bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient safety culture in Peking University Cancer Hospital in China: baseline assessment and comparative analysis for quality improvement
Authors: Zhong Xiyao , Song Yuqin , Dennis Christine , Slovensky Donna J. , Wei Lim Yee , Chen Jie , Ji Jiafu 
Published: December 2019

Abstract
Background
Limited information is available regarding the patient safety culture in Chinese hospitals. This study aims to assess the patient safety culture in Peking University Cancer Hospital and to identify opportunities for improving the organization’s safety culture.

Methods
A cross-sectional study was conducted in April 2018 and 2019, respectively. Data on patient safety culture were collected from clinical and administrative staffs using the Hospital Survey on Patient Safety Culture (HSOPSC).

Results
Twelve composite dimension variables were hierarchically clustered. Three highest positive response dimensions include ‘Organizational Learning and continuous improvement’ (92.9%), ‘Teamwork within units’ (89.7%), and ‘Hospital management support for patient safety’ (83.7%), while 3 lowest positive response dimensions included ‘Frequency of events reported’ (43.9%), ‘Non-punitive response to error’ (51.1%), ‘Communication openness’ (52.2%), and ‘Staffing’ (53.7%). Compared to the average scores of the United States, the scores of the Peking University Cancer Hospital was significantly lower on ‘Communication openness’ and ‘Frequency of events reported’. After targeted continuous improvement based on results in 2018, all 12 dimensions surprisingly increased in the safety culture conducted in 2019.

Conclusion
Inadequate feedback and communications about error and lack of communication openness are key challenges for patient safety in the delivery of care in this hospital. Results of this baseline survey indicate the need for a modified approach and attention to context when designing interventions aimed at improving the safety culture in this organization.
Efficient production of α-acetolactate by whole cell catalytic transformation of fermentation-derived pyruvate
Authors: Dorau Robin , Chen Lin , Liu Jianming , Jensen Peter Ruhdal , Solem Christian 
Published: December 2019

AbstractBackgroundDiacetyl provides the buttery aroma in products such as butter and margarine. It can be made via a harsh set of chemical reactions from sugarcane bagasse, however, in dairy products it is normally formed spontaneously from α-acetolactate, a compound generated by selected lactic acid bacteria in the starter culture used. Due to its bacteriostatic properties, it is difficult to achieve high levels of diacetyl by fermentation. Here we present a novel strategy for producing diacetyl based on whole-cell catalysis, which bypasses the toxic effects of diacetyl.ResultsBy expressing a robust α-acetolactate synthase (ALS) in a metabolically optimizedLactococcus lactisstrain we obtained a whole-cell biocatalyst that efficiently converted pyruvate into α-acetolactate. After process optimization, we achieved a titer for α-acetolactate of 172 ± 2 mM. Subsequently we used a two-stage production setup, where pyruvate was produced by an engineeredL. lactisstrain and subsequently used as the substrate for the biocatalyst. Using this approach, 122 ± 5 mM and 113 ± 3 mM α-acetolactate could be made from glucose or lactose in dairy waste, respectively. The whole-cell biocatalyst was robust and fully active in crude fermentation broth containing pyruvate.ConclusionsAn efficient approach for converting sugar into α-acetolactate, via pyruvate, was developed and tested successfully. Due to the anaerobic conditions used for the biotransformation, little diacetyl was generated, and this allowed for efficient biotransformation of pyruvate into α-acetolactate, with the highest titers reported to date. The use of a two-step procedure for producing α-acetolactate, where non-toxic pyruvate first is formed, and subsequently converted into α-acetolactate, also simplified the process optimization. We conclude that whole cell catalysis is suitable for converting lactose in dairy waste into α-acetolactate, which favors resource utilization.
Associations between GUCY1A3 genetic polymorphisms and large artery atherosclerotic stroke risk in Chinese Han population: a case-control study
Authors: Li Jian-li , Liu Liu-yu , Jiang Dong-dong , Jiang Yi-ying , Zhou Guo-qiu , Mo Dong-can , Luo Man 
Published: December 2019

Abstract
Background
Previous genome-wide association studies have found two single nucleotide polymorphisms (SNP) rs7692387 and rs1842896 located on or near the GUCY1A3 gene were associated with coronary artery disease (CAD). GUCY1A3 was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of the GUCY1A3 and large artery atherosclerotic (LAA) stroke. This study aimed to investigate the associations between the GUCY1A3 rs7692387, rs1842896 polymorphisms and LAA stroke susceptibility.

Methods
A total of 298 LAA stroke patients and 300 control subjects from a southern Chinese Han population were included. SNaPshot technique was used for genotype analysis. Associations between genotypes and LAA stroke susceptibility were analyzed with logistic regression model.

Results
Our study found that under the recessive model (TT vs. GT + GG), the GUCY1A3 rs1842896 polymorphism was significantly correlated with LAA stroke (OR = 1.48, 95%CI: 1.07–2.04, P = 0.018). After adjustment for its effects on age, gender, cigarette smoking, total cholesterol, low-density lipoprotein cholesterol, HbA1c, hypertension, diabetes mellitus, and CAD, the rs1842896 TT genotype retained association with increased susceptibility to LAA stroke (recessive model: adjusted OR = 1.96, 95%CI: 1.22–3.17, P = 0.006). However, association between rs7692387 polymorphism with LAA stroke was not observed.

Conclusion
Our results indicate that the GUCY1A3 rs1842896 polymorphism is an LAA stroke risk factor in Southern Han Chinese.
Pathophysiological importance of bile cholesterol reabsorption: hepatic NPC1L1-exacerbated steatosis and decreasing VLDL-TG secretion in mice fed a high-fat diet
Authors: Toyoda Yu , Takada Tappei , Yamanashi Yoshihide , Suzuki Hiroshi 
Published: December 2019

AbstractBackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, although its pathogenesis remains to be elucidated. A recent study revealed that hepatic Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol re-absorber from bile to the liver expressed on the bile canalicular membrane, is an exacerbation factor of NAFLD. Indeed, transgenic mice with hepatic expression of human NPC1L1 under a liver-specific promoter (L1-Tg mice) developed steatosis with a high-fat diet (HFD) containing cholesterol within a few weeks. However, the mechanism underlying diet-induced hepatic NPC1L1-mediated lipid accumulation is poorly defined.MethodsTo achieve a deeper understanding of steatosis development in L1-Tg mice, the biochemical features of hepatic NPC1L1-mediated steatosis were investigated. Hemizygous L1-Tg mice and wild-type littermate controls fed a HFD or control-fat diet were used. At the indicated time points, the livers were evaluated for cholesterol and triglyceride (TG) contents as well as mRNA levels of hepatic genes involved in the maintenance of lipid homeostasis. The hepatic ability to secrete very low-density lipoprotein (VLDL)-TG was also investigated.ResultsUnlike the livers of wild-type mice that have little expression of hepatic Npc1l1, the livers of L1-Tg mice displayed time-dependent changes that indicated steatosis formation. In steatosis, there were three different stages of development: mild accumulation of hepatic cholesterol and TG (early stage), acceleration of hepatic TG accumulation (middle stage), and further accumulation of hepatic cholesterol (late stage). In the early stage, between WT and L1-Tg mice fed a HFD for 2 weeks, there were no significant differences in the hepatic expression of Pparα, Acox1, Fat/Cd36, Srebf1, and Srebf2; however, the hepatic ability to secrete VLDL-TG decreased in L1-Tg mice (P < 0.05). Furthermore, this decrease was completely prevented by administration of ezetimibe, an NPC1L1-selective inhibitor.ConclusionHepatic NPC1L1 exacerbates diet-induced steatosis, which was accompanied by decreased hepatic ability of VLDL-TG secretion. The obtained results provide a deeper understanding of L1-Tg mice as a promising NAFLD animal model that is able to re-absorb biliary-secreted cholesterol similar to humans. Furthermore, this work supports further studies of the pathophysiological impact of re-absorbed biliary cholesterol on the regulation of hepatic lipid homeostasis.
BAP31 regulates IRAK1-dependent neuroinflammation in microglia
Authors: Liu Xia , Jiao Kun , Jia Cong-cong , Li Guo-xun , Yuan Qing , Xu Ji-kai , Hou Yue , Wang Bing 
Published: December 2019

AbstractBackgroundMicroglia, the mononuclear immune cells of the central nervous system (CNS), are essential for the maintenance of CNS homeostasis. BAP31, a resident and ubiquitously expressed protein of the endoplasmic reticulum, serves as a sorting factor for its client proteins, mediating the subsequent export, retention, and degradation or survival. Recently, BAP31 has been defined as a regulatory molecule in the CNS, but the function of BAP31 in microglia has yet to be determined. In the present study, we investigated whether BAP31 is involved in the inflammatory response of microglia.MethodsThis study used the BV2 cell line and BAP31 conditional knockdown mice generated via the Cre/LoxP system. A BAP31 knockdown experiment was performed to elucidate the role of BAP31 in the endogenous inflammatory cytokine production by microglial BV2 cells. A mouse model of lipopolysaccharide (LPS)-induced cognitive impairment was established to evaluate the neuroprotective effect of BAP31 against neuroinflammation-induced memory deficits. Behavioral alterations were assessed with the open field test (OFT), Y maze, and Morris water maze. The activation of microglia in the hippocampus of mice was observed by immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and reverse transcription quantitative real-time polymerase chain reaction (RT-PCR) were used to clarify the mechanisms.ResultsBAP31 deficiency upregulates LPS-induced proinflammatory cytokines in BV2 cells and mice by upregulating the protein level of IRAK1, which in turn increases the translocation and transcriptional activity of NF-κB p65 and c-Jun, and moreover, knockdown of IRAK1 or use of an IRAK1 inhibitor reverses these functions. In the cognitive impairment animal model, the BAP31 knockdown mice displayed increased severity in memory deficiency accompanied by an increased expression of proinflammatory factors in the hippocampus.ConclusionsThese findings indicate that BAP31 may modulate inflammatory cytokines and cognitive impairment induced by neuroinflammation through IRAK1, which demonstrates that BAP31 plays an essential role in microglial inflammation and prevention of memory deficits caused by neuroinflammation.
CXCR5-negative natural killer cells ameliorate experimental autoimmune myasthenia gravis by suppressing follicular helper T cells
Authors: Yang Chun-Lin , Zhang Peng , Liu Ru-Tao , Zhang Na , Zhang Min , Li Heng , Du Tong , Li Xiao-Li , Dou Ying-Chun , Duan Rui-Sheng 
Published: December 2019

Abstract
Background
Recent studies have demonstrated that natural killer (NK) cells can modulate other immune components and are involved in the development or progression of several autoimmune diseases. However, the roles and mechanisms of NK cells in regulating experimental autoimmune myasthenia gravis (EAMG) remained to be illustrated.

Methods
To address the function of NK cells in experimental autoimmune myasthenia gravis in vivo, EAMG rats were adoptively transferred with splenic NK cells. The serum antibodies, and splenic follicular helper T (Tfh) cells and germinal center B cells were determined by ELISA and flow cytometry. The roles of NK cells in regulating Tfh cells were further verified in vitro by co-culturing splenocytes or isolated T cells with NK cells. Moreover, the phenotype, localization, and function differences between different NK cell subtypes were determined by flow cytometry, immunofluorescence, and ex vivo co-culturation.

Results
In this study, we found that adoptive transfer of NK cells ameliorated EAMG symptoms by suppressing Tfh cells and germinal center B cells. Ex vivo studies indicated NK cells inhibited CD4+ T cells and Tfh cells by inducing the apoptosis of T cells. More importantly, NK cells could be divided into CXCR5- and CXCR5+ NK subtypes according to the expression of CXCR5 molecular. Compared with CXCR5- NK cells, which were mainly localized outside B cell zone, CXCR5+ NK were concentrated in the B cell zone and exhibited higher expression levels of IL-17 and ICOS, and lower expression level of CD27. Ex vivo studies indicated it was CXCR5- NK cells not CXCR5+ NK cells that suppressed CD4+ T cells and Tfh cells. Further analysis revealed that, compared with CXCR5- NK cells, CXCR5+ NK cells enhanced the ICOS expression of Tfh cells.

Conclusions
These findings highlight the different roles of CXCR5- NK cells and CXCR5+ NK cells. It was CXCR5- NK cells but not CXCR5+ NK cells that suppressed Tfh cells and inhibited the autoimmune response in EAMG models.
Equitable access to mental healthcare integrated in primary care for people with severe mental disorders in rural Ethiopia: a community-based cross-sectional study
Authors: Hailemariam Maji , Fekadu Abebaw , Medhin Girmay , Prince Martin , Hanlon Charlotte 
Published: December 2019

Abstract
Background
Integration of mental healthcare into non-specialist settings is advocated to expand access to care for people with severe mental disorders (SMD) in low-income countries. However, the impact upon equitable access for disenfranchised members of society has not been investigated. The purpose of this study was to (1) estimate contact coverage for SMD of a new service in primary healthcare (PHC) in a rural Ethiopian district, and (2) investigate equity of access for rural residents, women, people with physical impairments and people of low socio-economic status.

Methods
Community key informants were trained to identify and refer people with probable SMD in Sodo district, south-central Ethiopia, using vignettes of typical presentations. Records of those referred to the new PHC-based service were linked to healthcare records to identify people who engaged with care and non-engagers over a 6 month period. Standardised interviews by psychiatric nurses were used to confirm the diagnosis in those attending PHC. Non-engagers were visited in their homes and administered the Psychosis Symptom Questionnaire. Socio-economic status, discrimination, disability, substance use, social support and distance to the nearest health facility were measured.

Results
Contact coverage for the new service was estimated to be 81.3% (300 engaged out of 369 probable cases of SMD identified). Reimbursement for transport and time may have elevated coverage estimates. In the fully adjusted multivariable model, rural residents had 3.81 increased odds (95% CI 1.22, 11.89) of not accessing care, in part due to geographical distance from the health facility (odds ratio 3.37 (1.12, 10.12)) for people living more than 180 min away. There was no association with lower socioeconomic status, female gender or physical impairment. Higher levels of functional impairment were associated with increased odds of engagement. Amongst non-engagers, the most frequently endorsed barriers were thinking the problem would get better by itself and concerns about the cost of treatment.

Conclusion
Integrating mental healthcare into primary care can achieve high levels of coverage in a rural African setting, which is equitable with respect to gender and socio-economic status. Service outreach into the community may be needed to achieve better contact coverage for rural residents.
Kallistatin inhibits tumour progression and platinum resistance in high-grade serous ovarian cancer
Authors: Wu Huan , Li Rongrong , Zhang Zhiwei , Jiang Huiyang , Ma Hanlin , Yuan Cunzhong , Sun Chenggong , Li Yingwei , Kong Beihua 
Published: December 2019

AbstractOvarian cancer is the most lethal gynaecologic malignancy. Although there are various subtypes of ovarian cancer, high-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer deaths. Chemoresistance is the primary reason for the unfavourable prognosis of HGSOC. Kallistatin (KAL), also known as SERPINA4, is part of the serpin family. Kallistatin has been discovered to exert multiple effects on angiogenesis, inflammation and tumour progression. However, the roles and clinical significance of kallistatin in HGSOC remain unclear. Here, we showed that kallistatin was significantly downregulated in HGSOC compared to normal fallopian tube (FT) tissues. Low expression of kallistatin was associated with unfavourable prognosis and platinum resistance in HGSOC. Overexpression of kallistatin significantly inhibited proliferation and metastasis, and enhanced platinum sensitivity and apoptosis in ovarian cancer cells. Collectively, these findings demonstrate that kallistatin serves as a prognostic predictor and provide a potential therapeutic target for HGSOC.
Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species
Authors: Manara Serena , Asnicar Francesco , Beghini Francesco , Bazzani Davide , Cumbo Fabio , Zolfo Moreno , Nigro Eleonora , Karcher Nicolai , Manghi Paolo , Metzger Marisa Isabell , Pasolli Edoardo , Segata Nicola 
Published: December 2019

Abstract
Background
Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches.

Results
We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories.

Conclusions
The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.
Tools and best practices for retrotransposon analysis using high-throughput sequencing data
Authors: Teissandier Aurélie , Servant Nicolas , Barillot Emmanuel , Bourc’his Deborah 
Published: December 2019

Abstract
Background
Sequencing technologies give access to a precise picture of the molecular mechanisms acting upon genome regulation. One of the biggest technical challenges with sequencing data is to map millions of reads to a reference genome. This problem is exacerbated when dealing with repetitive sequences such as transposable elements that occupy half of the mammalian genome mass. Sequenced reads coming from these regions introduce ambiguities in the mapping step. Therefore, applying dedicated parameters and algorithms has to be taken into consideration when transposable elements regulation is investigated with sequencing datasets.

Results
Here, we used simulated reads on the mouse and human genomes to define the best parameters for aligning transposable element-derived reads on a reference genome. The efficiency of the most commonly used aligners was compared and we further evaluated how transposable element representation should be estimated using available methods. The mappability of the different transposon families in the mouse and the human genomes was calculated giving an overview into their evolution.

Conclusions
Based on simulated data, we provided recommendations on the alignment and the quantification steps to be performed when transposon expression or regulation is studied, and identified the limits in detecting specific young transposon families of the mouse and human genomes. These principles may help the community to adopt standard procedures and raise awareness of the difficulties encountered in the study of transposable elements.
Serotype distribution, antimicrobial susceptibility, antimicrobial resistance genes and virulence genes of Salmonella isolated from a pig slaughterhouse in Yangzhou, China
Authors: Li Quan , Yin Jian , Li Zheng , Li Zewei , Du Yuanzhao , Guo Weiwei , Bellefleur Matthew , Wang Shifeng , Shi Huoying 
Published: December 2019

AbstractSalmonella is an important food-borne pathogen associated with public health and high economic losses. To investigate the prevalence and the characteristics of Salmonella in a pig slaughterhouse in Yangzhou, a total of 80 Salmonella isolates were isolated from 459 (17.43%) samples in 2016–2017. S. Derby (35/80, 43.75%) was the most prevalent, followed by S. Rissen (16/80, 20.00%) and S. Newlands (11/80, 13.75%). The highest rates of susceptibility were observed to cefoxitin (80/80, 100.0%) and amikacin (80/80, 100.0%), followed by aztreonam (79/80, 98.75%) and nitrofurantoin (79/80, 98.75%). The highest resistance rate was detected for tetracycline (65/80, 81.25%), followed by ampicillin (60/80, 75.00%), bactrim (55/80, 68.75%), and sulfisoxazole (54/80, 67.50%). Overall, 91.25% (73/80) of the isolates were resistant to at least one antibiotic, while 71.25% (57/80) of the isolate strains were multidrug resistant in the antimicrobial susceptibility tested. In addition, 86.36% (19/22) of the 22 antimicrobial resistance genes in the isolates were identified. Our data indicated that the resistance to certain antimicrobials was significantly associated, in part, with antimicrobial resistance genes. Furthermore, 81.25% (65/80) isolates harbored the virulence gene of mogA, of which 2 Salmonella Typhimurium isolates carried the mogA, spvB and spvC virulence genes at the same time. The results showed that swine products in the slaughterhouse were contaminated with multidrug resistant Salmonella commonly, especially some isolates carry the spv virulence genes. The virulence genes might facilitate the dissemination of the resistance genes to consumers along the production chain, suggesting the importance of controlling Salmonella during slaughter for public health.