13 results on '"Altieri GI"'
Search Results
2. MOLECULAR CHARACTERIZATION OF PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE WITH 'EXTREME LDL-C PHENOTYPES'
- Author
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Oliviero Olivieri, V. Ingrassia, Angelo B. Cefalù, F. Brucato, C. Scrimali, C.M. Barbagallo, Gabriella Misiano, Domenico Girelli, F. Busti, Nicola Martinelli, Francesca Fayer, Maurizio Averna, A. Giammanco, Davide Noto, Rossella Spina, G.I. Altieri, Brucato, F, Martinelli, N, Spina, R, Busti, F, Ingrassia, V, Scrimali, C, Altieri, GI, Noto, D, Misiano, G, Giammanco, A, Barbagallo, CM, Fayer, F, Cefalu, AB, Olivieri, O, Girelli, D, and Averna, M
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Coronary artery disease ,medicine.medical_specialty ,genotyping ,business.industry ,Internal medicine ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Phenotype ,LDL - Published
- 2020
3. PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study
- Author
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Francesca Fayer, Maurizio Averna, Carlo M. Barbagallo, G.I. Altieri, Gabriella Misiano, Vincenza Valenti, C. Scrimali, Davide Noto, Rossella Spina, Angelo B. Cefalù, Antonina Giammanco, V. Ingrassia, F. Brucato, Valenti V, Noto D, Giammanco A, Fayer F, Spina R, Altieri GI, Ingrassia V, Scrimali C, Barbagallo CM, Brucato F, Misiano G, Cefalu AB, and Averna M.
- Subjects
0301 basic medicine ,Small peptides ,media_common.quotation_subject ,030204 cardiovascular system & hematology ,Decoy strategy ,PCSK9 ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Internalization ,Cells, Cultured ,media_common ,Expression vector ,Epidermal Growth Factor ,Chemistry ,PCSK9 Inhibitors ,Transfection ,Proprotein convertase ,PCSK9 inhibition ,In vitro ,Cell biology ,EGF-A domain ,030104 developmental biology ,LDLR ,Receptors, LDL ,LDL receptor ,Mutation ,Kexin ,lipids (amino acids, peptides, and proteins) ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine - Abstract
Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradation in vitro. Methods Huh7 human hepatoma cells were transiently transfected to overexpress the gain-of-function D374Y PCSK9 mutation, which has been associated with severe hypercholesterolemia in humans. Results Transient transfection of cells with PCSK9-D374Y expression vector very effectively enhanced degradation of mature LDLR in Huh7. Treatment with both EGF-A and EGF-A truncated peptides inhibited this effect and showed increased LDLR protein in Huh7 cells transfected with PCSK9-D374Y in a clear concentration dependent manner. Huh7 transfected cells treated with increasing concentration of EGF-A analogs also showed an increase internalization of labeled Dil-LDL. Conclusions The result of our study shows that EGF-A analogs are able to effectively hamper the enhanced degradation of LDLR in liver cells expressing PCSK9-D374Y.
- Published
- 2019
4. Mutation in candidate genes account for a small minority of hypobetalipoproteinemias and NGS analysis support polygenicity in mutation-negative patients
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Gabriella Misiano, G.I. Altieri, Maurizio Averna, Rossella Spina, A. Giammanco, C.M. Barbagallo, Vincenza Valenti, Davide Noto, A. Ganci, V. Ingrassia, F. Brucato, Francesca Fayer, C. Scrimali, Angelo B. Cefalù, Giammanco, Antonina, Scrimali, C, Spina, R, Ingrassia, V, Brucato, F, Valenti, V, Cefalu, AB, Misiano, G, Altieri, GI, Noto, D, Barbagallo, CM, Ganci, A, Fayer, F, and Averna, M
- Subjects
Genetics ,POLYGENIC ,Candidate gene ,Mutation (genetic algorithm) ,Biology ,Cardiology and Cardiovascular Medicine ,HYPOBETALIPOPROTEINEMIAS ,NGS ANALYSIS - Published
- 2020
5. Identification Of P.Leu167Del Apoe Gene Mutation By Next Generation Sequencing In A Large Hypercholesterolemic Family
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V. Ingrassia, Maurizio Averna, G.I. Altieri, F. Brucato, Francesca Fayer, C. Scrimali, Davide Noto, C.M. Barbagallo, A. Giammanco, Vincenza Valenti, Rossella Spina, Angelo B. Cefalù, Gabriella Misiano, Scrimali, C, Spina, R, Ingrassia, V, Cefalu, AB, Brucato, F, Misiano, G, Valenti, V, Noto, D, Altieri, GI, Fayer, F, Giammanco, A, Barbagallo, C, and Averna, M
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Apolipoprotein E ,Genetics ,Settore MED/09 - Medicina Interna ,NEXT GENERATION SEQUENCING HYPERCHOLESTEROLEMIA ,Mutation (genetic algorithm) ,APOE GENE ,Identification (biology) ,Biology ,Cardiology and Cardiovascular Medicine ,MUTATION ,DNA sequencing - Published
- 2019
6. A NOVEL APOB MUTATION IDENTIFIED BY EXOME SEQUENCING COSEGREGATES WITH STEATOSIS, LIVER CANCER AND HYPOCHOLESTEROLEMIA
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SPINA, Rossella, CEFALU', Angelo Baldassare, ALTIERI, Grazia Ida, VALENTI, Vincenza, FAYER, Francesca, PALESANO, Ornella, AVERNA, Maurizio, Pirruccello, JP, Noto, D, Gabriel, S, Gupta, N, Tarugi, P, Kathiresan, S, Spina, R, Cefalù AB, Pirruccello, JP, Altieri, GI, Noto, D, Gabriel, S, Valenti, V, Gupta, N, Fayer, F, Palesano, O, Tarugi, P, Kathiresan, S, and Averna, M
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Settore MED/09 - Medicina Interna ,FHBL ,HCC ,fatty liver - Abstract
Objective. In familial hypobetalipoproteinemia (FHBL), fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein (LDL) cholesterol, fatty liver and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results. The proband was a 25 year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis and four more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutation in this family, we performed exome sequencing in two participants with hypocholesterolemia and fatty liver. Approximately 22,400 single nucleotide variants were identi- ed in each sample. After variant ltering, 300 novel shared variants remained. A nonsense variant, p.K2240X due to an A>T mutation in exon 26 of APOB (c.6718A>T) was identi ed and this variant was con rmed by Sanger sequencing. The gentotypic analysis of 16 family members in total showed that this mutation segregated with the low cholesterol trait. In addition, genotyping of the PNPLA3 p.I148M did not show signi cant frequency differences between carriers and non-carriers of the c.6718A>T APOB gene mutation. Conclusions. We used exome sequencing to discover a novel nonsense mutation in exon 26 of APOB (p.K2240X) responsible for low cholesterol and fatty liver in a large kindred. This mutation may also be responsible for cirrhosis and liver cancer in this family.
- Published
- 2013
7. Identification of a novel ANGPTL3 mutation splicing associeted to severe hypobetalipoproteinemia
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SPINA, Rossella, VALENTI, Vincenza, ALTIERI, Grazia Ida, FAYER, Francesca, BARBAGALLO, Carlo Maria, CEFALU', Angelo Baldassare, AVERNA, Maurizio, Crisci, I, Noto, D, Cannizzaro, A, Miccoli, R, Spina, R, Crisci, I, Valenti, V, Altieri, GI, Fayer, F, Barbagallo, CM, Noto, D, Cannizzaro, A, Miccoli, R, Cefalù, AB, and Averna, M
- Subjects
Settore MED/09 - Medicina Interna ,ANGPTL3 ,mutation ,Hypobetalipoproteinemia - Abstract
Introduction. Primary hypobetalipoproteinemia (pHBL) is a monogenic heterogeneous condition inherited as a dominant or recessive trait characterized by total cholesterol (TC) and/or LDL cholesterol (LDL-C) and/or apolipoprotein B (APOB) levels below the 5th percentile of the reference population. Heterozygous APOB gene mutations are responsible for the majority of the dominant pHBL causing the familial hypobetalipoproteinemia (FHBL). Loss-of-function mutations in the PCSK9 gene also cause FHBL. Familial combined hypolipidemia is a recently discovered dyslipidemic phenotype characterized by low levels of TC, triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol (HDL-C). The genetic cause of familial combined hypolipidemia has been attributed to mutations in the ANGPTL3 gene. methods and Results. In this report we describe a case of a young men with severe hypolipidemia characterized by low levels of total cholesterol, triglycerides and HDL- (54 mg/dl, 26 mg/dl, 17 mg/dl respectively). The proband’s mother and father showed normal plasma lipid values suggesting a recessive mode of inheritance of the phenotype. In order to identify the molecular defects the analysis of MTP and SARA2 genes was carried out and no mutations were identified in both genes. We extended our analysis to the other known genes responsible for pHBL and we were able to identify in the ANGPTL3 gene a novel splicing mutation (insT+3, IVS5) in homozigosity. Both parents were carriers of the same mutation in heterozygosity. InsT+3, IVS5 is predict to alter the correct splicing as predicted by in silico analysis. Conclusion. We describe a clinical case with severe hypolipidemia with a recessive mode of inheritance carrying a novel mutation in Intron 5 of ANGPTL3. The mode of inheritance and the clinical implications of familial combined hypolipidemia need to be further characterized.
- Published
- 2012
8. rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography.
- Author
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Noto D, Cefalù AB, Martinelli N, Giammanco A, Spina R, Barbagallo CM, Caruso M, Novo S, Sarullo F, Pernice V, Brucato F, Ingrassia V, Fayer F, Altieri GI, Scrimali C, Misiano G, Olivieri O, Girelli D, and Averna MR
- Subjects
- Age Factors, Aged, Biomarkers blood, Coronary Stenosis blood, Coronary Stenosis epidemiology, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Italy epidemiology, Lipids blood, Male, Middle Aged, Phenotype, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, Severity of Illness Index, Time Factors, Cadherins genetics, Coronary Angiography, Coronary Stenosis diagnostic imaging, Coronary Stenosis genetics, Polymorphism, Single Nucleotide
- Abstract
Background and Aims: Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients., Methods and Results: The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG. The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04-1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04-1.96) and 1.39 (1.22-1.58) respectively]., Conclusions: rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
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9. PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study.
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Valenti V, Noto D, Giammanco A, Fayer F, Spina R, Altieri GI, Ingrassia V, Scrimali C, Barbagallo CM, Brucato F, Misiano G, Cefalù AB, and Averna MR
- Subjects
- Cells, Cultured, Humans, Mutation, Proprotein Convertase 9 genetics, Epidermal Growth Factor pharmacology, PCSK9 Inhibitors, Proprotein Convertase 9 physiology, Receptors, LDL metabolism
- Abstract
Background and Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradation in vitro., Methods: Huh7 human hepatoma cells were transiently transfected to overexpress the gain-of-function D374Y PCSK9 mutation, which has been associated with severe hypercholesterolemia in humans., Results: Transient transfection of cells with PCSK9-D374Y expression vector very effectively enhanced degradation of mature LDLR in Huh7. Treatment with both EGF-A and EGF-A truncated peptides inhibited this effect and showed increased LDLR protein in Huh7 cells transfected with PCSK9-D374Y in a clear concentration dependent manner. Huh7 transfected cells treated with increasing concentration of EGF-A analogs also showed an increase internalization of labeled Dil-LDL., Conclusions: The result of our study shows that EGF-A analogs are able to effectively hamper the enhanced degradation of LDLR in liver cells expressing PCSK9-D374Y., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
10. Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing.
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Cefalù AB, Spina R, Noto D, Ingrassia V, Valenti V, Giammanco A, Fayer F, Misiano G, Cocorullo G, Scrimali C, Palesano O, Altieri GI, Ganci A, Barbagallo CM, and Averna MR
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- Adult, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Phenotype, DNA Mutational Analysis, High-Throughput Nucleotide Sequencing, Hypertriglyceridemia genetics, Membrane Proteins genetics
- Abstract
Background: Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins., Objective: The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG., Methods: We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL-10 mmol/L): 4 positive controls in whom pathogenic mutations had previously been identified by Sanger sequencing and 7 patients in whom the molecular defect was still unknown., Results: The customized panel was accurate, and it allowed to confirm genetic variants previously identified in all positive controls with primary severe HTG. Only 1 patient of 7 with HTG was found to be carrier of a homozygous pathogenic mutation of the third novel mutation of LMF1 gene (c.1380C>G-p.Y460X). The clinical and molecular familial cascade screening allowed the identification of 2 additional affected siblings and 7 heterozygous carriers of the mutation., Conclusions: We showed that our targeted resequencing approach for genetic diagnosis of severe HTG appears to be accurate, less time consuming, and more economical compared with traditional Sanger resequencing. The identification of pathogenic mutations in candidate genes remains challenging and clinical resequencing should mainly intended for patients with strong clinical criteria for monogenic severe HTG., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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11. Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.
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Noto D, Cefalù AB, Barbagallo CM, Ganci A, Cavera G, Fayer F, Palesano O, Spina R, Valenti V, Altieri GI, Caldarella R, Giammanco A, Termini R, Burrascano M, Crupi G, Falletta A, Scafidi V, Sbordone D, La Seta F, and Averna MR
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- Aged, Area Under Curve, Biomarkers blood, Blood Glucose metabolism, Cardiovascular Diseases diagnosis, Cardiovascular Diseases prevention & control, Chi-Square Distribution, Diet, Healthy, Diet, Mediterranean, Disease-Free Survival, Female, Humans, Incidence, Insulin Resistance, Italy epidemiology, Lipids blood, Male, Metabolic Syndrome blood, Metabolic Syndrome diagnosis, Middle Aged, Multivariate Analysis, Neoplasms diagnosis, Neoplasms prevention & control, Obesity diagnosis, Prevalence, Proportional Hazards Models, Protective Factors, ROC Curve, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Cardiovascular Diseases epidemiology, Metabolic Syndrome epidemiology, Neoplasms epidemiology, Obesity epidemiology
- Abstract
Background and Aims: Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity., Methods and Results: As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log
10 ) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]., Conclusions: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)- Published
- 2016
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12. FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease.
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Di Gaudio F, Indelicato S, Monastero R, Altieri GI, Fayer F, Palesano O, Fontana M, Cefalù AB, Greco M, Bongiorno D, Indelicato S, Aronica A, Noto D, and Averna MR
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- Aged, Aged, 80 and over, Case-Control Studies, Chromatography, High Pressure Liquid, Humans, Molecular Structure, Tandem Mass Spectrometry, Alzheimer Disease metabolism, Lipids chemistry
- Abstract
Lipidomic analysis is able to measure simultaneously thousands of compounds belonging to a few lipid classes. In each lipid class, compounds differ only by the acyl radical, ranging between C10:0 (capric acid) and C24:0 (lignoceric acid). Although some metabolites have a peculiar pathological role, more often compounds belonging to a single lipid class exert the same biological effect. Here, we present a lipidomics workflow that extracts the tandem mass spectrometry data from individual files and uses them to group compounds into structurally homogeneous clusters by chemical structure hierarchical clustering analysis (CHCA). The case-to-control peak area ratios of the metabolites are then analyzed within clusters. We created two freely available applications to assist the workflow: FragClust to generate the tables to be subjected to CHCA, and TestClust to perform statistical analysis on clustered data. We used the lipidomics data from the plasma of Alzheimer's disease (AD) patients in comparison with healthy controls to test the workflow. To date, the search for plasma biomarkers in AD has not provided reliable results. This article shows that the workflow is helpful to understand the behavior of whole lipid classes in plasma of AD patients.
- Published
- 2016
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13. Erratum to: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease.
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Di Gaudio F, Indelicato S, Monastero R, Altieri GI, Fayer F, Palesano O, Fontana M, Cefalu AB, Greco M, Bongiorno D, Indelicato S, Aronica A, Noto D, and Averna MR
- Published
- 2016
- Full Text
- View/download PDF
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