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Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma:Lights and shadows

World Journal of Gastrointestinal Oncology 2022年第9期14卷 1622-1636页

作者： federico Costante Carlo Airola Francesco Santopaolo antonio Gasbarrini Maurizio Pompili Francesca Romana Ponziani Internal Medicine and Gastroenterology-Hepatology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSRoma 00168Italy Catholic University Largo Francesco Vito 100168 RomaItaly

About one-fourth of adults globally suffer from nonalcoholic fatty liver disease(NAFLD), which is becoming a leading cause of chronic liver disease worldwide. Its prevalence has rapidly increased in recent years, and is projected to increase even more. NAFLD is a leading cause of hepatocellular carcinoma(HCC), the sixth-most prevalent cancer worldwide and the fourth most common cause of cancer-related death. Although the molecular basis of HCC onset in NAFLD is not completely known, inflammation is a key player. The tumor microenvironment(TME) is heterogeneous in patients with HCC, and is characterized by complex interactions between immune system cells, tumor cells and other stromal and resident liver cells. The etiology of liver disease plays a role in controlling the TME and modulating the immune response. Markers of immune suppression in the TME are associated with a poor prognosis in several solid tumors. Immunotherapy with immune checkpoint inhibitors(ICIs) has become the main option for treating cancers, including HCC. However, meta-analyses have shown that patients with NAFLD-related HCC are less likely to benefit from therapy based on ICIs alone. Conversely, the addition of an angiogenesis inhibitor showed better results regarding the objective response rate and progression-free survival. Adjunctive diagnostic and therapeutic strategies, such as the application of novel biomarkers and the modulation of gut microbiota, should be considered in the future to guide personalized medicine and improve the response to ICIs in patients with NAFLD-related HCC.

关键词： Hepatocellular carcinoma Immunotherapy Liver cancer Nonalcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Obesity

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实际塑性铰链位置对延性框架行为的影响（英文）

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2014年第7期15卷 482-495页

作者： Massimiliano FRALDI antonio GESUALDO federico GUARRACINO Department of Structural Engineering University of Naples "Federico Ⅱ"

研究目的:通过有限元分析和极限分析,研究了在纵向和横向载荷下钢框架的最大负荷和坍塌模式,并考虑了塑性铰链在轴向力和弯曲力矩的作用下在实际旋转时的运动学。研究方法:在垂直和水平方向载荷共存的情况下,基于轴向力和弯曲力矩的交... 详细信息

研究目的:通过有限元分析和极限分析,研究了在纵向和横向载荷下钢框架的最大负荷和坍塌模式,并考虑了塑性铰链在轴向力和弯曲力矩的作用下在实际旋转时的运动学。研究方法:在垂直和水平方向载荷共存的情况下,基于轴向力和弯曲力矩的交互作用,研究延性框架的极限载荷和坍塌模式对产生于塑性铰链的真实运动学的敏感性。通过两个基本的案例和通过成功地评估非线性有限元分析和直接实施的极限分析步骤,并利用MATHEMATICA?,揭示了其敏感性。重要结论:在标准规程的框架下,即使在最简单的案例中,极限分析的主要结果也会考虑在坍塌时的运动学,这与设计和加固的目的都是相关的。如果没有对所有的结构元件的轴向力和弯曲力矩的交互作用进行合理的计算,塑性铰链的定位计算可能得出不正确的坍塌机理和误导性的安全系数。就具体方面而言,本文清楚地表明,在设计新的结构或者为现有结构进行加固时,即使是使用看起来已经非常完备的经典步骤,也必须非常小心。本文的模型可以为处理规程设计的执业工程师和标准化委员会提供参考。

关键词：钢框架极限分析实际塑胶铰链位置坍塌运动学

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Pitfalls of barcodes in the study of worldwide SARSCoV-2 variation and phylodynamics

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Zoological Research 2021年第1期42卷 87-93页

作者： Jacobo Pardo-Seco Alberto Gómez-Carballa Xabier Bello federico Martinón-Torres antonio Salas Unidade de Xenética Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigación Sanitaria(IDIS)Hospital Clínico Universitario de Santiago(SERGAS)Galicia 15706Spain Genetics Vaccines and Pediatric Infectious Diseases Research Group(GENVIP)Instituto de Investigación Sanitaria de Santiago(IDIS)and Universidad de Santiago de Compostela(USC)Galicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clínico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain

DEAR EDITOR,Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several *** show that purely mathematical procedures for site selection should be supervised by known phylogeny(i)to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties,and(ii)to avoid phylogenetic *** propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites(as a proxy for phylogenetic-based criteria).This procedure demonstrates that,for short barcodes(e.g.,11 sites),there are thousands of informative site combinations that improve previous *** also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny,such that most representative genomes in these ancestral nodes are no longer in ***,coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.

关键词： dynamics properly purely

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Biogeographical informativeness of Y-STR haplotypes

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Science Bulletin 2019年第19期64卷 1381-1384页

作者： Jacobo Pardo-Seco Alberto Gómez-Carballa Xabier Bello federico Martinón-Torres antonio Salas Unidade de Xenética Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstitutode Investigaciones Sanitarias(IDIS)Hospital Clínico Universitario de Santiago(SERGAS)GaliciaSpain Grupo de Investigación en Genética VacunasInfecciones y Pediatría(GENVIP)Universidade de Santiago de Compostelaand Hospital Clínico Universitario de Santiago(SERGAS)GaliciaSpain

Research on biogeographical ancestry(BGA)is becoming of growing interest in forensic genetics and in the biomedical literature(1)Thus,for instance,the need to predict ethnicity of an unknown suspect based on DNA profiles found at the crime scene is of maximum interest in criminalistics[2],and several autosomal SNP panels have been designed and tested for BGA investigations[3,4].Most of these panels aim at discriminating three main continental groups(sub-Saharan Africans,Europeans,and Asians)by way of testing a number of ancestry informative markers(AIMs)that run from a few dozens to a few hundred[5](see more background in Supplementary data online).

关键词： BGA STR Biogeographical informativeness of Y-STR haplotypes

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Changing trends in corneal graft surgery： a ten-year review

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International Journal of Ophthalmology(English edition) 2016年第1期9卷 48-52页

作者： Ugo de Sanctis camilla alovisi Luigi Bauchiero Guido Caramello Gianfranco Girotto Claudio Panico Luisa Vinai federico Genzano antonio Amoroso federico grignolo Department of Surgical Sciences Eye Clinic University of Turin Turin 10121 Italy Ophthalmic Unit Hospital of Ivrea Ivrea 10015 Italy Ophthalmic Unit Hospital Santa Croce e Carle Cuneo 12100 Italy Unit for Ocular Trauma Turin Eye Hospital Turin 10121Italy Eye Bank of Piedmont Citta della Salute Turin 10126 Italy Department of Medical Sciences University of Turin Turin 10126 Italy

AIM：To review indications and corneal tissue use for penetrating and lamellar surgery between 2002 and 2011.·METHODS：The surgical reports of corneal grafts performed during 2002-2011,using tissues supplied by the Eye Bank of Piedmont（Italy）,were reviewed *** demographic data,date of intervention,indication for surgery,and surgical technique used were *** techniques included penetrating keratoplasty（PK）,deep anterior lamellar keratoplasty（DALK）and endothelial keratoplasty（EK）.The2test was used to compare the distribution of indications and types of surgical technique used,for corneal grafts done during 2002-2006 versus those done during 2007-2011.·RESULTS：The number of corneal grafts increased by30.7%from 2002-2006 to 2007-2011（from 1567 to 2048）.Comparing the two periods,both main indications and surgical techniques changed *** 2007-2011,the proportion of interventions for aphakic/pseudophakic bollous keratopathy（from 16.8%to 21.3%）,graft failure（from 16.4%to 19.1%）and Fuchs endothelial dystrophy（from 12.8%to 16.7%）all increased significantly（〈0.05）,while those for keratoconus decreased significantly（from35.6%to 27.3%;〈0.001）.In 2007-2011,the proportion of PK decreased significantly（from 92.4%to 57.2%;〈0.001）while that of EK and DALK went from 0.4%to48 30.2%（〈0.001）and from 7.2%to 12.6%（〈0.001）respectively.·CONCLUSION：During 2002-2011 the number of interventions increased significantly for corneal endothelial diseases and graft *** growing demand for interventions for these diseases corresponded to the widespread adoption of EK *** use of DALK also increased,but more moderately than EK procedures.

关键词： indications for corneal graft lamellarkeratoplasty penetrating keratoplasty

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Phylogeography of SARS-CoV-2 pandemic in Spain:a story of multiple introductions,micro-geographic stratification,founder effects,and super-spreaders

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Zoological Research 2020年第6期41卷 605-620页

作者： Alberto Gomez-Carballa Xabier Bello Jacobo Pardo-Seco Maria Luisa Perez del Molino federico Martinon-Torres antonio Salas Unidade de Xendtica Instituto de Ciencias Forenses(I NCI FOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigaci6n Sanitaria(IDIS)Hospital Clinico Universitario de Santiago(SERGAS)Galicia 15706Spain Genetics Vaccines and Pediatric Infectious Diseases Research Group(GENVIP)Instituto de Investigacion Sanitaria de Santiago(IDIS)and Universidade de Santiago de Compostela(USC)Galicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Servicio de Microbiologia y Parasitologia Complejo Hospitalario Universitario de Santiago de CompostelaSantiago de CompostelaGalicia15706 Spain

Spain has been one of the main global pandemic epicenters for coronavirus disease 2019(COVID-19).Here,we analyzed>41000 genomes(including>26000 high-quality(HQ)genomes)downloaded from the GISAID repository,including 1245(922 HQ)sampled in *** aim of this study was to investigate genome variation of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and reconstruct phylogeographic and transmission patterns in *** analysis suggested at least 34 independent introductions of SARS-CoV-2 to Spain at the beginning of the *** lineages spread very successfully in the country,probably favored by super-spreaders,namely,A2 a4(7.8%),A2 a5(38.4%),A2 a10(2.8%),B3 a(30.1%),and B9(8.7%),which accounted for 87.9% of all genomes in the Spanish *** distinct feature of the Spanish SARS-Cov-2 genomes was the higher frequency of B lineages(39.3%,mainly B3 a+B9)than found in any other European *** B3 a,B9,(and an important sub-lineage of A2 a5,namely,A2 a5 c)most likely originated in Spain,the other three haplogroups were imported from other European *** B3 a strain may have originated in the Basque Country from a B3 ancestor of uncertain geographic origin,whereas B9 likely emerged in *** time of the most recent common ancestor(TMRCA)of SARS-CoV-2 suggested that the first coronavirus entered the country around 11 February 2020,as estimated from the TMRCA of B3 a,the first lineage detected in the ***,earlier claims that the D614 G mutation is associated to higher transmissibility is not consistent with the very high prevalence of COVID-19 in Spain when compared to other countries with lower disease incidence but much higher frequency of this mutation(56.4% in Spain vs.82.4% in rest of Europe).Instead,the data support a major role of genetic drift in modeling the micro-geographic stratification of virus strains across the country as well as the role of SARS-CoV-2 super-spreaders.

关键词： Covid-19 SARS-CoV-2 Genomics Phylogeny Phylogeography

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Iron and Heart Failure: Current Concepts and Emerging Pharmacological Paradigms

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World Journal of Cardiovascular Diseases 2024年第4期14卷 195-216页

作者： Maria Rosaria De Pascale Maria Beatrice Rondinelli Flora Ascione Vincenzo Maffei Chiara Di Lorenzo Sarah Scagliarini Raffaella Faraonio antonio Faiella Immunohematology and Transfusion Medicine Unit Cardarelli Hospital Naples Italy Immunohematology and Transfusion Medicine Unit San Camillo-Forlanini Hospital Rome Italy Health Management Office Cardarelli Hospital Naples Italy Anesthesiology Unit Cardarelli Hospital Naples Italy Department of Medical and Translational Sciences University of Naples Federico II Naples Italy Oncology Unit Cardarelli Hospital Naples Italy Department of Molecular Medicine and Medical Biotechnologies University of Naples Federico II Naples Italy

Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) and several trials have established that iron administration improves myocardial asset and clinical scenario in HF. Purpose: Recent acquisitions suggest that iron deficiency represents a concrete bias in the pathogenetic mechanism of chronic HF, so we have investigated the putative role of the hepcidin/ferroportin axis in the cardiovascular setting to advocate novel pharmacological and clinical approaches. Methods: Here, after an excursus on iron metabolism, we first reviewed the ongoing studies on novel iron targeted compounds. Then, we summarize large clinical interventional studies conducted on patient suffering from iron deficiency and HF which have tested the effects of drugging iron regard QoL, hospitalizations and cardiovascular death. Results: Novel compounds such as hepcidin agonist (PTG 300), synthetic human hepcidin (LJPC-401) and anti FPN (Vamifeport) are ongoing in iron overloaded patients, while the hepcidin blocker (PRS-080) is under investigation in anemic patients. Noteworthy, novel insights could arise from the results of a Phase IV interventional study regarding the modification of hepcidin pathway in a large cohort of HF patients (n = 1992) by sodium glucose cotransporter 2 inhibitors. To date, several studies highlight the beneficial effect of iron administration in cardiovascular setting and latest evidences consider hepcidin level as a novel biomarker of cardiac injury and atherosclerosis. Conclusions: We advocate that data from ongoing studies will suggest novel iron targeted therapies for diagnosis, prognosis and therapy transferable in selected heart failed patients.

关键词： Heart Failure Iron Anemia Iron Deficiency Hepcidin

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Y-chromosome Peruvian origin of the 500-year-old Inca child mummy sacrificed in Cerro Aconcagua (Argentina)

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Science Bulletin 2018年第22期63卷 1457-1459页

作者： antonio Salas Laura Catelli Jacobo Pardo-Seco Alberto Gomez-Carballa federico Martinon-Torres Joaquin Roberto-Barcena Carlos Vullo Unidade de Xenetica Instituto de Ciencias ForensesFacultade de MedicinaUniversidade de Santiago de Compostela (USC)and GenPoB Research GroupInstituto de Investigaciones Sanitarias (IDIS)Hospital Clinico Universitario de Santiago (SERGAS)GaliciaSpain Equipo Argentino de Antropologia Forense Independencia 644-3AEdif.EME1CordobaArgentina Translational Pediatrics and Infectious Diseases Hospital Clinico Universitario de SantiagoSantiago de CompostelaSpain GENVIP Research Group (***) Instituto de Investigacion Sanitaria de SantiagoGaliciaSpain Instituto Etnologico de la Universidad Nacional de Cuyo (UNC) MendozaArgentina

A frozen mummy was found in Cerro Aconcagua (Argentina)in 1985(Fig.1a-c).Archaeologists identified this mummy as a seven-year-old Inca sacrifice victim living at the time of the Inca Civilization about 500years ago [1].The child was sacrificed following an Incan ritual known as *** complete mitochondrial DNA (mtDNA) genome of this mummy was recently analyzed in Gomez-Carballa et al.[2].This mitogenome belongs to a new sub-branch of the Native American phylogeny named C1bi dated to approximately 14 thousand years ago (loja).Information retrieved from a large database of mtDNA profiles indicated the existence of a few closely related haplotypes in Peru (including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire)and the Aymaras from *** these data suggested a Peruvian Inca origin for this C1bi haplotype,in good agreement with archaeological reports [1].

关键词：木乃伊儿童

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Consonance of Complex Tones with Harmonics of Different Intensity

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Open Journal of Acoustics 2014年第2期4卷 78-89页

作者： antonio Bernini federico Talamucci Dipartimento di Matematica e Informatica “U. Dini” (DIMAI) Universita di Firezne Firenze Italy

The starting point of this study is the theory of tonal consonance by Plomp and Levelt. The major reference point is the theory of Critical Band and its use for evaluating consonance of simple tones. On the basis of such empirical criterion, our aim consists in providing a method of estimating the value of consonance of complex tones, by taking account not only of the number of harmonics, but also of the intensity of the partials which contribute to forming the tone. By introducing a specific algorithm, the level of consonance of a chord of complex tones is expressed in terms both of frequency differences and sound intensity of the partials. The results give rise to a series of considerations and applications, ranging from displaying the order of consonance of all intervals within the octave up to evaluating the hierarchy of chords in the frame of a musical scale.

关键词： Consonance Complex Tones Scale Critical Bandwidth Intensity of Harmonics Loudness

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Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

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World Journal of Gastroenterology 2006年第40期12卷 6464-6472页

作者： Alfredo Santana Carlos Medina Maria Cristina Paz-Cabrera federico Díaz-Gonzalez Esther Farré antonio Salas Marek W Radomski Enrique Quintero Gastroenterology Department and Research Unit Hospital Universitario de Canarias Tenerife Spain Reumathology Department Hospital Universitario de Canrias Tenerife Spain Pathology Department Hospital Mutua de Terrassa Barcelona Spain Institute of Molecular Medicine University of Texas Houston-Texas United States

AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in ***: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

关键词： Matrix metalloproteinases MMP-9-deficient Dextran sodium sulphate Inflammatory bowel disease Experimental colitis

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