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https://www.readbyqxmd.com/read/28738478/-less-common-variants-association-study-and-statistical-analysis
#1
X Liao, J Deng, J Y Xun, J X Yan
In the past decade, based on the "common disease-common variant" hypothesis, genomewide association studies (GWAS) have been extensively used to dissect the genetic components of complex diseases and quantitative traits. However, the identified disease-associated common variants by GWASs can only explain small part of the corresponding disease heritability. "Common disease-rare variant" hypothesis has been proposed to explore the missed heritability. With the development of the next generation sequencing technology, various association studies of less common variants are ongoing...
July 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28738240/computational-training-for-the-next-generation-of-neuroscientists
#2
REVIEW
Mark S Goldman, Michale S Fee
Neuroscience research has become increasingly reliant upon quantitative and computational data analysis and modeling techniques. However, the vast majority of neuroscientists are still trained within the traditional biology curriculum, in which computational and quantitative approaches beyond elementary statistics may be given little emphasis. Here we provide the results of an informal poll of computational and other neuroscientists that sought to identify critical needs, areas for improvement, and educational resources for computational neuroscience training...
July 21, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28737886/ex-vivo-rat-eye-model-for-investigating-transport-of-next-generation-precision-polyester-nanosystems-p2ns
#3
Raghu Ganugula, Meenakshi Arora, Majeti N V Ravi Kumar
We present for the first time a robust ex vivo rat eye model for investigating the transport of precision polyester nanosystems (P2Ns) across the blood-retinal barrier, intended for systemic administration. The P2Ns-GA actively transport exploiting transferrin receptors present in the inner retinal barrier and co-localize in ganglion cells. Such delivery approaches have the potential to deliver drugs to posterior segments of the eye, which is still a major challenge in treating posterior ocular disorders.
July 24, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28737278/multicellular-vascularized-engineered-tissues-through-user-programmable-biomaterial-photodegradation
#4
Christopher K Arakawa, Barry A Badeau, Ying Zheng, Cole A DeForest
A photodegradable material-based approach to generate endothelialized 3D vascular networks within cell-laden hydrogel biomaterials is introduced. Exploiting multiphoton lithography, microchannel networks spanning nearly all size scales of native human vasculature are readily generated with unprecedented user-defined 4D control. Intraluminal channel architectures of synthetic vessels are fully customizable, providing new opportunities for next-generation microfluidics and directed cell function.
July 24, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28737273/recovery-free-of-heart-failure-after-acute-coronary-syndrome-and-coronary-revascularization
#5
Alec Falkenham, Manu K Saraswat, Chloe Wong, Kareem Gawdat, Tanya Myers, Jahanara Begum, Karen J Buth, Ian Haidl, Jean Marshall, Jean-Francois Légaré
AIMS: Previous studies have examined risk factors for the development of heart failure (HF) subsequent to acute coronary syndrome (ACS). Our study seeks to clarify the clinical variables that best characterize patients who remain free from HF after coronary artery bypass grafting (CABG) surgery for ACS to determine novel biological factors favouring freedom from HF in prospective translational studies. METHODS AND RESULTS: Nova Scotia residents (1995-2012) undergoing CABG within 3 weeks of ACS were included...
July 24, 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28736935/3d-orientational-control-in-self-assembled-thin-films-with-sub-5-nm-features-by-light
#6
Koen Nickmans, Gerardus M Bögels, Carlos Sánchez-Somolinos, Jeffrey N Murphy, Philippe Leclère, Ilja K Voets, Albertus P H J Schenning
While self-assembled molecular building blocks could lead to many next-generation functional organic nanomaterials, control over the thin-film morphologies to yield monolithic sub-5 nm patterns with 3D orientational control at macroscopic length scales remains a grand challenge. A series of photoresponsive hybrid oligo(dimethylsiloxane) liquid crystals that form periodic cylindrical nanostructures with periodicities between 3.8 and 5.1 nm is studied. The liquid crystals can be aligned in-plane by exposure to actinic linearly polarized light and out-of-plane by exposure to actinic unpolarized light...
July 24, 2017: Small
https://www.readbyqxmd.com/read/28736761/phase-ii-study-of-dovitinib-in-patients-progressing-on-anti-vascular-endothelial-growth-factor-therapy
#7
Thomas J Semrad, Edward J Kim, Michael S Tanaka, Jacob Sands, Chris Roberts, Rebekah A Burich, Yu Li, David R Gandara, Primo Lara, Philip C Mack
BACKGROUND: Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-vascular endothelial growth factor (VEGF) therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment. METHODS: Patients with measurable advanced colorectal or non-small cell lung cancer with progression despite anti-VEGF treatment within 56 days, good performance status and adequate organ function were eligible...
2017: Cancer Treat Res Commun
https://www.readbyqxmd.com/read/28736630/current-biologics-for-treatment-of-biliary-tract-cancers
#8
REVIEW
Diana Y Zhao, Kian-Huat Lim
Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#9
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736571/evaluation-of-quality-assessment-protocols-for-high-throughput-genome-resequencing-data
#10
REVIEW
Matteo Chiara, Giulio Pavesi
Large-scale initiatives aiming to recover the complete sequence of thousands of human genomes are currently being undertaken worldwide, concurring to the generation of a comprehensive catalog of human genetic variation. The ultimate and most ambitious goal of human population scale genomics is the characterization of the so-called human "variome," through the identification of causal mutations or haplotypes. Several research institutions worldwide currently use genotyping assays based on Next-Generation Sequencing (NGS) for diagnostics and clinical screenings, and the widespread application of such technologies promises major revolutions in medical science...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28736530/identification-and-expression-profiling-of-chemosensory-genes-in-dendrolimus-punctatus-walker
#11
Su-Fang Zhang, Hui-Hui Liu, Xiang-Bo Kong, Hong-Bin Wang, Fu Liu, Zhen Zhang
Dendrolimus punctatus Walker is a serious pest affecting conifers in southern China. As extensive pesticide spraying is currently required to control D. punctatus, new control strategies are urgently needed. Chemosensory genes represent potential molecular targets for development of alternative pest control strategies, and the expression characteristics of these genes provide an indication of their function. To date, little information is available regarding chemosensory genes in D. punctatus or their expression profiles at different development stages and in various tissues...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28736317/next-generation-proteomics-and-its-application-to-clinical-breast-cancer-research
#12
REVIEW
Mariya Mardamshina, Tamar Geiger
Proteomics technology aims to map the protein landscapes of biological samples, and can be applied to a variety of samples, including cells, tissues, and body fluids. As the proteins are the main functional molecules in the cells, their levels reflect much more accurately the cellular phenotype and the regulatory processes within them than gene levels, mutations, and even mRNA levels. With the advancement in the technology, it is possible nowadays to obtain comprehensive views of the biological systems, and study large patient cohorts in a streamlined manner...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28736296/a-new-targeted-cftr-mutation-panel-based-on-next-generation-sequencing-technology
#13
Marco Lucarelli, Luigi Porcaro, Alice Biffignandi, Lucy Costantino, Valentina Giannone, Luisella Alberti, Sabina Maria Bruno, Carlo Corbetta, Erminio Torresani, Carla Colombo, Manuela Seia
Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we tested the clinical and laboratory validity of an extended search for mutations in CFTR using a next-generation sequencing-based method, with a panel of 188 CFTR mutations customized for the Italian population...
July 19, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28736295/digital-multiplex-ligation-dependent-probe-amplification-for-detection-of-key-copy-number-alterations-in-t-and-b-cell-lymphoblastic-leukemia
#14
Anne Benard-Slagter, Ilse Zondervan, Karel de Groot, Farzaneh Ghazavi, Virinder Sarhadi, Pieter Van Vlierberghe, Barbara De Moerloose, Claire Schwab, Kim Vettenranta, Christine J Harrison, Sakari Knuutila, Jan Schouten, Tim Lammens, Suvi Savola
Recurrent and clonal genetic alterations are characteristic of different subtypes of T- and B-cell lymphoblastic leukemia (ALL), and several subtypes are strong independent predictors of patient outcome. A next-generation sequencing-based multiplex ligation-dependent probe amplification variant (digitalMLPA) has been developed enabling simultaneous detection of copy number alterations (CNAs) of up to 1000 target sequences. This novel digitalMLPA assay was designed and optimized to detect CNAs of 56 key target genes and regions in ALL...
July 19, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28736264/mesenchymal-stem-stromal-cell-extracellular-vesicles-from-active-principle-to-next-generation-drug-delivery-system
#15
REVIEW
Barbara Crivelli, Theodora Chlapanidas, Sara Perteghella, Enrico Lucarelli, Luisa Pascucci, Anna Teresa Brini, Ivana Ferrero, Mario Marazzi, Augusto Pessina, Maria Luisa Torre
It has been demonstrated that the biological effector of mesenchymal stem/stromal cells (MSCs) is their secretome, which is composed of a heterogeneous pool of bioactive molecules, partially enclosed in extracellular vesicles (EVs). Therefore, the MSC secretome (including EVs) has been recently proposed as possible alternative to MSC therapy. The secretome can be considered as a protein-based biotechnological product, it is probably safer compared with living/cycling cells, it presents virtually lower tumorigenic risk, and it can be handled, stored and sterilized as an Active Pharmaceutical/Principle Ingredient (API)...
July 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28736138/how-viral-genetic-variants-and-genotypes-influence-disease-and-treatment-outcome-of-chronic-hepatitis-b-time-for-an-individualized-approach
#16
REVIEW
Neil Rajoriya, Christophe Combet, Fabien Zoulim, Harry L A Janssen
Chronic hepatitis B virus (HBV) infection remains a global problem. Several HBV (sub)genotypes exist with different biology and geographical preponderances. While the future aim of HBV treatment remains virus eradication, current strategies of treatment aim to suppress the virus and prevent the progression of liver disease. Current strategies also involve identification of patients for treatment - those at risk of progressive liver disease. Identification of HBV genotype, HBV mutants and other predictive factors allow for tailored treatments, and also risk-surveillance pathways such as for hepatocellular cancer screening...
July 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#17
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28735491/nanofluidic-allele-specific-digital-pcr-method-for-quantifying-idh1-and-idh2-mutation-burden-in-acute-myeloid-leukemia
#18
Daniel H Wiseman, Tim C P Somervaille
Precise quantitation of allelic burden for a pathogenic mutation has diverse clinical and research applications but can be difficult to achieve with conventional qPCR-based techniques, especially at lower mutant allele frequencies. Digital PCR overcomes many of the limitations of qPCR and can be highly quantitative even for single-nucleotide variants, with distinct advantages over next-generation sequencing approaches. Here we describe a method combining the principles of TaqMan(®)-chemistry SNP genotyping with microfluidic digital PCR to generate a highly sensitive, quantitative allele-specific digital PCR assay for the six most common IDH1 and IDH2 mutations encountered in myeloid malignancy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735489/a-zebrafish-model-for-evaluating-the-function-of-human-leukemic-gene-idh1-and-its-mutation
#19
Alvin C H Ma, Xiangguo Shi, Bai-Liang He, Yuhan Guo, Anskar Y H Leung
The recent advent of next-generation sequencing (NGS) has greatly accelerated identification of gene mutations in myeloid malignancies at unprecedented speed that will soon outpace their functional validation by conventional laboratory techniques and animal models. A high-throughput whole-organism model is useful for the functional validation of new mutations. We recently reported the use of zebrafish to evaluate the hematopoietic function of isocitrate dehydrogenase 1 (IDH1) and the effects of expressing human IDH1-R132H that is frequently identified in human acute myeloid leukemia (AML), in myelopoiesis, with a view to develop zebrafish as a model of AML...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735488/bioinformatics-data-analysis-of-next-generation-sequencing-data-from-heterogeneous-tumor-samples
#20
Sean R Landman, Tae Hyun Hwang
Tumor heterogeneity is a major challenge when it comes to treating cancer and also complicates research aimed at determining genetic sources for tumorigenesis. Leveraging high-throughput sequencing technology has been an effective approach for advancing our understanding of genetic diseases, and this type of data can also be used to better understand and make inferences about tumor heterogeneity. Here we describe the basics of genomics data analysis, as well as analysis pipelines for investigating tumor heterogeneity with next-generation sequencing data...
2017: Methods in Molecular Biology
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