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A relevant number of adenomas can be missed during colonoscopy.Assess the current status of colonoscopy procedures in Italian centers.A prospective observational study involving 17 hospitals (34 endoscopists) included consecutive patients undergoing standard colonoscopy. In the first phase, endoscopists performed consecutive colonoscopies. In the second phase, retraining via an online learning platform was planned, while in the third phase data were collected analogously to phase 1.A total of 3,504 patients were enrolled. Overall, a BBPS score ≥6 was obtained in 95.6% of cases (94.8% and 96.9% in the pre- and post-training phases, respectively). 88.4% of colonoscopies had a withdrawal time ≥6 min (88.2% and 88.7% in the pre- and post-training phases). Median adenoma detection rate (ADR) was 39.1%, with no significant differences between the pre- and post-training phases (40.1% vs 36.9%; P = 0.83). In total, 81% of endoscopists had a ADR performance above the 25% threshold.High colonoscopy quality standards are achieved by the Italian hospitals involved. Quality improvement initiatives and repeated module-based colonoscopy-training have been promoted in Italy during the last decade, which appear to have had a significant impact on quality colonoscopy metrics together with the activation of colorectal cancer screening programs.

Technological development in terms of the power requirement for data acquisition and processing opens new perspectives in the field of environmental monitoring. Near real-time data flow about the sea condition and a possible direct interface with applications and services devoted to marine weather networks would have a significant impact on several aspects, such as, for example, safety and efficiency. In this scenario, the needs of buoy networks have been analyzed, and the estimation of directional wave spectra from buoys’ data has been deeply investigated. Two methods have been implemented, namely the truncated Fourier series and the weighted truncated Fourier series, and they have been tested by both simulated and real experimental data, representative of typical Mediterranean Sea conditions. From simulation, the second method proved to be more efficient. From the application to real case studies, it emerged that it works effectively in real conditions, as confirmed by parallel meteorological observations. The estimation of the main propagation direction was possible with a small uncertainty of a few degrees, yet the method exhibits a limited directional resolution, which suggests the need for undertaking further studies, briefly addressed in the conclusions.

CRC is an adult-onset carcinoma representing the third most common cancer and the second leading cause of cancer-related deaths in the world. EO-CRC (

An important task in biomechanics is human body articulations’ internal torques measurement. This is known as a kinetic or inverse-dynamics problem. Its solution requires a combination of kinematic and dynamic measurements with a biomechanical model, involving subject-related anthropometric parameters. The uncertainty-evaluation thereof is here considered. The method poses on a probabilistic model of the associated measurement system, according to the “Guide to the expression of uncertainty in measurement” general principles. We consider a comprehensive set of influence quantities, including markers’ misplacement or parasite movements. The anthropometric parameters’ uncertainty is discussed in detail. The proposed approach helps to identify the most influential experimental factors.

Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed a precancerous colonic lesion and had a clinical suspicion of LS. The proband was found to have a somatic MSI-H status. Analysis of the coding sequences and flanking introns of the MLH1 and MSH2 genes by Sanger sequencing led to the identification of the variant of uncertain significance, namely, c.589-9_589-6delGTTT in the MLH1 gene. Further investigation revealed that this variant was likely pathogenetic. Subsequent next-generation sequencing panel analysis revealed the presence of two variants of uncertain significance in the ATM gene. We conclude that the phenotype of our index case is likely the result of a synergistic effect of these identified variants. Future studies will allow us to understand how risk alleles in different colorectal-cancer-prone genes interact with each other to increase an individual’s risk of developing cancer.

Biomechanical analysis of human movement is based on dynamic measurements of reference points on the subject’s body and orientation measurements of body segments. Collected data include positions’ measurement, in a three-dimensional space. Signal enhancement by proper filtering is often recommended. Velocity and acceleration signal must be obtained from position/angular measurement records, needing numerical processing effort. In this paper, we propose a comparative filtering method study procedure, based on measurement uncertainty related parameters’ set, based upon simulated and experimental signals. The final aim is to propose guidelines to optimize dynamic biomechanical measurement, considering the measurement uncertainty contribution due to the processing method. Performance of the considered methods are examined and compared with an analytical signal, considering both stationary and transient conditions. Finally, four experimental test cases are evaluated at best filtering conditions for measurement uncertainty contributions.

A general probabilistic model of the measurement process is discussed, showing how it can address both static and dynamic measurements. Emphasis is placed on the latter, and two main kinds of dynamic measurements are considered: direct, where the goal is to monitor a phenomenon over time, and indirect, where an alternative representation is sought, such as, typically, the spectrum. It is shown that both cases can be treated in the same framework, through a proper interpretation of the variables involved. Then, direct measurements are investigated in greater detail, and the application of this approach is discussed, in the case of a Markovian model with a uniform prior for the measurand, and an illustrative numerical example is presented. These results may pave the way to a better harmonization of measurements, grounded on a sound scientific foundation.

The paper focuses on the fatigue life assessment of mooring lines for floating offshore wind turbines, deployed on intermediate water depths. The nonlinear hydrodynamic model in the time-domain is preliminarily discussed. Subsequently, several spectrum estimation methods are outlined and embodied to carefully assess the low and high-frequency components of the stress process in the mooring lines and estimate the cumulative fatigue damage by the combined spectrum approach. The spectral reconstruction methods are applied to a reference case study, focusing on three different loading conditions. Current results are discussed and some suggestions are also provided to carefully assess the fatigue life of mooring lines for floating offshore wind turbines.

After the lockdown during the emergency phase of the Covid-19 pandemic, we have to deal with phase 2, a period of uncertain duration, with a controlled and progressive return to normalization, in which we need to reconcile our work and our movements with the presence of the virus on our territory. Digestive endoscopic activity is a high-risk transmission procedure for Covid-19. The measures put in place to protect healthcare personnel and patients are stressful and "time-consuming" and lead to a reduction in the number of endoscopic procedures that can be performed. In this scenario, the Oncological Institutes are forced to make a rigorous selection of patients to undergo endoscopic examinations and treatments, according to lists of exceptional priorities, in order to guarantee cancer patients and subjects at high risk of developing digestive tumors, a preferential diagnostic and therapeutic process, protected from contagion risks. For this purpose, cuts and postponing times of endoscopic performances are here proposed, which go beyond the guidelines of scientific societies and have little evidences in the literature. These changes should be applied limited to this exceptional period and in proportion to the capacity of each operating unit in order to meet the demands of the patients.

Dynamic measurement are currently deeply studied due to their practical importance and for the benefit that may outcome from a metrological approach, where close attention is paid to the reduction and evaluation of the associated uncertainty. In this communication, a simple and effective method for performing dynamic compensation is presented. This is an extension of a previous work, where the method was firstly introduced and fully developed only for first order systems, whilst here the important case of a second order device is considered and worked out. The effectiveness of the method is proved by the simulation of the behavior of an accelerometer.

The monitoring of sea state conditions, either for weather forecasting or ship seakeeping analysis, requires the reliable assessment of the sea spectra encountered by the ship, either as a final result or intermediate step for the measurement of the relevant wave-motion parameters. In current analyses, different spectrum estimation methods, namely the Welch, Thomson and ARMA models, have been applied and compared based on a set of random wave signals, with different durations, representative of several sea state conditions. Subsequently, two sea spectrum reconstruction techniques were described and applied in order to detect the main sea state parameters, namely the significant wave height, the mean wave period and the spectrum peak enhancement factor. The performances of both spectral analysis and sea state reconstruction methods are discussed in order to provide some preliminary guidelines for practical application purposes. In this respect, based on current results, the Welch and Thomson methods seem to be the most promising techniques, combined with the nonlinear least-square reconstruction technique.

Measurement aims at obtaining a numerical description of objects/events/persons in the real world by means of a measuring system. Measurement is widely used as a key way for obtaining high quality information from the real world, across disciplines. In the present day, there is growing consensus in holding that measurement is characterized by the use of something that qualifies as a “measuring system”. Therefore, we discuss sufficient conditions for an empirical system to qualify as a measuring system and we present a formal model of the measuring system, in terms of empirical relations among objects to be measured and the measuring device. The theory applies to all the main structures of metrological interest – order, difference, intensive and extensive, and we hope that this may help to fill a gap in these studies. We also briefly address practical applications of the theory, including calibration, modelling of measuring devices and performance statement.

The WNT pathway interconnects a network of signaling events involved in a huge plethora of cellular processes, from organogenesis to tissue homeostasis. Despite its importance, the exiguity of organic drugs directly targeting the members of the Frizzled family of WNT receptors has hampered progress across the whole spectrum of biological fields in which the signaling is involved. We here present FzM1.8, a small molecule acting as an allosteric agonist of Frizzled receptor FZD4. FzM1.8 derives from FzM1, a negative allosteric modulator of the receptor. Replacement of FzM1 thiophene with a carboxylic moiety induces a molecular switch in the lead and transforms the molecule into an activator of WNT signaling. We here show that, in the absence of any WNT ligand, FzM1.8 binds to FZD4, promotes recruitment of heterotrimeric G proteins, and biases WNT signaling toward a noncanonical route that involves PI3K. Finally, in colon cancer cells, we prove that the FZD4/PI3K axis elicited by FzM1.8 preserves stemness and promotes proliferation of undifferentiated cells.

Resternotomy (RS) is a common occurrence in cardiac surgical practice. It is associated with an increased risk of injury to old conduits, cardiac structures, catastrophic hemorrhage and subsequent high morbidity and mortality rate in the operating room or during the recovery period. To mitigate this risk, we evaluated the role of multidetector CT (MDCT) in planning repeat cardiac surgery. We evaluated sternal compartment abnormalities, sternal/ascending aorta distance, pre-reoperative assessment of the aorta (wall, diameters, lumen, valve), sternal/right ventricle distance, diaphragm insertion, pericardium and cardiac chambers, sternal/innominate vein distance, connection of the grafts to the predicted median sternotomy cut, graft patency and anatomic course, possible aortic cannulation and cross-clamping sites and additional non-cardiovascular significant findings. Based on the MDCT findings, surgeons employed tailored operative strategies, including no-touch technique, clamping strategy and cardiopulmonary bypass (CPB) via peripheral cannulation assisted resternotomy. Our experience suggests that MDCT provides information which contributes to the safety of re-operative heart surgery reducing operative mortality and adverse outcomes. The radiologist must be aware of potential surgical options, including in the report any findings relevant to possible resternotomy complications.

Intercostal artery pseudoaneurysms (IAP) are extremely rare but its sudden rupture represents a life-threatening complication. We report an unusual case of a late intercostal artery pseudoaneurysm, after a video-assisted thoracoscopic surgery, presenting as a large intra-parenchymal lung mass. Diagnosis was made by biphasic computed tomography angiography and contrast-enhanced pulsed-wave doppler ultrasound. To minimize the risk of aneurysm bleeding immediate angiographic embolization was planned and successfully performed.IAP should be considered in presence of lung mass in patients who have previously undergone an intervention with intercostal approach to prevent life-threatening complications.

Objective. To investigate CT morphologic and densitometric features and 18-FDG PET findings of surgically excised lung adenocarcinomas “mixed subtype” with predominant lepidic component, appearing as solid solitary pulmonary nodules (SPNs) on CT scan. Materials and Methods. Approval for this study was given from each local institutional review board according to its retrospective nature. Nodules pathologically classified as lung adenocarcinoma mixed subtype with bronchioloalveolar otherwise lepidic predominant component, in three different Italian institutions (Napoli; Varese; Parma), were retrospectively selected. Results. 22 patients were identified. The number of SPNs with smooth margins was significantly lower with respect to the number of SPNs with spiculated margins (p: 0.033), radiating spiculations (p: 0.019), and notch sign (p: 0.011). Mean contrast enhancement (CE) was 53.34 HU (min 5.5 HU, max 112 HU); considering 15 HU as cut-off value, CE was positive in 20/22 cases. No significant correlation was found between size and CE. Mean SUVmax was 2.21, ranging from 0.2 up to 7.5 units; considering 2.5 units as cut-off, SUVmax was positive in 7/22 cases. The number of SPNs with positive CE was significantly higher than the number of SPNs with positive SUVmax (p: 0.0005). Conclusion. CT generally helps in identifying solid SPN suspicious for malignancy but 18-FDG PET may result in false-negative evaluation; when 18-FDG PET findings of a solid SPN are negative even though CT morphology and CE suggest malignancy, radiologist should consider that lepidic component may be present inside the invasive tumor, despite the absence of ground glass.

A first order probabilistic logic is developed and presented in both intuitive and formal terms. It is shown how it can be successfully applied to the development of probabilistic representations for the main structures and scales involved in (one-dimensional) measurement. As a part of the current debate on the nature of probability in measurement, this result provides a way for overcoming the traditional opposition between Bayesian and orthodox statistics.

The probabilistic modelling of measurement systems is discussed, showing how it provides a practical and effective way for addressing uncertainty evaluation, that does not require any commitment to specific philosophical schools, such as the frequentistic and the Bayesian ones. Firstly, different ways of modelling the same measuring device are compared and discussed, considering both the designer’s and the user’s standpoints. Then philosophical issues concerning both the nature of probability and the probabilistic inferences related to the measurement process are considered, in the perspective of this model-based approach. Applications to education and to the revision of international guides for measurement are finally addressed.

We propose a new approach to addressing the expression and evaluation of uncertainty in measurement, which at the one hand maintains the same original goals of the Guide to the Expression of Uncertainty in Measurement (GUM), as expressed by the original recommendations from the CIPM, on the other significantly differs in proposing how to implement them, for a closer orientation to the needs of the expected users, supported by a sound theoretical background. We suggest that this new approach may overcome some of the setbacks that have been experimented in the years in the application of the GUM, thus helping a wider diffusion of the practice of evaluating measurement uncertainty, by establishing a close link with the current state of the art of measurement science.

Epithelial‑to‑mesenchymal transition (EMT) confers stem cell‑like phenotype and more motile properties to carcinoma cells. During EMT, the expression of E‑cadherin decreases, resulting in loss of cell‑cell adhesion and increased migration. Expression of Twist1 and other pleiotropic transcription factors, such as Snail, is known to activate EMT. We established primary colon cancer cell cultures from samples of operated patients and validated cultures by cytogenetic and molecular biology approaches. Western blot assay, quantitative real‑time PCR and immunofluorescence were performed to investigate the expression of E‑cadherin, vimentin, β‑catenin, cytokeratin‑20 and ‑18, Twist1, Snail, CD44, cyclooxygenase‑2 (COX2), Sox2, Oct4 and Nanog. Moreover, cell differentiation was induced by incubation with LiCl‑containing medium for 10 days. We observed that these primary colorectal cancer (CRC) cells lost expression of the E‑cadherin epithelial marker, which was instead expressed in cancer and normal colon mucosa of the same patient, while overexpressed vimentin (mesenchymal marker), Twist1, Snail (EMT markers) and COX2. Cytokeratin‑18 was expressed both in tissues and cell cultures. Expression of stem cell markers, such as CD44, Oct4 and Nanog, were also observed. Following differentiation with the glycogen synthase kinase 3β (GSK3β) inhibitor LiCl, the cells began to express E‑cadherin and, at once, Twist1 and Snail expression was strongly downregulated, suggesting a MET‑reverting process. In conclusion, we established primary colon mesenchymal cancer cell cultures expressing mesenchymal and epithelial biomarkers together with high level of EMT transcription factors. We propose that they could represent a good model for studying EMT and its reverting mechanism, the mesenchymal‑to‑epithelial transition (MET). Our observation indicates that LiCl, a GSK3β inhibitor, induces MET in vitro, suggesting that LiCl and GSK3β could represent, respectively, interesting drug, and target for CRC therapy.

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

Pulmonary sequestration (PS) is a rare congenital broncho-pulmonary malformation. The main feature of this disease is that partial lung tissues separate from the main lung during the embryonic period, receiving blood supply from systemic circulation arteries. Pathogenesis of PS is not clear, and categorized into congenital and acquired PS. We report a case of a 38 year old woman smoker with medical history characterized by difficult to treat asthma with frequent exacerbations and infections since childhood. CT scan showed a partial PS of left lower lobe, supplied by an abnormal artery arising from supradiaphragmatic aortic diverticulum. Surgical treatment through a lung sequestrectomy and laterobasal segment resection was performed.