Genetic variants in patients with recurrent pericarditis.

Aims: Presence of family cases and multiple recurrences of pericarditis suggest the existence of a possible genetic background in at least 10% of cases. The aim of the present study is to describe the genetic landscape of a cohort of patients with multiple recurrences (at least two recurrences).

Methods: Retrospective cohort study of consecutive adult patients referred for at least two episodes of recurrences in a tertiary referral centre.

Chromoanagenesis of chromosome 22 in a subject with obesity and borderline cognitive performance.

Chromoanagenesis events consist of complex chromosome rearrangements with multiple breakpoints in one or few chromosomes. Mechanisms of chromoanagenesis are split into three major groups: chromothripsis, chromoanasynthesis and chromoplexy. This study aims to delineate a chromoanagenesis event at the level of chromosome 22 in an individual showing obesity and borderline cognitive performance as major disturbances.

The impact of the European Society of Cardiology guidelines and whole exome sequencing on genetic testing in hereditary cardiac diseases.

In the last decade, an incredible improvement has been made in elucidating the genetic bases of cardiomyopathies. Here we report the impact of either the European Society of Cardiology (ESC) guidelines or the use of whole exome sequencing (WES) in terms of a number of variants of uncertain significance (VUS) and missed diagnoses in a series of 260 patients affected by inherited cardiac disorders. Samples were analyzed using a targeted gene panel of 128 cardiac-related genes and/or WES in a subset of patients, with a three-tier approach.

Filamin C (FLNC) truncating mutation in a fatal arrhythmogenic left ventricular cardiomyopathy (ALVC).

Forensic pathologists are frequently asked to investigate cases of sudden death (SD), and identifying the cause of death can be of particular importance, especially where it may be necessary to perform family screening among the relatives of the victim. A multidisciplinary approach inclusive of genetic analysis is therefore strongly recommended. According to forensic practice, arrhythmogenic cardiomyopathy (ACM) is a well-known cause of SD.

Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients' Plasma.

The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation.

Somatic genomic imbalances in 'tumour-free' surgical margins of oral cancer.

Up to 30% of oral squamous cell carcinoma (OSCC) patients develop local recurrence and distant metastasis. The molecular status of histologically cancer-free tumour margins could be a critical factor in predicting tumour behaviour. The aim of this study was to detect somatic genomic imbalances in OSCC with emphasis on the surgical margins.

Novel IGFALS mutations with predicted pathogenetic effects by the analysis of AlphaFold structure.

Purpose: According to the American College of Medical Genetics (ACMG) classification, variants of uncertain significance (VUS) are gene variations whose impact on the disease risk is not yet known. VUS, therefore, represent an unmet need for genetic counselling. Aim of the study is the use the AlphaFold artificial intelligence algorithm to predict the impact of novel mutations of the IGFALS gene, detected in a subject with short stature and initially classified as VUS according to the ACMG classification.

Role of m6A RNA Methylation in Thyroid Cancer Cell Lines.

N6-methyladenosine (m6A) is the most abundant internal modification of RNA in eukaryotic cells, and, in recent years, it has gained increasing attention. A good amount of data support the involvement of m6A modification in tumorigenesis, tumor progression, and metastatic dissemination. However, the role of this RNA modification in thyroid cancer still remains poorly investigated.

Challenges in promoter methylation analysis in the new era of translational oncology: a focus on liquid biopsy.

Toward the discovery of novel reliable biomarkers, epigenetic alterations have been repeatedly proposed for the diagnosis and the development of therapeutic strategies against cancer. Indeed, for promoter methylation to actively become a tumor marker for clinical use, it must be combined with a highly informative technology evaluated in an appropriate biospecimen. Methodological standardization related to epigenetic research is, in fact, one of the most challenging tasks.

Local occurrence and fast spread of B.1.1.7 lineage: A glimpse into Friuli Venezia Giulia.

In-depth study of the entire SARS-CoV-2 genome has uncovered many mutations, which have replaced the lineage that characterized the first wave of infections all around the world. In December 2020, the outbreak of variant of concern (VOC) 202012/01 (lineage B.1.

A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome.

Background: Cornelia de Lange syndrome (CdLS) is a rare and clinically variable syndrome characterized by growth impairment, multi-organ anomalies, and a typical set of facial dysmorphisms. Here we describe a 2-year-old female child harboring a novel de novo missense variant in HDAC8, whose phenotypical score, according to the recent consensus on CdLS clinical diagnostic criteria, allowed the diagnosis of a non-classic CdLS.

Methods: Clinical exome sequencing was performed on the trio, identifying a de novo heterozygous variant in HDAC8 (NM_018486; c.

Pro-Inflammatory Microenvironment Modulates the Transfer of Mutated TP53 Mediated by Tumor Exosomes.

Exosomes released from tumor cells are instrumental in shaping the local tumor microenvironment to allow cancer progression. Recently, it has been shown that tumor exosomes carry large fragments of dsDNA, which may reflect the mutational status of parental cells. Although it has been described that a stressful microenvironment can influence exosomal cargo, the effects on DNA packing and its transfer into recipient cells have yet to be investigated.

Bank Risk Appetite Communication and Risk Taking: The Key Role of Integrated Reports.

This article investigates whether qualitative information provided by banks about risk appetite (RA) sheds substantive insight on their effective risk taking (RT) and whether this latter in turn affects RA disclosure, as well as the role played by specific types of banks' reports (i.e., integrated report, annual report, Pillar 3 report) on such relations.

Integrated multi-omics analyses on patient-derived CRC organoids highlight altered molecular pathways in colorectal cancer progression involving PTEN.

Background: Colorectal cancer (CRC) represents the fourth leading cause of cancer-related deaths. The heterogeneity of CRC identity limits the usage of cell lines to study this type of tumor because of the limited representation of multiple features of the original malignancy. Patient-derived colon organoids (PDCOs) are a promising 3D-cell model to study tumor identity for personalized medicine, although this approach still lacks detailed characterization regarding molecular stability during culturing conditions.

A novel de novo NIPA1 missense mutation associated to hereditary spastic paraplegia.

SPG6 accounts for 1% of autosomal dominant Hereditary Spastic Paraplegia (HSP) and is caused by pathogenic variants in NIPA1, which encodes a magnesium transporter located in plasma membrane and early endosomes, implicated in neuronal development and maintenance. Here we report a 39-year-old woman affected by progressive gait disturbance associated to absence seizures episodes within childhood. Clinical exome sequencing identified a likely pathogenic de novo heterozygous variant in NIPA1 (NM_144599.

Validation of a One-Step Reverse Transcription-Droplet Digital PCR (RT-ddPCR) Approach to Detect and Quantify SARS-CoV-2 RNA in Nasopharyngeal Swabs.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread worldwide from the beginning of 2020. Quantitative reverse transcription-PCR (RT-qPCR) is, to this day, the preferred methodology for viral RNA detection, even if not without problems. To overcome some of the limitations still existing for the detection and quantification of nucleic acids in various applications, the use of one-step reverse transcription-droplet digital PCR (RT-ddPCR) has been established.

A Streamlined Approach to Rapidly Detect SARS-CoV-2 Infection Avoiding RNA Extraction: Workflow Validation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread worldwide from the beginning of 2020. The presence of viral RNA in samples by nucleic acid (NA) molecular analysis is the only method available to diagnose COVID-19 disease and to assess patients' viral load. Since the demand for laboratory reagents has increased, there has been a worldwide shortage of RNA extraction kits.