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  • 1
    Online Resource
    Online Resource
    TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 23 ( 2022-12-06), p. 15366-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 23 ( 2022-12-06), p. 15366-
    Abstract: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need for new treatments. Tumors harboring fusions involving one of the neurotrophin receptor tyrosine kinase (NTRK) genes are now actionable with targeted inhibitors. NTRK-fused genes have been identified in neuroendocrine tumors of other sites; thus, a series of 76 MCCs were firstly analyzed with pan-TRK immunohistochemistry and the positive ones with real-time RT-PCR, RNA-based NGS, and FISH to detect the eventual underlying gene fusion. Despite 34 MCCs showing pan-TRK expression, NTRK fusions were not found in any cases. As in other tumors with neural differentiation, TRK expression seems to be physiological and not caused by gene fusions.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232315366
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 2
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    Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’
    Springer Science and Business Media LLC ; 2020
    In:  Nature Vol. 584, No. 7821 ( 2020-08-20), p. 425-429
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 584, No. 7821 ( 2020-08-20), p. 425-429
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-020-2488-1
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 3
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    Table_7.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-11)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-11)
    Abstract: SARS-CoV-2 induces a spectrum of clinical conditions ranging from asymptomatic infection to life threatening severe disease. Host microRNAs have been involved in the cytokine storm driven by SARS-CoV-2 infection and proposed as candidate biomarkers for COVID-19. Methods To discover signatures of circulating miRNAs associated with COVID-19, disease severity and mortality, small RNA-sequencing was performed on serum samples collected from 89 COVID-19 patients (34 severe, 29 moderate, 26 mild) at hospital admission and from 45 healthy controls (HC). To search for possible sources of miRNAs, investigation of differentially expressed (DE) miRNAs in relevant human cell types in vitro . Results COVID-19 patients showed upregulation of miRNAs associated with lung disease, vascular damage and inflammation and downregulation of miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis, and stress response. Compared with mild/moderate disease, patients with severe COVID-19 had a miRNA signature indicating a profound impairment of innate and adaptive immune responses, inflammation, lung fibrosis and heart failure. A subset of the DE miRNAs predicted mortality. In particular, a combination of high serum miR-22-3p and miR-21-5p, which target antiviral response genes, and low miR-224-5p and miR-155-5p, targeting pro-inflammatory factors, discriminated severe from mild/moderate COVID-19 (AUROC 0.88, 95% CI 0.80-0.95, p & lt;0.0001), while high leukocyte count and low levels of miR-1-3p, miR-23b-3p, miR-141-3p, miR-155-5p and miR-4433b-5p predicted mortality with high sensitivity and specificity (AUROC 0.95, 95% CI 0.89-1.00, p & lt;0.0001). In vitro experiments showed that some of the DE miRNAs were modulated directly by SARS-CoV-2 infection in permissive lung epithelial cells. Conclusions We discovered circulating miRNAs associated with COVID-19 severity and mortality. The identified DE miRNAs provided clues on COVID-19 pathogenesis, highlighting signatures of impaired interferon and antiviral responses, inflammation, organ damage and cardiovascular failure as associated with severe disease and death.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
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    URL: Article
    URL: Article
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    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.968991
    DOI: 10.3389/fimmu.2022.968991.s001
    DOI: 10.3389/fimmu.2022.968991.s002
    DOI: 10.3389/fimmu.2022.968991.s003
    DOI: 10.3389/fimmu.2022.968991.s004
    DOI: 10.3389/fimmu.2022.968991.s005
    DOI: 10.3389/fimmu.2022.968991.s006
    DOI: 10.3389/fimmu.2022.968991.s007
    DOI: 10.3389/fimmu.2022.968991.s008
    DOI: 10.3389/fimmu.2022.968991.s009
    DOI: 10.3389/fimmu.2022.968991.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
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    SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 5 ( 2021-02-26), p. 2356-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 5 ( 2021-02-26), p. 2356-
    Abstract: In this Review, we briefly describe the basic virology and pathogenesis of SARS-CoV-2, highlighting how stem cell technology and organoids can contribute to the understanding of SARS-CoV-2 cell tropisms and the mechanism of disease in the human host, supporting and clarifying findings from clinical studies in infected individuals. We summarize here the results of studies, which used these technologies to investigate SARS-CoV-2 pathogenesis in different organs. Studies with in vitro models of lung epithelia showed that alveolar epithelial type II cells, but not differentiated lung alveolar epithelial type I cells, are key targets of SARS-CoV-2, which triggers cell apoptosis and inflammation, while impairing surfactant production. Experiments with human small intestinal organoids and colonic organoids showed that the gastrointestinal tract is another relevant target for SARS-CoV-2. The virus can infect and replicate in enterocytes and cholangiocytes, inducing cell damage and inflammation. Direct viral damage was also demonstrated in in vitro models of human cardiomyocytes and choroid plexus epithelial cells. At variance, endothelial cells and neurons are poorly susceptible to viral infection, thus supporting the hypothesis that neurological symptoms and vascular damage result from the indirect effects of systemic inflammatory and immunological hyper-responses to SARS-CoV-2 infection.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22052356
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 5
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    Role of the Extracytoplasmic Function Sigma Factor SigE in the Stringent Response of Mycobacterium tuberculosis
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum Vol. 11, No. 2 ( 2023-04-13)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 2 ( 2023-04-13)
    Abstract: Bacteria respond to nutrient starvation implementing the stringent response, a stress signaling system resulting in metabolic remodeling leading to decreased growth rate and energy requirements. A well-characterized model of stringent response in Mycobacterium tuberculosis is the one induced by growth in low phosphate. The extracytoplasmic function (ECF) sigma factor SigE was previously suggested as having a key role in the activation of stringent response. In this study, we challenge this hypothesis by analyzing the temporal dynamics of the transcriptional response of a sigE mutant and its wild-type parental strain to low phosphate using RNA sequencing. We found that both strains responded to low phosphate with a typical stringent response trait, including the downregulation of genes encoding ribosomal proteins and RNA polymerase. We also observed transcriptional changes that support the occurring of an energetics imbalance, compensated by a reduced activity of the electron transport chain, decreased export of protons, and a remodeling of central metabolism. The most striking difference between the two strains was the induction in the sigE mutant of several stress-related genes, in particular, the genes encoding the ECF sigma factor SigH and the transcriptional regulator WhiB6. Since both proteins respond to redox unbalances, their induction suggests that the sigE mutant is not able to maintain redox homeostasis in response to the energetics imbalance induced by low phosphate. In conclusion, our data suggest that SigE is not directly involved in initiating stringent response but in protecting the cell from stress consequent to the low phosphate exposure and activation of stringent response. IMPORTANCE Mycobacterium tuberculosis can enter a dormant state enabling it to establish latent infections and to become tolerant to antibacterial drugs. Dormant bacteria’s physiology and the mechanism(s) used by bacteria to enter dormancy during infection are still unknown due to the lack of reliable animal models. However, several in vitro models, mimicking conditions encountered during infection, can reproduce different aspects of dormancy (growth arrest, metabolic slowdown, drug tolerance). The stringent response, a stress response program enabling bacteria to cope with nutrient starvation, is one of them. In this study, we provide evidence suggesting that the sigma factor SigE is not directly involved in the activation of stringent response as previously hypothesized, but it is important to help the bacteria to handle the metabolic stress related to the adaptation to low phosphate and activation of stringent response, thus giving an important contribution to our understanding of the mechanism behind stringent response development.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.02944-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2807133-5
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  • 6
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    A specific anti‐COVID‐19 BNT162b2 vaccine‐induced early innate immune signature positively correlates with the humoral protective response in healthy and multiple sclerosis vaccine recipients
    Wiley ; 2023
    In:  Clinical & Translational Immunology Vol. 12, No. 3 ( 2023-01)
    Details
    In: Clinical & Translational Immunology, Wiley, Vol. 12, No. 3 ( 2023-01)
    Abstract: The very rapidly approved mRNA‐based vaccines against SARS‐CoV‐2 spike glycoprotein, including Pfizer‐BioNTech BNT162b2, are effective in protecting from severe coronavirus disease 2019 (COVID‐19) in immunocompetent population. However, establishing the duration and identifying correlates of vaccine‐induced protection will be crucial to optimise future immunisation strategies. Here, we studied in healthy vaccine recipients and people with multiple sclerosis (pwMS), undergoing different therapies, the regulation of innate immune response by mRNA vaccination in order to correlate it with the magnitude of vaccine‐induced protective humoral responses. Methods Healthy subjects ( n  = 20) and matched pwMS ( n  = 22) were longitudinally sampled before and after mRNA vaccination. Peripheral blood mononuclear cell (PBMC)‐associated type I and II interferon (IFN)‐inducible gene expression, serum innate cytokine/chemokine profile as well as binding and neutralising anti‐SARS‐COV‐2 antibodies (Abs) were measured. Results We identified an early immune module composed of the IFN‐inducible genes Mx1, OAS1 and IRF1, the serum cytokines IL‐15, IL‐6, TNF‐α and IFN‐γ and the chemokines IP‐10, MCP‐1 and MIG, induced 1 day post second and third BNT162b2 vaccine doses, strongly correlating with magnitude of humoral response to vaccination in healthy and MS vaccinees. Moreover, induction of the early immune module was dramatically affected in pwMS treated with fingolimod and ocrelizumab, both groups unable to induce a protective humoral response to COVID‐19 vaccine. Conclusion Overall, this study suggests that the vaccine‐induced early regulation of innate immunity is mediated by IFN signalling, impacts on the magnitude of adaptive responses and it might be indicative of vaccine‐induced humoral protection.
    Type of Medium: Online Resource
    ISSN: 2050-0068 , 2050-0068
    URL: Issue
    URL: Article
    DOI: 10.1002/cti2.v12.3
    DOI: 10.1002/cti2.1434
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2694482-0
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  • 7
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    Comparative analysis of bioinformatics tools to characterize SARS-CoV-2 subgenomic RNAs
    Life Science Alliance, LLC ; 2023
    In:  Life Science Alliance Vol. 6, No. 12 ( 2023-12), p. e202302017-
    Details
    In: Life Science Alliance, Life Science Alliance, LLC, Vol. 6, No. 12 ( 2023-12), p. e202302017-
    Abstract: During the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), positive-sense genomic RNA and subgenomic RNAs (sgRNAs) are synthesized by a discontinuous process of transcription characterized by a template switch, regulated by transcription-regulating sequences (TRS). Although poorly known about makeup and dynamics of sgRNAs population and function of its constituents, next-generation sequencing approaches with the help of bioinformatics tools have made a significant contribution to expand the knowledge of sgRNAs in SARS-CoV-2. For this scope to date, Periscope, LeTRS, sgDI-tector, and CORONATATOR have been developed. However, limited number of studies are available to compare the performance of such tools. To this purpose, we compared Periscope, LeTRS, and sgDI-tector in the identification of canonical (c-) and noncanonical (nc-) sgRNA species in the data obtained with the Illumina ARTIC sequencing protocol applied to SARS-CoV-2–infected Caco-2 cells, sampled at different time points. The three software showed a high concordance rate in the identification and in the quantification of c-sgRNA, whereas more differences were observed in nc-sgRNA. Overall, LeTRS and sgDI-tector result to be adequate alternatives to Periscope to analyze Fastq data from sequencing platforms other than Nanopore.
    Type of Medium: Online Resource
    ISSN: 2575-1077
    URL: Article
    DOI: 10.26508/lsa.202302017
    Language: English
    Publisher: Life Science Alliance, LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2948687-7
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  • 8
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    Effects of the age of vaccination on the humoral responses to a human papillomavirus vaccine
    Springer Science and Business Media LLC ; 2022
    In:  npj Vaccines Vol. 7, No. 1 ( 2022-03-15)
    Details
    In: npj Vaccines, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2022-03-15)
    Abstract: Adult vaccination programs are receiving increasing attention however, little is known regarding the impact of age on the maintenance of the immune response. We investigated this issue in the context of a human papillomavirus (HPV) vaccination program collecting real-world data on the durability of humoral immunity in 315 female subjects stratified according to vaccination age (adolescents and adults) and sampled at early or late time points after the last vaccine dose. HPV-specific IgGs, but not memory B cells, were induced and maintained at higher levels in subjects vaccinated during adolescence. Nonetheless, antibody functions waned over time to a similar degree in adolescents and adults. To shed light on this phenomena, we analyzed quantitative and qualitative properties of lymphocytes. Similar biochemical features were observed between B-cell subsets from individuals belonging to the two age groups. Long term humoral responses toward vaccines administered at an earlier age were comparably maintained between adolescents and adults. The percentages of naïve B and CD4 + T cells were significantly higher in adolescents, and the latter directly correlated with IgG titers against 3 out of 4 HPV types. Our results indicate that age-specific HPV vaccine responsiveness is mostly due to quantitative differences of immune cell precursors rather than qualitative defects in B cells. In addition, our results indicate that adults also have a good humoral immunogenic profile, suggesting that their inclusion in catch-up programmes is desirable.
    Type of Medium: Online Resource
    ISSN: 2059-0105
    URL: Article
    DOI: 10.1038/s41541-022-00458-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2882262-6
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  • 9
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    Intravascular large B‐cell lymphoma affecting multiple cranial nerves: A histopathological study
    Wiley ; 2021
    In:  Neuropathology Vol. 41, No. 5 ( 2021-10), p. 396-405
    Details
    In: Neuropathology, Wiley, Vol. 41, No. 5 ( 2021-10), p. 396-405
    Abstract: Intravascular large B‐cell lymphoma (IVLBCL) is a rare form of lymphomas with poor prognosis, characterized by atypical lymphocytes selectively growing within the lumen of small or medium‐sized vessels. Here, we report a case of intracerebral IVLBCL in a 54‐year‐old man who died three months after symptom onset. The diagnosis was made by postmortem pathological examination, based on the identification of multiple ischemic lesions, with small or medium‐sized vessels filled with malignant B‐cells, in the cerebral hemispheres, cerebellum, midbrain, and medulla oblongata, including the external cuneate nucleus and trigeminal spinal tract nucleus. Apart from necrotic lesions, specific histopathological search for occluded vessels in the other brain stem structures permitted identification of significant involvement of the cuneate nucleus, solitary tract nucleus, hypoglossal nucleus, and inferior olivary complex. Small vessels affected by IVLBCL were also found in the trunks of the oculomotor, trigeminal, glossopharyngeal, vagal, and hypoglossal nerves. These histopathological findings were consistent with some cranial nerve symptoms/signs ascertained during hospitalization, such as diplopia, dysphonia, and asymmetry/hypomotility of the palatal veil. The case study presented here reports novel insights on radiological, anatomical, and clinical correlations of the IVLBCL, including the possible involvement of nuclei and trunks of multiple cranial nerves. The reported findings may help clinicians in the early identification of this rapidly progressive disease that can be easily misdiagnosed, through integrated neuroradiological, neurological and neuropathological approaches.
    Type of Medium: Online Resource
    ISSN: 0919-6544 , 1440-1789
    URL: Issue
    URL: Article
    DOI: 10.1111/neup.v41.5
    DOI: 10.1111/neup.12767
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2008290-3
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  • 10
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    Epidemiology, surveillance and diagnosis of Usutu virus infection in the EU/EEA, 2012 to 2021
    European Centre for Disease Control and Prevention (ECDC) ; 2023
    In:  Eurosurveillance Vol. 28, No. 33 ( 2023-08-17)
    Details
    In: Eurosurveillance, European Centre for Disease Control and Prevention (ECDC), Vol. 28, No. 33 ( 2023-08-17)
    Abstract: Usutu virus (USUV) is a flavivirus with an enzootic cycle between birds and mosquitoes; humans are incidental dead-end hosts. In Europe, the virus was first detected in Italy in 1996; since then, it has spread to many European countries. Aim We aimed to report on the epidemiology, surveillance, diagnosis and prevention of USUV infection in humans, mosquitoes and other animals in the European Union/European Economic Area (EU/EEA) from 2012 to 2021. Methods We collected information through a literature review, an online survey and an expert meeting. Results Eight countries reported USUV infection in humans (105 cases, including 12* with neurological symptoms), 15 countries in birds and seven in mosquitoes. Infected animals were also found among pets, wild and zoo animals. Usutu virus was detected primarily in Culex pipiens but also in six other mosquito species. Detection of USUV infection in humans is notifiable only in Italy, where it is under surveillance since 2017 and now integrated with surveillance in animals in a One Health approach. Several countries include USUV infection in the differential diagnosis of viral encephalitis and arbovirus infections. Animal USUV infection is not notifiable in any EU/EEA country. Conclusion Human USUV infections, mainly asymptomatic and, less frequently, with a febrile illness or a neuroinvasive disease, have been reported in several EU/EEA countries, where the virus is endemic. Climate and environmental changes are expected to affect the epidemiology of USUV. A One Health approach could improve the monitoring of its evolution in Europe.
    Type of Medium: Online Resource
    ISSN: 1560-7917
    URL: Article
    DOI: 10.2807/1560-7917.ES.2023.28.33.2200929
    Language: English
    Publisher: European Centre for Disease Control and Prevention (ECDC)
    Publication Date: 2023
    detail.hit.zdb_id: 2059112-3
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