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Mariella G Filbin, Dominik Sturm
Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features...
February 2018: Seminars in Neurology
Elizabeth R Gerstner, Kristian W Pajtler
Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades...
February 2018: Seminars in Neurology
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Philipp Kickingereder, Ovidiu Cristian Andronesi
Magnetic resonance imaging plays a key role in diagnosis and treatment monitoring of brain tumors. Novel imaging techniques that specifically interrogate aspects of underlying tumor biology and biochemical pathways have great potential in neuro-oncology. This review focuses on the emerging role of 2-hydroxyglutarate-targeted magnetic resonance spectroscopy, as well as radiomics and radiogenomics in establishing diagnosis for isocitrate dehydrogenase mutant gliomas, and for monitoring treatment response and predicting prognosis of this group of brain tumor patients...
February 2018: Seminars in Neurology
Edouard Louis
Biologic treatments have revolutionized the way we treat inflammatory bowel disease patients (IBD). Anti-tumor necrosis factor (anti-TNF) antibodies are superior to conventional therapies to achieve sustained remission without steroids and mucosal healing. The objective of IBD treatment has evolved from symptom alleviation to a combination of absence of symptoms and intestinal healing. Nevertheless, biologics are expensive and are associated with an increased risk of infections and possibly skin cancers. Therefore, the duration of these treatments may be questioned, and stopping them may be contemplated by some patients and clinicians, while it is sometimes even imposed by some jurisdictions across the world...
March 14, 2018: Inflammatory Bowel Diseases
A Hillary Steinhart
No abstract text is available yet for this article.
March 14, 2018: Inflammatory Bowel Diseases
Henry T Peng, Catherine Tenn, Oshin Vartanian, Shawn G Rhind, Jerzy Jarmasz, Homer Tien, Andrew Beckett
Introduction: Tactical Combat Casualty Care (TCCC) training imposes psychophysiological stress on medics. It is unclear whether these stress levels vary with the training modalities selected. It is also unclear how stress levels could have an impact on medical performance and skill uptake. Materials and Methods: We conducted a pilot study to compare the effects of live tissue (LT) with a high-fidelity patient simulator (SIM) on the level of stress elicited, performance, and skill uptake during battlefield trauma training course in an operating room (OR) and in a simulated battlefield scenario (field)...
March 14, 2018: Military Medicine
P D Tar, N A Thacker, M Babur, Y Watson, S Cheung, R A Little, R G Gieling, K J Williams, J P B O'Connor
Motivation: Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both normal development and also in response to treatment. The large variations observed in control group tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design, rather than due to therapeutic failure...
March 14, 2018: Bioinformatics
Maxime Lamontagne, Jean-Christophe Bérubé, Ma'en Obeidat, Michael H Cho, Brian D Hobbs, Phuwanat Sakornsakolpat, Kim de Jong, H Marike Boezen, David Nickle, Ke Hao, Wim Timens, Maarten van den Berge, Philippe Joubert, Michel Laviolette, Don D Sin, Peter D Paré, Yohan Bossé
Causal genes of chronic obstructive pulmonary disease (COPD) remain elusive. The current study aims at integrating genome-wide association studies (GWAS) and lung expression quantitative loci (eQTL) data to map COPD candidate causal genes and gain biological insights into the recently discovered COPD susceptibility loci. Two complementary genomic datasets on COPD were studied. First, the lung eQTL dataset which included whole-genome gene expression and genotyping data from 1,038 individuals. Second, the largest COPD GWAS to date from the International COPD Genetics Consortium (ICGC) with 13,710 cases and 38,062 controls...
March 14, 2018: Human Molecular Genetics
Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Igor S Pessi, Yannick Lara, Benoit Durieu, Pedro de C Maalouf, Elie Verleyen, Annick Wilmotte
The terrestrial Antarctic Realm has recently been divided into 16 Antarctic Conservation Biogeographic Regions (ACBRs) based on environmental properties and the distribution of biota. Despite their prominent role in the primary production and nutrient cycling in Antarctic lakes, cyanobacteria were only poorly represented in the biological dataset used to delineate these ACBRs. Here we provide a first high-throughput sequencing (HTS) insight into the spatial distribution of benthic cyanobacterial communities in Antarctic lakes located in four distinct, geographically distant ACBRs and covering a range of limnological conditions...
March 14, 2018: FEMS Microbiology Ecology
Clément Niel, Christine Sinoquet, Christian Dina, Ghislain Rocheleau
Motivation: Large scale genome-wide association studies (GWAS) are tools of choice for discovering associations between genotypes and phenotypes. To date, many studies rely on univariate statistical tests for association between the phenotype and each assayed single nucleotide polymorphism (SNP). However, interaction between SNPs, namely epistasis, must be considered when tackling the complexity of underlying biological mechanisms. Epistasis analysis at large scale entails a prohibitive computational burden when addressing the detection of more than two interacting SNPs...
March 14, 2018: Bioinformatics
Uzochukwu C Ugochukwu, Alfred Ochonogor, Chika M Jidere, Chizoba Agu, Frida Nkoloagu, John Ewoh, Virginia U Okwu-Delunzu
In this study, the human and livestock (cattle) health risks of exposure to polycyclic aromatic hydrocarbons (PAHs) in a wetland of Obuaku, Abia State Nigeria contaminated by hydrocarbon spill due to incidents of hydrocarbon theft and pipeline vandalization were assessed. Gas chromatography-flame ionization detector and gas chromatography-mass spectrometry were employed in analyzing the TPH and PAHs respectively. The contaminated soil was delineated into sub-locations AOC-1, AOC-2, AOC-3, AOC-4, AOC-5 and AOC-6 to reflect the discrete patches (areas) of the contaminated site and for effective planning of remedial actions...
March 13, 2018: Environment International
Masafumi Yoshinaga, Hiromasa Ninomiya, M M Aeorangajeb Al Hossain, Makoto Sudo, Anwarul Azim Akhand, Nazmul Ahsan, Md Abdul Alim, Md Khalequzzaman, Machiko Iida, Ichiro Yajima, Nobutaka Ohgami, Masashi Kato
Chromium (Cr) pollution caused by wastewater from tanneries is a worldwide environmental problem. To develop a countermeasure, we performed a comprehensive study using Hazaribagh, the tannery area in Dhaka City, Bangladesh, as a model. Our environmental monitoring indicated that the soluble form of Cr, but not barium or arsenic, in Buriganga River is derived from Hazaribagh. Our chemical analysis next showed that Cr, the primary pollutant in canal water at Hazaribagh, consisted of ≤0.7 μM hexavalent Cr [Cr(VI)] and ≤1705 μM trivalent Cr [Cr(III)]...
March 5, 2018: Chemosphere
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Silvia Salerno, Aída Nelly García-Argáez, Elisabetta Barresi, Sabrina Taliani, Francesca Simorini, Concettina La Motta, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
Inhibition of angiogenesis via blocking vascular endothelial growth factor receptor (VEGFR) signaling pathway emerged as an established approach in anticancer therapy. So far, many monoclonal antibodies and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1-21 featuring different substitution patterns on the pendant phenyl moiety, combined with H, OCH3 , or Cl at 8-position...
March 7, 2018: European Journal of Medicinal Chemistry
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
David M Thal, Ziva Vuckovic, Christopher J Draper-Joyce, Yi-Lynn Liang, Alisa Glukhova, Arthur Christopoulos, Patrick M Sexton
G protein-coupled receptors (GPCRs) are the largest superfamily of cell surface receptor proteins and are important drug targets for many human diseases. In the last decade, remarkable progress has been made in the determination of atomic structures of GPCRs with over 200 structures from 53 unique receptors having been solved. Technological advances in protein engineering and X-ray crystallography have driven much of the progress to date. However, recent advances in cryo-electron microscopy have facilitated the structural determination of three new structures of active-state GPCRs in complex with heterotrimeric G protein...
March 13, 2018: Current Opinion in Structural Biology
Davy Guillarme, Vincent Desfontaine, Sabine Heinisch, Jean-Luc Veuthey
Mass spectrometry (MS) is considered today as one of the most popular detection methods, due to its high selectivity and sensitivity. In particular, this detector has become the gold standard for the analysis of complex mixtures such as biological samples. The first successful SFC-MS hyphenation was reported in the 80's, and since then, several ionization sources, mass analyzers and interfacing technologies have been combined. Due to the specific physicochemical properties and compressibility of the SFC mobile phase, directing the column effluent into the ionization source is more challenging than in LC...
March 7, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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