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https://www.readbyqxmd.com/read/29146178/use-of-mathematical-modelling-to-assess-the-impact-of-vaccines-on-antibiotic-resistance
#1
REVIEW
Katherine E Atkins, Erin I Lafferty, Sarah R Deeny, Nicholas G Davies, Julie V Robotham, Mark Jit
Antibiotic resistance is a major global threat to the provision of safe and effective health care. To control antibiotic resistance, vaccines have been proposed as an essential intervention, complementing improvements in diagnostic testing, antibiotic stewardship, and drug pipelines. The decision to introduce or amend vaccination programmes is routinely based on mathematical modelling. However, few mathematical models address the impact of vaccination on antibiotic resistance. We reviewed the literature using PubMed to identify all studies that used an original mathematical model to quantify the impact of a vaccine on antibiotic resistance transmission within a human population...
November 13, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29140767/genomic-medicine-without-borders-which-strategies-should-developing-countries-employ-to-invest-in-precision-medicine-a-new-fast-second-winner-strategy
#2
Konstantinos Mitropoulos, David N Cooper, Christina Mitropoulou, Spiros Agathos, Jürgen K V Reichardt, Fatima Al-Maskari, Wasun Chantratita, Ambroise Wonkam, Collet Dandara, Theodora Katsila, Catalina Lopez-Correa, Bassam R Ali, George P Patrinos
Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a "one-size-fits-all-countries" development strategy, in the same way that drug treatments should be customized...
November 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/29132317/development-of-amplicon-deep-sequencing-markers-and-data-analysis-pipeline-for-genotyping-multi-clonal-malaria-infections
#3
Anita Lerch, Cristian Koepfli, Natalie E Hofmann, Camilla Messerli, Stephen Wilcox, Johanna H Kattenberg, Inoni Betuela, Liam O'Connor, Ivo Mueller, Ingrid Felger
BACKGROUND: Amplicon deep sequencing permits sensitive detection of minority clones and improves discriminatory power for genotyping multi-clone Plasmodium falciparum infections. New amplicon sequencing and data analysis protocols are needed for genotyping in epidemiological studies and drug efficacy trials of P. falciparum. METHODS: Targeted sequencing of molecular marker csp and novel marker cpmp was conducted in duplicate on mixtures of parasite culture strains and 37 field samples...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29128423/amorphous-solid-dispersions-and-nanocrystal-technologies-for-poorly-water-soluble-drug-delivery-an-update
#4
Scott V Jermain, Chris Brough, Robert O Williams
Poor water-solubility remains a typical property of drug candidates in pharmaceutical development pipelines today. Various processes have been developed to increase the solubility, dissolution rate, and bioavailability of these active ingredients belonging to biopharmaceutical classification system (BCS) II and IV classifications. Since the early 2000s, nanocrystal delivery and amorphous solid dispersions are more established techniques to overcome the limitations of poorly-water soluble drugs in FDA available products...
November 8, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29126202/activedriverdb-human-disease-mutations-and-genome-variation-in-post-translational-modification-sites-of-proteins
#5
Michal Krassowski, Marta Paczkowska, Kim Cullion, Tina Huang, Irakli Dzneladze, B F Francis Ouellette, Joseph T Yamada, Amelie Fradet-Turcotte, Jüri Reimand
Interpretation of genetic variation is needed for deciphering genotype-phenotype associations, mechanisms of inherited disease, and cancer driver mutations. Millions of single nucleotide variants (SNVs) in human genomes are known and thousands are associated with disease. An estimated 21% of disease-associated amino acid substitutions corresponding to missense SNVs are located in protein sites of post-translational modifications (PTMs), chemical modifications of amino acids that extend protein function. ActiveDriverDB is a comprehensive human proteo-genomics database that annotates disease mutations and population variants through the lens of PTMs...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29121053/adept-a-semantically-enriched-pipeline-for-extracting-adverse-drug-events-from-free-text-electronic-health-records
#6
Ehtesham Iqbal, Robbie Mallah, Daniel Rhodes, Honghan Wu, Alvin Romero, Nynn Chang, Olubanke Dzahini, Chandra Pandey, Matthew Broadbent, Robert Stewart, Richard J B Dobson, Zina M Ibrahim
Adverse drug events (ADEs) are unintended responses to medical treatment. They can greatly affect a patient's quality of life and present a substantial burden on healthcare. Although Electronic health records (EHRs) document a wealth of information relating to ADEs, they are frequently stored in the unstructured or semi-structured free-text narrative requiring Natural Language Processing (NLP) techniques to mine the relevant information. Here we present a rule-based ADE detection and classification pipeline built and tested on a large Psychiatric corpus comprising 264k patients using the de-identified EHRs of four UK-based psychiatric hospitals...
2017: PloS One
https://www.readbyqxmd.com/read/29121043/the-poverty-related-neglected-diseases-why-basic-research-matters
#7
Peter J Hotez
Together, malaria and the neglected tropical diseases (NTDs) kill more than 800,000 people annually, while creating long-term disability in millions more. International support for mass drug administration, bed nets, and other preventive measures has resulted in huge public health gains, while support for translational research is leading to the development of some new neglected disease drugs, diagnostics, and vaccines. However, funding for basic science research has not kept up, such that we are missing opportunities to create a more innovative pipeline of control tools for parasitic and related diseases...
November 2017: PLoS Biology
https://www.readbyqxmd.com/read/29119409/recent-developments-in-adc-technology-preclinical-studies-signal-future-clinical-trends
#8
REVIEW
Penelope M Drake, David Rabuka
The antibody-drug conjugate (ADC) field is in a transitional period. Older approaches to conjugate composition and dosing regimens still dominate the ADC clinical pipeline, but preclinical work is driving a rapid evolution in how we strategize to improve efficacy and reduce toxicity towards better therapeutic outcomes. These advances are largely based upon a body of investigational studies that together offer a deeper understanding of the absorption, distribution, metabolism, and excretion (ADME) and drug metabolism and pharmacokinetics (DMPK) fates of both the intact conjugate and its small-molecule component...
November 8, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29116600/recent-progress-in-the-pharmacotherapy-of-alzheimer-s-disease
#9
Rita Khoury, Kush Patel, Jake Gold, Stephanie Hinds, George T Grossberg
Alzheimer's disease is the most common major neurocognitive disorder with substantial social and economic impacts. This article is an update on current pharmacotherapy, advancements in biomarker use, and drugs in the pipeline for this disease. To date, no new drug has qualified to be added to the current therapeutic arsenal comprising cholinesterase inhibitors and the NMDA receptor antagonist memantine. Drugs in the pipeline include symptomatic therapies that are neurotransmitter-based, but mostly disease-modifying therapies...
November 7, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/29112695/recent-development-of-antismash-and-other-computational-approaches-to-mine-secondary-metabolite-biosynthetic-gene-clusters
#10
Kai Blin, Hyun Uk Kim, Marnix H Medema, Tilmann Weber
Many drugs are derived from small molecules produced by microorganisms and plants, so-called natural products. Natural products have diverse chemical structures, but the biosynthetic pathways producing those compounds are often organized as biosynthetic gene clusters (BGCs) and follow a highly conserved biosynthetic logic. This allows for the identification of core biosynthetic enzymes using genome mining strategies that are based on the sequence similarity of the involved enzymes/genes. However, mining for a variety of BGCs quickly approaches a complexity level where manual analyses are no longer possible and require the use of automated genome mining pipelines, such as the antiSMASH software...
November 3, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29110597/the-in-silico-drug-discovery-toolbox-applications-in-lead-discovery-and-optimization
#11
Agostino Bruno, Gabriele Costantino, Luca Sartori, Marco Radi
Discovery and development of a new drug is a long lasting and expensive journey that takes around 15 years from starting idea to approval and marketing of new medication. Despite the R&D expenditures have been constantly increasing in the last few years, number of new drugs introduced into market has been steadily declining. This is mainly due to preclinical and clinical safety issues, which still represent about 40% of drug discontinuation. From this point of view, it is clear that if we want to increase drug-discovery success rate and reduce costs associated with development of a new drug, a comprehensive evaluation/prediction of potential safety issues should be conducted as soon as possible during early drug discovery phase...
November 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29106664/proteomicsdb
#12
Tobias Schmidt, Patroklos Samaras, Martin Frejno, Siegfried Gessulat, Maximilian Barnert, Harald Kienegger, Helmut Krcmar, Judith Schlegl, Hans-Christian Ehrlich, Stephan Aiche, Bernhard Kuster, Mathias Wilhelm
ProteomicsDB (https://www.ProteomicsDB.org) is a protein-centric in-memory database for the exploration of large collections of quantitative mass spectrometry-based proteomics data. ProteomicsDB was first released in 2014 to enable the interactive exploration of the first draft of the human proteome. To date, it contains quantitative data from 78 projects totalling over 19k LC-MS/MS experiments. A standardized analysis pipeline enables comparisons between multiple datasets to facilitate the exploration of protein expression across hundreds of tissues, body fluids and cell lines...
November 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29101083/draft-genome-sequence-of-a-tigecycline-resistant-kpc-2-producing-klebsiella-pneumoniae-st15-clinical-isolate-from-china
#13
Juan Xu, Meng Gao, Yan Hong, Fang He
OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have emerged worldwide as a serious challenge to public health. Tigecycline is regarded as one of the last-resort antimicrobials for CRKP infections. Here we report the draft genome sequence of a clinical tigecycline-resistant KPC-2-producing K. pneumoniae isolate (TRKP1). METHODS: Whole-genome sequencing of strain TRKP1 was performed using an Illumina Hiseq™ X Ten system. The generated reads were assembled using CLC Genomics Workbench...
October 31, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29096824/history-of-lipidology-and-lipoprotein-apheresis
#14
Ulrich Julius
This review tells the story of atherosclerosis research in the beginning of the 20th century. It presents the significance of cardiovascular diseases and addresses major questions currently being discussed among lipidologists and the current thinking with respect to low LDL-cholesterol levels and HDL. It provides an overview of the period during which lipid-modifying drugs were introduced and their relevance with respect to cardiovascular outcome data and lists possible reasons why some patients develop new cardiovascular events while being treated with statins...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29084285/influence-of-surface-geometry-on-the-culture-of-human-cell-lines-a-comparative-study-using-flat-round-bottom-and-v-shaped-96-well-plates
#15
Sara Shafaie, Victoria Hutter, Marc B Brown, Michael T Cook, David Y S Chau
In vitro cell based models have been invaluable tools for studying cell behaviour and for investigating drug disposition, toxicity and potential adverse effects of administered drugs. Within this drug discovery pipeline, the ability to assess and prioritise candidate compounds as soon as possible offers a distinct advantage. However, the ability to apply this approach to a cell culture study is limited by the need to provide an accurate, in vitro-like, microenvironment in conjunction with a low cost and high-throughput screening (HTS) methodology...
2017: PloS One
https://www.readbyqxmd.com/read/29082492/live-cell-high-content-screening-in-drug-development
#16
Milan Esner, Felix Meyenhofer, Marc Bickle
In the past decade, automated microscopy has become an important tool for the drug discovery and development process. The establishment of imaging modalities as screening tools depended on technological breakthroughs in the domain of automated microscopy and automated image analysis. These types of assays are often referred to as high content screening or high content analysis (HCS/HCA). The driving force to adopt imaging for drug development is the quantity and quality of cellular information that can be collected and the enhanced physiological relevance of cellular screening compared to biochemical screening...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29081013/emerging-technologies-in-flow-diverters-and-stents-for-cerebrovascular-diseases
#17
REVIEW
Michael Karsy, Jian Guan, Andrea A Brock, Anubhav Amin, Min S Park
PURPOSE OF REVIEW: Stents and flow diverters have revolutionized the treatment of cerebrovascular disease. Guglielmi coils, flexible microcatheters, and first-generation intracranial stents, such as Neuroform (Stryker Neurovascular) and Enterprise stents (Codman/DePuy-Synthes), have paved the way for the development of the Pipeline Embolization Device (PED) (ev3/Covidien/Medtronic) and other endovascular approaches. RECENT FINDINGS: This review discusses the historical development of flow diverter technologies from the PED to similar devices, such as the Surpass stent (Stryker Neurovascular), the Flow-Redirection Endoluminal Device (FRED; MicroVention, Inc...
October 28, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/29071404/scalable-cardiac-differentiation-of-pluripotent-stem-cells-using-specific-growth-factors-and-small-molecules
#18
Henning Kempf, Robert Zweigerdt
The envisioned routine application of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) for therapies and industry-compliant screening approaches will require efficient and highly reproducible processes for the mass production of well-characterized CM batches.On their way toward beating CMs, hPSCs initially undergo an epithelial-to-mesenchymal transition into a primitive-streak (PS)-like population that later gives rise to all endodermal and mesodermal lineages, including cardiovascular progenies (CVPs)...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/29069336/arachnoserver-3-0-an-online-resource-for-automated-discovery-analysis-and-annotation-of-spider-toxins
#19
Sandy S Pineda, Pierre-Alain Chaumeil, Anne Kunert, Quentin Kaas, Mike W C Thang, Lien Li, Michael Nuhn, Volker Herzig, Natalie J Saez, Ben Cristofori-Armstrong, Raveendra Anangi, Sebastian Senff, Dominique Gorse, Glenn F King
Abstract: ArachnoServer is a manually curated database that consolidates information on the sequence, structure, function, and pharmacology of spider-venom toxins. Although spider venoms are complex chemical arsenals, the primary constituents are small disulfide-bridged peptides that target neuronal ion channels and receptors. Due to their high potency and selectivity, these peptides have been developed as pharmacological tools, bioinsecticides, and drug leads. A new version of ArachnoServer (v3...
October 23, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29067343/alzheimer-s-disease-drug-development-pipeline-2017
#20
REVIEW
Jeffrey Cummings, Garam Lee, Travis Mortsdorf, Aaron Ritter, Kate Zhong
INTRODUCTION: There is an urgent need to develop new treatments for Alzheimer's disease (AD) and to understand the drug development process for new AD therapies. METHODS: We assessed the agents in the AD pipeline as documented in clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017. RESULTS: There are 105 agents in the AD treatment development pipeline, of which 25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II, and 28 agents are in 42 trials in phase III...
September 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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