The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC

DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson's correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1, CCNB2, CDK2, CDK4, CHECK1, E2F1, FANCD2, and PRKDC) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy

The Challenge of Using an Antigen Test as a Screening Tool for SARS-CoV-2 Infection in an Emergency Department: Experience of a Tertiary Care Hospital in Southern Italy

Background. In emergency hospital settings, rapid diagnosis and isolation of SARS-CoV-2 patients are required. The aim of the study was to evaluate the performance of an antigen chemiluminescence enzymatic immunoassay (CLEIA) and compare it with that of Real-time Reverse transcription-Polymerase Chain Reaction (RT-qPCR), the gold standard assay, to assess its suitability as a rapid diagnostic method for managing patients in the emergency department (ED). Methods. Consecutive patients with no previous history of SARS-CoV-2 infection attending the ED of the Policlinico Hospital of Bari between 23rd October and 4th November 2020 were enrolled. Clinical and demographic data were collected for all patients. Nasopharyngeal swabs collected on admission were subjected both to molecular (RT-qPCR) and antigen (CLEIA) tests for SARS-CoV-2. The performance of the CLEIA antigen test was analyzed using R Studio software and Microsoft Excel. Receiver operating characteristics were also performed. Results. A total of 911 patients were enrolled, of whom 469 (51.5%) were male. Of the whole cohort, 23.7% tested positive for SARS-CoV-2 by RT-qPCR and 24.5% by CLEIA. The overall concordance rate was 96.8%. The sensitivity, specificity, positive predictive value, and negative predictive value of the antigen test were 94.9% (95% CI, 91.9–97.0), 97.4% (95% CI, 96.5–98.1), 91.9% (95% CI, 89.0–94.0), and 98.4% (95% CI, 97.4–99.1), respectively. The area under the curve (AUC) was 0.99. The kappa coefficient was 0.91. The overall positive and negative likelihood ratios were 37 (95% CI 23-58) and 0.05 (95% CI, 0.03–0.09), respectively. Conclusions. Data analysis demonstrated that the antigen test showed very good accuracy for discriminating SARS-CoV-2-infected patients from negative participants. The CLEIA is suitable for rapid clinical diagnosis of patients in hospital settings, particularly in EDs with a high prevalence of symptomatic patients and where a rapid turnaround time is critical. Timely and accurate testing for SARS-CoV-2 plays a crucial role in limiting the spread of the virus

Update on the Epidemiology of Macrolide-Resistant Mycoplasma pneumoniae in Europe: A Systematic Review

Macrolide-resistant Mycoplasma pneumoniae (MR-MP) infections cause upper and lower respiratory tract infections in both children and adults, and are characterized by a longer duration of symptoms. Here, we undertook a systematic review of studies on MR-MP in Europe. The review meets PRISMA guidelines. The PubMed, Scopus, and Science Direct databases were searched using suitable keywords to identify relevant studies published from 2010 to 2021; 21 studies were included. Overall, a low level of MR-MP spread was reported in Europe. MR-MP spread increased during epidemic waves registered in Europe, particularly in Italy and Scotland, where the highest MR-MP infection rates were registered during the 2010–2011 epidemic. By contrast, no MR-MP infections were reported in Finland and the Netherlands. Continued monitoring of MR-MP in Europe is needed to maintain the low rates of infection. Moreover, a coordinated and structured pan-European surveillance program adequate for public health surveillance is advisable, with the purpose of containing the spread of antimicrobial resistance

Rapid Spread of the SARS-CoV-2 Variant of Concern 202012/01 in Southern Italy (December 2020–March 2021)

Epidemiological and virological studies have revealed that SARS-CoV-2 variants of concern (VOCs) are emerging globally, including in Europe. The aim of this study was to evaluate the spread of B.1.1.7-lineage SARS-CoV-2 in southern Italy from December 2020–March 2021 through the detection of the S gene target failure (SGTF), which could be considered a robust proxy of VOC B.1.1.7. SGTF was assessed on 3075 samples from week 52/2020 to week 10/2021. A subset of positive samples identified in the Apulia region during the study period was subjected to whole-genome sequencing (WGS). A descriptive and statistical analysis of the demographic and clinical characteristics of cases according to SGTF status was performed. Overall, 20.2% of samples showed SGTF; 155 strains were confirmed as VOC 202012/01 by WGS. The proportion of SGTF-positive samples rapidly increased over time, reaching 69.2% in week 10/2021. SGTF-positive cases were more likely to be symptomatic and to result in hospitalization (p < 0.0001). Despite the implementation of large-scale non-pharmaceutical interventions (NPIs), such as the closure of schools and local lockdowns, a rapid spread of VOC 202012/01 was observed in southern Italy. Strengthened NPIs and rapid vaccine deployment, first among priority groups and then among the general population, are crucial both to contain the spread of VOC 202012/01 and to flatten the curve of the third wav

Proyecto de especificidad curricular para trastornos en el espectro autista: una experiencia en Latinoamérica: Currículo escolar en autismo

Els nens amb trastorns a l'espectre autista (TEA) necessiten un ensenyament explícit, declaratiu, per les seves maneres diferents de processar la informació. L'objectiu del projecte va ser desenvolupar un programa educatiu individualitzat per a alumnes amb autisme, capacitar per a l'especialització teoricopràctica els docents involucrats en equips de tota una província i establir un sistema d'avaluació de continguts tant per als alumnes com per a l'especificitat a la formació docent. MÈTODES: Es va establir una comissió curricular per al desenvolupament del programa d'ensenyament, un curs teòric setmanal i una supervisió en servei pràctica, de freqüència mensual dels equips docents de tota la província. Es va completar amb un disseny de butlletí de qualificacions per als alumnes, dels continguts del currículum específic. Pels docents i equips tècnics, es va valorar amb un examen final i enquestes, sobre els aprenentatges rebuts. RESULTATS: Va ser possible aplicar l‟especificitat curricular en el procés d‟inclusió educativa en els alumnes al llarg d‟un any. Els docents van aprovar totalment el curs de capacitació i es van obtenir les enquestes de satisfacció favorables als aprenentatges incorporats en relació a l'especialització curricular. Fou possible el canvi conceptual en els professionals, en relació amb l'especificitat de l'aprenentatge dels alumnes amb TEA. Children with autism spectrum disorders (ASD) need explicit and declarative teaching due to their different ways of processing information. The objective of the project was to develop an individualized educational program for students with autism, to train teachers involved in teams from across a province for theoretical and practical specialization, and establish a content evaluation system for both students and specificity in the teacher training. METHODS: A curricular commission was established for the development of the teaching program, a weekly theoretical training and a monthly supervision in practical service for the teaching teams of the entire province. It was completed with a design of a report card for the students, about the contents of the specific curriculum. For teachers and technical teams, it was assessed with a final exam and surveys, about the training received. RESULTS: It was possible to apply the curricular specificity in the process of educational inclusion in the students with autism throughout a year. The teachers fully approved the training course and satisfaction surveys were obtained favorable to the learning in relation to the curricular specialization. The conceptual change in the professionals was possible, in relation to the specificity of the learning of students with ASD. Los niños con trastornos en el espectro autista (TEA), necesitan una enseñanza explícita, declarativa, por sus modos diferentes de procesar la información. El objetivo del proyecto fue desarrollar un programa educativo individualizado para alumnos con autismo, capacitar  para la especialización teórico-practica a los docentes involucrados en equipos de toda una provincia y establecer un sistema de evaluación de contenidos tanto para los alumnos como para la especificidad en la formación docente. METODOS: Se estableció una comisión curricular para el desarrollo del programa de enseñanza, un curso teórico semanal y una supervisión en servicio práctica, de frecuencia mensual de los equipos docentes  de toda la provincia. Se completó con un diseño de boletín de calificaciones para los alumnos, de los contenidos del currículum específico. Para los docentes y equipos técnicos, se valoró con un examen final y encuestas, sobre los aprendizajes recibidos. RESULTADOS: Fue posible aplicar la especificidad curricular en el proceso de inclusión educativa en los alumnos a lo largo de un año. Los docentes aprobaron en su totalidad el curso de capacitación y se obtuvieron las encuestas de satisfacción favorables a los aprendizajes incorporados en relación a la especialización curricular. Fue posible el cambio conceptual en los profesionales, en relación a la especificidad del aprendizaje de los alumnos con TEA.&nbsp

Changing Features of COVID-19: Characteristics of Infections with the SARS-CoV-2 Delta (B.1.617.2) and Alpha (B.1.1.7) Variants in Southern Italy

Differences in the demographic and clinical characteristics of patients infected with the Alpha and Delta SARS‐CoV‐2 variants of concern in a large region of Southern Italy were assessed. Two cohorts of positive patients were compared. The Alpha group consisted of 11,135 subjects diagnosed between 21 March and 21 April 2021, and the Delta group consisted of 499 positive subjects diagnosed between 21 July and 21 August 2021. A descriptive and statistical analysis of the demographic and clinical characteristics of the two groups was performed. The proportion of patients with mild and moderate infections was significantly higher in the Delta than in the Alpha group (p < 0.001). In fully vaccinated patients, the proportion of symptomatic individuals was significantly higher in the Delta than in the Alpha group. The Delta group showed odds ratios of 3.08 (95% CI, 2.55–3.72) for symptomatic infection and 2.66 (95% CI, 1.76–3.94) for hospitalization. Improving COVID‐19 vaccination rates is a priority, since infection with the SARS‐CoV‐2 Delta variant has a significant impact on patient outcomes. Additional targeted prevention strategies such as social distancing, the use of masks in indoor settings irrespective of vaccination status, and the use of a sanitary passport could be crucial to contain further spread of SARS‐CoV‐2 infection

Life-course socioeconomic status and DNA methylation of genes regulating inflammation

Background: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. Methods: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. Results: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. Conclusions: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease ris

Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the european prospective investigation into nutrition and cancer (EPIC-Italy) cohort

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset