A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors.

Purpose: The combination of afatinib, an irreversible ErbB family blocker, with paclitaxel and bevacizumab was assessed in patients with advanced solid tumors.

Methods: This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab. Safety, pharmacokinetics, and anti-tumor activity were also assessed.

P-Hacking in Orthopaedic Literature: A Twist to the Tail.

Background: "P-hacking" occurs when researchers preferentially select data or statistical analyses until nonsignificant results become significant. We wanted to evaluate if the phenomenon of p-hacking was evident in orthopaedic literature.

Methods: We text-mined through all articles published in three top orthopaedic journals in 2015.

Understanding Peptide Oligomeric State in Langmuir Monolayers of Amphiphilic 3-Helix Bundle-Forming Peptide-PEG Conjugates.

Coiled-coil peptide-polymer conjugates are an emerging class of biomaterials. Fundamental understanding of the coiled-coil oligomeric state and assembly process of these hybrid building blocks is necessary to exert control over their assembly into well-defined structures. Here, we studied the effect of peptide structure and PEGylation on the self-assembly process and oligomeric state of a Langmuir monolayer of amphiphilic coiled-coil peptide-polymer conjugates using X-ray reflectivity (XR) and grazing-incidence X-ray diffraction (GIXD).

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.].

Introducing pharmacogenetic testing with clinical decision support into primary care: a feasibility study.

Background: Inappropriate prescribing increases patient illness and death owing to adverse drug events. The inclusion of genetic information into primary care medication practices is one solution. Our aim was to assess the ability to obtain and genotype saliva samples and to determine the levels of use of a decision support tool that creates medication options adjusted for patient characteristics, drug-drug interactions and pharmacogenetics.

Multidrug-Resistant Pseudomonas aeruginosa Infection in a Child with Cystic Fibrosis.

We describe a pediatric cystic fibrosis patient who developed a pulmonary exacerbation due to two multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. In addition to these MDR organisms, the case was further complicated by β-lactam allergy. Despite the MDR phenotype, both isolates were susceptible to an antimicrobial combination.

Dosage Mutator Genes in Saccharomyces cerevisiae: A Novel Mutator Mode-of-Action of the Mph1 DNA Helicase.

Mutations that cause genome instability are considered important predisposing events that contribute to initiation and progression of cancer. Genome instability arises either due to defects in genes that cause an increased mutation rate (mutator phenotype), or defects in genes that cause chromosome instability (CIN). To extend the catalog of genome instability genes, we systematically explored the effects of gene overexpression on mutation rate, using a forward-mutation screen in budding yeast.

Internal Structure of 15 nm 3-Helix Micelle Revealed by Small-Angle Neutron Scattering and Coarse-Grained MD Simulation.

3-Helix micelles (3HM) formed by self-assembly of peptide-polymer conjugate amphiphiles have shown promise as a nanocarrier platform due to their long-circulation, deep tumor penetration, selective accumulation in tumor, and ability to cross the blood-brain barrier (BBB) for glioblastoma therapy. There is a need to understand the structural contribution to the high in vivo stability and performance of 3HM. Using selective deuteration, the contrast variation technique in small-angle neutron scattering, and coarse-grained molecular dynamics simulation, we determined the spatial distribution of each component within 3HM.

Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer.

Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors.

One-Pot Synthesis of Fe(III)-Polydopamine Complex Nanospheres: Morphological Evolution, Mechanism, and Application of the Carbonized Hybrid Nanospheres in Catalysis and Zn-Air Battery.

We report one-pot synthesis of Fe(III)-polydopamine (PDA) complex nanospheres, their structures, morphology evolution, and underlying mechanism. The complex nanospheres were synthesized by introducing ferric ions into the reaction mixture used for polymerization of dopamine. It is verified that both the oxidative polymerization of dopamine and Fe(III)-PDA complexation contribute to the "polymerization" process, in which the ferric ions form coordination bonds with both oxygen and nitrogen, as indicated by X-ray absorption fine-structure spectroscopy.

Down but not out in posterior cingulate cortex: Deactivation yet functional coupling with prefrontal cortex during demanding semantic cognition.

The posterior cingulate cortex (pCC) often deactivates during complex tasks, and at rest is often only weakly correlated with regions that play a general role in the control of cognition. These observations led to the hypothesis that pCC contributes to automatic aspects of memory retrieval and cognition. Recent work, however, has suggested that the pCC may support both automatic and controlled forms of memory processing and may do so by changing its communication with regions that are important in the control of cognition across multiple domains.

Mutagen Synergy: Hypermutability Generated by Specific Pairs of Base Analogs.

Unlabelled: We tested pairwise combinations of classical base analog mutagens in Escherichia coli to study possible mutagen synergies. We examined the cytidine analogs zebularine (ZEB) and 5-azacytidine (5AZ), the adenine analog 2-aminopurine (2AP), and the uridine/thymidine analog 5-bromodeoxyuridine (5BrdU). We detected a striking synergy with the 2AP plus ZEB combination, resulting in hypermutability, a 35-fold increase in mutation frequency (to 53,000 × 10(-8)) in the rpoB gene over that with either mutagen alone.

Feasibility and Perceptions of Cell Phone-Based, Health-Related Communication With Adolescents in an Economically Depressed Area.

We examined the feasibility and perception of cell-based (texting, voicemail [VM], and email/social media), health-related communication with adolescents in Genesee County, MI, where 22% reside below the poverty level. Results of an anonymous survey found that 86% of respondents owned a cell phone, 87% had data, 96% texted, 90.5% emailed/used social media, and 68% had VM.

Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.

PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosing with class I PI3K inhibitor pictilisib (GDC-0941). These candidate metabolomics biomarkers were evaluated in a phase I dose-escalation clinical trial of pictilisib.

Leaders' smiles reflect cultural differences in ideal affect.

Cultures differ in the emotions they teach their members to value ("ideal affect"). We conducted 3 studies to examine whether leaders' smiles reflect these cultural differences in ideal affect. In Study 1, we compared the smiles of top-ranked American and Chinese government leaders, chief executive officers, and university presidents in their official photos.

Self-Assembly-Induced Alternately Stacked Single-Layer MoS2 and N-doped Graphene: A Novel van der Waals Heterostructure for Lithium-Ion Batteries.

In this article, a simple self-assembly strategy for fabricating van der Waals heterostructures from isolated two-dimensional atomic crystals is presented. Specifically, dopamine (DOPA), an excellent self-assembly agent and carbon precursor, was adsorbed on exfoliated MoS2 monolayers through electrostatic interaction, and the surface-modified monolayers self-assembled spontaneously into DOPA-intercalated MoS2. The subsequent in situ conversion of DOPA to highly conductive nitrogen-doped graphene (NDG) in the interlayer space of MoS2 led to the formation of a novel NDG/MoS2 nanocomposite with well-defined alternating structure.

Acetaminophen overdose associated with double serum concentration peaks.

Acetaminophen is the most commonly used analgesic-antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning.

Spread Films of Human Serum Albumin at the Air-Water Interface: Optimization, Morphology, and Durability.

It has been known for almost one hundred years that a lower surface tension can be achieved at the air-water interface by spreading protein from a concentrated solution than by adsorption from an equivalent total bulk concentration. Nevertheless, the factors that control this nonequilibrium process have not been fully understood. In the present work, we apply ellipsometry, neutron reflectometry, X-ray reflectometry, and Brewster angle microscopy to elaborate the surface loading of human serum albumin in terms of both the macroscopic film morphology and the spreading dynamics.

Self-assembled 20-nm (64)Cu-micelles enhance accumulation in rat glioblastoma.

There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers.

Supervised, Unsupervised, and Semi-Supervised Feature Selection: A Review on Gene Selection.

Recently, feature selection and dimensionality reduction have become fundamental tools for many data mining tasks, especially for processing high-dimensional data such as gene expression microarray data. Gene expression microarray data comprises up to hundreds of thousands of features with relatively small sample size. Because learning algorithms usually do not work well with this kind of data, a challenge to reduce the data dimensionality arises.