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The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13

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Cellular & Molecular Immunology 2021年第6期18卷 1512-1527页

作者： floriana Mulas Xu Wang Shanshan Song Gopala Nishanth Wenjing Yi Anna Brunn Pia-Katharina Larsen Berend Isermann Ulrich Kalinke Antonio Barragan Michael Naumann Martina Deckert Dirk Schlüter Institute of Medical Microbiology and Hospital Hygiene Otto-von-Guericke University Magdeburg39120MagdeburgGermany Institute of Medical Microbiology and Hospital Epidemiology Hannover Medical School30625HannoverGermany Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical University325035WenzhouChina Department of Neuropathology Faculty of Medicine and University Hospital CologneUniversity of Cologne50931CologneGermany Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Researcha joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research30625HannoverGermany Institute for Clinical Chemistry and Pathobiochemistry Otto-von-Guericke University Magdeburg39120MagdeburgGermany Cluster of Excellence-Resolving Infection Susceptibility(RESIST) Hannover Medical School30625HannoverGermany Department of Molecular Biosciences Stockholm University10691StockholmSweden Institute for Experimental Internal Medicine Otto-von-Guericke University Magdeburg39120MagdeburgGermany

Dendritic cells(DCs)are indispensable for defense against pathogens but may also contribute to *** of DCs upon the sensing of pathogens by Toll-like receptors(TLRs)is largely mediated by pattern recognition receptor/nuclear factor-κB(NF-κB)signaling and depends on the appropriate ubiquitination of the respective signaling ***,the ubiquitinating and deubiquitinating enzymes involved and their interactions are only incompletely ***,we reveal that the deubiquitinase OTU domain,ubiquitin aldehyde binding 1(OTUB1)is upregulated in DCs upon murine Toxoplasma gondii infection and lipopolysaccharide *** of DCs with the TLR11/12 ligand *** profilin and the TLR4 ligand lipopolysaccharide induced an increase in NF-κB activation in OTUB1-competent cells,resulting in elevated interleukin-6(IL-6),IL-12,and tumor necrosis factor(TNF)production,which was also observed upon the specific stimulation of TLR2,TLR3,TLR7,and ***,OTUB1 promoted NF-κB activity in DCs by K48-linked deubiquitination and stabilization of the E2-conjugating enzyme UBC13,resulting in increased K63-linked ubiquitination of IRAK1(IL-1 receptor-associated kinase 1)and TRAF6(TNF receptor-associated factor 6).Consequently,DC-specific deletion of OTUB1 impaired the production of cytokines,in particular IL-12,by DCs over the first 2 days of *** infection,resulting in the diminished production of protective interferon-γ(IFN-γ)by natural killer cells,impaired control of parasite replication,and,finally,death from chronic ***,all of which could be prevented by low-dose IL-12 treatment in the first 3 days of *** contrast,impaired OTUB1-deficient DC activation and cytokine production by OTUB1-deficient DCs protected mice from lipopolysaccharide-induced ***,these findings identify OTUB1 as a potent novel regulator of DCs during infectious and inflammatory diseases.

关键词： OTUB1 dendritic cell signal transduction ubiquitination innate immunity

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Assessment of SARS-CoV-2 RNA shedding in semen of 36 males with symptomatic,asymptomatic,and convalescent infection during the first and second wave of COVID-19 pandemic in Italy

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Asian Journal of Andrology 2022年第2期24卷 135-138页

作者： Carlo Pavone Giovanni M Giammanco Andrea Pio Cascino Davide Baiamonte Mirko Pinelli Enrico Cangelosi Chiara Filizzolo Giuseppa Sciortino Simona De Grazia floriana Bonura Section of Urology Department of SurgicalOncological and Oral SciencesUniversity of PalermoPalermo 90127Italy Section of Microbiology Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesUniversity of PalermoPalermo 90127Italy Section of Internal Medicine Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesUniversity of PalermoPalermo 90127Italy

The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)receptor,angiotensin-converting enzyme 2(ACE2),has been identified in the human testis,but the risk of transmission of SARS-CoV-2 through sexual intercourse still needs to be *** goal of our study was to determine if SARS-CoV-2 is detectable in the semen of patients suffering or recovering from coronavirus disease-19(COVID-19),still testing positive at nasopharyngeal swabs but showing mild or no symptoms at the time of *** of SARS-CoV-2 RNA in semen was performed by real-time reverse transcriptase-polymerase chain reaction(RT-PCR)and nested PCR targeting open reading frame(ORF)*** history of the enrolled patients was taken,including COVID-19-correlated symptoms,both at the time of diagnosis and at the time of *** of real-time RT-PCR and nested PCR in semen showed no evidence of SARS-CoV-2 RNA in the 36 patients suffering or recovering from COVID-19 but still positive in a nasopharyngeal swab,from over 116 patients enrolled in the ***-CoV-2 detection and persistence in semen would have an impact on both clinical practice and public health strategies,but our results would suggest that SARS-CoV-2 is not present in the semen of men recovering from COVID-19.

关键词： coronavirus COVID-19 Italy SARS-CoV-2 semen sexual transmission

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Reversal of IgM deficiency following a gluten-free diet in seronegative celiac disease

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World Journal of Gastroenterology 2014年第46期20卷 17686-17689页

作者： Lucia Montenegro Domenico Piscitelli floriana Giorgio Claudia Covelli Maria Grazia Fiore Giuseppe Losurdo Andrea Iannone Enzo Ierardi Alfredo Di Leo Mariabeatrice Principi Department of Emergency and Organ Transplantation University of Bari70124 BariItaly Gastroenterology Unit Policlinico Hospital70124 BariItaly

Selective Ig M deficiency(s IGMD)is very rare;it may be associated with celiac disease(CD).We present the case of an 18-year-old man with s IGMD masking seronegative *** included abdominal pain,diarrhea and weight *** tests showed reduced Ig M,DQ2-HLA and negative *** atrophy and diffuse immature lymphocytes were observed at *** transglutaminase m RNA mucosal levels showed a 6-fold *** patient was treated with a gluten-free diet(GFD)and six months later the symptoms had disappeared,the villous architecture was restored and mucosal tissue transglutaminase m RNA was comparable to that of healthy *** 1 year of GFD,a complete restoration of normal Ig M values was observed and duodenal biopsy showed a reduction of immature lymphocytes and normal appearance of mature immune cells.

关键词： Selective IgM deficiency Seronegative celiac disease Tissue transglutaminase Gluten-free diet

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Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives

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World Journal of Gastroenterology 2019年第38期25卷 5773-5788页

作者： Antonio Pellino Erika Riello floriana Nappo Stefano Brignola Sabina Murgioni Selma Ahcene Djaballah Sara Lonardi Vittorina Zagonel Massimo Rugge Fotios Loupakis Matteo Fassan Department of Oncology Veneto Institute of Oncology IOV-IRCCSPadua 35100Italy Department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35100Italy Surgical Pathology&Cytopathology Unit Department of MedicineUniversity of PaduaPadua 35100Italy Veneto Cancer Registry Padua 35100Italy

Gastric cancer(GC)represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every *** the last decade,the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treatment options for advanced GC and granted better survival expectations to the *** the same time,global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression ***,several randomized studies aimed at exploring new innovative agents,such as immune checkpoint inhibitors,failed to demonstrate clinically meaningful survival ***,it is essential to further improve the molecular characterization of GC subgroups in order to provide researchers and medical oncologists with new tools for patients’selection and stratification in future clinical development programs and subsequent *** aim of the present manuscript is to provide a global overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.

关键词： Gastric cancer Personalized medicine Predictive biomarkers Molecular diagnostic The Cancer Genome Atlas Asian Cancer Research Group

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Management of single pulmonary metastases from colorectal cancer:State of the art

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World Journal of Gastrointestinal Oncology 2022年第4期14卷 820-832页

作者： Marco Chiappetta Lisa Salvatore Maria Teresa Congedo Maria Bensi Viola De Luca Leonardo PetraccaCiavarella floriana Camarda Jessica Evangelista Vincenzo Valentini Giampaolo Tortora StefanoMargaritora Filippo Lococo Department of Thoracic Surgery Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy Oncologia Medica Comprehensive Cancer Center Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy Department of Radiation Therapy Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy

Colorectal cancer(CRC)is one of the most common causes of death from *** seeding occurs in approximately 10%of patients surgically treated for primary CRC with radical intent:the lung is the most common site of metastases after the *** surgical treatment of liver metastases is widely accepted to affect long-term outcomes,more controversial and not standardized is the therapy for CRC patients developing lung *** suggests the potential curative role of pulmonary metastasectomy,especially in oligometastatic ***,the optimal strategy of care and the definition of prognostic factors after treatment still need to be *** review focused on the uncommon scenario of single pulmonary metastases from *** explored pertinent literature and provide an overview of the epidemiology,clinical characteristics and imaging of single pulmonary metastases from ***,we identified the best available evidence for overall *** particular,we analyzed the role and results of locoregional approaches(surgery,radiotherapy or ablative procedures)and their integration with systemic therapy.

关键词： Colorectal cancer Pulmonary metastases Oligometastases Chemotherapy Surgery Radiotherapy

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New fecal test for non-invasive Helicobacter pylori detection:A diagnostic accuracy study

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World Journal of Gastroenterology 2018年第27期24卷 3021-3029页

作者： Andrea Iannone floriana Giorgio Francesco Russo Giuseppe Riezzo Bruna Girardi Maria Pricci Suetonia C Palmer Michele Barone Mariabeatrice Principi Giovanni FM Strippoli Alfredo Di Leo Enzo Ierardi Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Emergency and Organ Transplantation University of BariBari 70124Italy THD SpA Correggio(Reggio Emilia)42015Italy National Institute of Gastroenterology “S De Bellis”Research HospitalCastellanaGrotte(Bari)70013Italy Department of Medicine University of Otago ChristchurchChristchurch 8011New Zealand Diaverum Academy Lund 22229Sweden Diaverum Medical Scientific Office Lund 22229Sweden Sydney School of Public Health University of SydneySydney NSW-2000Australia Section of Nephrology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy

AIM To assess the diagnostic accuracy of a new fecal test for detecting Helicobacter pylori(H. pylori), using ^(13)Curea breath test as the reference standard, and explore bacterial antibiotic resistance. METHODS We conducted a prospective two-center diagnostic test accuracy study. We enrolled consecutive people≥ 18 years without previous diagnosis of H. pylori infection, referred for dyspepsia between February and October 2017. At enrollment, all participants underwent 13 C-urea breath test. Participants aged over 50 years were scheduled to undergo upper endoscopy with histology. Participants collected stool samples 1-3 d after enrollment for a new fecal investigation(THD fecal test). The detection of bacterial 23 S rRNA subunit gene indicated H. pylori infection. We also used the index diagnostic test to examine mutations conferring resistance to clarithromycin and levofloxacin. Independent investigators analyzed index test and reference test standard results blinded to the other test findings. We estimated sensitivity, specificity, positive(PPV) and negative(NPV) predictive value, diagnostic accuracy, positive and negative likelihood ratio(LR), together with 95% confidence intervals(CI).RESULTS We enrolled 294 consecutive participants(age: Median 37.0 years, IQR: 29.0-46.0 years; men: 39.8%). Ninetyfive(32.3%) participants had a positive ^(13)C-urea breath test. Twenty-three(7.8%) participants underwent upper endoscopy with histology, with a full concordance between ^(13)C-urea breath test and histology in detecting H. pylori infection. Four(1.4%) out of the 294 participants withdrew from the study after the enrollment visit and did not undergo THD fecal testing. In the 290 participants who completed the study, the THD fecal test sensitivity was 90.2%(CI: 84.2%-96.3%), specificity 98.5%(CI:96.8%-100%), PPV 96.5%(CI: 92.6%-100%), NPV 95.6%(CI: 92.8%-98.4%), accuracy 95.9%(CI: 93.6%-98.2%), positive LR 59.5(CI: 19.3-183.4), negative LR 0.10(CI: 0.05-0.18). Out of 8

关键词： Helicobacter pylori Fecal test Feces Stools 23S rRNA Molecular analysis Antibiotic resistance Diagnostic accuracy

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May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis?

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World Journal of Gastroenterology 2016年第35期22卷 8017-8025页

作者： Giuseppe Losurdo floriana Giorgio Domenico Piscitelli Lucia Montenegro Claudia Covelli Maria Grazia Fiore Antonio Giangaspero Andrea Iannone Mariabeatrice Principi Annacinzia Amoruso Michele Barone Alfredo Di Leo Enzo Ierardi Section of Gastroenterology Department of Emergency and Organ Transplantation University of Bari Section of Pathology Department of Emergency and Organ Transplantation University of Bari

AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and *** After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus

关键词： Celiac disease MyD 88 Microscopic enteritis Gluten sensitivity Tissue transglutaminase Interferon gamma Toll-like receptor 2

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The Influence of the Foreign Companies in Developing the Technological Absorption Capacity of the Romanian Economy During the Current Financial Crisis

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Chinese Business Review 2011年第3期10卷 157-167页

作者： Constantinescu Lucretia Mariana Cucui Ion Cucui floriana Andra Goldbach Ioana Raluca University Valahia of Targoviste Targoviste Romania

Creating companies abroad, in ex-socialist countries of Central and Eastern Europe, has experienced a strong progression, following the amplification process of globalization of world markets, intensification of international trade and technological development. We are witnessing a regional disparity regarding the volume of foreign investments in this area, which is due to the difference of attractiveness of host countries economy. The attractiveness of these economies is conditioned, in its turn, by the importance of economic factors and the quality of existing infrastructures, which is at their turn facing an increasing complexity of technology. Business relocation of foreign investors is influenced also by the institutional environment, because foreign investors hope to capitalize on the collateral effects offered by the investment environment in the host country, such as research laboratories and existing infrastructure, without neglecting the benefits of a highly qualified workforce at reduced costs, some geopolitical advantages, etc.. After EU accession, the attractiveness index of business environment in Romania has increased from （-59%） in 2005 to 66% （2008）, and Romania was considered among the most attractive economies in Central and Eastern Europe, along with Russia where the attractiveness index increased from 63% （2007） to 72% （2008） and Ukraine which has seen an increase in the attractiveness index of the business environment from 56% （2007） to 67% （2008）. This paper aims to highlight the positive effects induced by international business companies in assessing technological absorption capacity of the Romanian economy and to provide economic analysis of the ＂cause-effect＂ link between the attractiveness of the Romanian economy-governance--the intake of foreign investment straight to the active processing export of Romania under the impact of the overall effects of international financial crisis.

关键词： direct foreign investment Romanian economy attractiveness competitiveness governance foreign trade

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How antibiotic resistances could change Helicobacter pylori treatment:A matter of geography?

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World Journal of Gastroenterology 2013年第45期19卷 8168-8180页

作者： Enzo Ierardi floriana Giorgio Giuseppe Losurdo Alfredo Di Leo Mariabeatrice Principi Division of Gastroenterology Department of Emergency and Organ Transplantation 70124 Bari Italy

Therapeutic management of Helicobacter pylori(***)remains an unsolved ***,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard *** antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of ***,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic *** the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different *** real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic ***,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic *** additional use of probiotics may help to reduce adverse events,but their therapeutic impact is *** conclusion,the"ideal therapy",paradoxically,appears to be a"utopia",despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of *** ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid *** these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic *** this context,geography must be considered a relevant matter.

关键词： Helicobacter pylori Antibiotic resistance Geography Therapeutic regimens Therapeutic outcome

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The use of virtual surgical planning and navigation in the treatment of orbital trauma

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Chinese Journal of Traumatology 2017年第1期20卷 9-13页

作者： Alan Scott Herford Meagan Miller floriana Lauritano Gabriele Cervino Fabrizio Signorino Carlo Maiorana Oral and Maxillofacial Surgery 11092 Anderson St. Loma Linda CA 92350 USA Department of Medical Sciences and Odontostomatology University of Messina ME Italy Odontostomatologic Surgery University of Milan Milan 20122 Italy

Virtual surgical planning （VSP） has recently been introduced in craniomaxillofacial surgery with the goal of improving efficiency and precision for complex surgical operations. Among many indications, VSP can also be applied for the treatment of congenital and acquired craniofacial defects, including orbital fractures. VSP permits the surgeon to visualize the complex anatomy of craniofacial region, showing the relationship between bone and neurovascular structures. It can be used to design and print using three- dimensional （3D） printing technology and customized surgical models. Additionally, intraoperative navigation may be useful as an aid in performing the surgery. Navigation is useful for both the surgical dissection as well as to confirm the placement of the implant. Navigation has been found to be especially useful for orbit and sinus surgery. The present paper reports a case describing the use of VSP and computerized navigation for the reconstruction of a large orbital floor defect with a custom implant.

关键词： Neuronavigation Orbital trauma Orbital implants Virtual surgical planning

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