Publications by authors named "Riccardo Rossi"

103 Publications

Lacrimal bone agenesis in a dog.

Can Vet J 2021 May;62(5):505-508

Eastcott Referrals, Edison Park, Dorcan Way, Swindon SN3 3RB, Wiltshire, United Kingdom (Rossi, Sainato, Renfrew); Langford Vets, University of Bristol School of Veterinary Sciences, Langford House, Langford, Bristol, BS40 5DU, United Kingdom (Kumaratunga).

A 20-month-old neutered male dachshund dog was referred because of a 10-week history of swelling close to the medial canthus of the left eye. Recurrence of the lesion and cytological appearance of the fluid content were suggestive of inflammation. Computed tomography revealed a triangular-shaped bone defect in the skull deep to the lesion. Computed tomography dacryocystography demonstrated contrast medium pooling within the maxillary recess and nasal cavity rather than filling the lacrimal duct. Lacrimal bone agenesis was diagnosed. Key clinical message: Congenital skull including lacrimal bone agenesis may be responsible for swelling of the medial canthus of the eye and computed tomography dacryocystography is helpful in making a diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048203PMC
May 2021

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies.

Int J Mol Sci 2021 Apr 16;22(8). Epub 2021 Apr 16.

Department of Health Surveillance and Bioethics, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete's heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.
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http://dx.doi.org/10.3390/ijms22084124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074148PMC
April 2021

Visual Feedback Effectiveness in Reducing Over Speeding of Moped-Riders.

Front Psychol 2021 11;12:611603. Epub 2021 Mar 11.

Department of General Psychology, University of Padua, Padua, Italy.

The use of assistance systems aimed at reducing road fatalities is spreading, especially for car drivers, but less effort has been devoted to developing and testing similar systems for powered two-wheelers (PTWs). Considering that over speeding represents one of the main causal factors in road crashes and that riders are more vulnerable than drivers, in the present study we investigated the effectiveness of an assistance system which signaled speed limit violations during a simulated moped-driving task, in optimal and poor visibility conditions. Participants performed four conditions of simulated riding: one baseline condition without Feedback, one Fog condition in which visual feedback was provided so as to indicate to the participants when a speed limit (lower than that indicated by the traffic signals) was exceeded, and two post-Feedback conditions with and without Fog, respectively, in which no feedback was delivered. Results showed that participants make fewer speeding violations when the feedback is not provided, after 1 month, and regardless of the visibility condition. Finally, the feedback has been proven effective in reducing speed violations in participants with an aggressive riding style, as measured in the baseline session.
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http://dx.doi.org/10.3389/fpsyg.2021.611603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990878PMC
March 2021

ADAM10 hyperactivation acts on piccolo to deplete synaptic vesicle stores in Huntington's disease.

Hum Mol Genet 2021 Feb 18. Epub 2021 Feb 18.

Department of Biosciences, University of Milan, 20133 Milan, Italy.

Synaptic dysfunction and cognitive decline in Huntington's disease (HD) involve hyperactive A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). To identify the molecular mechanisms through which ADAM10 is associated with synaptic dysfunction in HD, we performed an immunoaffinity purification-mass spectrometry (IP-MS) study of endogenous ADAM10 in the brains of wild-type and HD mice. In the normal brain, proteins implicated in synapse organization, synaptic plasticity, and vesicle and organelles trafficking interact with ADAM10, suggesting that it may act as a hub protein at the excitatory synapse. Importantly, the ADAM10 interactome is enriched in presynaptic proteins and ADAM10 coimmunoprecipitates with piccolo (PCLO), a key player in the recycling and maintenance of synaptic vesicles (SVs). In contrast, reduced ADAM10/PCLO immunoprecipitation occurs in the HD brain, with decreased density of SVs in the reserve and docked pool at the HD presynaptic terminal. Conditional heterozygous deletion of ADAM10 in the forebrain of HD mice reduces active ADAM10 to wild-type level, and normalizes ADAM10/PCLO complex formation and SVs density and distribution. The results indicate that presynaptic ADAM10 and PCLO are a relevant component of HD pathogenesis.
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http://dx.doi.org/10.1093/hmg/ddab047DOI Listing
February 2021

On the Potential of Time Delay Neural Networks to Detect Indirect Coupling between Time Series.

Entropy (Basel) 2020 May 21;22(5). Epub 2020 May 21.

Department of Industrial Engineering, University of Rome "Tor Vergata", via del Politecnico 1, 00100 Roma, Italy.

Determining the coupling between systems remains a topic of active research in the field of complex science. Identifying the proper causal influences in time series can already be very challenging in the trivariate case, particularly when the interactions are non-linear. In this paper, the coupling between three Lorenz systems is investigated with the help of specifically designed artificial neural networks, called time delay neural networks (TDNNs). TDNNs can learn from their previous inputs and are therefore well suited to extract the causal relationship between time series. The performances of the TDNNs tested have always been very positive, showing an excellent capability to identify the correct causal relationships in absence of significant noise. The first tests on the time localization of the mutual influences and the effects of Gaussian noise have also provided very encouraging results. Even if further assessments are necessary, the networks of the proposed architecture have the potential to be a good complement to the other techniques available in the market for the investigation of mutual influences between time series.
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http://dx.doi.org/10.3390/e22050584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517103PMC
May 2020

Upgrading Model Selection Criteria with Goodness of Fit Tests for Practical Applications.

Entropy (Basel) 2020 Apr 15;22(4). Epub 2020 Apr 15.

Department of Industrial Engineering, University of Rome "Tor Vergata", via del Politecnico 1, 01100 Roma, Italy.

The Bayesian information criterion (BIC), the Akaike information criterion (AIC), and some other indicators derived from them are widely used for model selection. In their original form, they contain the likelihood of the data given the models. Unfortunately, in many applications, it is practically impossible to calculate the likelihood, and, therefore, the criteria have been reformulated in terms of descriptive statistics of the residual distribution: the variance and the mean-squared error of the residuals. These alternative versions are strictly valid only in the presence of additive noise of Gaussian distribution, not a completely satisfactory assumption in many applications in science and engineering. Moreover, the variance and the mean-squared error are quite crude statistics of the residual distributions. More sophisticated statistical indicators, capable of better quantifying how close the residual distribution is to the noise, can be profitably used. In particular, specific goodness of fit tests have been included in the expressions of the traditional criteria and have proved to be very effective in improving their discriminating capability. These improved performances have been demonstrated with a systematic series of simulations using synthetic data for various classes of functions and different noise statistics.
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http://dx.doi.org/10.3390/e22040447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516921PMC
April 2020

Quantifying Total Influence between Variables with Information Theoretic and Machine Learning Techniques.

Entropy (Basel) 2020 Jan 24;22(2). Epub 2020 Jan 24.

Associazione EURATOM-ENEA, University of Rome "Tor Vergata", 00133 Rome, Italy.

The increasingly sophisticated investigations of complex systems require more robust estimates of the correlations between the measured quantities. The traditional Pearson correlation coefficient is easy to calculate but sensitive only to linear correlations. The total influence between quantities is, therefore, often expressed in terms of the mutual information, which also takes into account the nonlinear effects but is not normalized. To compare data from different experiments, the information quality ratio is, therefore, in many cases, of easier interpretation. On the other hand, both mutual information and information quality ratio are always positive and, therefore, cannot provide information about the sign of the influence between quantities. Moreover, they require an accurate determination of the probability distribution functions of the variables involved. As the quality and amount of data available are not always sufficient to grant an accurate estimation of the probability distribution functions, it has been investigated whether neural computational tools can help and complement the aforementioned indicators. Specific encoders and autoencoders have been developed for the task of determining the total correlation between quantities related by a functional dependence, including information about the sign of their mutual influence. Both their accuracy and computational efficiencies have been addressed in detail, with extensive numerical tests using synthetic data. A careful analysis of the robustness against noise has also been performed. The neural computational tools typically outperform the traditional indicators in practically every respect.
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http://dx.doi.org/10.3390/e22020141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516551PMC
January 2020

Adaptive Quasi-Unsupervised Detection of Smoke Plume by LiDAR.

Sensors (Basel) 2020 Nov 18;20(22). Epub 2020 Nov 18.

Department of Industrial Engineering, University of Rome "Tor Vergata", Via del Politecnico 1, 00133 Rome, Italy.

The early detection of fire is one of the possible applications of LiDAR techniques. The smoke generated by a fire is mainly compounded of CO, HO, particulate, and other combustion products, which involve the local variation of the scattering of the electromagnetic wave at specific wavelengths. The increases of the backscattering coefficient are transduced in peaks on the signal of the backscattering power recorded by the LiDAR system, located exactly where the smoke plume is, allowing not only the detection of a fire but also its localization. The signal processing of the LiDAR signals is critical in the determination of the performances of the fire detection. It is important that the sensitivity of the apparatus is high enough but also that the number of false alarms is small, in order to avoid the trigger of useless and expensive countermeasures. In this work, a new analysis method, based on an adaptive quasi-unsupervised approach was used to ensure that the algorithm is continuously updated to the boundary conditions of the system, such as the weather and experimental apparatus issues. The method has been tested on an experimental campaign of 227 pulses and the performances have been analyzed in terms of sensitivity and specificity.
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http://dx.doi.org/10.3390/s20226602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698937PMC
November 2020

RUES2 hESCs exhibit MGE-biased neuronal differentiation and muHTT-dependent defective specification hinting at SP1.

Neurobiol Dis 2020 12 13;146:105140. Epub 2020 Oct 13.

Laboratory of Stem Cell Biology and Pharmacology of Neurodegenerative Diseases, Department of Biosciences, University of Milan, 20122 Milan, Italy; Istituto Nazionale Genetica Molecolare, Romeo ed Enrica Invernizzi, Milan 20122, Italy. Electronic address:

RUES2 cell lines represent the first collection of isogenic human embryonic stem cells (hESCs) carrying different pathological CAG lengths in the HTT gene. However, their neuronal differentiation potential has yet to be thoroughly evaluated. Here, we report that RUES2 during ventral telencephalic differentiation is biased towards medial ganglionic eminence (MGE). We also show that HD-RUES2 cells exhibit an altered MGE transcriptional signature in addition to recapitulating known HD phenotypes, with reduced expression of the neurodevelopmental regulators NEUROD1 and BDNF and increased cleavage of synaptically enriched N-cadherin. Finally, we identified the transcription factor SP1 as a common potential detrimental co-partner of muHTT by de novo motif discovery analysis on the LGE, MGE, and cortical genes differentially expressed in HD human pluripotent stem cells in our and additional datasets. Taken together, these observations suggest a broad deleterious effect of muHTT in the early phases of neuronal development that may unfold through its altered interaction with SP1.
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http://dx.doi.org/10.1016/j.nbd.2020.105140DOI Listing
December 2020

FAM46C and FNDC3A Are Multiple Myeloma Tumor Suppressors That Act in Concert to Impair Clearing of Protein Aggregates and Autophagy.

Cancer Res 2020 11 22;80(21):4693-4706. Epub 2020 Sep 22.

INGM, National Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi," Milan, Italy.

Multiple myeloma is a plasma cell neoplasm characterized by the production of unfolded immunoglobulins, which cause endoplasmic reticulum (ER) stress and sensitivity to proteasome inhibition. The genomic landscape of multiple myeloma is characterized by the loss of several genes rarely mutated in other cancers that may underline specific weaknesses of multiple myeloma cells. One of these is that is lost in more than 10% of patients with multiple myeloma. We show here that FAM46C is part of a new complex containing the ER-associated protein FNDC3A, which regulates trafficking and secretion and, by impairing autophagy, exacerbates proteostatic stress. Reconstitution of FAM46C in multiple myeloma cells that had lost it induced apoptosis and ER stress. Apoptosis was preceded by an increase of intracellular aggregates, which was not linked to increased translation of IgG mRNA, but rather to impairment of autophagy. Biochemical analysis showed that FAM46C requires interaction with ER bound protein FNDC3A to reside in the cytoplasmic side of the ER. FNDC3A was lost in some multiple myeloma cell lines. Importantly, depletion of FNDC3A increased the fitness of FAM46C-expressing cells and expression of FNDC3A in cells that had lost it recapitulated the effects of FAM46C, inducing aggregates and apoptosis. FAM46C and FNDC3A formed a complex that modulates secretion routes, increasing lysosome exocytosis. The cellular landscape generated by FAM46C/FNDC3A expression predicted sensitivity to sphingosine kinase inhibition. These results suggest that multiple myeloma cells remodel their trafficking machinery to cope with ER stress. SIGNIFICANCE: This study identifies a new multiple myeloma-specific tumor suppressor complex that regulates autophagy and unconventional secretion, highlighting the sensitivity of multiple myeloma cells to the accumulation of protein aggregates.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1357DOI Listing
November 2020

Blood L-Lactate Concentration as an Indicator of Outcome in Roe Deer () Admitted to a Wildlife Rescue Center.

Animals (Basel) 2020 Jun 20;10(6). Epub 2020 Jun 20.

Department of Veterinary Medicine, University of Milan, 26900 Lodi, Italy.

Roe deer () are among the most frequent patients of rescue centers in Italy. Three outcomes are possible: natural death, euthanasia, or treatment and release. The aim of the present study is to propose blood L-lactate concentration as a possible prognostic biomarker that may assist veterinarians in the decision-making process. Sixty-three roe deer, admitted to one rescue center in the period between July 2018 and July 2019, were sampled and divided into 4 groups according to their outcome: (1) spontaneous death (17 cases), (2) humanely euthanized (13 cases), (3) fully recovered and released (13 cases), and (4) euthanized being unsuitable for release (20 cases). In addition, blood samples from 14 hunted roe deer were analyzed as controls. Whole blood lactate concentrations were measured with a point of care lactate meter. Differences among groups were close to statistical significance ( = 0.51). A cut-off value of 10.2 mmol/L was identified: all the animals with higher values died or were humanely euthanized. The results suggest that roe deer with lactatemia higher than 10.2 mmol/L at admission, have a reduced prognosis for survival during the rehabilitation period, regardless of the reason for hospitalization and the injuries reported. Therefore, humane euthanasia should be considered for these animals.
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http://dx.doi.org/10.3390/ani10061066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341283PMC
June 2020

Performances Evaluation of a Low-Cost Platform for High-Resolution Plant Phenotyping.

Sensors (Basel) 2020 Jun 2;20(11). Epub 2020 Jun 2.

CNR-IBE, via Madonna del Piano 10, 50019 Florence, Italy.

This study aims to test the performances of a low-cost and automatic phenotyping platform, consisting of a Red-Green-Blue (RGB) commercial camera scanning objects on rotating plates and the reconstruction of main plant phenotypic traits via the structure for motion approach (SfM). The precision of this platform was tested in relation to three-dimensional (3D) models generated from images of potted maize, tomato and olive tree, acquired at a different frequency (steps of 4°, 8° and 12°) and quality (4.88, 6.52 and 9.77 µm/pixel). Plant and organs heights, angles and areas were extracted from the 3D models generated for each combination of these factors. Coefficient of determination (R), relative Root Mean Square Error (rRMSE) and Akaike Information Criterion (AIC) were used as goodness-of-fit indexes to compare the simulated to the observed data. The results indicated that while the best performances in reproducing plant traits were obtained using 90 images at 4.88 µm/pixel (R = 0.81, rRMSE = 9.49% and AIC = 35.78), this corresponded to an unviable processing time (from 2.46 h to 28.25 h for herbaceous plants and olive trees, respectively). Conversely, 30 images at 4.88 µm/pixel resulted in a good compromise between a reliable reconstruction of considered traits (R = 0.72, rRMSE = 11.92% and AIC = 42.59) and processing time (from 0.50 h to 2.05 h for herbaceous plants and olive trees, respectively). In any case, the results pointed out that this input combination may vary based on the trait under analysis, which can be more or less demanding in terms of input images and time according to the complexity of its shape (R = 0.83, rRSME = 10.15% and AIC = 38.78). These findings highlight the reliability of the developed low-cost platform for plant phenotyping, further indicating the best combination of factors to speed up the acquisition and elaboration process, at the same time minimizing the bias between observed and simulated data.
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http://dx.doi.org/10.3390/s20113150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308841PMC
June 2020

Enhancing Radiation Detection by Drones through Numerical Fluid Dynamics Simulations.

Sensors (Basel) 2020 Mar 23;20(6). Epub 2020 Mar 23.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.

This study addresses the optimization of the location of a radioactive-particle sensor on a drone. Based on the analysis of the physical process and of the boundary conditions introduced in the model, computational fluid dynamics simulations were performed to analyze how the turbulence caused by drone propellers may influence the response of the sensors. Our initial focus was the detection of a small amount of radioactivity, such as that associated with a release of medical waste. Drones equipped with selective low-cost sensors could be quickly sent to dangerous areas that first responders might not have access to and be able to assess the level of danger in a few seconds, providing details about the source terms to Radiological-Nuclear (RN) advisors and decision-makers. Our ultimate application is the simulation of complex scenarios where fluid-dynamic instabilities are combined with elevated levels of radioactivity, as was the case during the Chernobyl and Fukushima nuclear power plant accidents. In similar circumstances, accurate mapping of the radioactive plume would provide invaluable input-data for the mathematical models that can predict the dispersion of radioactivity in time and space. This information could be used as input for predictive models and decision support systems (DSS) to get a full situational awareness. In particular, these models may be used either to guide the safe intervention of first responders or the later need to evacuate affected regions.
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http://dx.doi.org/10.3390/s20061770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147154PMC
March 2020

Precision teaching to improve drivers' lane maintenance.

J Safety Res 2020 02 31;72:225-229. Epub 2020 Jan 31.

Department of Psychology , University of Padova, Via 8 Febbraio 1848, 2 Padova, Italy.

Introduction: This study investigates the effect of precision teaching signals on lane maintenance.

Methods: In experiment 1, the control group drove a simulator with no signals. In experiment 2, drivers were presented with auditory signals depending on their position within or outside the lane. In experiment 3, visual signals were presented in addition to auditory signals to examine the effect of redundancy on drivers' lane maintenance.

Results: Results showed an improvement in lane maintenance in experiment 2. Cross-experiment analysis indicated this effect not to be the result of learning. Data from experiment 3 also showed that presenting redundant signals did not further reduce lane variability or help drivers maintain a more central position within the lane.

Conclusions: Taken together, data suggest precision teaching be effective as an educational tool to improve lane maintenance. Practical Applications: Our study shows the potential for precision teaching to serve as a valuable tool in driver training.
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http://dx.doi.org/10.1016/j.jsr.2019.12.020DOI Listing
February 2020

Laparoscopic hyperthermic intraperitoneal chemotherapy for appendiceal tumors.

Asian J Endosc Surg 2020 Oct 29;13(4):614-617. Epub 2020 Jan 29.

Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.

Introduction: The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal and appendix cancer at risk of peritoneal seeding is an appealing strategy to prevent peritoneal metastases. Here, we present the technical details and postoperative outcomes of laparoscopic HIPEC performed with prophylactic intent in three patients with low-grade appendiceal neoplasm (LAMN) considered at risk of peritoneal recurrence.

Materials And Surgical Technique: Three patients with LAMN previously treated outside our department were selected for second-look laparoscopic exploration and HIPEC. The study received institutional review board approval. A Hasson trocar was inserted around the umbilicus. Four additional 10-mm trocars were inserted-one each in the left and right upper and lower quadrants. After full abdominal exploration, laparoscopic cytoreductive surgery was performed. Perfusion catheters were inserted through the four lateral trocars in the abdominal quadrants. HIPEC was performed with mitomycin 12 mg/m and cisplatin 90 mg/m for 60 minutes at a target temperature of 41.0°C. The postoperative course was uneventful, except for an episode of fluid leak due to dural tear (treated with supine bed rest for 48 hours and resulting in no adverse sequelae). The median length of hospital stay was 11 days. After a median follow-up of 36 months, all patients were asymptomatic with no evidence of recurrence.

Discussion: Laparoscopic HIPEC for LAMN at risk of peritoneal recurrence appeared to be feasible, safe, and associated with a favorable postoperative outcome. More studies with larger samples of patients and with a standardized design are needed to better analyze the oncological value of this approach.
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http://dx.doi.org/10.1111/ases.12784DOI Listing
October 2020

Computational modeling of the fluid flow in type B aortic dissection using a modified finite element embedded formulation.

Biomech Model Mechanobiol 2020 Oct 23;19(5):1565-1583. Epub 2020 Jan 23.

Centre Internacional de Mètodes Numèrics en Enginyeria, CIMNE, Barcelona, Spain.

This work explores the use of an embedded computational fluid dynamics method to study the type B aortic dissection. The use of the proposed technique makes it possible to easily test different intimal flap configurations without any need of remeshing. To validate the presented methodology, we take as reference test case an in vitro experiment present in the literature. This experiment, which considers several intimal flap tear configurations (number, size and location), mimics the blood flow in a real type B aortic dissection. We prove the correctness and suitability of the presented approach by comparing the pressure values and waveform. The obtained results exhibit a remarkable similarity with the experimental reference data. Complementary, we present a feasible surgical application of the presented computer method. The aim is to help the clinicians in the decision making before the type B aortic dissection surgical fenestration. The capabilities of the proposed technique are exploited to efficiently create artificial reentry tear configurations. We highlight that only the radius and center of the reentry tear need to be specified by the clinicians, without any need to modify neither the model geometry nor the mesh. The obtained computational surgical fenestration results are in line with the medical observations in similar clinical studies.
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http://dx.doi.org/10.1007/s10237-020-01291-xDOI Listing
October 2020

Cross-sectional study to identify risk factors associated with the occurrence of antimicrobial resistance genes in honey bees Apis mellifera) in Umbria, Central Italy.

Environ Sci Pollut Res Int 2020 Mar 10;27(9):9637-9645. Epub 2020 Jan 10.

Medicina Veterinaria, Laboratorio di Ispezione degli Alimenti di Origine Animale, Università degli Studi di Perugia, 06126, Perugia, Italy.

The use antimicrobials for therapeutic and metaphylactic purpose in humans and agriculture exerts selective pressure on animal and environmental microbiota resulting in the survival and spread of antimicrobial resistance genes among bacteria and subsequent development of resistance in bacteria. Previous studies have shown that honey bees' microbiota (Apis mellifera) can accumulate antimicrobial resistance genes in their microbiome and act as collectors and disseminators of resistance genes. The aim of this study was to investigate to what extent honey bees act as reservoir of select antimicrobial resistance genes. This study was conducted on 35 groups of bees. Bees were collected from 35 sites in Umbria, Italy. PCR was used to screen pooled ground bees' specimens for genes that code for resistance against antimicrobials that are commonly used in humans and in veterinary medicine including aminoglycosides (aph), beta-lactams (blaZ), tetracycline (tetM) and sulphonamides (sul1 and sul2). Twenty-four samples out of 35 (68.57%) were positive for at least one antimicrobial resistance gene. Two samples were positive for the aph, 5.71%; eight for blaZ, 22.86%; three for tetM, 8.57%; ten for sul1, 28.57% and eighteen for sul2, 51.43%. Positivity to more than one antimicrobial resistance gene was observed in nine samples, 25.71%. The multivariate analysis identified "presence of farms nearby" as the factor most closely related to PCR positivity. Honey bees (Apis mellifera) from Umbria, Italy, carry antimicrobial resistance genes and can be used as indicators of the presence of resistance genes in the environment.
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http://dx.doi.org/10.1007/s11356-020-07629-3DOI Listing
March 2020

PU.1 subcellular localization in acute myeloid leukaemia with mutated NPM1.

Br J Haematol 2020 01 25;188(1):184-187. Epub 2019 Nov 25.

Department of Medicine, University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.1111/bjh.16344DOI Listing
January 2020

Post-mortem computed tomography for forensic applications: A systematic review of gunshot deaths.

Med Sci Law 2020 01 19;60(1):54-62. Epub 2019 Nov 19.

Institute of Public Health, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Italy.

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http://dx.doi.org/10.1177/0025802419883164DOI Listing
January 2020

Laser-induced fluorescence (LIF) as a smart method for fast environmental virological analyses: validation on Picornaviruses.

Sci Rep 2019 08 29;9(1):12598. Epub 2019 Aug 29.

Department of Industrial Engineering, University of Rome "Tor Vergata", Via del Politecnico 1, Rome, 00133, Italy.

Virological analysis is time-consuming and expensive. The aim of this work is to demonstrate the applicability of laser-induced fluorescence (LIF) to the classification of viruses, reducing the time for this analysis and its costs. Experimental tests were performed in which different viruses were irradiated with a UV laser emitting at 266 nm and the emitted spectra were recorded by a spectrometer. The classification techniques show the possibility of discriminating viruses. Although the application of the LIF technique to biological agents has been thoroughly studied by many researchers over the years, this work aims at validating for the first time its applicability to virological analyses. The development of a fast virological analysis may revolutionize this field, allowing fast responses to epidemiologic events, reducing their risks and improving the efficiency of monitoring environments. Moreover, a cost reduction may lead to an increase in the monitoring frequency, with an obvious enhancement of safety and prevention.
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http://dx.doi.org/10.1038/s41598-019-49005-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715700PMC
August 2019

FOXP1 circular RNA sustains mesenchymal stem cell identity via microRNA inhibition.

Nucleic Acids Res 2019 06;47(10):5325-5340

Laboratory of Regenerative Medicine - Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy.

Stem cell identity and plasticity are controlled by master regulatory genes and complex circuits also involving non-coding RNAs. Circular RNAs (circRNAs) are a class of RNAs generated from protein-coding genes by backsplicing, resulting in stable RNA structures devoid of free 5' and 3' ends. Little is known of the mechanisms of action of circRNAs, let alone in stem cell biology. In this study, for the first time, we determined that a circRNA controls mesenchymal stem cell (MSC) identity and differentiation. High-throughput MSC expression profiling from different tissues revealed a large number of expressed circRNAs. Among those, circFOXP1 was enriched in MSCs compared to differentiated mesodermal derivatives. Silencing of circFOXP1 dramatically impaired MSC differentiation in culture and in vivo. Furthermore, we demonstrated a direct interaction between circFOXP1 and miR-17-3p/miR-127-5p, which results in the modulation of non-canonical Wnt and EGFR pathways. Finally, we addressed the interplay between canonical and non-canonical Wnt pathways. Reprogramming to pluripotency of MSCs reduced circFOXP1 and non-canonical Wnt, whereas canonical Wnt was boosted. The opposing effect was observed during generation of MSCs from human pluripotent stem cells. Our results provide unprecedented evidence for a regulatory role for circFOXP1 as a gatekeeper of pivotal stem cell molecular networks.
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http://dx.doi.org/10.1093/nar/gkz199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547427PMC
June 2019

Early assessment of weight velocity can support frontline health workers in predicting malnutrition in HIV-exposed infants: preliminary results from a DREAM cohort in Malawi.

Minerva Pediatr 2020 Feb 21;72(1):14-21. Epub 2019 Mar 21.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Background: Children born to HIV-positive mothers are particularly susceptible to malnutrition. Currently, monitoring programs rely on punctual anthropometric measurements to assess child growth. Growth velocities could be an additional tool in identifying critical time windows for prevention and implementation of early intervention for malnutrition.

Methods: A retrospective analysis was conducted using data from 817 HIV exposed but uninfected children extracted from DREAM program database. By using the WHO reference for growth standards, patterns of weight velocity for different intervals of assessment from one to 18 months of age were explored. Odds ratios and multinomial logistic regressions between selected weight velocity Z-scores thresholds and successive malnutrition indices (at 6, 12, 18 months of age) were calculated.

Results: Weight velocity was above the standard mean in the first 3 months, then progressively declined over time. In children with normal nutritional status, significant risks of becoming malnourished (mild malnutrition - underweight [OR 10.8; 95% CI: 4.5-26], chronic malnutrition - stunting [OR 8.3; 95% CI: 2-34.9] and acute malnutrition - wasting [OR 11.7; 95% CI: 1.5-90.5]) started when weight velocity Z-scores <0, at all interval ages. Multinomial regression showed that in the first 6 months, the weight velocity decrements strongly impacted on underweight (OR 17.9; 95% CI: 4-80.7), while the risk of Stunting occurred later at 18 months (OR 8.7; 95% CI: 4.3-17.6), with highest impact at the lowest thresholds.

Conclusions: The assessment of weight velocity Z-scores, coupled with the already validated malnutrition indices, can support frontline health workers in early prediction of child malnutrition and performing nutritional counselling in the context of HIV/AIDS and food insecurity.
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http://dx.doi.org/10.23736/S0026-4946.19.05417-3DOI Listing
February 2020

Computation and Selection of Optimal Biomarker Combinations by Integrative ROC Analysis Using CombiROC.

Methods Mol Biol 2019 ;1959:247-259

Bioinformatics, Istituto Nazionale Genetica Molecolare, Milan, Italy.

The diagnostic accuracy of biomarker-based approaches can be considerably improved by combining multiple markers. A biomarker's capacity to identify specific subjects is usually assessed using receiver operating characteristic (ROC) curves. Multimarker signatures are complicated to select as data signatures must be integrated using sophisticated statistical methods. CombiROC, developed as a user-friendly web tool, helps researchers to accurately determine optimal combinations of markers identified by a range of omics methods. With CombiROC, data of different types, such as proteomics and transcriptomics, can be analyzed using Sensitivity/Specificity filters: the number of candidate marker panels arising from combinatorial analysis is easily optimized bypassing limitations imposed by the nature of different experimental approaches. Users have full control over initial selection stringency, then CombiROC computes sensitivity and specificity for all marker combinations, determines performance for the best combinations, and produces ROC curves for automatic comparisons. All steps can be visualized in a graphic interface. CombiROC is designed without hard-coded thresholds, to allow customized fitting of each specific dataset: this approach dramatically reduces computational burden and false-negative rates compared to fixed thresholds. CombiROC can be accessed at www.combiroc.eu .
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http://dx.doi.org/10.1007/978-1-4939-9164-8_16DOI Listing
July 2019

P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus.

J Exp Med 2019 02 17;216(2):317-336. Epub 2019 Jan 17.

Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland

Altered control of T follicular helper (Tfh) cells can lead to generation of autoantibodies and autoimmune manifestations. Signaling pathways that selectively limit pathogenic responses without affecting the protective function of Tfh cells are unknown. Here we show that the ATP-gated ionotropic P2X7 receptor restricts the expansion of aberrant Tfh cells and the generation of self-reactive antibodies in experimental murine lupus, but its activity is dispensable for the expansion of antigen-specific Tfh cells during vaccination. P2X7 stimulation promotes caspase-mediated pyroptosis of Tfh cells and controls the development of pathogenic ICOS IFN-γ-secreting cells. Circulating Tfh cells from patients with systemic lupus erythematosus (SLE) but not primary antiphospholipid syndrome (PAPS), a nonlupus systemic autoimmune disease, were hyporesponsive to P2X7 stimulation and resistant to P2X7-mediated inhibition of cytokine-driven expansion. These data point to the P2X7 receptor as a checkpoint regulator of Tfh cells; thus, restoring P2X7 activity in SLE patients could selectively limit the progressive amplification of pathogenic autoantibodies, which deteriorate patients' conditions.
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http://dx.doi.org/10.1084/jem.20171976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363434PMC
February 2019

Eomesodermin controls a unique differentiation program in human IL-10 and IFN-γ coproducing regulatory T cells.

Eur J Immunol 2019 01 29;49(1):96-111. Epub 2018 Nov 29.

INGM-National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.

Whether human IL-10-producing regulatory T cells ("Tr1") represent a distinct differentiation lineage or an unstable activation stage remains a key unsolved issue. Here, we report that Eomesodermin (Eomes) acted as a lineage-defining transcription factor in human IFN-γ/IL-10 coproducing Tr1-like cells. In vivo occurring Tr1-like cells expressed Eomes, and were clearly distinct from all other CD4 T-cell subsets, including conventional cytotoxic CD4 T cells. They expressed Granzyme (Gzm) K, but had lost CD40L and IL-7R expression. Eomes antagonized the Th17 fate, and directly controlled IFN-γ and GzmK expression. However, Eomes binding to the IL-10 promoter was not detectable in human CD4 T cells, presumably because critical Tbox binding sites of the mouse were not conserved. A precommitment to a Tr1-like fate, i.e. concominant induction of Eomes, GzmK, and IFN-γ, was promoted by IL-4 and IL-12-secreting myeloid dendritic cells. Consistently, Th1 effector memory cells contained precommitted Eomes GzmK T cells. Stimulation with T-cell receptor (TCR) agonists and IL-27 promoted the generation of Tr1-like effector cells by inducing switching from CD40L to IL-10. Importantly, CD4 Eomes T-cell subsets were present in lymphoid and nonlymphoid tissues, and their frequencies varied systemically in patients with inflammatory bowel disease and graft-versus-host disease. We propose that Eomes Tr1-like cells are effector cells of a unique GzmK-expressing CD4 T-cell subset.
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http://dx.doi.org/10.1002/eji.201847722DOI Listing
January 2019

HPV infection and pre-neoplastic cervical lesions among 321 HIV+ women in Florence, Italy, 2006-2016: prevalence and associated factors.

New Microbiol 2018 10 25;41(4):268-273. Epub 2018 Sep 25.

Infectious Disease Unit, Santa Maria Annunziata Hospital, Bagno a Ripoli (Florence), Italy.

Women living with HIV (WLWH) are at higher risk for HPV-related malignancies. To estimate the factors associated to HPV infection and to pre-neoplastic cervical lesions, we observed 321 WLWH in an HIV care-centre in Florence, Italy. In 2006-2016, WLWH followed at S. Maria Annunziata Hospital underwent to gynaecological examination including HPV-test, Pap-smear, colposcopy and, if needed, cervical biopsy. Demographical and clinical information were collected and linear logistic regression was performed. Among 321 WLWH, 161 (50.2%) resulted HPV+. Multiple genotypes were identified in 35%, and cancer high-risk genotypes in 61%. Younger age, not-caucasic origin, increasing number of partners, and shorter duration of HIV are associated with HPV infection. A colposcopy was performed in 154 HIV+/HPV+ women: histological lesions were present in 47 (30%). Among these, CIN1, CIN2 and CIN3 were present in 16, 4, and 1 patients, respectively. Being caucasic, smoking 1-20 cigarettes/day, having 2 partners in the last year, and being an injective-drug-user are associated with cervical lesions. The use of bi-valent, 4-valent and 9-valent HPV vaccines would potentially prevent lesions in 19%, 33%, and 48%. Among WLWH efficaciously in care for HIV, demographic and behavioral factors mainly contribute to acquisition of HPV and to development of cervical lesions.
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October 2018

Photodynamic therapy with topical photosensitizers in mucosal and semimucosal areas: Review from a dermatologic perspective.

Photodiagnosis Photodyn Ther 2018 Sep 15;23:119-131. Epub 2018 Apr 15.

University of Florence School of Health Sciences, Department of Surgical and Translational Medicine, Section of Dermatology, P. Palagi Hospital, Viale Michelangelo 41, 50125, Florence, Italy.

Photodynamic Therapy is a procedure based on the interaction between a Photosensitizer, a light source with a specific wavelength and oxygen. The aim of this review is to provide a brief and updated analysis of scientific reports on the use of PDT with topical PS in the management of oncological, infectious, and inflammatory disorders involving mucosal and semimucosal areas, with a specific focus on diseases of dermatologic interest.
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http://dx.doi.org/10.1016/j.pdpdt.2018.04.005DOI Listing
September 2018

Evaluation of tenascin-C by tenatumomab in T-cell non-Hodgkin lymphomas identifies a new target for radioimmunotherapy.

Oncotarget 2018 Feb 3;9(11):9766-9775. Epub 2018 Jan 3.

Hematology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy.

The clinical outcome of T-cell non-Hodgkin lymphoma (NHL) is poor and innovative treatments are needed. Tenascin-C is a large extracellular glycoprotein not expressed under physiological conditions, but overexpressed in cancer. Aim of the study was to evaluate tenascin-C expression within pathologic tissue of T-cell NHL and determine its clinical significance. We used an immunohistochemistry approach using the anti-tenascin-C monoclonal antibody Tenatumomab in 75 systemic T-cell NHL (including 72 mature and 3 precursor T-cell NHL), and 25 primary cutaneous T-cell NHL. Data were analyzed in terms of staining intensity, proportion of involved areas and histologic pattern, and results were correlated with clinical characteristics and outcome. Ninety-three percent of the cases were tenascin-C positive and 59% of systemic diseases were characterized by a predominant involvement (>50%). Stromal expression was detected in all the cases while vascular and vascular plus cytoplasmic expression was present in 49% and 23%. The constant overexpression of the tenascin-C gene was observed in two independent publicly available T-cell NHL gene expression datasets. In conclusions, tenascin-C represents an attractive target that sets the rationale to investigate the therapeutic activity of radiolabeled Tenatumomab in T-cell NHL.
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http://dx.doi.org/10.18632/oncotarget.23919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839400PMC
February 2018

Lack of Methyl-CpG Binding Protein 2 (MeCP2) Affects Cell Fate Refinement During Embryonic Cortical Development.

Cereb Cortex 2018 05;28(5):1846-1856

San Raffaele Rett Research Unit, Division of Neuroscience, San Raffaele Hospital, 20132 Milan, Italy.

During differentiation, neurons progressively restrict their fate repressing the expression of specific genes. Here we describe the involvement in such developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic factor that participates to chromatin folding and transcriptional regulation. We previously reported that, due to transcriptional impairments, the maturation of Mecp2 null neurons is delayed. To evaluate whether this could stem from altered progenitors proliferation and differentiation, we investigated whether lack of Mecp2 affects these features both in vitro and in vivo. We show that in Mecp2 null embryonic cortexes the expression of genes defining the identity of proliferating neuroprogenitors is enriched and that their permanence in the G1 phase is prolonged. Moreover, the number of cells transitioning from a stage of maturation to a more mature one is increased in Mecp2 null embryonic cortices, in line with the central role of G1 for cell identity refinement. We thus suggest that, possibly due to the lack of proper transcriptional control normally exerted by Mecp2, fate refinement is impaired in developing null cells. We propose that the maturation delay affecting the developing Mecp2 null cortex originates, at least in part, from deranged mechanisms of cell fate refinement.
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http://dx.doi.org/10.1093/cercor/bhx360DOI Listing
May 2018