bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of surface proteins in a clinical Staphylococcus haemolyticus isolate by bacterial surface shaving
Authors: Wolden Runa , Pain Maria , Karlsson Roger , Karlsson Anders , Aarag Fredheim Elizabeth G. , Cavanagh Jorunn Pauline 
Published: April 2020

Abstract
Background
The skin commensal Staphylococcus haemolyticus is an emerging nosocomial pathogen. Despite its clinical relevance, published information about S. haemolyticus virulence factors is scarce. In this study, the adhesive and biofilm forming properties of ten clinical and ten commensal S. haemolyticus strains were examined using standard adhesion and biofilm assays. One of the clinical strains was used to identify expressed surface proteins using bacterial surface shaving. Protein abundance was examined by a comparative analysis between bacterial protein expression after human keratinocyte (HaCaT) colonization and growth in cell culture media supplemented with serum. Relative protein quantification was performed by labeling peptides with tandem mass tags (TMT) prior to Mass Spectrometry analysis. Surface proteins can be used as novel targets for antimicrobial treatment and in diagnostics.

Results
Adherence to fibronectin, collagen and plastic was low in all tested strains, but with significantly higher adhesion to fibronectin (p = 0.041) and collagen (p = 0.001) in the commensal strains. There was a trend towards higher degree of biofilm formation in the clinical strains (p = 0.059).
By using surface shaving, 325 proteins were detected, of which 65 were classified as surface proteins. Analyses showed that the abundance of nineteen (5.8%) proteins were significantly changed following HaCaT colonization. The bacterial Toll/interleukin-1 like (TIRs) domain containing protein (p = 0.04), the transglycosylase SceD (p = 0.01), and the bifunctional autolysin Atl (p = 0.04) showed a 1.4, 1.6- and 1.5-fold increased abundance. The staphylococcal secretory antigen (SsaA) (p = 0.04) was significantly downregulated (− 1.5 fold change) following HaCaT colonization.
Among the 65 surface proteins the elastin binding protein (Ebps), LPXAG and LPXSG domain containing proteins and five LPXTG domain containing proteins were identified; three Sdr-like proteins, the extracellular matrix binding protein Embp and a SasH-like protein.

Conclusions
This study has provided novel knowledge about expression of S. haemolyticus surface proteins after direct contact with eukaryotic cells and in media supplemented with serum. We have identified surface proteins and immune evasive proteins previously only functionally described in other staphylococcal species. The identification of expressed proteins after host-microbe interaction offers a tool for the discovery and design of novel targets for antimicrobial treatment.
Sequential analysis of transcript expression patterns improves survival prediction in multiple cancers
Authors: Mandel Jordan , Avula Raghunandan , Prochownik Edward V. 
Published: April 2020

Abstract
Background
Long-term survival in numerous cancers often correlates with specific whole transcriptome profiles or the expression patterns of smaller numbers of transcripts. In some instances, these are better predictors of survival than are standard classification methods such as clinical stage or hormone receptor status in breast cancer. Here, we have used the method of “t-distributed stochastic neighbor embedding” (t-SNE) to show that, collectively, the expression patterns of small numbers of functionally-related transcripts from fifteen cancer pathways correlate with long-term survival in the vast majority of tumor types from The Cancer Genome Atlas (TCGA). We then ask whether the sequential application of t-SNE using the transcripts from a second pathway improves predictive capability or whether t-SNE can be used to refine the initial predictive power of whole transcriptome profiling.

Methods
RNAseq data from 10,227 tumors in TCGA were previously analyzed using t-SNE-based clustering of 362 transcripts comprising 15 distinct cancer-related pathways. After showing that certain clusters were associated with differential survival, each relevant cluster was re-analyzed by t-SNE with a second pathway’s transcripts. Alternatively, groups with differential survival identified by whole transcriptome profiling were subject to a second, t-SNE-based analysis.

Results
Sequential analyses employing either t-SNE➔t-SNE or whole transcriptome profiling➔t-SNE analyses were in many cases superior to either individual method at predicting long-term survival. We developed a dynamic and intuitive R Shiny web application to explore the t-SNE based transcriptome clustering and survival analysis across all TCGA cancers and all 15 cancer-related pathways in this analysis. This application provides a simple interface to select specific t-SNE clusters and analyze survival predictability using both individual or sequential approaches. The user can recreate the relationships described in this analysis and further explore many different cancer, pathway, and cluster combinations. Non-R users can access the application on the web at https://chpupsom19.shinyapps.io/Survival_Analysis_tsne_umap_TCGA. The application, R scripts performing survival analysis, and t-SNE clustering results of TCGA expression data can be accessed on GitHub enabling users to download and run the application locally with ease (https://github.com/RavulaPitt/Sequential-t-SNE/).

Conclusions
The long-term survival of patients correlated with expression patterns of 362 transcripts from 15 cancer-related pathways. In numerous cases, however, survival could be further improved when the cohorts were re-analyzed using iterative t-SNE clustering or when t-SNE clustering was applied to cohorts initially segregated by whole transcriptome-based hierarchical clustering.
HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells
Authors: Dizanzo María Paula , Marziali Federico , Brunet Avalos Clarisse , Bugnon Valdano Marina , Leiva Santiago , Cavatorta Ana Laura , Gardiol Daniela 
Published: April 2020

Abstract
Background
Persistent infection with high-risk Human Papillomavirus (HPVs) is associated with the development of cervical cancer. The transforming capacity of these viruses relies on the cooperative action of the E6 and E7 viral oncoproteins. Among the oncogenic activities of E6, the interaction and interference with cell polarity PDZ proteins have been well established. One of the most characterized PDZ targets of HPV E6 is human Disc large 1 (DLG1), a scaffolding protein involved in the control of cell polarity and proliferation. Interestingly, in cervical squamous intraepithelial lesions, alterations in DLG1 expression were observed in association to tumour progression. Moreover, the expression of both HPV E6 and E7 proteins may be responsible for the changes in DLG1 abundance and cell localization observed in the HPV-associated lesions.

Methods
Due to the relevance of DLG1 deregulation in tumour development, we have performed an in-depth investigation of the expression of DLG1 in the presence of the HPV oncoproteins in epithelial cultured cells. The effects of HPV E6 and E7 proteins on DLG1 abundance and subcellular localization were assessed by western blot and confocal fluorescence microscopy, respectively.

Results
We demonstrated that the relative abundance of HPV-18 E6 and DLG1 is a key factor that contributes to defining the expression abundance of both proteins. We also show here that a high expression level of DLG1 may negatively affect HPV-18 E6 nuclear expression. Moreover, the co-expression of HPV-18 E6 and E7 produces a striking effect on DLG1 subcellular localization and a co-distribution in the cytoplasmic region. Interestingly, HPV-18 E7 is also able to increase DLG1 levels, likely by rescuing it from the E6-mediated proteasomal degradation.

Conclusions
In general, the data suggest that HPV-18 E6 and E7 may have opposing activities in regards to the regulation of DLG1 levels and may cooperatively contribute to its subcellular redistribution in the HPV context. These findings constitute a step forward in understanding the differential expression of DLG1 during tumour progression in an HPV-associated model.
Chronic respiratory symptoms and pulmonary function status in Ethiopian agricultural workers: a comparative study
Authors: Woldeamanuel Gashaw Garedew , Mingude Alemu Basazin , Yitbarek Getachew Yideg , Taderegew Mitku Mammo 
Published: April 2020

AbstractBackgroundWork-related respiratory disorders are major contributors to the global burden of respiratory diseases. Agricultural workers are exposed to a number of dusts, which may contribute to the development of respiratory disorders. However, the knowledge about the prevalence of respiratory symptoms and pulmonary function status in African farmers was limited. This study was conducted to assess the prevalence of chronic respiratory symptoms and pulmonary function status of Ethiopian farmers exposed to farming activities.MethodsA community based comparative cross sectional study was conducted among 288 agricultural workers (farmers) aged 18 to 65 years and 288 control subjects (non-agricultural workers). Data were collected by interviewer administered structured questionnaires adopted from British Medical Research Council respiratory questionnaire and American Thoracic Society Division of Lung Diseases questionnaire. Moreover, all study participants underwent spirometry.ResultsThe prevalence of chronic respiratory symptoms was higher in farmers than in controls, with significant difference for cough (20.5% vs. 9.0%,p = 0.001) and phlegm (19.1% vs. 9.0%,p = 0.001). Chronic respiratory symptoms among farmers were significantly associated with duration of agricultural exposure (p = 0.014). The mean values of all spirometric parameters were lower in farmers than in controls with significant difference for FVC, FEV1, FEF25%, FEF50%, FEF25–75%and PEFR. Moreover, the mean values of all spirometric parameters of farmers have found to be decreased with increased duration of workplace exposure. Lung function test results also showed a higher prevalence of obstructive (15.6% vs. 10.8%,p = 0.085) and restrictive type (12.8% vs. 3.1%,p <  0.001) of pulmonary function impairment in farmers than in controls. However, the difference was not significant for obstructive type of impairment.ConclusionThis study indicated that farmers are at high risk for the development of chronic respiratory symptoms and reduced pulmonary function indices. Hence, a comprehensive occupational safety practices are important to maintain the respiratory health of farmers.
Assessing the preparedness of foundation year 1 (FY1) doctors during the transition from medical school to the foundation training programme
Authors: Michaelides Athena , Mahr Melina , Pydisetty Gaurav , Loyala Jerocin Vishani 
Published: April 2020

Abstract
Background
To assess how ready current FY1 doctors felt when starting their first posting as newly qualified doctors.

Methods
We created an online survey where 45 FY1 doctors in South Yorkshire rated how confident they were across different domains (Induction and Assistantship, Hospital Systems, and Skills) using a scale ranging from 0 (no confidence performing task) to 5 (highly confident).

Results
The ICE system and observations had a mean rating of 3.645 (95% CI 3.446 to 3.844), and 4.425 (95% CI 4.248 to 4.602) with a standard deviation (SD) of 1.10 and 0.83 respectively. The radiological platform, referral system, telephone system, and hospital notes had a mean score of 3.149 (95% CI 2.876 to 3.422), 2.340 (95% CI 2.096 to 2.584), 3.573 (95% CI 3.407 to 3.739) and 4.061 (95% CI 3.931 to 4.191), with a SD of 1.281, 1.153, 0.961 and 0.752 respectively. Patient needs and diagnostic procedures had a mean score of 3.933 (95% CI 3.749 to 4.117) and 4.250 (95% CI 4.140 to 4.360) with a SD of 1.190 and 0.944 respectively. Patient care, prescribing, and therapeutic procedures gave a mean score of 3.634 (95% CI 3.432 to 3.836), 4.130 (95% CI 3.959 to 4.301), 3.386 (95% CI 3.228 to 3.544) with a SD of 1.133, 0.958 and 1.256 respectively. No statistically significant difference in the overall mean score was found between respondents who attended medical schools in Yorkshire, and those who had not.

Conclusion
Overall, confidence differs across different domains and categories. A larger sample size across a wider geographical area would allow us to compare and contrast results across the different regions in the UK.
Re-engineering the Cypriot healthcare service system
Authors: Pallari Elena , Samoutis George , Rudd Anthony 
Published: April 2020

AbstractBackgroundThe Cypriot healthcare system has undergone a number of major transformations since the induction of the Republic of Cyprus in the European Union over 10 years ago. Currently Cyprus is undergoing a major reform, namely the introduction of a primary care driven national healthcare system. The aim of the study was to assess the existing state of training, support, quality, guidelines and infrastructure towards a better healthcare system in Cyprus.MethodsThis is a mixed-methods study combining statistical data until October 2016 and workshop discussions delivered in Cyprus in November 2015. We used anonymised data provided: (1a) by the Cyprus Medical Association of all registered medical doctors up to October 2016; (1b); by the Ministry of Health (MoH) Health Monitoring Unit up to October 2016; (2) during a workshop organised with representatives from the Royal College of Physicians, the European Commission and the Health Insurance Organization.ResultsThe gender ratio of men over women is disproportionate, with over 85% of the medical doctors undertaking their training in Greece, Eastern Europe and neighbouring countries, while the current record does not hold a relevant specialty information for 4 out of 10 doctors. The results show lack of statutory inspection systems, application of revalidation principles or implementation of peer-review clinical services on the island. There are eight proposed recommendations made by the workshop participants towards the transformation of the Cypriot healthcare system and the development of the Cyprus Quality Improvement Institute. These are aimed at addressing gaps in quality of care, adherence to clinical guidelines and implementation of audits, development of doctors’ revalidation and peer-review of clinical services, accreditation of service implementation, establishment of a statutory inspection system as well as the set-up of an incentives program as part of the general healthcare system (GHS) of Cyprus.ConclusionsCurrent efforts for the implementation of the new GHS in Cyprus call for adequate training and support of the medical workforce, transparent and safer quality of care provision through the implementation of clinical guidelines and capacity-building infrastructure.
Improving the usability and comprehensiveness of microbial databases
Authors: Loeffler Caitlin , Karlsberg Aaron , Martin Lana S. , Eskin Eleazar , Koslicki David , Mangul Serghei 
Published: April 2020

AbstractMetagenomics studies leverage genomic reference databases to generate discoveries in basic science and translational research. However, current microbial studies use disparate reference databases that lack consistent standards of specimen inclusion, data preparation, taxon labelling and accessibility, hindering their quality and comprehensiveness, and calling for the establishment of recommendations for reference genome database assembly. Here, we analyze existing fungal and bacterial databases and discuss guidelines for the development of a master reference database that promises to improve the quality and quantity of omics research.
Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study
Authors: Erkamp Jan S. , Voerman Ellis , Steegers Eric A. P. , Mulders Annemarie G. M. G. J. , Reiss Irwin K. M. , Duijts Liesbeth , Jaddoe Vincent W. V. , Gaillard Romy 
Published: April 2020

Abstract
Background
Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimester ultrasound in addition to maternal characteristics at the start of pregnancy are optimal to detect fetuses at risk for preterm birth, SGA and LGA.

Methods
In a prospective population-based cohort among 7677 pregnant women, we measured second and third trimester estimated fetal weight (EFW), and uterine artery pulsatility and umbilical artery resistance indices as placenta flow measures. Screen positive was considered as EFW or placenta flow measure < 10th or > 90th percentile. Information about maternal age, body mass index, ethnicity, parity, smoking, fetal sex and birth outcomes was available from questionnaires and medical records. Screening performance was assessed via receiver operating characteristic (ROC) curves and area under the curve (AUC) along with sensitivity at different false-positive rates.

Results
Maternal characteristics only and in combination with second trimester EFW had a moderate performance for screening for each adverse birth outcome. Screening performance improved by adding third trimester EFW to the maternal characteristics (AUCs for preterm birth 0.64 (95%CI 0.61 to 0.67); SGA 0.79 (95%CI 0.78 to 0.81); LGA 0.76 (95%CI 0.75; 0.78)). Adding third trimester placenta measures to this model improved only screening for risk of preterm birth (AUC 0.72 (95%CI 0.66 to 0.77) with sensitivity 37% at specificity 90%) and SGA (AUC 0.83 (95%CI 0.81 to 0.86) with sensitivity 55% at specificity 90%). Combining second and third trimester fetal and placental ultrasound did not lead to a better performance as compared to using only third trimester results.

Conclusions
Combining single third trimester fetal and placental ultrasound results with maternal characteristics has the best screening performance for risks of preterm birth, SGA and LGA. As compared to second trimester screening, third trimester screening may double the detection of fetuses at risk of common adverse birth outcomes.
Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases
Authors: Wu Yi-Ying , Kuo Hung-Chih 
Published: April 2020

AbstractRecent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.
Current developments on polyhydroxyalkanoates synthesis by using halophiles as a promising cell factory
Authors: Mitra Ruchira , Xu Tong , Xiang Hua , Han Jing 
Published: April 2020

AbstractPlastic pollution is a severe threat to our environment which necessitates implementation of bioplastics to realize sustainable development for a green world. Polyhydroxyalkanoates (PHA) represent one of the potential candidates for these bioplastics. However, a major challenge faced by PHA is the high production cost which limits its commercial application. Halophiles are considered to be a promising cell factory for PHA synthesis due to its several unique characteristics including high salinity requirement preventing microbial contamination, high intracellular osmotic pressure allowing easy cell lysis for PHA recovery, and capability to utilize wide spectrum of low-cost substrates. Optimization of fermentation parameters has made it plausible to achieve large-scale production at low cost by using halophiles. Further deeper insights into halophiles have revealed the existence of diversified and even novel PHA synthetic pathways within different halophilic species that greatly affects PHA type. Thus, precise metabolic engineering of halophiles with the help of advanced tools and strategies have led to more efficient microbial cell factory for PHA production. This review is an endeavour to summarize the various research achievements in these areas which will help the readers to understand the current developments as well as the future efforts in PHA research.
Individual and contextual correlates of mosquito net use among women in Nigeria
Authors: Adedokun Sulaimon T. , Uthman Olalekan A. 
Published: April 2020

Abstract
Background
Malaria has been described as an urgent public health priority with almost half of the world’s population being at risk. Use of insecticide-treated nets is considered one of the effective ways of preventing malaria. Nigeria, which is ranked among the five countries that are responsible for almost half of the global malaria cases, has less than half of its women population using mosquito nets. This study examined the effects of individual and contextual factors on the use of mosquito nets among women of reproductive age in Nigeria.

Methods
This study used data obtained from 2015 Nigeria Malaria Indicator Survey (NMIS) which involved 6048 women aged 15–49 who possessed at least one mosquito net. Multilevel binary logistic regression models were applied in the multivariable analysis.

Results
About 53% of the women used mosquito nets with more than 60% of uneducated and poor women in this category. The use of mosquito nets was significantly associated with being from poor households, having knowledge about the cause of malaria, having access to malaria messages, possessing knowledge about the efficacy of malaria prevention drugs during pregnancy, having knowledge about the importance of tests to detect malaria, maintaining small household size and living in the most socioeconomically disadvantaged communities and states.

Conclusions
The study revealed that mosquito net use among women in Nigeria is affected by individual and contextual factors. It is important for policy makers to design a mosquito-net-use model which would take individual and contextual factors into consideration.