Chemical Synthesis of Δ-4,5 Unsaturated Heparan Sulfate Oligosaccharides for Biomarker Discovery.

A methodology is described that can provide heparan sulfate oligosaccharides having a Δ4,5-double bond, which are needed as analytical standards and biomarkers for mucopolysaccharidoses. It is based on chemical oligosaccharide synthesis followed by modification of the C-4 hydroxyl of the terminal uronic acid moiety as methanesulfonate. This leaving group is stable under conditions used to remove temporary protecting groups, -sulfation, and hydrogenolysis.

Does the acceptance of hybrid learning affect learning approaches in France?

Purpose: Acceptance of a learning technology affects students' intention to use that technology, but the influence of the acceptance of a learning technology on learning approaches has not been investigated in the literature. A deep learning approach is important in the field of health, where links must be created between skills, knowledge, and habits. Our hypothesis was that acceptance of a hybrid learning model would affect students' way of learning.

Heparan Sulfate Microarray Reveals That Heparan Sulfate-Protein Binding Exhibits Different Ligand Requirements.

Heparan sulfates (HS) are linear sulfated polysaccharides that modulate a wide range of physiological and disease-processes. Variations in HS epimerization and sulfation provide enormous structural diversity, which is believed to underpin protein binding and regulatory properties. The ligand requirements of HS-binding proteins have, however, been defined in only a few cases.

Extension and validation of the GLYCAM force field parameters for modeling glycosaminoglycans.

Glycosaminoglycans (GAGs) are an important class of carbohydrates that serve critical roles in blood clotting, tissue repair, cell migration and adhesion, and lubrication. The variable sulfation pattern and iduronate ring conformations in GAGs influence their polymeric structure and nature of interaction. This study characterizes several heparin-like GAG disaccharides and tetrasaccharides using NMR and molecular dynamics simulations to assist in the development of parameters for GAGs within the GLYCAM06 force field.

Using visual analytics for presenting comparative information on new drugs.

Objective: When a new drug is marketed, physicians must decide whether they will consider it for their future practice. However, information about new drugs can be biased or hard to find. In this work, our objective was to study whether visual analytics could be used for comparing drug properties such as contraindications and adverse effects, and whether this visual comparison can help physicians to forge their own well-founded opinions about a new drug.

Design of a Visual Interface for Comparing Antibiotics Using Rainbow Boxes.

Non-optimal prescriptions of antibiotics have a negative impact on patients and population. Clinical practice guidelines are not always followed by doctors because the rationale of the recommendations is not always clear and can be difficult to understand. In this paper, we propose a new approach consisting in presenting the properties of antibiotics for allowing doctors to compare them and choose the most appropriate one.

Parallel Design of Browsing Scheme and Data Model for Multi-Level Hierarchical Application Devoted to Management of Patient with Infectious Disease in Primary Care.

Many decision systems are based on a hierarchical approach, enriching the known context used to finally choose the right potential action. Designing the scheme for browsing the clinical guidelines is a task devoted to expert in infectious diseases. Designing the data model is a task devoted to the expert in data modeling.

De Novo Sequencing of Complex Mixtures of Heparan Sulfate Oligosaccharides.

Here, we describe the first sequencing method of a complex mixture of heparan sulfate tetrasaccharides by LC-MS/MS. Heparin and heparan sulfate (HS) are linear polysaccharides that are modified in a complex manner by N- and O-sulfation, N-acetylation, and epimerization of the uronic acid. Heparin and HS are involved in various essential cellular communication processes.

Abstractive Summarization of Drug Dosage Regimens for Supporting Drug Comparison.

Complicated dosage regimens often reduce adherence to drug treatments. The ease-of-administration must thus be taken into account when prescribing. Given one drug, there exists often several dosage regimens.

Design and evaluation of a software for the objective and easy-to-read presentation of new drug properties to physicians.

Background: When new pharmaceutical products appear on the market, physicians need to know whether they are likely to be useful in their practices. Physicians currently obtain most of their information about the market release and properties of new drugs from pharmaceutical industry representatives. However, the official information contained in the summary of product characteristics (SPCs) and evaluation reports from health agencies, provide a more complete view of the potential value of new drugs, although they can be long and difficult to read.

PyMedTermino: an open-source generic API for advanced terminology services.

The integration of terminologies is still a challenging problem in medical informatics research and software applications, due to the high number of heterogeneous terminologies. In this paper, we present a generic API (Application Programming Interface) for a multi-terminology multilingual terminology service, and PyMedTermino, its open-source implementation in Python with 5 terminological resources (ICD10, SNOMED CT, MedDRA, CDF, VCM iconic language) and the UMLS compendium. This service has been designed for research and educational purpose.

Using an iconic language to improve access to electronic medical records in general medicine.

Physicians have difficulties to access and analyse information in a medical record. In a previous work on drug databanks, we have shown that with an iconic language as VCM, an icon-based presentation can help physicians to access medical information. Our objective, herein, is to study whether VCM can be used in an electronic medical record for facilitating physician access in general practice.

Towards evidence-based CDSSs implementing the medical reasoning contained in CPGs: application to antibiotic prescription.

Unlabelled: Clinical practice guidelines (CPGs) are documents giving recommendations based on expert reasoning, weighing up the pros and cons of treatments on the basis of the available evidence. We propose a new approach to the construction of clinical decision support systems (CDSS), making use of the evidence-based medical reasoning used by experts in CPGs. In this study, we determined whether this approach could retrieve the recommendations for antibiotic prescription for empirical treatment in primary care.

Improving access to clinical practice guidelines with an interactive graphical interface using an iconic language.

Background: Clinical practice guidelines are useful for physicians, and guidelines are available on the Internet from various websites such as Vidal Recos. However, these guidelines are long and difficult to read, especially during consultation. Similar difficulties have been encountered with drug summaries of product characteristics.

Design and usability study of an iconic user interface to ease information retrieval of medical guidelines.

Background And Objective: Doc'CISMeF (DC) is a semantic search engine used to find resources in CISMeF-BP, a quality controlled health gateway, which gathers guidelines available on the internet in French. Visualization of Concepts in Medicine (VCM) is an iconic language that may ease information retrieval tasks. This study aimed to describe the creation and evaluation of an interface integrating VCM in DC in order to make this search engine much easier to use.

Evaluating alignment quality between iconic language and reference terminologies using similarity metrics.

Background: Visualization of Concepts in Medicine (VCM) is a compositional iconic language that aims to ease information retrieval in Electronic Health Records (EHR), clinical guidelines or other medical documents. Using VCM language in medical applications requires alignment with medical reference terminologies. Alignment from Medical Subject Headings (MeSH) thesaurus and International Classification of Diseases - tenth revision (ICD10) to VCM are presented here.

An Algorithm Using Twelve Properties of Antibiotics to Find the Recommended Antibiotics, as in CPGs.

Background: Clinical Decision Support Systems (CDSS) incorporating justifications, updating and adjustable recommendations can considerably improve the quality of healthcare. We propose a new approach to the design of CDSS for empiric antibiotic prescription, based on implementation of the deeper medical reasoning used by experts in the development of clinical practice guidelines (CPGs), to deduce the recommended antibiotics.

Methods: We investigated two methods ("exclusion" versus "scoring") for reproducing this reasoning based on antibiotic properties.

High-field asymmetric-waveform ion mobility spectrometry and electron detachment dissociation of isobaric mixtures of glycosaminoglycans.

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is shown to be capable of resolving isomeric and isobaric glycosaminoglycan negative ions and to have great utility for the analysis of this class of molecules when combined with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tandem mass spectrometry. Electron detachment dissociation (EDD) and other ion activation methods for tandem mass spectrometry can be used to determine the sites of labile sulfate modifications and for assigning the stereochemistry of hexuronic acid residues of glycosaminoglycans (GAGs). However, mixtures with overlapping mass-to-charge values present a challenge, as their precursor species cannot be resolved by a mass analyzer prior to ion activation.

Comparison of two kinds of interface, based on guided navigation or usability principles, for improving the adoption of computerized decision support systems: application to the prescription of antibiotics.

Context: It is important to consider the way in which information is presented by the interfaces of clinical decision support systems, to favor the adoption of these systems by physicians. Interface design can focus on decision processes (guided navigation) or usability principles.

Objective: The aim of this study was to compare these two approaches in terms of perceived usability, accuracy rate, and confidence in the system.

A guideline-derived model to facilitate the implementation of test-ordering rules within a hospital information system.

The culture of evidence-based practice includes also the field of laboratory medicine. Clinical laboratory expenditure is growing rapidly for various reasons including increased utilization. Delivering decision support to requesters at the point of care is one of the main incentives for implementing laboratory guidelines.

A semi-automatic semantic method for mapping SNOMED CT concepts to VCM Icons.

VCM (Visualization of Concept in Medicine) is an iconic language for representing key medical concepts by icons. However, the use of this language with reference terminologies, such as SNOMED CT, will require the mapping of its icons to the terms of these terminologies. Here, we present and evaluate a semi-automatic semantic method for the mapping of SNOMED CT concepts to VCM icons.

Comparing the use of SNOMED CT and ICD10 for coding clinical conditions to implement laboratory guidelines.

Laboratory medicine is responsible for an important part of hospital expenditure. Providing appropriate decision support to laboratory test requesters at the point of care is one of the main incentives for implementing laboratory guidelines, which can improve medical care. Laboratory guidelines developed by local experts in the Parisian region and two national guidelines for dyslipidemia were analyzed to extract test ordering recommendations.

Designing concept maps for a precise and objective description of pharmaceutical innovations.

Background: When a new drug is launched onto the market, information about the new manufactured product is contained in its monograph and evaluation report published by national drug agencies. Health professionals need to be able to determine rapidly and easily whether the new manufactured product is potentially useful for their practice. There is therefore a need to identify the best way to group together and visualize the main items of information describing the nature and potential impact of the new drug.

Fluorous supported modular synthesis of heparan sulfate oligosaccharides.

The modular synthesis of heparan sulfate fragments is greatly facilitated by employing an anomeric aminopentyl linker protected by a benzyloxycarbonyl group modified by a perfluorodecyl tag, which made it possible to purify highly polar intermediates by fluorous solid phase extraction. This tagging methodology made it also possible to perform repeated glycosylations to drive reactions to completion.

ELECTRON DETACHMENT DISSOCIATION OF SYNTHETIC HEPARAN SULFATE GLYCOSAMINOGLYCAN TETRASACCHARIDES VARYING IN DEGREE OF SULFATION AND HEXURONIC ACID STEREOCHEMISTRY.

Glycosaminoglycan (GAG) carbohydrates provide a challenging analytical target for structural determination due to their polydisperse nature, non-template biosynthesis, and labile sulfate modifications. The resultant structures, although heterogeneous, contain domains which indicate a sulfation pattern or code that correlates to specific function. Mass spectrometry, in particular electron detachment dissociation Fourier transform ion cyclotron resonance (EDD FT-ICR MS), provides a highly sensitive platform for GAG structural analysis by providing cross-ring cleavages for sulfation location and product ions specific to hexuronic acid stereochemistry.