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Epidemiology,therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont,Italy

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 761-772页

作者： Christian Bracco Marta Gallarate Marco Badinella Martini Corrado Magnino Salvatore D'Agnano Roberta Canta Giulia Racca remo Melchio Cristina Serraino Valentina Polla Mattiot Giovanni Gollè Luigi Fenoglio Department of Internal Medicine Santa Croce e Carle General HospitalCuneo 12100Italy Department of Medical Sciences "City of Health and Science"University HospitalTorino 10100Italy

BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide.It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate.HCC patients have increasingly complex and constantly changing characteristics,thus up-to-date and comprehensive data are fundamental.AIM To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.METHODS In this retrospective study,we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at"Santa Croce e Carle"Hospital in Cuneo(Italy)between 1 January 2010 and 31 December 2019.To highlight possible changes in HCC patterns over the 10-year period,we split the population into two 5-year groups,according to the diagnosis period(2010-2014 and 2015-2019).RESULTS Of the 328 HCC patients who were included(M/F 255/73;mean age 68.9±11.3 years),154 in the first period,and 174 in the second.Hepatitis C virus infection was the most common HCC risk factor(41%,135 patients).The alcoholic etiology rate was 18%,the hepatitis B virus infection etiology was 5%,and the non-viral/non-alcoholic etiology rate was 22%.The Child-Pugh score distribution of the patients was:class A 75%,class B 21%and class C 4%.The average Mayo end-stage liver disease score was 10.6±3.7.A total of 55 patients(17%)were affected by portal vein thrombosis and 158(48%)by portal hypertension.The average nodule size of the HCC was 4.6±3.1 cm.A total of 204 patients(63%)had more than one nodule<3,and 92%(305 patients)had a non-metastatic stage of the disease.The Barcelona Clinic Liver Cancer(BCLC)staging distribution of all patients was:4%very early,32%early,23%intermediate,34%advanced,and 7%terminal.Average survival rate was 1.6±0.3 years.Only 20%of the patients underwent treatment.Age,presence of ascites,BCLC stage and therapy were predictors of a better prognosis(P<0.01).A c

关键词： Hepatocellular carcinoma Hepatitis virus Alcoholic hepatitis Non-alcoholic fatty liver disease Diagnosis Etiology Treatment

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies.PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment.Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC.Here,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation.We report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC patients.Mechanistically,we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting.In miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient deprivation.In a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction.Consistently,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner.Overall,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

Variation in the Content of Cyanogenic Glycosides in Flaxseed Meal from Twenty-One Varieties

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Food and Nutrition Sciences 2014年第15期5卷 1456-1462页

作者： Roberto Russo remo reggiani Istituto di Biologia e Biotecnologia Agraria CNR Milano Italy

Flaxseed meal from twenty-one varieties has been evaluated for content of cyanogenic glycosides (linamarin, linustatin and neolinustatin). Varieties belonging to three different groups of productive attitude (oil, fiber and intermediate) were considered. The total content of cyanogenic glycosides ranged from 0.74 to 1.60 g?Kg?1 CN?. As expected, linamarin was a minority component accounting for only 2% - 14% of total glycosides. Linustatin resulted statistically lower in the intermediate group than that in the other groups and, in particular, it was the lowest in the Festival variety. Neolinustatin resulted lower in the fiber group although the variety Ventimiglia (belonging to oil group) showed a negligible level of this compound. Neolinustatin was positively correlated to total cyanogenic glycosides (r = 0.709) and inversely correlated to linustatin (r = ?0.326). The variability observed in the content of the various forms of glycosides could be exploited in breeding programs to reduce the content of these toxic compounds in flaxseed meal.

关键词： High Performance Liquid Chromatography Linamarin Linustatin Neolinustatin Flaxseed Meal

Evaluation of Protein Concentration, Amino Acid Profile and Antinutritional Compounds in Hempseed Meal from Dioecious and Monoecious Varieties

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American Journal of Plant Sciences 2015年第1期6卷 14-22页

作者： Roberto Russo remo reggiani Istituto di Biologia e Biotecnologia Agraria CNR Via Bassini 15 Milano Italy

Hempseed meal from three dioecious and three monoecious varieties has been evaluated for content and quality of the protein and for the concentration of antinutritional compounds. Hemp seeds were obtained from plants grown in two experimental fields for two consecutive years (2011-2012). For all the varieties, hempseed meal resulted in a rich source of protein (34% mean content) with an amino acid profile extremely rich in arginine and slightly poor in lysine. Differences between dioecious and monoecious varieties were observed in the content of antinutritional compounds. They were more concentrated in monoecious varieties in comparison with those dioecious. The concentration of phytic acid in hempseed meal deserves attention in both groups, being 63 and 75.4 g·kg-1 of dry matter in dioecious and monocieous varieties, respectively. The results show that, besides the recognized value of hemp oil, also the hempseed cake could find application in animal feed as a substitute of other cakes (soybean, rapeseed). From this point of view, the dioecious varieties showing lower contents of antinutritional compounds with respect to the monoecious varieties would be preferred.

关键词： Antinutritional Compounds Amino acid Profile Dioecious Monoecious Protein

Glucosinolates and Sinapine in Camelina Meal

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Food and Nutrition Sciences 2017年第12期8卷 1063-1073页

作者： Roberto Russo remo reggiani Istituto di Biologia e Biotecnologia Agraria CNR Milano Italy

Forty seven accessions of camelina (Camelina sativa L. Crantz) were analyzed for glucosinolates (GSLs) and sinapine in defatted meal. These antinutritional compounds are undesirable in camelina meal for use in animal feeding and therefore we show their variability to identify the best varieties for future breeding programs. Total GSLs ranged from 19.6 to 40.3 mmol Kg-1 dry weight (DW) with an average of 30.3 mmol kg-1 DW. Great variability has also been observed in the levels of individual GSLs (GSL1, GSL2 and GSL3), so that the content of GSL1 and GSL3 were not correlated to each other in the accessions of camelina. Five out of six winter forms of camelina showed low content of GSLs. Sinapine ranged from 1.09 to 4.75 g Kg-1 DW with an average of 2.57 g kg-1 DW. The sinapine content was not correlated with that of GSLs. The use of camelina meal is only limited by the presence of GSLs while sinapine content can be ignored in camelina varieties.

关键词： Camelina sativa L. Crantz Glucosinolates Sinapine Meal Feeding

Antinutritive Compounds in Twelve <i>Camelina sativa </i>Genotypes

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American Journal of Plant Sciences 2012年第10期3卷 1408-1412页

作者： Roberto Russo remo reggiani Istituto di Biologia e Biotecnologia Agraria CNR Milano Italy

Camelina sativa is an oilseed crop becoming important in North America and Europe for biodiesel production. The use of Camelina flours in animal diet may be limited by antinutritive compounds. The content of glucosinolates, phytic acid, sinapine and condensed tannins was evaluated in twelve accessions of Camelina sativa. All compounds showed significant differences among genotypes. Only the concentration of glucosinolates in the flour deserves attention, while the content of phytic acid, sinapine and condensed tannins are to acceptable levels. Camelina showed the presence of three different glucosinolates (GSL1, GSL2 and GSL3) in the flour, with differences among genotypes regarding the relative abundance of each glucosinolate. The content of glucosinolates is inversely correlated with that of sinapine. The glucosinolate content in Camelina flour has to be reduced to increase the use of this flour in animal diet, but avoiding altering the sinapine content.

关键词： Camelina sativa Glucosinolate Sinapine Phytic Acid Condensed Tannins

Variability in Glucosinolate Content among <i>Camelina</i>Species

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American Journal of Plant Sciences 2014年第3期5卷 294-298页

作者： Roberto Russo Incoronata Galasso remo reggiani Istituto di Biologia e Biotecnologia Agraria CNR Milano Italy

Glucosinolate content in Camelina sativa (L.) Crantz (false flax, gold-of-pleasure) and its relatives C. microcarpa, C. alyssum, C. rumelica and C. hispida was investigated. With the exception of C. hispida in which GSL3 was absent, in all remaining species, three characteristic glucosinolates (GSL1, GSL2 and GSL3) were identified. Camelina genotypes of spring type (C. sativa CAM134, C. alyssum CAM21) showed a typical pattern of glucosenolates with GSL1 > GSL3. GSL1 was present in traces in C. microcarpa and at low levels in C. rumelica and C. alyssum subsp. alyssum. In C. hispida, the GSL1 content was greater than GSL2 and, only in this specie, GSL2 represented less than 50% of total glucosinolates. These differences in the glucosinolate pattern among Camelina species could be exploited to reduce the total content of glucosinolates in C. sativa.

关键词： Camelina Species Glucosinolate Flour Winter and Spring Type Oilseed Crop

Use of anticoagulation reversal therapy in the emergency department:a single-center real-life retrospective study

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World Journal of Emergency Medicine 2023年第1期14卷 56-58页

作者： Jacopo Davide Giamello Andrea Pisano Fabrizio Corsini remo Melchio Luca Bertolaccini Enrico Lupia Giuseppe Lauria School of Emergency Medicine University of TurinTurin 10100Italy Department of Emergency Medicine Santa Croce e Carle HospitalCuneo 12100Italy Department of Internal Medicine Santa Croce e Carle HospitalCuneo 12100Italy Department of Thoracic Surgery IEOEuropean Institute of Oncology IRCCSMilan 20141Italy Department of Emergency Medicine Cittàdella Salute e della Scienza HospitalTurin 10126Italy Department of Medical Sciences University of TurinTurin 10100Italy

The incidence of atrial fibrillation(AF)and deep vein thrombosis/pulmonary embolism(DVT/PE)has increased in the last decades as a consequence of global aging and th refinement of diagnostic techniques;thus,the consumption o anticoagulant drugs has increased significantly.[1,2]Prescription of direct oral anticoagulants(DOACs)have overtaken thos of vitamin K antagonists(VKA)since the mid-2010s.[3]Consequently,the incidence of these drugs’side effects has also increased;the most relevant side effect in terms of morbidity and mortality is bleeding.In addition to critically ill bleeding patients,another indication of anticoagulant reversal therapy is the need for emergency surgery or for a procedure with high risk of bleeding.

关键词： drugs vitamin mortality

Blockchain-as-a-Service and Blockchain-as-a-Partner: Implementation options for supply chain optimization

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Blockchain(Research and Applications) 2023年第2期4卷 12-27页

作者： Paolo Bottoni Claudio Di Ciccio remo Pareschi Domenico Tortola Nicola Gessa Gilda Massa Department of Computer Science Sapienza University of RomeViale Regina Elena295Rome00161RMItaly Stake Lab University of MoliseC.da Fonte LapponePesche86090ISItaly Department of Bioscience and Territory University of MoliseC.da Fonte LapponePesche86090ISItaly TERIN-SEN-CROSS ENEA-Agenzia nazionale per le nuove tecnologiel'energia e lo sviluppo economico sostenibileVia Martiri di Monte Sole 4Bologna40129BOItaly e TERIN-SEN-CROSSENEA-Agenzia nazionale per le nuove tecnologiel'energia lo sviluppo economico sostenibile Piazzale Enrico Fermi 1Portici80055NAItaly

Smart contracts show a high potential to make supply chain management strategies epochally leap towards higher levels of productivity,not only in the functioning of production processes but also in terms of product innovation and overall economic returns.This article illustrates the principle of Income Sharing as a highly performing economic strategy for supply chains with a natural implementation in blockchain smart contracts.It proposes a blockchain-based architecture that uses smart contracts to implement various algorithmic versions of the Income Sharing principle among companies participating in a supply chain.The formation of the total income and its consequent redistribution are calculated taking into account the role of the technological platform automating these procedures,which therefore becomes a party to the inter-company business project of a supply chain in the alternative roles,as feasible in business practice,of Blockchain-as-a-Service and Blockchain-as-a-Partner.The approach is implemented on Hyperledger Fabric,the most widespread platform for private and consortium blockchains.We compare and justify this design choice with the alternative given by public blockchains,with specific attention to Ethereum.

关键词： Supply chain management Decentralized autonomous organization Income sharing Smart contract Distributed ledger Hyperledger fabric