bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic structure characteristics and treatment for Listeria monocytogenes infections
Authors: Yu Wei , Huang Yicheng , Guo Lihua , Zhang Jiajie , Zhan Yaqiong , Zhang Li , Qiu Yunqing 
Published: January 2020

Abstract
Background: Invasive Listeria monocytogenes (Lm) carry a high mortality despite antibiotic treatment. The aim of this study was to investigate the mechanism of pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated as well. Methods: Three Lm isolates were collected and 15 antibiotics susceptibility tests were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Furthermore, the effect of meropenem, linezolid, benzylpenicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay.Results: Two sequence types (STs) were identified for isolate 23949 (ST87), 26530 (ST3), 34096 (ST87), respectively. All isolates were resistant to fosfomycin and daptomycin. The resistant genes fosX, mprF, norB and vgaALC were identified in all isolates. Furthermore, 80 virulence genes were detected and 72 genes were found in all three isolates. There were 26 virulent genes associated with the structure, biosynthesis, motor switch of flagellum. And other virulent genes were involved in chemotaxis, protease, internalin and metabolism. It is of note that 8 genes (inlJ, llsB, llsD, llsG, llsH, llsP, llsX, llsY) were only found in 26530 isolated from cerebrospinal fluid (CSF), 7 of which were associated with haemolysin. Further in vitro time-kill assay found trimethoprim/sulfamethoxazole at serum or CSF concentrations had bactericidal effect (>3.5 log10 CFU/ml) against three tested Lm strains at 24 h. Conclusions: The involved virulence factors were mainly associated with bacterial pathogenicity. Notably, trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm bloodstream infection or intracranial infection.
A Critical Realist Evaluation of an Integrated Care Project for Vulnerable Families in Sydney, Australia
Authors: Tennant Elaine , Miller Erin , Costantino Kathryn , De Souza Denise , Coupland Heidi , Fotheringham Penelope , Eastwood John 
Published: January 2020

Abstract
Background Healthy Homes and Neighbourhoods (HHAN) Integrated Care Initiative was established to improve the care of families with complex health and social needs who reside in Sydney Local Health District. HHAN seeks to provide long-term multi-disciplinary care coordination as well as enhance capacity building and promotion of integrated care. We describe the qualitative component of a critical realist pilot case study aimed at exploring, explaining and refining emerging HHAN programme theories in relation to care coordination. Methods Semi-structured qualitative interviews with HHAN clients (n=12), HHAN staff and other stakeholders (n=21). Emerging themes informed the development of Context-Mechanism-Outcome configurations aimed at evaluating HHAN’s effectiveness and refining the programme theory. Results HHAN’s effectiveness was based on two process mechanisms: Engagement of vulnerable clients and integration of services. The relational mechanisms underpinning effective engagement of clients by care coordinators included: building trust, leveraging other family, social and organisational relationships, meeting clients on their own terms, demonstrating staff effectiveness as quickly as possible, and client empowerment. Operational mechanisms for enhancing care integration included knowledge transfer activities and shared learning among collaborators, structural and cultural changes, enhancing mutual respect, co-location of multidisciplinary and/or interagency staff and cultivating faith in positive change among staff. Conclusions Use of a critical realism case study approach served to elucidate the varied influences of contexts and mechanisms on programme outcomes, to highlight what works for whom and in what context. Findings supported the initial programme theory that engagement and trust building with clients, alongside enhanced collaboration and integration of services, improved outcomes for vulnerable families with complex needs. Further research is needed to explore the cost-effectiveness of integrated care initiatives, in view of the long term nature of service provision and the risk of staff burnout.
Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017
Authors: Aas Christer frode , Vold Jørn Henrik , Skurtveit Svetlana , Odsbu Ingvild , Chalabianloo Fatemeh , Johansson Kjell Arne , Fadnes Lars Thore 
Published: January 2020

Abstract
Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate cumulative frequency of HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were adjusted for age, gender, and OAT medications and studied in a logistic regression model. Results In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV treatment uptake increased in both countries, giving a cumulative frequency of around one-third in both countries at the end of the study period. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients during the introduction period of new direct-acting treatment regimens. However, a further scale-up is crucial to be able to control and eliminate the HCV endemic among OAT patients.
Classification of muscle-invasive bladder cancer based on tumor stromal compartment
Authors: Wei Kang-Lai , Shi Lin , Liang Zhi-Jie , Liang Hai-wei , Guo Yi-Nan , Liu Yu , Zhu Dan-Dan , Wu Fang-Xiao , Yi Xiao-Lin , Mo Steven , Qi Zhong-Quan , Li Hongmian 
Published: January 2020

Abstract
Purpose There has been a resurgence of interest in the tumor stroma in recent years. Whether the relative abundance of various stromal cells can be used as a classification system for muscle-invasive bladder cancer (MIBC) remain elusive.Methods We applied single-cell RNA-sequence (scRNA-seq) data from two MIBCs to identify stromal cell (CD45 negative cells) clusters and the marker gene set of each cell cluster. The single sample gene set enrichment analysis method is used to estimate the relative abundance of the cell clusters in each MIBC sample from The Cancer Genome Atlas. Subsequently, k-means clustering was performed to cluster the MIBCs. Prognosis, oncogenic pathway enrichment score, epithelial-mesenchymal transition (EMT) score, gene mutation frequency, and tumor infiltrating lymphocytes (TILs) were compared among the stromal component-based types of MIBC.ResultsIn the scRNA-seq analysis, a total of nine cell clusters mainly composed of four types of cells were identified. Cell clusters 0, 1, 2, 3, 4, and 7 were considered as bladder epithelial cells, the cells in clusters 5 and 8 were mainly recognized as stem cells and fibroblasts, and the cell cluster 6 was recognized were endothelial cells. The 408 MIBC samples were classified into three types. Type 1 and 3, the “stromal-sufficient” type I and II with higher stromal cells, and Type 2, the “stromal-desert” type with lower stromal cells. The stromal-desert type had significantly better overall survival. As the tumor progresses, the stromal component of the stromal-desert type increases and change into the stromal-sufficient type. Increased stromal cells may come from EMT. The enrichment scores of multiple oncogenic pathways in stromal-sufficient types were significantly higher than those in stromal-desert type. More TILs were found in stromal-sufficient type, but their function may be inhibited by stromal cells. In addition, the three stromal types of MIBC may have specific gene mutation characteristics.Conclusions We proposed a novel stromal component-based classification system to divided into MIBC three phenotype. The three types of MIBC differ in various biological characteristics. The progress of MIBC may be summarized as the process of gradually increasing stromal components and constructing a microenvironment suitable for cancer cells.
Capturing complex vaccine-immune-disease relationships for free-ranging koalas: IL17 production is an important intermediate factor against chlamydial disease
Authors: Lizárraga David , Timms Peter , Quigley Bonnie L , Hanger Jon , Carver Scott 
Published: January 2020

Abstract
Background Disease is a major factor negatively affecting koala populations. Vaccination is a promising treatment option that would result in immune-mediated protection against disease. Measuring and assessing vaccine efficacy can be challenging owing to both direct and indirect interactions caused by vaccination. In this study, we investigate vaccine-immune-chlamydial load-disease relationships from MOMP (major outer membrane protein) vaccine trials to protect healthy free-ranging koalas against Chlamydia -related diseases. Methods We created a priori hypotheses based on data sources and perceived direct and indirect interactions from koalas vaccinated six months prior. Each hypothesis was tested as a structural equation model to evaluate possible causality among measured variables. Model averaging was used as multiple models fit the data, and the strength of relationships were examined through averaged coefficients and the raw data. Results Despite multiple potential sources of variation owing to the koalas in this study being free-ranging, our analyses provide unique insights into the effects of vaccinating against Chlamydia . We found more relationships in urogenital models with interleukin 17 (IL17) production compared to models with interferon gamma (IFNγ) production. In the averaged model with IL17, urogenital chlamydial load was positively associated with disease and negatively associated with IL17 production. MOMP vaccination had a trending effect for reducing chlamydial load and also had a strong effect on increasing IL17 production. This indicated a link between MOMP vaccination, reduction of urogenital chlamydial load, and increased production of IL17. Not surprisingly, urogenital chlamydial load was a positive predictor for the development of urogenital disease at six months post-vaccination. Conclusions Using structural equation modelling, this study has helped illuminate that the immune cytokine IL17 may be an important intermediate factor linking MOMP vaccination with chlamydial pathogenesis and protection, enhancing previous investigations. Going beyond univariate statistics, the methods used in this study can be applied to other preclinical vaccination experiments to identify important direct and indirect factors underpinning the effects of a vaccine.
Comparison of Choriocapillary Flow Density Between Fellow eyes of Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration
Authors: Luo Mingyue , Yuan Mingzhen , Yang Jingyuan , Zhao Nan , Dai Rongping , Chen Youxin 
Published: January 2020

Abstract
Background To compare the choriocapillary flow density (CFD) among the contralateral eyes of polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD) and healthy controls with spectral-domain optical coherence angiography tomography (SD-OCTA).Methods This is a cross-sectional study. 36 eyes of 36 PCV patients, 35 eyes of nAMD patients and 34 control eyes were included. All sujects underwent the HD Angio Retina 6.0 mm scan pattern of OCTA (RTVue XR Avanti AngioVue; Optovue, Inc., Fremont, CA, USA). Circles with radius of 1.00, 1.50 and 3.00 mm were manually selected in choriocapillaries (CC) slab, and CFD was calculated as the percentage of flow area to the whole selected area as CFD-1.00, 1.50, 3.00 respectively. Multivariate linear regression analysis was performed to evaluate the differences of CFD among the three groups after adjusting for age, gender and the existence of drusen.Results Mean CFD-1.00, 1.50, 3.00 of nAMD group were 61.09, 62.65 and 65.67, significantly lower than PCV group (65.80, 66.75, 67.86, P= 0.000, 0.000, 0.022) and control (66.17, 66.45, 68.08, P= 0.000, 0.001, 0.025), while no difference were detected between PCV group and control ( P= 0.507, 0.798, 0.575).Conclusions CFD of nAMD fellow eyes were significantly lower than that of PCV and control eyes, while no difference was detected between PCV and control group, indicating different role of CC loss in early pathogenesis of nAMD and PCV.
Isolation and characterization of bacteriaophages against virulent Aeromonas hydrophila
Authors: Liu Jin , Gao Shanshan , Dong Yuhao , Lu Chengping , Liu Yongjie 
Published: January 2020

Abstract
Background: Aeromonas hydrophila is an important water-borne pathogen that leads to a great economic loss in aquaculture. Along with the abuse of antibiotics, drug-resistant strains rise rapidly. In addition, the biofilms formed by this bacterium limited the antibacterial effect of antibiotics. Bacteriaophages have been attracted increasing attention as a potential alternative to antibiotics against bacterial infections. Results: Five phages against pathogenic A. hydrophila, named N21, W3, G65, Y71 and Y81, were isolated. Morphological analysis by transmission electron microscopy revealed that phages N21, W3 and G65 belong to the family Myoviridae, while Y71 and Y81 belong to the Podoviridae. These phages were found to have broad host spectra, although their burst sizes were varied per infected host cell at their optimal multiplicity of infection. They were sensitive to high temperature but had a wide adaptability to the pH. In addition, the phages G65 and Y81 showed considerable effect on growth and biofilm inhibition of A. hydrophila; and the phages G65, W3 and N21 were able to scavenge mature biofilm effectively. Phage treatments applied to the pathogenic A. hydrophila in mice model resulted in a significantly decreased bacterial loads in tissues. Conclusions: Five A. hydrophila phages were isolated with broad host ranges, low latent periods, and wide pH and thermal tolerance. And the phages exhibited varying abilities in controlling A. hydrophila infection. This work presents promising data supporting the future use of phage therapy.
Clinical and microbiological characteristics of Cryptococcus gattii isolated from China
Authors: Jin Liang , Cao Jingrong , Xue Xinying , Wu Hua , Wang Lifeng , Guo Ling , Shen Dingxia 
Published: January 2020

Abstract
Background: Infection, even outbreak, caused by Cryptococcus gattii (C. gattii ) has been reported in Canada and the United States, but there were sparsely-reported cases of C. gattii in China. Our interest in occurrence, clinical manifestation, laboratory identification and molecular characterization of Chinese C. gattii strains leads us to this research. Methods: A total of 254 clinical isolates primarily identified as Cryptococcus neoformans (C. neoformans ) were collected. VITEK 2 compact, canavanine glycine bromothymol blue (CGB) agar and Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used for strain identification. Multi-locus sequence typing (MLST) was performed for genotyping. Antifungal susceptibility test was carried out with commercial kits of both ATB fungus 3 and Yeast one. Clinical information of patients was reviewed retrospectively. Label-free proteome technique was used to quantitatively analyze the differential proteins of C. gattii. Results: Out of 254 clinical isolates, we identified eight strains as C. gattii. MLST showed genotype VGI accounted for the most (6 / 8), the other two strains were genotype VGII（VGIIa and VGIIb respectively）with 3 specific spectra of molecular weight about 4342, 8686, 9611 Dalton by MALDI-TOF MS. The minimal inhibitory concentrations (MICs) of Fluconazole with Yeast one was 2～4 times higher than that with ATB fungus 3. Higher MICs of antifungal agents were exhibited against VGII strains than against VGI strains. C. gattii genotype VGII and VGI possessed 418 and 774 specific proteins respectively. Comparative proteome analysis showed that 180 proteins were highly expressed in C. gattii VGII and 329 proteins were highly expressed in C. gattii VGI. The enrichment of differentially expressed proteins between VGII and VGI was directed to Golgi complex.Conclusions: Infection by C. gattii in China might have been underestimated because of initial mis-identification. Genotype VGI was predominant but VGII was more resistant to antifungal agents. There was significant difference in protein expression profile between VGII and VGI C. gattii.
A novel gene expression system for Ralstonia eutropha based on the T7 promoter
Authors: Bi Changhao , Xiong Bin , Hu Muzi , Li Zhongkang , Liu Li , Li Siwei , Zhang Chunzhi , Zhang Xueli 
Published: January 2020

Abstract
Background: Ralstonia eutropha (syn. Cupriavidus necator) is a model microorganism for the metabolism of polyhydroxyalkanoates (PHAs) and a potential chassis for protein expression. Although current plasmid systems for R. eutropha provide a basic platform for gene expression, the performance of the induction systems is still limited. In addition, the sizes of the cloned genes is limited due to the large sizes of the plasmid backbones.Results: In this study, an R. eutropha T7 expression system was established by integrating a T7 RNA polymerase gene driven by the PBAD promoter into genome of R. eutropha, and cloning the T7 promoter into a pBBR1-derived plasmid for gene expression. In addition, the essential sequence necessary for pBBR1 plasmid replication was identified, and the redundant parts were deleted, reducing the expression plasmid size to 3392 bp, and the electroporation efficiency was improved 4 times. As a result, the highest expression level of Rfp was enhanced slightly, and the L-arabinose concentration necessary for induction was decreased 20 times. Conclusions: R. eutropha with the T7 expression system provides an efficient platform for protein expression and synthetic biology applications.
Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center
Authors: Masri Hiba EL , Hollingworth Samantha , Driel Mieke van , Benham Helen , McGuire Treasure 
Published: January 2020

Abstract
BackgroundDisease modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm be a barrier to use.MethodsIn a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes.ResultsThere were 1,547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling.ConclusionConsumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.
Mean Platelet Volume (MPV): New diagnostic indices for co-morbidity of Tuberculosis and Diabetes Mellitus
Authors: Qin Yongwei , qu shengyan , xu feifan , Wang lin 
Published: January 2020

Abstract
Background: Tuberculosis (TB) and type 2 diabetes mellitus (DM) are global health diseases with high morbidity and lethality . Few studies had focus on the platelet indices in TB-DM co-morbidity patients. The objective of this work was to analyze the platelet indices in TB, DM and TB+DM to assess the predictive value of platelet index for the risk of these diseases. Methods: In total, 246 patients were distribute d into three groups (113 TB, 59 DM and 74 TB+DM) admitted in our hospital along with 133 healthy controls (HC). Platelet indices namely platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW) were compared among the four groups and explored the relationship with inflammatory markers by using statistical software. Results: Our study discovered that MPV and PCT were significantly down-expressed in TB+DM patients (9.95±1.25fL, 0.20±0.05%, P <0.0001, P =0.0121, separately ) than those in DM individuals (10.92±1.17fL, 0.22±0.04%). Moreover, on comparison of TB (9.42±1.01fL), the changes of MPV were significantly higher in TB+DM patients (9.95±1.25fL, P =0.0041). No differences were found in PLT and PDW among the four groups ( P >0.05). The sensitivity and specificity of MPV in differential diagnosis of DM patients vs TB+DM patients were defined as 64.9% and 66.1% ( P <0.0001), as well as 60.8% and 66.4% of MPV in differ from TB patients and TB+DM patients ( P =0.003). MPV improved the diagnosis sensitivity when combined with clinical golden parameters as fasting blood glucose in DM and mycobacterium tuberculosis culture result in TB. In addition, the sensitivity and specificity of PCT in the differential diagnosis of DM patients vs TB+DM patients were defined as 69.5% and 59.4% ( P =0.008). PCT improved the diagnosis sensitivity when combined with fasting blood glucose in DM (72.9% vs 64.9%, P =0.004). In addition, MPV was connected with CRP and ESR in the TB+DM patients rather than PCT. Conclusions: Our research shows that MPV and PCT might be the clinical laboratory markers distinguished TB+DM patients from TB or DM individuals, thus providing support for earlier clinical diagnosis, prevention, and therapy.