Characterization of miR-146a and miR-155 in blood, tissue and cell lines of head and neck squamous cell carcinoma patients and their impact on cell proliferation and migration.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide with an unchanged 5-year survival rate during the last decade. To detect reliable prognostic markers and improve patients' outcome in future, the aim of our study was to detect differences in microRNA (miRNA; miR) expression profile and further on to analyze the functional role of selected miRNAs.

Methods: Blood samples from HNSCC patients and sex- and age-matched healthy volunteers were analyzed by microarrays and validated by quantitative real-time PCR.

Naphthalenebisimides as photofunctional surfactants for SWCNTs - towards water-soluble electron donor-acceptor hybrids.

A water soluble naphthalenebisimide derivative (NBI) was synthesized and probed to individualize, suspend, and stabilize single wall carbon nanotubes (SWCNTs). Besides a comprehensive photophysical and electrochemical characterization of NBI, stable suspensions of SWCNTs were realized in buffered DO. Overall, the dispersion efficiency of the NBI surfactant was determined by comparison with naphthalene based references.

From Single Variants to Protein Cascades: MULTISCALE MODELING OF SINGLE NUCLEOTIDE VARIANT SETS IN GENETIC DISORDERS.

Understanding the role of genetics in disease has become a central part of medical research. Non-synonymous single nucleotide variants (nsSNVs) in coding regions of human genes frequently lead to pathological phenotypes. Beyond single variations, the individual combination of nsSNVs may add to pathogenic processes.

Towards Clinical Applications of Blood-Borne miRNA Signatures: The Influence of the Anticoagulant EDTA on miRNA Abundance.

Background: Circulating microRNAs (miRNAs) from blood are increasingly recognized as biomarker candidates for human diseases. Clinical routine settings frequently include blood sampling in tubes with EDTA as anticoagulant without considering the influence of phlebotomy on the overall miRNA expression pattern. We collected blood samples from six healthy individuals each in an EDTA blood collection tube.

Pathway-based variant enrichment analysis on the example of dilated cardiomyopathy.

Genome-wide association (GWA) studies have significantly contributed to the understanding of human genetic variation and its impact on clinical traits. Frequently only a limited number of highly significant associations were considered as biologically relevant. Increasingly, network analysis of affected genes is used to explore the potential role of the genetic background on disease mechanisms.

Next-generation sequencing identifies altered whole blood microRNAs in neuromyelitis optica spectrum disorder which may permit discrimination from multiple sclerosis.

Background: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) have a similar clinical phenotype but represent distinct diseases, requiring different therapies. MicroRNAs (miRNAs) are short non-coding RNAs whose expression profiles can serve as diagnostic biomarkers and which may be involved in the pathophysiology of neuroinflammatory diseases. Here, we analyzed miRNA profiles in serum and whole blood of patients with NMOSD and clinically isolated syndrome (CIS)/relapsing-remitting MS (RRMS) as well as healthy controls by next-generation sequencing (NGS).

Genome-wide copy number profiling of mouse neural stem cells during differentiation.

There is growing evidence that gene amplifications were present in neural stem and progenitor cells during differentiation. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of mouse neural stem cells using TGF-ß and FCS for differentiation induction. Array data were deposited in GEO (Gene Expression Omnibus, NCBI) under accession number GSE35523.

Genome-wide copy number profiling to detect gene amplifications in neural progenitor cells.

DNA sequence amplification occurs at defined stages during normal development in amphibians and flies and seems to be restricted in humans to drug-resistant and tumor cells only. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of human neural progenitor cells. Here, we describe cell culture features, DNA extraction, and comparative genomic hybridization (CGH) analysis tailored towards the identification of genomic copy number changes.

Cardiac remodeling in Gαq and Gα11 knockout mice.

Background: Although both Gαq- and Gα11-protein signaling are believed to be involved in the regulation of cardiac hypertrophy, their detailed contribution to myocardial function remains elusive.

Methods And Results: We studied remodeling processes in healthy transgenic mice with genetically altered Gαq/Gα11-expression, in particular a global Gα11-knockout and a novel inducible cardiac specific Gαq-knockout, as well as a combined double knockout (dKO) mouse line. Echocardiography and telemetric ECG recordings revealed that compared with wild type mice, hearts of dKO mice showed an increased ejection fraction and a decreased heart rate, irrespective of age resulting in a maintained cardiac output.

Liquid exfoliation of solvent-stabilized few-layer black phosphorus for applications beyond electronics.

Few-layer black phosphorus (BP) is a new two-dimensional material which is of great interest for applications, mainly in electronics. However, its lack of environmental stability severely limits its synthesis and processing. Here we demonstrate that high-quality, few-layer BP nanosheets, with controllable size and observable photoluminescence, can be produced in large quantities by liquid phase exfoliation under ambient conditions in solvents such as N-cyclohexyl-2-pyrrolidone (CHP).

A Proactive Approach to Neonates Born at 23 Weeks of Gestation.

Objective: To evaluate in-hospital survival, survival without major morbidity, and neurodevelopmental impairment for neonates born at 23 weeks of gestation provided proactive, coordinated, and comprehensive perinatal and neonatal management.

Methods: This was a retrospective cohort study conducted at a single, tertiary care center between 2004 and 2013. Enrollment was limited to mother-neonate dyads at 23 weeks of gestation who were provided a proactive approach defined as documented evidence of antenatal corticosteroid administration, willingness to provide cesarean delivery for fetal distress, and neonatal resuscitation and intensive care.

On-surface derivatisation of aromatic molecules on graphene: the importance of packing density.

An efficient, high-throughput method for the formation of densely packed molecular films on graphene is reported. The films exhibit high stability and remain intact during a subsequent derivatisation reaction, offering a versatile route for the non-covalent functionalisation of graphene.

Timing of umbilical cord clamping among infants born at 22 through 27 weeks' gestation.

Objective: To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation.

Study Design: This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s).

Results: Forty mother-infant pairs were randomized.

Understanding and optimising the packing density of perylene bisimide layers on CVD-grown graphene.

The non-covalent functionalisation of graphene is an attractive strategy to alter the surface chemistry of graphene without damaging its superior electrical and mechanical properties. Using the facile method of aqueous-phase functionalisation on large-scale CVD-grown graphene, we investigated the formation of different packing densities in self-assembled monolayers (SAMs) of perylene bisimide derivatives and related this to the amount of substrate contamination. We were able to directly observe wet-chemically deposited SAMs in scanning tunnelling microscopy (STM) on transferred CVD graphene and revealed that the densely packed perylene ad-layers adsorb with the conjugated π-system of the core perpendicular to the graphene substrate.

Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial.

Objective: Delayed umbilical cord clamping (DCC) at birth may provide a better neonatal health status than early umbilical cord clamping (ECC). However, the safety and feasibility of DCC in infants with congenital heart disease (CHD) have not been tested. This was a pilot, randomized, controlled trial to establish the safety and feasibility of DCC in neonates with CHD.

Influence of next-generation sequencing and storage conditions on miRNA patterns generated from PAXgene blood.

Whole blood derived miRNA signatures determined by Next-Generation Sequencing (NGS) offer themselves as future minimally invasive biomarkers for various human diseases. The PAXgene system is a commonly used blood storage system for miRNA analysis. Central to all miRNA analyses that aim to identify disease specific miRNA signatures, is the question of stability and variability of the miRNA profiles that are generated by NGS.

BALL-SNP: combining genetic and structural information to identify candidate non-synonymous single nucleotide polymorphisms.

Background: High-throughput genetic testing is increasingly applied in clinics. Next-Generation Sequencing (NGS) data analysis however still remains a great challenge. The interpretation of pathogenicity of single variants or combinations of variants is crucial to provide accurate diagnostic information or guide therapies.

miFRame: analysis and visualization of miRNA sequencing data in neurological disorders.

Background: While in the past decades nucleic acid analysis has been predominantly carried out using quantitative low- and high-throughput approaches such as qRT-PCR and microarray technology, next-generation sequencing (NGS) with its single base resolution is now frequently applied in DNA and RNA testing. Especially for small non-coding RNAs such as microRNAs there is a need for analysis and visualization tools that facilitate interpretation of the results also for clinicians.

Methods: We developed miFRame, which supports the analysis of human small RNA NGS data.

Regulatory microRNA networks: complex patterns of target pathways for disease-related and housekeeping microRNAs.

Blood-based microRNA (miRNA) signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behind respective miRNA patterns is only partially understood. Moreover, "preserved" miRNAs, i.

RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish.

Alternative splicing is one of the major mechanisms through which the proteomic and functional diversity of eukaryotes is achieved. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts are only poorly understood. Here, we investigated the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system.

Longitudinal study on circulating miRNAs in patients after lung cancer resection.

There is an urgent need of comprehensive longitudinal analyses of circulating miRNA patterns to identify dynamic changes of miRNAs in cancer patients after surgery. Here we provide longitudinal analysis of 1,205 miRNAs in plasma samples of 26 patients after lung cancer resection at 8 time points over a period of 18 months and compare them to 12 control patients. First, we report longitudinal changes with respect to the number of detected miRNAs over time and identified a significantly increased number of miRNAs in patients developing metastases (p = 0.

The Doctors Hospital and Nationwide Children's Hospital Dually Accredited Pediatric Residency Program: A Potential Best Model for Pediatric Osteopathic GME Training.

With the commitment on the part of the American Osteopathic Association, the American Association of Colleges of Osteopathic Medicine, and the Accreditation Council for Graduate Medical Education to transition to a single graduate medical education accreditation system by 2020, a legitimate concern exists about the future of pediatric residency training that maintains an osteopathic focus. The authors describe a dually accredited pediatric residency program at one of the nation's largest children's hospitals, which may serve as a potential model of how to integrate a robust osteopathic-based education into a general pediatric residency program.

Basal-Plane Functionalization of Chemically Exfoliated Molybdenum Disulfide by Diazonium Salts.

Although transition metal dichalcogenides such as MoS2 have been recognized as highly potent two-dimensional nanomaterials, general methods to chemically functionalize them are scarce. Herein, we demonstrate a functionalization route that results in organic groups bonded to the MoS2 surface via covalent C-S bonds. This is based on lithium intercalation, chemical exfoliation and subsequent quenching of the negative charges residing on the MoS2 by electrophiles such as diazonium salts.

Circulating serum miRNAs as potential biomarkers for nephroblastoma.

Background: Nephroblastoma (or Wilms tumor-WT) is the most common childhood kidney cancer. In Europe, nephroblastoma is treated with preoperative chemotherapy without histological confirmation by biopsy. Therefore, minimal-invasive diagnostic markers confirming nephroblastoma diagnosis are highly warranted.