bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clostridiodes difficile: Colonisation versus Infection - The importance of appropriate laboratory testing to minimise risk of overdiagnosis and overtreatment
Authors: Karcher Anne Marie , Lichota Kacsper , Lee Jennifer , Parcell Ben 
Published: March 2020

Background
Clostridiodes difficile (C. difficile) colonisation rates have been reported as ranging from 4-15% in healthy adults to 4-51% in long term care facilities. Inappropriate treatment for C. difficile colonisation alters gut microbiota and can consequently result in C. difficileInfection (CDI). Laboratory testing needs to aid diagnosis while at the same time minimising risk of overdiagnosis and overtreatment.
Methods
An audit was conducted of the number of patients with indeterminate and positive results between 01.09.16 and 31.08.18 to determine the impact of Scottish National C. difficile laboratory testing and CDI case definition Guidance re-inforcement in September/October 2017. A question was also added at sample requesting stage re Pseudomembranous colitis/Toxic megacolon to ensure appropriate testing.

Results
After Guidance re-inforcement, a rapid fall in number of indeterminate results (av. 34/month to 15/month) was observed. Decrease was most marked for GP patients (av. 12/month to 3/month). There was also a decrease in the number of patients with confirmed positive results (av. 9/month to 5/month).

Conclusion
Alignment with National Guidance resulted in significant reduction in patient indeterminate and positive results and assisted clinicians in the clinical diagnosis of CDI. There was also a reduction in the number of laboratory tests and repeat tests for indeterminate results. Therefore, this alignment with National Guidance resulted in Infection Prevention and Control Team, clinical and laboratory time and cost savings.
Necrotizing Otitis Externa: Four theories behind the 15-year astronomic rise of this uncommon infection
Authors: Linton Stefan , Stapleton Emma 
Published: March 2020

INTRODUCTION:
NECROTIZING OTITIS EXTERNA (NOE) IS A SEVERE, LIFE THREATENING PROPAGATING OSTEOMYELITIS OF THE SKULL BASE THAT ORIGINATES FROM A SEVERE OTITIS EXTERNA. THIS RARE CONDITION MAY NOT BE AS UNCOMMON AS ONCE UNDERSTOOD. EPIDEMIOLOGIC DATA REVEALS AN UNEXPECTED AND DRASTIC RISE IN THE NUMBER OF REPORTED CASES OVER THE LAST 15 YEARS. USING NATIONAL DATA AND PUBLISHED LITERATURE, WE EXPLORE FOUR THEORIES BEHIND THE RISE IN INCIDENCE OF THIS CONDITION.

Methods:
A quantitative descriptive study was undertaken using epidemiological data obtained from the Hospital Episode Statistics (HES) database. NOE cases reported between 2002 – 2017 were compiled and analyzed. Using these results and current evidence within the published literature, four theories were formulated and explored to explain the upward trend in incidence.

Results:
There were a total of 7,327 NOE cases reported within the 15-year time period. The majority of cases (60%) occurred in the elderly (Age 75+) with a 5:2 male predominance. Mean length of stay and mean total bed days were 16.3 and 5,019 days, respectively.

Discussion:
The number of NOE cases has increased by more than 1000% within the 15-year time period, from 123 cases in 2002 to 1,405 in 2017. We theorize that this increase maybe due to:
(1) the rising prevalence of diabetes
(2) the increase in antibiotic resistance
(3) the rising ageing population
(4) improved physician awareness of NOE
Learning to prescribe antimicrobials in Northern Ireland
Authors: McKeating Cara , O'Gorman Ciaran 
Published: March 2020

Background: The appropriate use of antimicrobials has implications on individual patient care, drug resistance and worldwide public health. Learning to prescribe antimicrobials is therefore an important part of medical education. The aim of this study was to evaluate novice prescribers’ readiness to use antimicrobials, in order to design valid educational activities.
Methods: A mixed methods study was carried out amongst final year students at Queen’s University Belfast and foundation year 1 (FY1) doctors working in a Northern Ireland hospital. Data was initially collected using a survey, comprised of quantitative and qualitative elements. This was supplemented by semi-structured interviews.
Results: One hundred and fifty-eight students and eighteen doctors participated in the survey. Two students and two doctors were interviewed. Both groups appeared to feel only moderately prepared to prescribe antimicrobials. Agreement with survey statements relating to knowledge and confidence was 61% and 73% for students and FY1 doctors respectively. More focused contextual teaching and practical learning opportunities were felt to be required. Students perceived a long time gap between teaching and clinical exposure. Both groups conveyed the strong influence of the working environment and local prescribing culture. These were sometimes seen as barriers to optimal prescribing. Feedback on prescribing was felt to be useful but lacking.
Conclusion: This study suggests that medical students and foundation doctors do not feel adequately prepared to prescribe antimicrobials, which may lead them to be overly influenced by suboptimal prescribing cultures. A number of curriculum development and quality improvement initiatives are suggested as a result.
Predictions for the binding domain and potential new drug targets of 2019-nCoV
Authors: Zeng Zehua , Luo Zhi , Du Hongwu 
Published: March 2020

AbstractAn outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.
Antibody binding to native cytomegalovirus glycoprotein B predicts vaccine efficacy
Authors: Jenks Jennifer A. , Nelson Cody S. , Roark Hunter K. , Goodwin Matt , Pass Robert F. , Bernstein David I. , Walter Emmanuel B. , Edwards Kathryn M. , Wang Dai , Fu Tong-Ming , An Zhiqiang , Chan Cliburn , Permar Sallie R. 
Published: March 2020

AbstractHuman cytomegalovirus (HCMV) is the most common infectious cause of congenital disease and post-transplant complications worldwide, yet vaccine development remains hampered by a limited understanding of protective immune responses. We investigated humoral immune correlates of protection against HCMV acquisition elicited by the most efficacious HCMV vaccine tested to-date, soluble glycoprotein B (gB) with MF59 adjuvant (gB/MF59), which achieved ∼50% efficacy in two phase II clinical trials. Protection against primary infection correlated with high magnitude antibody binding to gB expressed on a cell surface, but not to the vaccine antigen. Further, we identified monoclonal antibodies that differentially recognized soluble and cell-associated gB, highlighting structural differences essential for protective immunity. These results indicate the importance of the native, cell-associated gB conformation in future HCMV vaccine design.One Sentence SummaryPartially-effective HCMV gB/MF59 vaccine-elicited IgG binding to cell-associated gB correlates with protection against HCMV
Structural and Evolutionary Analysis Indicate that the SARS-CoV-2 Mpro is an Inconvenient Target for Small-Molecule Inhibitors Design
Authors: Bzówka Maria , Mitusińska Karolina , Raczyńska Agata , Samol Aleksandra , Tuszyński Jack A. , Góra Artur 
Published: March 2020

AbstractThe novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mix-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar SARS Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins show major differences in both shape and size indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site’s conformational changes during the simulation time indicates its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicates that the virus’ mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.
Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13
Authors: Lv Longxian , Li Gaolei , Chen Jinhui , Liang Xinle , Li Yudong 
Published: March 2020

AbstractThe novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.
CALGARY NORMATIVE STUDY: STUDY DESIGN OF A PROSPECTIVE LONGITUDINAL STUDY TO CHARACTERIZE POTENTIAL QUANTITATIVE MR BIOMARKERS OVER THE ADULT LIFESPAN
Authors: McCreary Cheryl R , Salluzzi Marina , Andersen Linda B , Gobbi David , Lauzon M Louis , Saad Feryal , Smith Eric E , Frayne Richard 
Published: March 2020

ABSTRACTIntroductionA number of magnetic resonance (MR) imaging methods have been proposed to be useful, quantitative biomarkers of neurodegeneration in aging. The Calgary Normative Study (CNS) is an ongoing single-centre, prospective, longitudinal study that seeks to develop, test and assess quantitative MR methods as potential biomarkers. The CNS has three objectives: first and foremost, to evaluate and characterize the dependence of the selected quantitative neuroimaging biomarkers on age over the adult lifespan; secondly, to evaluate the precision, variability and repeatability of quantitative neuroimaging biomarkers as part of biomarker validation providing proof of-concept and proof-of-principle; and thirdly, provide a shared repository of normative data for comparison to various disease cohorts.Methods and AnalysisQuantitative MR mapping of the brain including longitudinal relaxation time (T1), transverse relaxation time (T2), T2*, magnetic susceptibility (QSM), diffusion and perfusion measurements, as well as morphological assessments are performed. The Montreal Cognitive Assessment (MoCA) and a brief, self-report medical history will be collected. Mixed regression models will be used to characterize changes in quantitative MR biomarker measures over the adult lifespan. In this report on study design, we report interim prevalence and demographic information of recruitment from 28 May 2013 to 31 December 2018.Ethics and DisseminationParticipants provide signed informed consent. Changes in quantitative MR biomarkers measured over the adult lifespan as well as estimates of measurement variance and repeatability will be disseminated through peer-reviewed scientific publication.STRENGTHS AND LIMITATIONSBoth cross-sectional and longitudinal quantitative MR data is being acquired in a large sample normal aging population to characterize changes in these potential neuroimaging biomarkers over the adult lifespan.Clinical and multiple quantitative imaging data are being collected and shared with the research community.Measures of repeatability and a process to update the imaging protocol are included in the study design.Associated self-reported medical history and cognitive assessments are limited
Bactopia: a flexible pipeline for complete analysis of bacterial genomes
Authors: Petit Robert A. , Read Timothy D. 
Published: March 2020

AbstractSequencing of bacterial genomes using Illumina technology has become such a standard procedure that often data are generated faster than can be conveniently analyzed. We created a new series of pipelines called Bactopia, built using Nextflow workflow software, to provide efficient comparative genomic analyses for bacterial species or genera. Bactopia consists of a dataset setup step (Bactopia Datasets; BaDs) where a series of customizable datasets are created for the species of interest; the Bactopia Analysis Pipeline (BaAP), which performs quality control, genome assembly and several other functions based on the available datasets and outputs the processed data to a structured directory format; and a series of Bactopia Tools (BaTs) that perform specific post-processing on some or all of the processed data. BaTs include pan-genome analysis, computing average nucleotide identity between samples, extracting and profiling the 16S genes and taxonomic classification using highly conserved genes. It is expected that the number of BaTs will increase to fill specific applications in the future. As a demonstration, we performed an analysis of 1,664 publicLactobacillusgenomes, focusing onL. crispatus, a species that is a common part of the human vaginal microbiome. Bactopia is an open source system that can scale from projects as small as one bacterial genome to thousands that allows for great flexibility in choosing comparison datasets and options for downstream analysis. Bactopia code can be accessed athttps://www.github.com/bactopia/bactopia.
HLA-class II specificity assessed by high-density peptide microarray interactions
Authors: Osterbye Thomas , Nielsen Morten , Dudek Nadine L. , Ramarathinam Sri H. , Purcell Anthony W. , Schafer-Nielsen Claus , Buus Soren 
Published: March 2020

AbstractThe ability to predict and/or identify MHC binding peptides is an essential component of T cell epitope discovery; something that ultimately should benefit the development of vaccines and immunotherapies. In particular, MHC class I (MHC-I) prediction tools have matured to a point where accurate selection of optimal peptide epitopes is possible for virtually all MHC-I allotypes; in comparison, current MHC class II (MHC-II) predictors are less mature. Since MHC-II restricted CD4+ T cells control and orchestrate most immune responses, this shortcoming severely hampers the development of effective immunotherapies. The ability to generate large panels of peptides and subsequently large bodies of peptide-MHC-II interaction data is key to the solution of this problem; a solution that also will support the improvement of bioinformatics predictors, which critically relies on the availability of large amounts of accurate, diverse and representative data. Here, we have used recombinant HLA-DRB1*01:01 and HLA-DRB1*03:01 molecules to interrogate high-density peptide arrays,in casucontaining 70,000 random peptides in triplicates. We demonstrate that the binding data acquired contains systematic and interpretable information reflecting the specificity of the HLA-DR molecules investigated. Collectively, with a cost per peptide reduced to a few cents combined with the flexibility of recombinant HLA technology, this poses an attractive strategy to generate vast bodies of MHC-II binding data at an unprecedented speed and for the benefit of generating peptide-MHC-II binding data as well as improving MHC-II prediction tools.
Validation of melomind™ signal quality: a proof of concept resting-state and ERPs study
Authors: Spinelli Giuseppe , Odouard Alexandre , Nierat Marie-Cécile , Campion Sébastien , Bensoussan Mickael , Grosselin Fanny , Pandremmenou Katerina , Breton Audrey , Raux Mathieu , Attal Yohan , Similowski Thomas , Navarro-Suné Xavier 
Published: March 2020

AbstractWearable EEG systems have become accessible to researchers and clinicians over the last decade, thus requiring neurotechnology companies to seek for outstanding EEG signal quality. Here, we show that the melomind™ headset equipped with dry electrodes (myBrain Technologies, Paris, France) allows the recording of reliable electro-cortical dynamics as compared to a wet-based standard-EEG system (actiCAP, Brain Products GmbH, Gilching, Germany). EEGs were acquired simultaneously from the two systems while thirteen subjects underwent a visual oddball, a steady-state visually-evoked potentials (SSVEPs) and two resting-state (RS) tasks. RS were acquired with eyes-closed and eyes-open (2 minutes each) and repeated twice (before and after the cognitive tasks). During the oddball task, participants responded on a gamepad when a target-stimulus was displayed. In the SSVEPs, visual responses were elicited at 15 and 20 Hz through a series of 15-second stimuli presented 5 times each. The power of theta- [4-8 Hz], alpha- [8-13 Hz], and beta- [13-30 Hz] band was extracted from the two RS. The signal-to-noise-ratio in the 15 (± 1) and 20 (± 1) Hz range was computed from the SSVEPs. The shape of the N2/P300 complex was analysed from the oddball task. Strong correlations resulted between the parameters obtained from the two EEG systems (0.53 < Pearson’s r < 0.97). Bland and Altman analysis revealed small dissimilarities between the two systems, with values laying in the 95% confidence interval in all the tasks. Our results demonstrate that the melomind™ is an affordable solution to reliably assess humans’ electro-cortical dynamics at-rest and during cognitive tasks, thus paving the way to its use in neuroscience studies and brain-computer interfaces.
Delivery of cell-penetrating chromatin sensor-actuators to human osteosarcoma cells
Authors: Tekel Stefan J. , Brookhouser Nicholas , Haynes Karmella A. 
Published: March 2020

ABSTRACTThe leading FDA-approved drugs for epigenetic cancer therapy are small molecule compounds that activate silenced tumor suppressors by inhibiting enzymes that generate aberrant repressive chromatin. Although promising, this approach is limited because chromatin-modifying enzymes often target non-chromatin proteins and can serve dual functions as gene repressors and activators. Previously, we have demonstrated that a transgenically expressed synthetic polycomb-derived transcription factor (PcTF) could activate genes in silenced chromatin via specific interactions with histone H3 trimethylated at lysine 27 (H3K27me3). Efficient non-viral intracellular delivery remains a challenge for protein-based biologics. Herein, we report the delivery of cell-penetrating PcTF (CP-PcTF) to cultured cells. We expressed and purified recombinant PcTF that was fused in frame with a nuclear localization signal and a cell penetrating peptide tag (TAT). We demonstrated rapid and efficient uptake of soluble CP-PcTF by osteosarcoma U-2 OS cells grown in 2-D monolayers and 3-D spheroids. However, CP-PcTF had a modest effect on gene expression and cell proliferation compared to transgenically-expressed PcTF from our previous work. Overall, these results suggest that TAT is a very effective delivery vehicle for the recombinant transcriptional regulator PcTF, and that further technical development is needed to deliver functional PcTF into cell nuclei.
Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics andin silicoapproaches
Authors: ul Qamar Muhammad Tahir , Rehman Abdur , Ashfaq Usman Ali , Awan Muhammad Qasim , Fatima Israr , Shahid Farah , Chen Ling-Ling 
Published: March 2020

AbstractCoronavirus disease 2019 (COVID-19) associated pneumonia caused by severe acute respiratory coronavirus 2 (SARS-COV-2) was first reported in Wuhan, China in December 2019. Till date, no vaccine or completely effective drug is available to cure COVID-19. Therefore, an effective vaccine against SARS-COV-2 is crucially needed. This study was conducted to design an effective multiepitope based vaccine (MEV) against SARS-COV-2. Seven antigenic proteins were taken as targets and different epitopes (B-cell, T-cell and IFN-γ inducing) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected epitopes indicated significant interactions with the HLA-binding alleles and 99.29% coverage of the world’s population. Finally, 505 amino acids long MEV was designed by connecting sixteen MHC class I and eleven MHC class II epitopes with suitable linkers and adjuvant. Linkers and adjuvant were added to enhance the immunogenicity response of the MEV. The antigenicity, allergenicity, physiochemical properties and structural details of MEV were analyzed in order to ensure safety and immunogenicity. MEV construct was non-allergenic, antigenic, stable and flexible. Molecular docking followed by molecular dynamics (MD) simulation analysis, demonstrated a stable and strong binding affinity of MEV with human pathogenic toll-like receptors (TLR), TLR3 and TLR8. Codon optimization andin silicocloning of MEV ensured increased expression in theEscherichia coliK-12 system. Designed MEV in present study could be a potential candidate for further vaccine production process against COVID-19. However, to ensure its safety and immunogenic profile, the proposed MEV needs to be experimentally validated.