Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families).

MicroRNA 483-3p overexpression unleashes invasive growth of metastatic colorectal cancer via NDRG1 downregulation and ensuing activation of the ERBB3/AKT axis.

In colorectal cancer, the mechanisms underlying tumor aggressiveness require further elucidation. Taking advantage of a large panel of human metastatic colorectal cancer xenografts and matched stem-like cell cultures (m-colospheres), here we show that the overexpression of microRNA 483-3p (miRNA-483-3p; also known as MIR-483-3p), encoded by a frequently amplified gene locus, confers an aggressive phenotype. In m-colospheres, endogenous or ectopic miRNA-483-3p overexpression increased proliferative response, invasiveness, stem cell frequency, and resistance to differentiation.

Liquid Biopsy of Cerebrospinal Fluid Enables Selective Profiling of Glioma Molecular Subtypes at First Clinical Presentation.

Purpose: Current glioma diagnostic guidelines call for molecular profiling to stratify patients into prognostic and treatment subgroups. In case the tumor tissue is inaccessible, cerebrospinal fluid (CSF) has been proposed as a reliable tumor DNA source for liquid biopsy. We prospectively investigated the use of CSF for molecular characterization of newly diagnosed gliomas.

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation.

Young athletes: Preventing sudden death by adopting a modern screening approach? A critical review and the opening of a debate.

Preventing sudden cardiac death (SCD) in athletes is a primary duty of sports cardiologists. Current recommendations for detecting high-risk cardiovascular conditions (hr-CVCs) are history and physical examination (H&P)-based. We discuss the effectiveness of H&P-based screening versus more-modern and accurate methods.

Interventricular Septal Rupture in a 62-Year-Old Man With Familial Amyloid Polyneuropathy.

Cardiac involvement in familial amyloid polyneuropathy consists of arrhythmias, conduction disturbances, and heart failure. To our knowledge, heart rupture has never been described in association with this condition. We report the case of a 62-year-old man with a 6-year history of refractory familial amyloid polyneuropathy who underwent liver transplantation.

A simplified integrated molecular and immunohistochemistry-based algorithm allows high accuracy prediction of glioblastoma transcriptional subtypes.

Glioblastomas (GBM) can be classified into three major transcriptional subgroups (proneural, mesenchymal, classical), underlying different molecular alterations, prognosis, and response to therapy. However, transcriptional analysis is not routinely feasible and assessment of a simplified method for glioblastoma subclassification is required. We propose an integrated molecular and immunohistochemical approach aimed at identifying GBM subtypes in routine paraffin-embedded material.

Cerebrospinal fluid tumor DNA for liquid biopsy in glioma patients' management: Close to the clinic?

Cell-free circulating tumor DNA (ct-DNA) reflecting the whole tumor spatial and temporal heterogeneity currently represents the most promising candidate for liquid biopsy strategy in glioma. Unlike other solid tumors, it is now widely accepted that the best source of ct-DNA for glioma patients is the cerebrospinal fluid, since blood levels are usually low and detectable only in few cases. A cerebrospinal fluid ct-DNA liquid biopsy approach may virtually support all the stages of glioma management, from facilitating molecular diagnosis when surgery is not feasible, to monitoring tumor response, identifying early recurrence, tracking longitudinal genomic evolution, providing a new molecular characterization at recurrence and allowing patient selection for targeted therapies.

Multimodal Biosensing on Paper-Based Platform Fabricated by Plasmonic Calligraphy Using Gold Nanobypiramids Ink.

In this work, we design new plasmonic paper-based nanoplatforms with interesting capabilities in terms of sensitivity, efficiency, and reproducibility for promoting multimodal biodetection via Localized Surface Plasmon Resonance (LSPR), Surface Enhanced Raman Spectroscopy (SERS), and Metal Enhanced Fluorescence (MEF). To succeed, we exploit the unique optical properties of gold nanobipyramids (AuBPs) deposited onto the cellulose fibers via plasmonic calligraphy using a commercial pen. The first step of the biosensing protocol was to precisely graft the previously chemically-formed p-aminothiophenol@Biotin system, as active recognition element for target streptavidin detection, onto the plasmonic nanoplatform.

Angiography vs transesophageal echocardiography-guided patent foramen ovale closure: A propensity score matched analysis of a two-center registry.

Objectives: The purpose of this study is to compare the long-term outcomes of patent foramen ovale (PFO) closure using angiography or transesophageal echocardiography as procedural guidance.

Background: The interventional treatment is emerging as a safe and efficient option for patients with high likelihood of PFO-related cryptogenic stroke and high risk of recurrence. The "gold-standard" guidance technique remains an issue.

A Molecularly Annotated Model of Patient-Derived Colon Cancer Stem-Like Cells to Assess Genetic and Nongenetic Mechanisms of Resistance to Anti-EGFR Therapy.

Patient-derived xenografts ("") of colorectal cancer metastases have been essential to identify genetic determinants of resistance to the anti-EGFR antibody cetuximab and to explore new therapeutic strategies. From xenopatients, a genetically annotated collection of stem-like cultures ("") was generated and characterized for response to targeted therapies. Xenospheres underwent exome-sequencing analysis, gene expression profile, and targeted treatments to assess genetic, biological, and pharmacologic correspondence with xenopatients, and to investigate nongenetic biomarkers of therapeutic resistance.

Genetic Evolution of Glioblastoma Stem-Like Cells From Primary to Recurrent Tumor.

Glioblastoma (GBM) is a lethal tumor that displays remarkable genetic heterogeneity. It is also known that GBM contains a cell hierarchy driven by GBM stem-like cells (GSCs), responsible for tumor generation, therapeutic resistance, and relapse. An important and still open issue is whether phylogenetically related GSCs can be found in matched primary and recurrent GBMs, and reflect tumor genetic evolution under therapeutic pressure.

Handle With Care: A Ductus Arteriosus Aneurysm in an Elderly Patient.

A ductus arteriosus aneurysm (DAA) was corrected with an 18 mm Amplatzer patent foramen ovale occluder. DAA is a rare finding, with sporadic cases reported (the vast majority in children and infants). In the elderly, it poses serious therapeutic challenges, as the risk of rupture is counterbalanced by the high risk of its correction, which requires surgery or placement of an endovascular prosthesis in a critical region such as the aortic arch.

Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer.

Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), with clinical and biological implications. Lineage-dependent stromal transcriptional components could therefore dominate over more subtle expression traits inherent to cancer cells. Since in patient-derived xenografts (PDXs) stromal cells of the human tumour are substituted by murine counterparts, here we deploy human-specific expression profiling of CRC PDXs to assess cancer-cell intrinsic transcriptional features.

MET inhibition overcomes radiation resistance of glioblastoma stem-like cells.

Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant to ionizing radiation and thus responsible for therapeutic failure and rapidly lethal tumor recurrence. It is known that GSC radioresistance relies on efficient activation of the DNA damage response, but the mechanisms linking this response with the stem status are still unclear. Here, we show that the MET receptor kinase, a functional marker of GSCs, is specifically expressed in a subset of radioresistant GSCs and overexpressed in human GBM recurring after radiotherapy.

Early repolarization: an evolving concept for the past 70 years.

For more than 70 years, early repolarization has been considered to be a common normal variant. In the general population, the prevalence ranges between 5 and 13%, and in athletes, a rising trend is observed from 20 to 90%. Nevertheless, from the latter half of the 1990s, a growing number of case reports, series, observational and prospective studies reported that the presence of various electrocardiographic patterns attributed to early repolarization may constitute a potential marker for the increased risk of sudden death in otherwise normal individuals, casting a dark shadow on this ECG peculiarity.

Percutaneous closure of atrial septal defect in adults: very long-term clinical outcome and effects on aortic and mitral valve function.

Aim: To investigate the very long-term clinical outcomes of atrial septal defect (ASD) percutaneous closure in adult patients and to evaluate the 12-month effects of the device on aortic and mitral valve function.

Methods: Over a 12-year period, a total of 110 consecutive patients underwent percutaneous ASD closure. A yearly clinical follow-up was conducted and any adverse event was recorded.

Percutaneous implantation of a second device in patients with residual right-to-left shunt after patent foramen ovale closure.

Introduction: The management of patients with residual right-to-left shunt (rRLS) after percutaneous patent foramen ovale (PFO) closure is debated. The aim of this study was to define the incidence of moderate-to-large rRLS and to report the feasibility, safety and long-term clinical outcome of transcatheter closure of rRLS.

Methods And Results: From June 2000 to March 2013, 322 subjects underwent percutaneous PFO closure.

Patent foramen ovale treatment strategy: an Italian large prospective study.

Aim: There is still controversy regarding the benefit of percutaneous closure of patent foramen ovale (PFO) among patients with cryptogenic stroke. Here we aimed to evaluate the factors associated with treatment choice and predictors of adverse events in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO.

Methods: Of 418 consecutive patients with PFO and cryptogenic stroke or TIA, 262 underwent percutaneous PFO closure, whereas 156 were medically treated.

Impact of transcatheter closure of patent foramen ovale in the evolution of migraine and role of residual shunt.

Objectives: To retrospectively evaluate the impact on daily activities of transcatheter closure of patent foramen ovale (PFO) versus medical therapy in patients with migraine and to analyze the role of the residual shunt after PFO closure.

Background: While non-controlled observational studies reported an improvement of migraine after PFO closure, a randomized trial has shown no benefit of such an intervention. The role of residual shunt after PFO closure is also poorly known.