Early radiological response as predictor of overall survival in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor mutations.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard treatment of advanced, -mutant non-small-cell lung cancer (NSCLC). Usually, radiographic assessment of response to chemotherapy is performed after the patient completes the second course of treatment. The optimal timing of response evaluation for patients receiving EGFR-TKIs is, however, not well-defined.

Maternal imprinting on cognition markers of wild type and transgenic Alzheimer's disease model mice.

The risk of suffering from Alzheimer's disease (AD) is higher in individuals from AD-affected mothers. The purpose of this investigation was to study whether maternal transmission might produce AD-related alterations in progenies of mice that do not have any genotypic alteration. We used cognitively-intact mothers harbouring in heterozygosity the transgene for overexpressing the Swedish double mutant version of the human amyloid precursor protein (hAβPPswe).

An Epigenetic Signature in Adipose Tissue Is Linked to Nicotinamide N-Methyltransferase Gene Expression.

Scope: The enzyme nicotinamide N-methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue.

Methods And Results: The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium Human Methylation 450 BeadChip array (discovery cohort: n = 11).

ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end-stage heart failure patients.

Aims: Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in ICM patients and relate these alterations to their haemodynamic and functional status.

A guideline update for the practice of echocardiography in the cardiac screening of sports participants: a joint policy statement from the British Society of Echocardiography and Cardiac Risk in the Young.

Sudden cardiac death (SCD) in an athlete is a rare but tragic event. In view of this, pre-participation cardiac screening is mandatory across many sporting disciplines to identify those athletes at risk. Echocardiography is a primary investigation utilized in the pre-participation setting and in 2013 the British Society of Echocardiography and Cardiac Risk in the Young produced a joint policy document providing guidance on the role of echocardiography in this setting.

Interventional Therapies in Pulmonary Hypertension.

Despite advances in drug therapy, pulmonary hypertension-particularly arterial hypertension (PAH)-remains a fatal disease. Untreatable right heart failure (RHF) from PAH eventually ensues and remains a significant cause of death in these patients. Lowering pulmonary input impedance with different PAH-specific drugs is the obvious therapeutic target in RHF due to chronically increased afterload.

Evaluation of Potential Mechanisms Controlling the Catalase Expression in Breast Cancer Cells.

Development of cancer cell resistance against prooxidant drugs limits its potential clinical use. MCF-7 breast cancer cells chronically exposed to ascorbate/menadione became resistant (Resox cells) by increasing mainly catalase activity. Since catalase appears as an anticancer target, the elucidation of mechanisms regulating its expression is an important issue.

Genetic ancestry of families of putative Inka descent.

This study focuses on the descendants of the royal Inka family. The Inkas ruled Tawantinsuyu, the largest pre-Columbian empire in South America, which extended from southern Colombia to central Chile. The origin of the royal Inkas is currently unknown.

Epigenomic signature of adrenoleukodystrophy predicts compromised oligodendrocyte differentiation.

Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN).

High contiguity Arabidopsis thaliana genome assembly with a single nanopore flow cell.

The handheld Oxford Nanopore MinION sequencer generates ultra-long reads with minimal cost and time requirements, which makes sequencing genomes at the bench feasible. Here, we sequence the gold standard Arabidopsis thaliana genome (KBS-Mac-74 accession) on the bench with the MinION sequencer, and assemble the genome using typical consumer computing hardware (4 Cores, 16 Gb RAM) into chromosome arms (62 contigs with an N50 length of 12.3 Mb).

Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody-Drug Conjugates.

Improved, streamlined total syntheses of natural tubulysins such as V (Tb45) and U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120), are described. Cytotoxicity evaluation of the synthesized compounds against certain cancer cell lines revealed a number of novel analogues with exceptional potencies [e.g.

Public smoking ban and socioeconomic inequalities in smoking prevalence and cessation: a cross-sectional population-based study in Geneva, Switzerland (1995-2014).

Introduction: Smoking bans were suggested to reduce smoking prevalence and increase quit ratio but their equity impact remains unclear. We aimed to characterise the socioeconomic status (SES)-related inequalities in smoking prevalence and quit ratio before and after the implementation of a public smoking ban.

Methods: We included data from 17 544 participants in the population-based cross-sectional Bus Santé study in Geneva, Switzerland, between 1995 and 2014.

Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response.

Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection.

Enclaves of genetic diversity resisted Inca impacts on population history.

The Inca Empire is claimed to have driven massive population movements in western South America, and to have spread Quechua, the most widely-spoken language family of the indigenous Americas. A test-case is the Chachapoyas region of northern Peru, reported as a focal point of Inca population displacements. Chachapoyas also spans the environmental, cultural and demographic divides between Amazonia and the Andes, and stands along the lowest-altitude corridor from the rainforest to the Pacific coast.

MGIS: managing banana (Musa spp.) genetic resources information and high-throughput genotyping data.

https://www.crop-diversity.org/mgis/.

Improving bone health in men with prostate cancer receiving androgen deprivation therapy: Results of a randomized phase 2 trial.

Background: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care.

Methods: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed.

Dirofilaria immitis JYD-34 isolate: whole genome analysis.

Background: Macrocyclic lactone (ML) anthelmintics are used for chemoprophylaxis for heartworm infection in dogs and cats. Cases of dogs becoming infected with heartworms, despite apparent compliance to recommended chemoprophylaxis with approved preventives, has led to such cases being considered as suspected lack of efficacy (LOE). Recently, microfilariae collected from a small number of LOE isolates were used as a source of infection of new host dogs and confirmed to have reduced susceptibility to ML in controlled efficacy studies using L3 challenge in dogs.

CD137 (4-1BB) Costimulation Modifies DNA Methylation in CD8 T Cell-Relevant Genes.

CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA methylation arrays were carried out on human peripheral blood CD8 T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy.

Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described.

In-bag enzymatic splenic digestion: a novel alternative to manual morcellation?

Background: Contained in-bag spleen morcellation is a conventional extraction technique for safe spleen removal during laparoscopic splenectomy. Existing data for the use of in-bag enzymatic splenic digestion as an alternative to morcellation are lacking. This proof-of-concept study sought to evaluate the effectiveness of single and combinatorial enzyme digestion of murine spleens.

Return to work and work-related disability among AML survivors.

Acute myeloid leukemia (AML) is an aggressive, acute-onset hematological malignancy. Greater use of intensive chemotherapy (IC), supportive care, and stem cell transplantation have led to an increasing number of long-term survivors. Few studies have examined employment issues among AML survivors and to our knowledge, no study has examined the long-term effects of treatment on return to work.

Epigenetics and Oxidative Stress in Aging.

Aging is a multifactorial process characterized by the progressive loss of physiological functions, leading to an increased vulnerability to age-associated diseases and finally to death. Several theories have been proposed to explain the nature of aging. One of the most known identifies the free radicals produced by the mitochondrial metabolism as the cause of cellular and DNA damage.

Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex.

The mammalian brain contains diverse neuronal types, yet we lack single-cell epigenomic assays that are able to identify and characterize them. DNA methylation is a stable epigenetic mark that distinguishes cell types and marks regulatory elements. We generated >6000 methylomes from single neuronal nuclei and used them to identify 16 mouse and 21 human neuronal subpopulations in the frontal cortex.