CMR for myocardial iron overload quantification: calibration curve from the MIOT Network.

Objectives: R2* cardiac magnetic resonance (CMR) allows the non-invasive measurement of myocardial iron. We calibrated cardiac R2* values against myocardial tissue-measured iron concentration by using a segmental approach and we assessed the iron distribution.

Methods: Five hearts of thalassemia patients were donated after death/transplantation to the CoreLab of the Myocardial Iron Overload in Thalassemia Network.

Author Correction: Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

New Predictive Equations for Estimating Resting Energy Expenditure in Adults With Crohn's Disease.

Background: Increased resting energy expenditure (REE) has been hypothesized to be a potential cause of weight loss in individuals with Crohn's disease (CD). This study aimed to develop and validate new predictive equations for estimating REE in adults with CD.

Methods: Adults, ages 18-65 years, with CD were recruited.

Particulate air pollution from different sources and mortality in 7.5 million adults - The Dutch Environmental Longitudinal Study (DUELS).

Background: Long-term exposure to particulate air pollution has been associated with mortality in urban cohort studies. Few studies have investigated the association between emission contributions from different particle sources and mortality in large-scale population registries, including non-urban populations.

Objectives: The aim of the study was to evaluate the associations between long-term exposure to particulate air pollution from different source categories and non-accidental mortality in the Netherlands based on existing national databases.

Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.

Pancreatic adenocarcinoma presents as a spectrum of a highly aggressive disease in patients. The basis of this disease heterogeneity has proved difficult to resolve due to poor tumor cellularity and extensive genomic instability. To address this, a dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic tumors.

Patient selection for a developmental therapeutics program using whole genome and Transcriptome analysis.

Introduction Given the high level of uncertainty surrounding the outcomes of early phase clinical trials, whole genome and transcriptome analysis (WGTA) can be used to optimize patient selection and study assignment. In this retrospective analysis, we reviewed the impact of this approach on one such program. Methods Patients with advanced malignancies underwent fresh tumor biopsies as part of our personalized medicine program (NCT02155621).

Fluorouracil sensitivity in a head and neck squamous cell carcinoma with a somatic structural variant.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and represents a heterogeneous group of tumors, the majority of which are treated with a combination of surgery, radiation, and chemotherapy. Fluoropyrimidine (5-FU) and its oral prodrug, capecitabine, are commonly prescribed treatments for several solid tumor types including HNSCC. 5-FU-associated toxicity is observed in ∼30% of treated patients and is largely caused by germline polymorphisms in , which encodes dihydropyrimidine dehydrogenase, a key enzyme of 5-FU catabolism and deactivation.

A few introductory notes on the special issue on the Evaluation Framework for Promoting Gender Equality in Research and Innovation (EFFORTI).

Being European with a long standing research interest in evaluation of gender policies, I could not begin my assignment as Editor in Chief with a better task. Readers will forgive me for these few biographical notes. Before presenting this special issue, I owe many thanks to Jonny Morell who involved me in its design as early as June 2018.

Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets.

Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. ILC2 development is dependent on the transcription factor retinoic acid receptor-related orphan receptor (RORα), which is also expressed in common ILC progenitors. To elucidate the developmental pathways of lung ILC2s, we generated RORα lineage tracer mice and performed single-cell RNA sequencing, flow cytometry, and functional analyses.

Screening young athletes for diseases at risk of sudden cardiac death: role of stress testing for ventricular arrhythmias.

Aims: The athletic preparticipation evaluation (PPE) protocol proposed by he European Society of Cardiology includes history, physical examination and resting electrocardiogram (ECG). The aim of this study was to assess the results of adding constant-load ECG stress testing (EST) to the protocol for the evaluation of ventricular arrhythmias (VA) inducibility.

Methods: We evaluated a consecutive cohort of young athletes with history, physical examination, resting ECG and EST.

Therapeutic Implication of Genomic Landscape of Adult Metastatic Sarcoma.

Purpose: This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options.

Methods: Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various histology subtypes who were enrolled in the Personalized OncoGenomics program at BC Cancer were included in this study. Fresh tumor tissues along with blood samples underwent whole-genome and transcriptome sequencing.

Surrounding green, air pollution, traffic noise exposure and non-accidental and cause-specific mortality.

Background: Most previous studies that investigated associations of surrounding green, air pollution or traffic noise with mortality focused on single exposures.

Objectives: The aim of this study was to evaluate combined associations of long-term residential exposure to surrounding green, air pollution and traffic noise with total non-accidental and cause-specific mortality.

Methods: We linked a national health survey (Public Health Monitor, PHM) conducted in 2012 to the Dutch longitudinal mortality database.

Mitochondrial DNA variation in Sub-Saharan Africa: Forensic data from a mixed West African sample, Côte d'Ivoire (Ivory Coast), and Rwanda.

This study provides 398 novel complete mitochondrial control region sequences that augment the still underrepresented data from Africa by three datasets: a mixed West African sample set deriving from 12 countries (n = 145) and datasets from Côte d'Ivoire (Ivory Coast) (n = 100) as well as Rwanda (n = 153). The analysis of mtDNA variation and genetic comparisons with published data revealed low random match probabilities in all three datasets and typical West African and East African diversity, respectively. Genetic parameters indicate that the presented mixed West African dataset may serve as first forensic mtDNA control region database for West Africa in general.

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material.

Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration.

Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features.

Bioelectrical impedance phase angle in sport: a systematic review.

Background: Phase angle (PhA) is a raw BIA variable that has been gaining attention in recent years because it is supposed to be an index of the ratio between extracellular and intracellular water, body cell mass, and cellular integrity. The aim of this systematic review was to evaluate the variability of PhA between different sports and its relationships with sport performance. Additionally, we investigated whether PhA depends on gender or age, and analyzed the differences between athletes and controls.

Evaluation of protocols for rRNA depletion-based RNA sequencing of nanogram inputs of mammalian total RNA.

Next generation RNA-sequencing (RNA-seq) is a flexible approach that can be applied to a range of applications including global quantification of transcript expression, the characterization of RNA structure such as splicing patterns and profiling of expressed mutations. Many RNA-seq protocols require up to microgram levels of total RNA input amounts to generate high quality data, and thus remain impractical for the limited starting material amounts typically obtained from rare cell populations, such as those from early developmental stages or from laser micro-dissected clinical samples. Here, we present an assessment of the contemporary ribosomal RNA depletion-based protocols, and identify those that are suitable for inputs as low as 1-10 ng of intact total RNA and 100-500 ng of partially degraded RNA from formalin-fixed paraffin-embedded tissues.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas.

[Tackle health inequality in prevention: state of the art through an assessment of 21 Regional preventive plan 2014-2018].

Background: the Italian health policies awareness on health inequalities (HI) issues is increasing. The National Plan for health prevention and promotion (2014-2018) (PNP) introduced in 2014 a clear political commitment aimed at reducing HI. During 2015, each Italian regions (IRs) elaborated and approved by law its prevention plan (PRP), according to the PNP.

Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer.

Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes.

Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer.

Design, Setting, And Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials.

Overexpression of 14-3-3 proteins enhances cold tolerance and increases levels of stress-responsive proteins of Arabidopsis plants.

14-3-3 proteins are a family of conserved proteins present in eukaryotes as several isoforms, playing a regulatory role in many cellular and physiological processes. In plants, 14-3-3 proteins have been reported to be involved in the response to stress conditions, such as drought, salt and cold. In the present study, 14-3-3ε and 14-3-3ω isoforms, which were representative of ε and non-ε phylogenetic groups, were overexpressed in Arabidopsis thaliana plants; the effect of their overexpression was investigated on H-ATPase activation and plant response to cold stress.

Dietary Quercetin and Kaempferol: Bioavailability and Potential Cardiovascular-Related Bioactivity in Humans.

Fruit and vegetable intake has been associated with a reduced risk of cardiovascular disease. Quercetin and kaempferol are among the most ubiquitous polyphenols in fruit and vegetables. Most of the quercetin and kaempferol in plants is attached to sugar moieties rather than in the free form.

Altered Gene Expression along the Glycolysis-Cholesterol Synthesis Axis Is Associated with Outcome in Pancreatic Cancer.

Purpose: Identification of clinically actionable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcome. Intertumoral metabolic heterogeneity contributes to cancer survival and the balance between distinct metabolic pathways may influence PDAC outcome. We hypothesized that PDAC can be stratified into prognostic metabolic subgroups based on alterations in the expression of genes involved in glycolysis and cholesterol synthesis.

Retrograde Ret signaling controls sensory pioneer axon outgrowth.

The trafficking mechanisms and transcriptional targets downstream of long-range neurotrophic factor ligand/receptor signaling that promote axon growth are incompletely understood. Zebrafish carrying a null mutation in a neurotrophic factor receptor, Ret, displayed defects in peripheral sensory axon growth cone morphology and dynamics. Ret receptor was highly enriched in sensory pioneer neurons and Ret51 isoform was required for pioneer axon outgrowth.