Background: Eversense CGM is the first implantable long-term continuous glucose monitoring system. Prior studies evaluated the safety of the system using a study design of one insertion and removal cycle. The purpose of this prospective PMCF registry was to assess the long-term safety of the Eversense CGM System after repeated insertions. Methods: Eversense users from 15 European countries were followed prospectively until the first 100 participants completed their 4th insertion cycle. Visits were made every 90 to 180 days (dependent on sensor configuration) to replace sensors once sensor end life was reached. At each visit, Adverse Events (AEs) that occurred during the visit or during use since the previous visit were recorded. The primary endpoint was the rate of serious adverse events (SAEs) that were device-related, procedure-related, or drug (dexamethasone acetate) related through the sensor insertion/removal cycles. Results: 3066 participants were enrolled in the study with 43% on 2 or more sensor cycles. There were no device- or procedure-related SAEs reported. A total of 130 potentially-related AEs were reported, of which 106 were adjudicated as related or possibly/probably related to the device or insertion/removal procedure. Conclusion: Repeat insertions of the Eversense CGM confirmed the promising safety profile of prior studies and show it to be safe for long-term continuous use. Disclosure G. Carlson: Consultant; Self; Abbott Laboratories, Edwards Lifesciences Corporation, Senseonics, St. Jude Medical. K.S. Tweden: Employee; Self; Senseonics. C. Mdingi: Employee; Self; Senseonics. H. Haridas: Employee; Self; Senseonics.

Background: Dexamethasone (DEX) is used in a variety of implantable medical devices to decrease inflammation and improve outcomes. The implantable Eversense® CGM System (Senseonics, Inc.) includes a silicone collar which slowly releases DEX acetate throughout the lifetime of the sensor. Studies were performed to characterize the potential user risk to dexamethasone acetate exposure. Methods: Clinical trial subjects underwent frequent blood sampling for analysis of plasma DEX levels. Chemical testing of 90-day sensor explants was used to measure residual DEX content. Finally, a post market clinical follow-up study (PMCF) is currently ongoing which monitors the rate of serious device-related, procedure-related, or drug (DEX) related adverse events through approximately 24 months. Results: In two trials (N=161, 86 with 2 sensors, 75 with 1 sensor), blood tests were performed to the 2 ng/mL level with no detectable plasma DEX. In a third trial (N=35), the limit of detection was reduced to 0.050 ng/mL. Blood samples from 8 patients inserted with one sensor had no measurable DEX plasma levels. Among 27 patients inserted with two sensors, the highest level of DEX detected was 0.114 ng/mL on day 2 post-insertion. All samples were below the detectable limit by day 8. Literature review states at plasma levels < 1 ng/mL no systemic effect occurs. Testing of sensor explants determined that 0.3 mg of DEX is eluted over 90 days. No adverse events related to exposure to DEX have been reported to date in the PMCF Conclusions: Dexamethasone acetate, which was selected to reduce the inflammatory response of the implantable sensor, was found to be safe. Plasma DEX levels after extended use are well below the concentration necessary for a pharmacological response, demonstrating safety of the Eversense Sensor with regard to clinical adverse effects attributable to chronic DEX exposure and that this risk should not grow over time. Disclosure E.L. Kelley: Employee; Self; Senseonics. H. Haridas: Employee; Self; Senseonics. C. Lorenz: Employee; Self; Senseonics.

Aggregation of the amyloid‐β peptide (Aβ) into fibrillar structures is a hallmark of Alzheimer's disease. Thus, preventing self‐assembly of the Aβ peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aβ aggregation. Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of Aβ42 but nonetheless inhibits amyloid growth. Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric Aβ42 by salt bridges with charged side chains, and van der Waals contacts with residues in and around the central hydrophobic cluster (17LVFFA21). NMR experiments on the nonaggregative fragment Aβ12–28 did not evidence specific intermolecular interactions between the peptide and carnosine, in agreement with MD simulations. However, a close inspection of the spectra revealed that carnosine interferes with the local propensity of the peptide to form backbone hydrogen bonds close to the central hydrophobic cluster (residues E22, S26 and N27). Finally, MD simulations of aggregation‐prone Aβ heptapeptide segments show that carnosine reduces the propensity to form intermolecular backbone hydrogen bonds in the region 18–24. Taken together, the experimental and simulation results (cumulative MD sampling of 0.2 ms) suggest that, despite the inability of carnosine to form stable contacts with Aβ, it might block the pathway toward toxic aggregates by perturbing the hydrogen bond network near residues with key roles in fibrillogenesis.

Background Collecting scientific publications related to a specific topic is crucial for different phases of research, health care and ‘effective text mining’. Available bio-literature search engines vary in their ability to scan different sections of articles, for the user-provided search terms and/or phrases. Since a thorough scientific analysis of all major bibliographic tools has not been done, their selection has often remained subjective. We have considered most of the existing bio-literature search engines (http://www.shodhaka.com/startbioinfo/LitSearch.html) and performed an extensive analysis of 18 literature search engines, over a period of about 3 years. Eight different topics were taken and about 50 searches were performed using the selected search engines. The relevance of retrieved citations was carefully assessed after every search, to estimate the citation retrieval efficiency. Different other features of the search tools were also compared using a semi-quantitative method. Results The study provides the first tangible comparative account of relative retrieval efficiency, input and output features, resource coverage and a few other utilities of the bio-literature search tools. The results show that using a single search tool can lead to loss of up to 75% relevant citations in some cases. Hence, use of multiple search tools is recommended. But, it would also not be practical to use all or too many search engines. The detailed observations made in the study can assist researchers and health professionals in making a more objective selection among the search engines. A corollary study revealed relative advantages and disadvantages of the full-text scanning tools.*Conclusion*While many studies have attempted to compare literature search engines, important questions remained unanswered till date. Following are some of those questions, along with answers provided by the current study:a) Which tools should be used to get the maximum number of relevant citations with a reasonable effort? ANSWER: _Using PubMed, Scopus, Google Scholar and HighWire Press individually, and then compiling the hits into a union list is the best option. Citation-Compiler (http://www.shodhaka.com/compiler) can help to compile the results from each of the recommended tool._b) What is the approximate percentage of relevant citations expected to be lost if only one search engine is used? ANSWER: _About 39% of the total relevant citations were lost in searches across 4 topics; 49% hits were lost while using PubMed or HighWire Press, while 37% and 20% loss was noticed while using Google Scholar and Scopus, respectively._c) Which full text search engines can be recommended in general? ANSWER: HighWire Press and Google Scholar. d) Among the mostly used search engines, which one can be recommended for best precision? ANSWER: EBIMed. e) Among the mostly used search engines, which one can be recommended for best recall? ANSWER: Depending on the type of query used, best recall could be obtained by HighWire Press or Scopus.

Background: Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G(3)X(n1)G3X(n2)G(3)X(n3)G(3) motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of G-quadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data.Results: We have used all quadruplex DNA structures deposited in the Nucleic Acid Database in order to select a list of fragments entailing a strand of three adjacent G's paired with another strand of three adjacent G's separated by a loop of one to four residues. These fragments were further clustered and representative fragments were finally selected. Further fragments were generated by assemblying the two strands of each fragment with loops from different fragments whenever the anchor G's were superimposable. The fragments were used to assemble G quadruplex based on a superimposability criterion.Conclusion: Molecular models have been generated for a large number of G3Xn1G3Xn2G3Xn3G3 sequences. For a given sequence not all topologies are possible with the available repertoire of fragments due to steric hindrance and low superimposability. Since all molecular models are generated by fragments coming from observed quadruplex structures, molecular models are in principle reliable and may be used for interpretation of experimental data. Some examples of applications are given.

With increasing number of bibliographic software, scientists and health professionals either make a subjective choice of tool(s) that could suit their needs or face a challenge of analyzing multiple features of a plethora of search programs. There is an urgent need for a thorough comparative analysis of the available bio-literature scanning tools, from the user’s perspective. We report results of the first time semi-quantitative comparison of 21 programs, which can search published (partial or full text) documents in life science areas. The observations can assist life science researchers and medical professionals to make an informed selection among the programs, depending on their search objectives. Some of the important findings are: 1. Most of the hits obtained from Scopus, ReleMed, EBImed, CiteXplore, and HighWire Press were usually relevant (i.e. these tools show a better precision than other tools). 2. But a very high number of relevant citations were retrieved by HighWire Press, Google Scholar, CiteXplore and Pubmed Central (they had better recall). 3. HWP and CiteXplore seemed to have a good balance of precision and recall efficiencies. 4. PubMed Central, PubMed and Scopus provided the most useful query systems. 5. GoPubMed, BioAsk, EBIMed, ClusterMed could be more useful among the tools that can automatically process the retrieved citations for further scanning of bio-entities such as proteins, diseases, tissues, molecular interactions, etc. The authors suggest the use of PubMed, Scopus, Google Scholar and HighWire Press - for better coverage, and GoPubMed - to view the hits categorized based on the MeSH and gene ontology terms. The article is relavant to all life science subjects.

With increasing number of bio-literature search engines, scientists and health professionals either make a subjective choice of tool(s) or face a challenge of analyzing multiple features of a plethora of bibliographic software. There is an urgent need for a thorough comparative analysis of the available literature scanning tools, from the user’s perspective. We report results of the first time semi-quantitative comparison of 21 search programs, which can search published (partial or full text) documents in life science areas. The observations can assist life science researchers and medical professionals to make an informed selection among the programs, depending on their search objectives. Some of the important findings are: 1. Most of the hits obtained from Scopus, ReleMed, EBImed, CiteXplore, and HighWire Press were usually relevant (i.e., these tools showed a better precision than other tools). 2. But a very high number of relevant citations were retrieved by HighWire Press, Google Scholar, CiteXplore and Pubmed Central (they had better recall). 3. HWP and CiteXplore seemed to have a good balance of precision and recall efficiencies. 4. PubMed Central, PubMed and Scopus provided the most useful query systems. 5. GoPubMed, BioAsk, EBIMed, ClusterMed could be more useful among the tools that can automatically process the retrieved citations for further scanning of bio-entities such as proteins, diseases, tissues, molecular interactions etc). The authors suggest the use of PubMed, Scopus, Google Scholar and HighWire Press - for better coverage, and GoPubMed - to view the hits categorized based on the MeSH and gene ontology terms.