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Watch and wait policy in advanced neuroendocrine tumors: What does it mean?

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World Journal of Clinical Oncology 2017年第2期8卷 96-99页

作者： nicola Fazio Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology

Neuroendocrine neoplasms(NENs) are a group of rare and heterogeneous malignancies, which can develop in various organs. The clinical course of NENs is quite heterogeneous, with different spontaneous growth rates after diagnosis, and different degrees of sensitivity to the same therapy even when they have similar characteristics. Watch and wait(W and W), is a term coined to indicate observation being conducted to assess the evolution of the tumor without administering any anti-tumor therapy. It has been applied to NENs since in extremely rare cases they tend to remain stable for a long time. Although W and W has been reported in several guidelines and recommendations it has never been validated, nor has it been specifically investigated. Furthermore it is not standardized. Therefore its application in clinical practice can differ in terms of tumor status assessment, type and timing of imaging or other exams utilized. In conclusion, while undertaking W and W to delay the first-line therapy by some weeks may be justified in good performance asymptomatic patients with low-grade NENs in order to usefully characterize the disease and patient and thereby choose the best therapy and therapeutic strategy, it seems to be far more difficult to justify W and W with the intent of avoiding an anti-tumor treatment. It should be considered that not only do NENs tend to grow even when they have very favorable biological characteristics but also that the alternative to W and W is most commonly a low toxic and effective treatment with somatostatin analogs.

关键词： Observation Wait and see Watch and wait Surveillance Neuroendocrine tumors

Radiative Effects on Mixed Convection in a Uniformly HeatedVertical Convergent Channel with an Unheated Moving Plate

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Advances in Applied Mathematics and Mechanics 2011年第3期3卷 280-296页

作者： Assunta Andreozzi nicola Bianco Vincenzo Naso DETEC-Universit`a di Napoli Federico II P.le Tecchio80-80125NapoliItaly

Fluids engineering is extremely important in a wide variety of materials processing systems,such as soldering,welding,extrusion of plastics and other polymeric materials,Chemical Vapor Deposition(CVD),composite materials *** particular,mixed convection due to moving surfaces is very important in these *** convection in a channel,as a result of buoyancy and motion of one of its walls has received little research attention and few guidelines are available for choosing the best performing channel configuration,particularly when radiative effects are *** this study a numerical investigation of the effect of radiation on mixed convection in air due to the interaction between a buoyancy flow and an unheated moving plate induced flow in a uniformly heated convergent vertical channel is carried *** moving plate has a constant velocity and moves in the buoyancy force *** principal walls of the channel are heated at uniform heat *** numerical analysis is accomplished by means of the commercial code *** effects of the wall emissivity,the minimum channel spacing,the converging angle and the moving plate velocity are investigated and results in terms of air velocity and temperature fields inside the channel and wall temperature profiles,both of the moving and the heated plates,are *** numbers,both accounting and not for the radiative contribution to heat removal,are also presented.

关键词： Mixed convection moving surfaces convergent channels radiative effects

HER2 inhibition in gastro-oesophageal cancer:A review drawing on lessons learned from breast cancer

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World Journal of Gastrointestinal Oncology 2018年第7期10卷 159-171页

作者： Hazel Lote nicola Valeri Ian Chau Centre for Molecular Pathology Institute of Cancer Research Department of Medicine Royal Marsden Hospital

Human epidermal growth factor receptor 2(HER2)-inhibition is an important therapeutic strategy in HER2-amplified gastro-oesophageal cancer(GOC).A significant proportion of GOC patients display HER2 amplification,yet HER2 inhibition in these patients has not displayed the success seen in HER2 amplified breast *** of the current evidence surrounding HER2 has been obtained from studies in breast cancer,and we are only recently beginning to improve our understanding of HER2-amplified *** there are numerous licensed HER2 inhibitors in breast cancer,trastuzumab remains the only licensed HER2 inhibitor for HER2-amplified *** trials investigating lapatinib,trastuzumab emtansine,pertuzumab and MM-111 in GOC have demonstrated disappointing results and have not yet changed the treatment *** deruxtecan may hold promise and is currently being investigated in phase Ⅱ ***2 amplified GOC differs from breast cancer due to inherent differences in the HER2 amino-truncation and mutation rate,loss of HER2 expression,alterations in HER2 signalling pathways and differences in insulin-like growth factor-1 receptor and MET *** alterations involving different micro RNA profiles in GOC as compared to breast cancer and intrinsic differences in the immune environment are likely to play a *** key to effective treatment of HER2 amplified GOC lies in understanding these mechanisms and tailoring HER2 inhibition for GOC patients in order to improve clinical outcomes.

关键词： Human epidermal growth factor receptor 2 Gastro-oesophageal cancer Trastuzumab Resistance Biomarkers Breast cancer

Neuroendocrine tumors resistant to mammalian target of rapamycin inhibitors:A difficult conversion from biology to the clinic

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World Journal of Clinical Oncology 2015年第6期6卷 194-197页

作者： nicola Fazio Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors European Institute of Oncology

Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors(NETs). m TOR inhibitors used in clinical practice are derived from rapamycin,an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin-derived m TOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderatelydifferentiated pancreatic NETs(p NETs). It inhibits specifically the m TORC1 subunit of m TOR,not interacting with m TORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with p NETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to m TOR inhibitors are Akt and PI3 K activation,by means of m TORC2 and insulin growth factor(IGF)- IGF receptor signaling,respectively. BEZ235 is a multi-targeted inhibitor binding to PI3 K,m TORC1 and m TORC2,therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in p NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase Ⅰ step of clinical development and the design of phase Ⅱ clinical trials.

关键词： Everolimus BEZ235 Mammalian target of rapamycin Phosphoinositide 3-kinase Mammalian target of rapamycin C Resistance Mammalian target of rapamycin inhibitor

Adolescent male genitalia dissatisfaction:a surgical perspective

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Asian Journal of Andrology 2022年第2期24卷 176-179页

作者： nicola Zampieri Ilaria Dando Francesco Saverio Camoglio Woman and Child Hospital Pediatric Surgical UnitUniversity of VeronaVerona 37100Italy Department of Neurosciences Biomedicine and Movement SciencesBiochemistry SectionUniversity of VeronaVerona 37100Italy

Genital dissatisfaction is well known in female and *** is known about male adolescents and their genital *** aim of this study was to investigate and report the role of surgery in male adolescents to improve the evaluation of their *** considered all patients treated for external genital pathology in the period of *** and exclusion criteria were *** underwent an evaluation test before and after *** the study period,137 patients were treated,and at the end of the study,98 cases were considered for *** most frequent pathologies were webbed penis and penile curvature.A postoperative score improvement was noted and patients with concealed penis and webbed penis showed a better postoperative *** was considered an important factor associated with a worse preoperative *** of the external genitalia is important in adolescents,and it is an understudied *** may be associated with a worse evaluation of one’s genital and should be clinically considered to avoid related social problems in ***,cosmetic genital surgery should be considered even in male adolescents.

关键词： adolescent esthetic genital dissatisfaction surgery

From Alliance to Tutelage： A Historical Analysis of Manchu-Mongol Relations before the Qing Conquest

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Frontiers of History in China 2012年第2期7卷 175-197页

作者： nicola Di Cosmo Institute for Advanced Study Princeton University Princeton NJ 08540 USA

Before 1644, the Manchu rulers pursued a deliberate policy of alliances with the southern （later ＂Inner＂） Mongol tribes. In the 1630s the system of treaties and alliances gave way to the creation of the League-Banner system, the jasaq system, and the Lifan Yuan. The new territorial and political organization meant that the southern Mongols, while retaining a degree of autonomy, became subjects of the Qing dynasty. This essay explores the historical circumstances of the transformation of the relationship between Manchus and Mongols from partnership to subordination. It also aims to explain the political principles deployed by the Manchus in the redefinition of their relationship with the Mongol elites. More specifically, the essay proposes that the new forms of administration of Inner Mongolia stemmed from a condition of ＂tutelage.＂ Tutelage was not simply imposed by the Manehus upon their erstwhile allies, but actively sought by Mongol aristocrats in the context of the intra-Mongol wars carried out by the Caqar leader Ligdan Khan.

关键词： Manchus Mongols southem Mongols Qing tutelage alliance Ligdan Khan

Performance evaluation of permissioned blockchains for financial applications: The ConsenSys Quorum case study

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Blockchain(Research and Applications) 2022年第1期3卷 1-12页

作者： Marco Mazzoni Antonio Corradi Vincenzo Di nicola Conio Inc. c/o The Orrick Building405 Howard StreetSan FranciscoCA94105USA Department of Computer Science and Engineering University of BolognaViale Risorgimento 2BolognaItaly

Given the availability of several blockchain technologies in permissioned contexts,blockchain application designers have to cope with the increasing complexity of choosing which technology and consensus algorithm best fit a specific use ***,the lack of a standard framework allowing to assess the scalability of permissioned blockchain platforms and to compare performances and features of consensus algorithms makes the development of a sensible evaluation a costly and difficult time-consuming *** this article,we propose a practical scalability and applicability evaluation of the Quorum blockchain and its consensus *** we apply our evaluation workflow to a financial use case,we define a methodology that can be generalized to any permissioned blockchain *** leverage Hyperledger Caliper as a benchmarking tool,and Docker as a deployment tool,making our analysis easy to be repeated,cross-platform,and cost-effective.

关键词： Blockchain Consensus Benchmark Quorum Cryptocurrency

MECHANICS OF CARBON NANOSCROLLS: A REVIEW

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Acta Mechanica Solida Sinica 2010年第6期23卷 484-497页

作者： Xinghua Shi nicola M. Pugno Huajian Gao School of Engineering Brown University 610 Barus & Holley 182 Hope Street Providence RI 02912 USA Laboratory of Bio-inspired Nanomechanics 'Giuseppe Maria Pugno ' Department of Structural Engineering Politecnico di Torino Corso Duca degli Abruzzi 24 10129 Torino Italy

Carbon nanoscrolls （CNSs） belong to the same class of carbon-based nanomaterials as carbon nanotubes but are much less studied in spite of their great potential for applications in nanotechnology and bioengineering. Fundamental description, understanding and regulation of such materials will ultimately lead to a new generation of integrated systems that utilize their unique properties. In this review, we describe some of the recent advances in theoretical investi- gation on structural and dynamical behavior of CNS, as well as relevant simulation techniques. Theoretically it has been found that a stable equilibrium core size of CNS can be uniquely determined or tuned from the basal graphene length, the interlayer spacing, the interaction energy between layers of CNS and the bending stiffness of graphene. Perturbations of the surface energy, which can be controlled by an electric field, will cause a CNS to undergo breathing oscillatory motion as well as translational rolling motion on a substrate. The tunable core size of CNS also enables it to serve potentially as transmembrane water channels in biological systems.

关键词： Graphene

Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

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World Journal of Gastroenterology 2008年第48期14卷 7335-7344页

作者： nicola Dioguardi Fabio Grizzi Barbara Fiamengo Carlo Russo Laboratories of Quantitative Medicine Istituto Clinico Humanitas IRCCS Department of Pathology Istituto Clinico Humanitas IRCCS

AIM： To describe a quantitative analysis method for liver biopsy sections with a machine that we have named ＂Dioguardi Histological Metriser＂ which automatically measures the residual hepatocyte mass （including hepatocytes vacuolization）, inflammation, fibrosis and the loss of liver tissue ***： We analysed digitised images of liver biopsy sections taken from 398 patients, The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring ***： The method provides：（1） the metrical extension in two-dimensions （the plane） of the residual hepatocellular set, including the area of vacuoles pertinent to abnormal lipid accumulation; （2） the geo- metric measure of the inflammation basin, which distinguishes intra-basin space and extra-basin dispersed parenchymal leukoo/tes; （3） the magnitude of collagen islets, （which were considered truncated fractals and classified into three degrees of magnitude）; and （4） the tectonic index that quantifies alterations （disorders） in the organization of liver tissue. Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm^2/s, scanning a whole section in 6-8 ***： The results are the first standardized metrical evaluation of the geometric properties of the parenchyma, inflammation, fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The present study confirms that biopsies are still valuable, not only for diagnosing chronic hepatitis, but also for quantifying changes in the organization and order of liver tissue structure.

关键词： Liver measurement Image analysis Liverlesion Liver tectonics