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Article: Diagnostic and prognostic value of alpha-fetoprotein, des-γ-carboxy prothrombin and squamous cell carcinoma antigen immunoglobulin M complexes in hepatocellular carcinoma.

Bertino, G / Neri, S / Bruno, C M / Ardiri, A M / Calvagno, G S / Malaguarnera, M / Toro, A / Clementi, S / Bertino, N / Di Carlo, I

Minerva medica

2011 Volume 102, Issue 5, Page(s) 363–371

Abstract: ... squamous cell carcinoma antigen-immunoglobulin M complexes (SCCA-IgM Cs) in the early diagnosis and in the prognosis ... squamous cell carcinoma antigen-immunoglobulin M complexes" (SCCA-IgM Cs). Despite the large number of studies devoted ...

Abstract	The hepatocellular carcinoma (HCC) is one of the most common malignant tumors. It carries a poor survival rate and has an increasing incidence worldwide. In most cases, HCC is diagnosed at a late stage. Therefore, the prognosis of patients with HCC is generally poor and has a less than 5% 5-year survival rate. The aim of this study was compare the accuracy of α-fetoprotein (AFP), des-γ- carboxy prothrombin (DCP), squamous cell carcinoma antigen-immunoglobulin M complexes (SCCA-IgM Cs) in the early diagnosis and in the prognosis of HCC. A literature search identified the markers for hepatocellular carcinoma. A search of the literature was made using cancer literature and the PubMed database for the following keywords: "markers and HCC", "α-fetoprotein (AFP) and HCC", "Des-γ-carboxy prothrombin"(DCP) and HCC, "squamous cell carcinoma antigen-immunoglobulin M complexes" (SCCA-IgM Cs). Despite the large number of studies devoted to the immunohistochemistry of HCC, at the present time, the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. In conclusion none of the three biomarkers (AFP, DCP, SCCA-IgM Cs) is optimal. According to recent reviews, these biomarkers should be measured simultaneously and in combination with imaging techniques to increase the sensitivity, specificity, diagnostic accuracy and to make a reliable prognosis. Currently the recommended screening strategy for patients with cirrhosis includes the determination of serum AFP levels and an abdominal ultrasound every six months to detect HCC at an earlier stage.
MeSH term(s)	Antigen-Antibody Complex/blood ; Antigens, Neoplasm/blood ; Biomarkers/blood ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/blood ; Carcinoma, Hepatocellular/diagnosis ; Humans ; Immunoglobulin M/blood ; Liver Neoplasms/blood ; Liver Neoplasms/diagnosis ; Prognosis ; Protein Precursors/blood ; Prothrombin ; Serpins/blood ; alpha-Fetoproteins/analysis
Chemical Substances	Antigen-Antibody Complex ; Antigens, Neoplasm ; Biomarkers ; Biomarkers, Tumor ; Immunoglobulin M ; Protein Precursors ; Serpins ; alpha-Fetoproteins ; squamous cell carcinoma-related antigen ; acarboxyprothrombin (53230-14-1) ; Prothrombin (9001-26-7)
Language	English
Publishing date	2011-10
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	123586-2
ISSN	1827-1669 ; 0026-4806
ISSN (online)	1827-1669
ISSN	0026-4806
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Article: 18. "Menopause, Andropause, Anti-Aging"-Kongress: "Das Ziel ist, mit 100 Jahren gesund ins Grab zu fallen!" Im Interview: M. Metka, W. Clementi

Metka, M. / Clementi, W.

Gyn-aktiv

2005 Volume -, Issue 6, Page(s) 43

Language	German
Document type	Article
ZDB-ID	2213296-X
ISSN	1605-8828
Database	Current Contents Medicine

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Zs.A 6202: Show issues

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Article ; Online: Auxiliary protein and chaperone regulation of neuronal nicotinic receptor subtype expression and function.

Gotti, Cecilia / Clementi, Francesco / Zoli, Michele

Pharmacological research

2024 Volume 200, Page(s) 107067

Abstract: Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of pentameric, ligand-gated ion channels that are located on the surface of neurons and non-neuronal cells and have multiple physiological and pathophysiological functions. In order to ... ...

Abstract	Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of pentameric, ligand-gated ion channels that are located on the surface of neurons and non-neuronal cells and have multiple physiological and pathophysiological functions. In order to reach the cell surface, many nAChR subtypes require the help of chaperone and/or auxiliary/accessory proteins for their assembly, trafficking, pharmacological modulation, and normal functioning in vivo. The use of powerful genome-wide cDNA screening has led to the identification and characterisation of the molecules and mechanisms that participate in the assembly and trafficking of receptor subtypes, including chaperone and auxiliary or accessory proteins. The aim of this review is to describe the latest findings concerning nAChR chaperones and auxiliary proteins and pharmacological chaperones, and how some of them control receptor biogenesis or regulate channel activation and pharmacology. Some auxiliary proteins are subtype selective, some regulate various subtypes, and some not only modulate nAChRs but also target other receptors and signalling pathways. We also discuss how changes in auxiliary proteins may be involved in nAChR dysfunctions.
MeSH term(s)	Receptors, Nicotinic/genetics ; Neurons/metabolism ; Synaptic Transmission ; Molecular Chaperones/metabolism ; Cell Membrane/metabolism
Chemical Substances	Receptors, Nicotinic ; Molecular Chaperones
Language	English
Publishing date	2024-01-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2024.107067
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Article ; Online: The role of an amphiphilic helix and transmembrane region in the efficient acylation of the M2 protein from influenza virus.

Meng, Xiaorong / Templeton, Clark / Clementi, Cecilia / Veit, Michael

Scientific reports

2023 Volume 13, Issue 1, Page(s) 18928

Abstract: Protein palmitoylation, a cellular process occurring at the membrane-cytosol interface, is orchestrated by members of the DHHC enzyme family and plays a pivotal role in regulating various cellular functions. The M2 protein of the influenza virus, which ... ...

Abstract	Protein palmitoylation, a cellular process occurring at the membrane-cytosol interface, is orchestrated by members of the DHHC enzyme family and plays a pivotal role in regulating various cellular functions. The M2 protein of the influenza virus, which is acylated at a membrane-near amphiphilic helix serves as a model for studying the intricate signals governing acylation and its interaction with the cognate enzyme, DHHC20. We investigate it here using both experimental and computational assays. We report that altering the biophysical properties of the amphiphilic helix, particularly by shortening or disrupting it, results in a substantial reduction in M2 palmitoylation, but does not entirely abolish the process. Intriguingly, DHHC20 exhibits an augmented affinity for some M2 mutants compared to the wildtype M2. Molecular dynamics simulations unveil interactions between amino acids of the helix and the catalytically significant DHHC and TTXE motifs of DHHC20. Our findings suggest that the binding of M2 to DHHC20, while not highly specific, is mediated by requisite contacts, possibly instigating the transfer of fatty acids. A comprehensive comprehension of protein palmitoylation mechanisms is imperative for the development of DHHC-specific inhibitors, holding promise for the treatment of diverse human diseases.
MeSH term(s)	Humans ; Influenza A virus/physiology ; Orthomyxoviridae ; Protein Domains ; Fatty Acids/metabolism ; Acylation
Chemical Substances	Fatty Acids
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-45945-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System.

Battini, Vera / Carnovale, Carla / Clementi, Emilio / Sessa, Maurizio

Expert opinion on drug safety

2023 Volume 22, Issue 11, Page(s) 1105–1112

Abstract: Background: In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database ... ...

Abstract	Background: In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database registering spontaneous reports. Research design and methods: ASCII files of quarterly extraction of FAERS data were downloaded from the FDA website up to the 3 Results: In total, 2010 and 3691 individual case safety reports (ICSRs) recorded in FAERS reported ubrogepant and rimegepant, respectively, as suspect drugs. Ten disproportionality signals for ubrogepant and 25 disproportionality signals for rimegepant were identified; these were mostly related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious type of adverse events. Conclusions: New safety aspects related to the treatment of ubrogepant and rimegepant using disproportionality analysis from spontaneous reporting databases were identified. Further studies are needed to confirm these findings.
MeSH term(s)	United States ; Humans ; Adverse Drug Reaction Reporting Systems ; United States Food and Drug Administration ; Piperidines ; Databases, Factual ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Drug-Related Side Effects and Adverse Reactions/etiology ; Pharmacovigilance
Chemical Substances	rimegepant sulfate (1383NM3Q0H) ; ubrogepant (AD0O8X2QJR) ; Piperidines
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2088728-0
ISSN	1744-764X ; 1474-0338
ISSN (online)	1744-764X
ISSN	1474-0338
DOI	10.1080/14740338.2023.2223958
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Article ; Online: Exploring the impact of co-exposure timing on drug-drug interactions in signal detection through spontaneous reporting system databases: a scoping review.

Cocco, Marianna / Carnovale, Carla / Clementi, Emilio / Barbieri, Maria Antonietta / Battini, Vera / Sessa, Maurizio

Expert review of clinical pharmacology

2024 , Page(s) 1–13

Abstract: Introduction: Drug-drug interactions (DDIs) are defined as the pharmacological effects produced by the concomitant administration of two or more drugs. To minimize false positive signals and ensure their validity when analyzing Spontaneous Reporting ... ...

Abstract	Introduction: Drug-drug interactions (DDIs) are defined as the pharmacological effects produced by the concomitant administration of two or more drugs. To minimize false positive signals and ensure their validity when analyzing Spontaneous Reporting System (SRS) databases, it has been suggested to incorporate key pharmacological principles, such as temporal plausibility. Areas covered: The scoping review of the literature was completed using MEDLINE from inception to March 2023. Included studies had to provide detailed methods for identifying DDIs in SRS databases. Any methodological approach and adverse event were accepted. Descriptive analyzes were excluded as we focused on automatic signal detection methods. The result is an overview of all the available methods for DDI signal detection in SRS databases, with a specific focus on the evaluation of the co-exposure time of the interacting drugs. It is worth noting that only a limited number of studies ( Expert opinion: Current guidelines for signal validation focus on factors like the number of reports and temporal association, but they lack guidance on addressing overlapping drug administration times, highlighting a need for further research and method development.
Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article ; Review
ISSN	1751-2441
ISSN (online)	1751-2441
DOI	10.1080/17512433.2024.2343875
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Article ; Online: Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues.

Battini, Vera / Barbieri, Maria Antonietta / Carnovale, Carla / Spina, Edoardo / Clementi, Emilio / Sessa, Maurizio

Journal of neurology

2024

Abstract: Introduction: The prevalence of major and mild cognitive impairment (CI) in type-2 diabetes older patients is 15-25% and 30-60%, respectively, thus affecting quality of life and health outcomes. There is, therefore, the need of head-to-head studies ... ...

Abstract	Introduction: The prevalence of major and mild cognitive impairment (CI) in type-2 diabetes older patients is 15-25% and 30-60%, respectively, thus affecting quality of life and health outcomes. There is, therefore, the need of head-to-head studies aiming at identifying the optimal treatment for individuals with type-2 diabetes at increased risk of mild and major CI. This study focuses on the risk of developing mild and major CI in Danish patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 analogues (GLP-1a) using administrative and healthcare registers. Methods: An active comparator design with a 3-year follow-up period was used. The main outcome was the hospital admission with a diagnosis of mild CI or major CI. Multivariate Cox Regression analysis was performed using the high-dimensional propensity score to obtain adjusted Hazard Ratio (HR) estimates. Inverse probability of treatment weighting (IPTW) and marginal structured model were used to calculate risk differences while accounting for the variations of confounders throughout the follow-up period. Results: Our results show a significant higher risk of major CI between DPP-4i and GLP-1a in unadjusted [HR (95% CI) = 3.13 (2.45-4.00), p < 0.001] and adjusted analyses [HR (95% CI) = 1.58 (1.22-2.06), p = 0.001]. No statistically significant differences were observed for mild CI. IPTW resulted stable throughout the follow-up period. Marginal structure modeling (β (95% CI) = 0.022 (0.020-0.024), p < 0.001) resulted in a higher risk of major CI for DPP-4i when compared to GLP-1a. Discussion: DPP-4i was associated with an increased risk of developing major CI when compared to GLP-1a among older individuals with type-2 diabetes.
Language	English
Publishing date	2024-03-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-024-12300-9
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Article ; Online: Smallpox vaccination-elicited antibodies cross-neutralize 2022-Monkeypox virus Clade II.

Criscuolo, Elena / Giuliani, Benedetta / Ferrarese, Roberto / Ferrari, Davide / Locatelli, Massimo / Clementi, Massimo / Mancini, Nicasio / Clementi, Nicola

Journal of medical virology

2023 Volume 95, Issue 3, Page(s) e28643

Abstract: Since early May 2022, some monkeypox virus (MPXV) infections have been reported from countries where the disease is not endemic. Within 2 months, the number of patients has increased extensively, becoming the most considerable MPXV outbreak described. ... ...

Abstract	Since early May 2022, some monkeypox virus (MPXV) infections have been reported from countries where the disease is not endemic. Within 2 months, the number of patients has increased extensively, becoming the most considerable MPXV outbreak described. Smallpox vaccines demonstrated high efficacy against MPXVs in the past and are considered a crucial outbreak control measure. However, viruses isolated during the current outbreak carry distinct genetic variations, and the cross-neutralizing capability of antibodies remains to be assessed. Here we report that serum antibodies elicited by first-generation smallpox vaccines can neutralize the current MPXV more than 40 years after vaccine administration.
MeSH term(s)	Humans ; Monkeypox virus ; Mpox (monkeypox)/epidemiology ; Mpox (monkeypox)/prevention & control ; Smallpox ; Smallpox Vaccine/genetics ; Vaccination
Chemical Substances	Smallpox Vaccine
Language	English
Publishing date	2023-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28643
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Article: α9-Containing Nicotinic Receptors in Cancer.

Pucci, Susanna / Zoli, Michele / Clementi, Francesco / Gotti, Cecilia

Frontiers in cellular neuroscience

2022 Volume 15, Page(s) 805123

Abstract: Neuronal nicotinic acetylcholine receptors containing the α9 or the α9 and α10 subunits are expressed in various extra-neuronal tissues. Moreover, most cancer cells and tissues highly express α9-containing receptors, and a number of studies have shown ... ...

Abstract	Neuronal nicotinic acetylcholine receptors containing the α9 or the α9 and α10 subunits are expressed in various extra-neuronal tissues. Moreover, most cancer cells and tissues highly express α9-containing receptors, and a number of studies have shown that they are powerful regulators of responses that stimulate cancer processes such as proliferation, inhibition of apoptosis, and metastasis. It has also emerged that their modulation is a promising target for drug development. The aim of this review is to summarize recent data showing the involvement of these receptors in controlling the downstream signaling cascades involved in the promotion of cancer.
Language	English
Publishing date	2022-01-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2021.805123
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Article ; Online: Skipping the Replica Exchange Ladder with Normalizing Flows.

Invernizzi, Michele / Krämer, Andreas / Clementi, Cecilia / Noé, Frank

The journal of physical chemistry letters

2022 , Page(s) 11643–11649

Abstract: We combine replica exchange (parallel tempering) with normalizing flows, a class of deep generative models. These two sampling strategies complement each other, resulting in an efficient method for sampling molecular systems characterized by rare events, ...

Abstract	We combine replica exchange (parallel tempering) with normalizing flows, a class of deep generative models. These two sampling strategies complement each other, resulting in an efficient method for sampling molecular systems characterized by rare events, which we call learned replica exchange (LREX). In LREX, a normalizing flow is trained to map the configurations of the fastest-mixing replica into configurations belonging to the target distribution, allowing direct exchanges between the two without the need to simulate intermediate replicas. This can significantly reduce the computational cost compared to standard replica exchange. The proposed method also offers several advantages with respect to Boltzmann generators that directly use normalizing flows to sample the target distribution. We apply LREX to some prototypical molecular dynamics systems, highlighting the improvements over previous methods.
Language	English
Publishing date	2022-12-09
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.2c03327
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