos EUB 7500. The elasticity score (ES), was assessed based on a colour elastogram, the blue colour being correlated with hard tissue, red colour with soft tissue, and green with intermediate hardness. Nodules were classified into four classes. A alleged diagnosis of malignancy was assigned to nodules with ES3 or 4 and a presumptive diagnosis of benignity was assigned to nodules with an ES1 or 2. More than half (55.6 %) of MTCs have a low-intermediate grade of elasticity. The hardest lesions (ES4) were those with ultrasonographic features highly suspicious for malignancy. In conclusion, most of MTCs present an elastographic pattern of benignity. Therefore, qualitative elastography does not add useful information in pointing out MTC on the basis of its hardness. Our data suggest a marginal role for this technique in MTC evaluation.

Recently, the core needle biopsy (CNB) has been proposed as a complementary test for thyroid nodules with inconclusive cytology by fine-needle aspiration (FNA). However, there have been no reports regarding patient comfort during and after CNB or tolerability of this procedure. Here we aimed to investigate and compare comfort with and tolerability of the CNB and FNA procedures. A 21 gauge needle was used for collection in CNB procedures, and a 23 gauge needle was used for collection in FNA procedures. Sixty-one consecutive patients underwent both biopsies and were asked to evaluate their comfort during and after these procedures by a structured questionnaire. A total of 58 (95 %) patients reported local pain during both biopsies. Two patients reported pain only during CNB, and one reported no pain. Mild pain was reported in 87 % of CNB cases. Local pain after biopsy was reported in 29 % of FNA and 45 % of CNB. The occurrence of pain in the first minutes following CNB was significantly higher than FNA (p = 0.008), while there was not a significant difference in pain at later time points after the procedures. Finally, patients were asked to evaluate the degree of tolerability of the two sampling techniques, and FNA and CNB were reported as tolerable in 82 and 83 %, respectively. The results from a questionnaire evaluating patients’ comfort level showed no significant difference between the tolerability of CNB and FNA. This finding suggests that CNB may be performed with a reasonable level of patient comfort.

Context Thyroid nodules are selected for biopsy on the basis of clinical and ultrasound (US) findings. Ultrasonography detects nodules at risk of malignancy, but its diagnostic accuracy does not rule out with certainty the possibility of cancer in lesions without suspicious findings. Objective The objective of the study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in thyroid nodules and to assess the improvement provided by combination of RTE, B-mode US, and color flow Doppler (CFD). Design This was a prospective multicenter study. Patients A consecutive series of 498 thyroid nodules was blindly evaluated by US, CFD, and RTE before biopsy or surgery. Nodules were classified at RTE by four-class color scale. Patients with benign cytology underwent follow-up over 12 months, whereas patients with indeterminate, suspicious, or malignant cytology were surgically treated. Results At follow-up, 126 nodules were malignant and 372 benign. RTE classes III-IV showed 81% sensitivity and 62% specificity. The presence of at least one US risk factor (hypoechogenicity, microcalcifications, irregular margins, intranodular vascularization, and taller than wide shape) had 85% sensitivity and 91% negative predictive value. When RTE was combined with US, the presence of at least one of the six parameters had 97% sensitivity and 97% negative predictive value, with an odds ratio of 15.8 (95% confidence interval 5.7-43.8). Conclusions RTE is a valuable tool for detecting malignant thyroid lesions with a sensitivity similar to traditional US and CFD features. By adding RTE evaluation, the sensitivity for malignancy of US findings is markedly increased and the selection of nodules that do not need cytology is made more reliable.

Background The reported reliability of core needle biopsy (CNB) is high in assessing thyroid nodules after inconclusive fine-needle aspiration (FNA) attempts. However, first-line use of CNB for nodules considered at risk by ultrasonography (US) has yet to be studied. The aim of this study were: 1) to evaluate the potential merit of using CNB first-line instead of conventional FNA in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of cancer. Methods Seventy-seven patients with a suspicious-appearing, recently discovered solid thyroid nodule were initially enrolled as study participants. No patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on study design, all patients were proposed to undergo CNB as first-line diagnostic aspiration, while those patients refusing to do so underwent conventional FNA. Results Five patients refused the study, and a total of 31 and 41 thyroid nodules were subjected to CNB and FNA, respectively. At follow-up, the overall rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic accuracy of CNB (97%) was significantly (P