Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors.

Purpose: mAbs targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of patients with cancer. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long noncoding RNA (lncRNA) expression in patients with cancer treated with anti-PD-1/PD-L1 immunotherapy.

The Neolithic site "La Marmotta": DNA metabarcoding to identify the microbial deterioration of waterlogged archeological wood.

Introduction: The evaluation of biological degradation of waterlogged archeological wood is crucial to choose the conservative and protective treatments to be applied to the wooden material. The waterlogged environmental conditions are characterized by oxygen scarcity, only allowing the growth of adapted microbes capable to degrade the organic wooden material, mainly erosion bacteria and soft-rot fungi. In this work, we characterized and evaluated the biodegradation state and the microbial communities of wooden fragments preserved in storage tanks.

A New Multi-Analyte LC-MS-MS Screening Method for the Detection of 120 NPSs and 49 Drugs in Hair.

Liquid chromatography coupled with mass spectrometry (LC-MS) has been increasingly used for screening purposes in forensic toxicology. High versatility and low time/resource consumption are the main advantages of this technology. Numerous multi-analyte methods have been validated in order to face the analytical challenge of new psychoactive substances (NPSs).

Multiproxy study of 7500-year-old wooden sickles from the Lakeshore Village of La Marmotta, Italy.

The lakeshore site of La Marmotta is one of the most important Early Neolithic sites of Mediterranean Europe. The site is famous for the exceptional preservation of organic materials, including numerous wooden artefacts related to navigation, agriculture, textile production, and basketry. This article presents interdisciplinary research on three of the most complete and well-preserved sickles recovered from the site, yet unpublished.

The Strange Case of the Nuragic Offerers Bronze Statuettes: A Multi-Analytical Study.

The Nuragic civilization (Sardinia, Italy, XVIII-VIII B.C) developed a flourishing bronze metallurgy with strong connections with other civilizations from the Mediterranean basin. Within the large bronze production, there are some peculiar representations of human figures, known in the archaeological environment of Sardinia as bronzetti, depicting warriors, priests, and offerers.

Maternal-foetal complications in pregnancy: a retrospective comparison between type 1 and type 2 diabetes mellitus.

Background: The aim of the study was a retrospective comparison of the differences in maternal-foetal outcomes between women with type 1 and type 2 diabetes mellitus (T1DM and T2DM).

Methods: A cohort of 135 patients with pregestational diabetes, 73 with T1DM (mean age 29 ± 5 years) and 62 with T2DM (mean age 33 ± 6 years), in intensive insulin treatment throughout pregnancy were evaluated. Clinical and metabolic parameters and the prevalence of maternal and foetal complications were assessed.

Domestic Violence and Its Effects on Women, Children, and Families.

Men and women experience severe domestic violence (DV) and intimate partner violence (IPV); however, women and children remain especially vulnerable. Violence along the DV/IPV continuum has been recognized as a type of child maltreatment and a child's awareness that a caregiver is being harmed or at risk of harm is sufficient to induce harmful sequelae. Consequences of these abusive behaviors are associated with mental and physical health consequences.

Direct dating reveals the early history of opium poppy in western Europe.

This paper aims to define the first chrono-cultural framework on the domestication and early diffusion of the opium poppy using small-sized botanical remains from archaeological sites, opening the way to directly date minute short-lived botanical samples. We produced the initial set of radiocarbon dates directly from the opium poppy remains of eleven Neolithic sites (5900-3500 cal BCE) in the central and western Mediterranean, northwestern temperate Europe, and the western Alps. When possible, we also dated the macrobotanical remains originating from the same sediment sample.

Correction: Migration, adaptation, innovation: The spread of Neolithic harvesting technologies in the Mediterranean.

[This corrects the article DOI: 10.1371/journal.pone.

Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus.

Tumor interferon (IFN) signaling promotes PD-L1 expression to suppress T cell-mediated immunosurveillance. We identify the IFN-stimulated non-coding RNA 1 (INCR1) as a long noncoding RNA (lncRNA) transcribed from the PD-L1 locus and show that INCR1 controls IFNγ signaling in multiple tumor types. Silencing INCR1 decreases the expression of PD-L1, JAK2, and several other IFNγ-stimulated genes.

Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: a real-life study.

Background: Conventional glucocorticoid treatment has a significant impact on liver in patients with adrenal insufficiency. Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement in anthropometric and metabolic parameters. We aimed to evaluate the effects of 12-month DR-HC treatment on the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, in patients with secondary adrenal insufficiency (SAI).

Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy.

Purpose: Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM.

Growth hormone and hematopoiesis: A retrospective analysis on a large cohort of children with growth hormone deficiency.

Objective: Few large-scale studies regarding the impact of GH deficiency (GHD) on hematopoiesis in children have been reported. Our aim was to investigate hematopoiesis indices in a large cohort of GHD children at diagnosis and during GH treatment (GHT) and any correlation with hormonal parameters.

Design: Clinical and biochemical data of children with idiopathic GHD at diagnosis and annually up to 36 months of GHT were retrospectively evaluated.

The metabolic outcomes of growth hormone treatment in children are gender specific.

Objective: To evaluate the impact of gender on the clinical and metabolic parameters in prepubertal growth hormone deficiency (GHD) children at diagnosis and during GH treatment (GHT).

Design: The data of 105 prepubertal children (61 males, 44 females, mean age 6.8 ± 0.

Correlation between adrenal function, growth hormone secretion, and insulin sensitivity in children with idiopathic growth hormone deficiency.

Purpose: Patients with growth hormone deficiency (GHD) demonstrate an increased cortisol/cortisone ratio which could potentially explain the metabolic features of GHD, while GH treatment (GHT) could increase the cortisol metabolism.

Methods: In 35 children (27 M, mean age 10.1 years) with idiopathic GHD at baseline and after 12 months of GHT and in 25 controls, in addition to metabolic parameters, we assessed adrenal function by morning serum cortisol, its peak, and its area under the curve (AUC) during insulin tolerance test (ITT).

MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells.

Large-scale transcriptomic profiling of glioblastoma (GBM) into subtypes has provided remarkable insight into the pathobiology and heterogeneous nature of this disease. The mechanisms of speciation and inter-subtype transitions of these molecular subtypes require better characterization to facilitate the development of subtype-specific targeting strategies. The deregulation of microRNA expression among GBM subtypes and their subtype-specific targeting mechanisms are poorly understood.

MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer.

Despite the importance of molecular subtype classification of glioblastoma (GBM), the extent of extracellular vesicle (EV)-driven molecular and phenotypic reprogramming remains poorly understood. To reveal complex subpopulation dynamics within the heterogeneous intratumoral ecosystem, we characterized microRNA expression and secretion in phenotypically diverse subpopulations of patient-derived GBM stem-like cells (GSCs). As EVs and microRNAs convey information that rearranges the molecular landscape in a cell type-specific manner, we argue that intratumoral exchange of microRNA augments the heterogeneity of GSC that is reflected in highly heterogeneous profile of microRNA expression in GBM subtypes.

The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches.

Long non-coding RNAs (lncRNAs) have an undefined role in the pathobiology of glioblastoma multiforme (GBM). These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs) that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs.

Extracellular Vesicles from High-Grade Glioma Exchange Diverse Pro-oncogenic Signals That Maintain Intratumoral Heterogeneity.

A lack of experimental models of tumor heterogeneity limits our knowledge of the complex subpopulation dynamics within the tumor ecosystem. In high-grade gliomas (HGG), distinct hierarchical cell populations arise from different glioma stem-like cell (GSC) subpopulations. Extracellular vesicles (EV) shed by cells may serve as conduits of genetic and signaling communications; however, little is known about how HGG heterogeneity may impact EV content and activity.

MicroRNA and extracellular vesicles in glioblastoma: small but powerful.

To promote the tumor growth, angiogenesis, metabolism, and invasion, glioblastoma (GBM) cells subvert the surrounding microenvironment by influencing the endogenous activity of other brain cells including endothelial cells, macrophages, astrocytes, and microglia. Large number of studies indicates that the intra-cellular communication between the different cell types of the GBM microenvironment occurs through the functional transfer of oncogenic components such as proteins, non-coding RNAs, DNA and lipids via the release and uptake of extracellular vesicles (EVs). Unlike the communication through the secretion of chemokines and cytokines, the transfer and gene silencing activity of microRNAs through EVs is more complex as the biogenesis and proper packaging of microRNAs is crucial for their uptake by recipient cells.