Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness.

Background: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties.

c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with a prevalence of 1%. Currently, RA treatment aims to achieve low disease activity or remission. Failure to achieve this goal causes disease progression with a poor prognosis.

Placental DNA methylation profile as predicting marker for autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impairs normal brain development and socio-cognitive abilities. The pathogenesis of this condition points out the involvement of genetic and environmental factors during in-utero life. Placenta, as an interface tissue between mother and fetus, provides developing fetus requirements and exposes it to maternal environment as well.

Folate in maternal rheumatoid arthritis-filial autism spectrum disorder continuum.

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease that affects women three times more than men. Epidemiological studies found that the incidence of Autism Spectrum Disorder (ASD), a neurological and developmental disorder, in children born to mothers suffering from RA is higher compared with the control population. Considering that the pathogenesis of ASD could be traced back to pregnancy and in uterine conditions, and the evidence of reduced folate levels in the brain of ASD-affected children, we aimed to study the role of folate, as an important nutritional factor during pregnancy, in associating maternal RA to ASD development in the offspring.

Seropositivity-Dependent Association between LINE-1 Methylation and Response to Methotrexate Therapy in Early Rheumatoid Arthritis Patients.

Background: Methotrexate (MTX) is considered the first choice among disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) treatment. However, response to it varies as approximately 40% of the patients do not respond and would lose the most effective period of treatment time. Therefore, having a predictive biomarker before starting MTX treatment is of utmost importance.

lncRNA-mediated synovitis in rheumatoid arthritis: A perspective for biomarker development.

Long noncoding RNAs (lncRNAs) are a regulatory class of noncoding RNAs with a wide range of activities such as transcriptional and post-transcriptional regulations. Emerging evidence has demonstrated that various lncRNAs contribute to the initiation and progression of Rheumatoid Arthritis (RA) through distinctive mechanisms. The present study reviews the recent findings on lncRNA role in RA development.

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2.

A long-shared evolutionary history is congruent with the multiple roles played by purinergic signaling in viral infection, replication and host responses that can assist or hinder viral functions. An overview of the involvement of purinergic signaling among a range of viruses is compared and contrasted with what is currently understood for SARS-CoV-2. In particular, we focus on the inflammatory and antiviral responses of infected cells mediated by purinergic receptor activation.

Epigenetic Studies for Evaluation of NPS Toxicity: Focus on Synthetic Cannabinoids and Cathinones.

In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e.

Prioritization of putatively detrimental variants in euploid miscarriages.

Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed GP , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages.

MTHFR promoter methylation might mitigate the effect of smoking at the level of LINE-1 in cleft lip tissues: A preliminary study.

Background: The medial and maxillary aspects of the upper lip originate at separate embryonic stages and therefore may experience different maternal exposure patterns which may affect methylation. Based on this hypothesis, we investigated the level of methylation of the methylene tetrahydrofolate reductase promoter gene (mMTHFR) in tissues from cleft lip, and mMTHFR levels by MTHFR c.677C > T genotype.

Rescuing effect of folates on methotrexate cytotoxicity in human trophoblast cells.

Objectives: Methotrexate (MTX)is a folate antagonist that is administered in several conditions such as rheumatoid arthritis. Its use may associate with adverse effects presumably originating from folate deficiency. Although MTX side effects could be decreased by folate supplementation, the current guideline on folate administration is not precisely established, which could result in irreversible damage especially in high-risk groups like women in childbearing-age.

LINE-1 methylation in cleft lip tissues: Influence of infant MTHFR c.677C>T genotype.

Objective: To investigate the influence of MTHFR c.677C>T genotype on LINE-1 methylation in lateral and medial tissues from cleft lip (CL).

Methods: Forty-five consecutive non-syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study.

Ultrastructural analysis of collagen fibril diameter distribution in cleft lip.

Objective: A preliminary study to determine collagen fibril diameter (CF-ED) distribution on medial and lateral sides of cleft lip (CL).

Material And Methods: Tissue samples from medial and lateral sides of CL were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide and embedded in Araldite CY212 resin for transmission electron microscopy.

Association between a common missense variant in LOXL3 gene and the risk of non-syndromic cleft palate.

To investigate possible association between functional common variants in the lysyl oxidase like 3 gene and non-syndromic cleft palate we selected a common missense variant p.Ile615Phe (rs17010021), which was predicted to have a probably damaging effect on the lysyl oxidase like 3 enzyme. We genotyped 258 non-syndromic cleft palate case-parent triads of European origin and tested genetic association using the transmission disequilibrium test and log-linear regression analyses of genotypic relative risks and of parent-of-origin effects.

Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample.

Background: Nonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci.

Evaluating LINE-1 methylation in cleft lip tissues and its association with early pregnancy exposures.

Aim: To pilot investigation of methylation of long interspersed nucleotide element-1 in lip tissues from infants with nonsyndromic cleft lip, and its association with maternal periconceptional exposures.

Methods: The lateral and medial sides of the cleft lips of 23 affected infants were analyzed for long interspersed nucleotide element-1 methylation by bisulfite conversion and pyrosequencing.

Results: The medial side showed 1.

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer.

Background: Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving.

Methods: We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients.

Genetic Interactions in Nonsyndromic Orofacial Clefts in Europe-EUROCRAN Study.

Background: Nonsyndromic cleft lip with or without cleft palate (nsCL±P) and nonsyndromic cleft palate (nsCP) are caused by a combination of genetic and environmental risk factors. We investigated gene-environment and gene-gene joint effects in a large multicenter study of case-parent triads.

Methods: The nsCL±P or nsCP triads were recruited in 11 European countries between 2001 and 2005.

Phosphorylated-insulin growth factor I receptor (p-IGF1R) and metalloproteinase-3 (MMP3) expression in advanced gastrointestinal stromal tumors (GIST). A GEIS 19 study.

Background: Most GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated the immunohistochemical (IHC) expression of p-IGF1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS).

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene.

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown.

Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts.

Orofacial clefts (OFCs) represent a large fraction of human birth defects and are one of the most common phenotypes affected by large copy number variants (CNVs). Due to the limited number of CNV patients in individual centers, CNV analyses of a large number of OFC patients are challenging. The present study analyzed 249 genomic deletions and 226 duplications from a cohort of 312 OFC patients reported in two publicly accessible databases of chromosome imbalance and phenotype in humans, DECIPHER and ECARUCA.

A new method of detecting changes in corneal health in response to toxic insults.

The size and arrangement of stromal collagen fibrils (CFs) influence the optical properties of the cornea and hence its function. The spatial arrangement of the collagen is still questionable in relation to the diameter of collagen fibril. In the present study, we introduce a new parameter, edge-fibrillar distance (EFD) to measure how two collagen fibrils are spaced with respect to their closest edges and their spatial distribution through normalized standard deviation of EFD (NSDEFD) accessed through the application of two commercially available multipurpose solutions (MPS): ReNu and Hippia.

Generation and Characterization of a Transgenic Mouse Carrying a Functional Human β -Globin Gene with the IVSI-6 Thalassemia Mutation.

Mouse models that carry mutations causing thalassemia represent a suitable tool to test in vivo new mutation-specific therapeutic approaches. Transgenic mice carrying the β-globin IVSI-6 mutation (the most frequent in Middle-Eastern regions and recurrent in Italy and Greece) are, at present, not available. We report the production and characterization of a transgenic mouse line (TG-β-IVSI-6) carrying the IVSI-6 thalassemia point mutation within the human β-globin gene.

Mechanism of inflammation in age-related macular degeneration: an up-to-date on genetic landmarks.

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD.