bluuebunny/crossref_metadata_2025_split huggingface dataset:
Junior doctors’ aspirations for careers in ophthalmology: 40 years of surveys of UK medical graduates
Authors: Lambert Trevor W , Barat Atena , Goldacre Michael J 
Published: May 2020

Objective Using data from 40 years of national surveys of UK medical graduates, we report on ophthalmology as a career choice. Design, setting, and participants Self-administered questionnaire surveys of all graduates from all UK medical schools in selected years of qualification between 1974 and 2015. Main outcome measures Career specialty preferences of doctors one, three, and five years after graduation; career specialty destinations 10 years after graduation. Results One year after graduation, ophthalmology was the first career preference of 1.6% of the qualifiers of 1974–83, 2.2% of 1993–2002, and 1.8% of 2005–15. The corresponding percentages three years after graduation were 1.5, 1.8, and 1.2%. Men were more likely than women to choose ophthalmology: among graduates of 2005–15, 2.4% of men and 1.4% of women did so at one year, as did 1.7% of men and 0.7% of women at five years. Seventy per cent of doctors practising as ophthalmologists 10 years after qualification had told us in their first post-qualification year that ophthalmology was their first choice of career. Conclusions There has been no systematic change in recent years in the proportion of recent medical graduates intending to have a career in ophthalmology when surveyed one year after graduation. However, the proportion at three and five years after graduation was lower than that at year 1. Suggestions for maintaining interest in the specialty include improved career advice, greater early clinical exposure to ophthalmology, and improved access to flexible training. Most practising ophthalmologists had made early decisions that this was their intended career.
Blood sampled from existing peripheral IV cannulae yields results equivalent to venepuncture: a systematic review
Authors: Lesser Finnian D , Lanham David A , Davis Daniel 
Published: May 2020

Summary Objectives To establish whether blood samples taken from used peripheral intravenous cannulae are clinically interchangeable with venepuncture. Design Systematic review. PubMed, Web of Science and Embase were searched for relevant trials. Setting Trials which compared blood samples from used peripheral intravenous cannulae to venepuncture and provided limits of agreement or data which allowed calculation of limits of agreement. Participants Seven trials with 746 participants. Blood tests included 13 commonly ordered biochemistry, haematology and blood gas measurements. Main outcome measures 95% limits of agreement. Data were pooled using inverse variance weighting and compared to a clinically acceptable range estimated by expert opinion from previous trials. Results Limits of agreement for blood samples from used peripheral intravenous cannulae were within the clinically acceptable range for sodium, chloride, urea, creatinine and haematology samples. Limits of agreement for potassium were ±0.47 mmol/L which exceeded the clinically acceptable range. Peripheral intravenous cannula samples for blood gas analysis gave limits of agreement which far exceeded the clinically acceptable range. Conclusions Blood sampling from used peripheral intravenous cannulae is a reasonable clinical practice for haematology and biochemistry samples. Potassium samples from used peripheral intravenous cannulae can be used in situations where error up to ±0.47 mmol/L is acceptable. Peripheral intravenous cannula samples should not be used for blood gas analysis.
An ecological study of publicly funded elective hip arthroplasties in Brazil and Scotland: do access inequalities reinforce the inverse care law?
Authors: Filippon Jonathan , Bremner Stephen , Giovanella Ligia , Pollock Allyson 
Published: May 2020

Objectives To compare elective hip arthroplasty rates funded by the public sector in Brazil and Scotland. Design Ecological study, 2009–13, of crude and directly standardised rates of elective primary hip arthroplasty rates (per 100,000) funded by the public sector at national and regional level for age (30 + years) and gender in Brazil and Scotland. Setting National Health Service Scotland and Unified Health System in Brazil. Participants Over 30 s who had undergone an elective hip arthroplasty funded by the public sector. Main outcome measures Publicly funded standardised elective hip arthroplasty rates in Brazil and Scotland. Results Between 2009 and 2013, there was a seven-fold difference in treatment rates between Brazil and Scotland, and an eight-fold regional difference in Brazil; Brazil (7.8–8.3/100,000, increase of 0.5 per 100,000, 95% confidence interval (CI) (0.3, 0.7) from 2009/10 to 2012/13) and Scotland (from 61.1 to 57.7/100,000, decrease of 3.4 per 100,000, 95% confidence interval (1.4, 5.8) per 100,000); a two-fold difference in number of public beds per head of population (Brazil 158.3/100,000 vs. Scotland 305.1/100,000) and general medical workforce (Brazil 198.8/100,000 vs. Scotland 327.4/100,000); numbers of orthopaedic surgeons per head of population in the two countries were similar in 2013 (Brazil 5.2/100,000 vs. Scotland 4.3/100,000). Conclusion Although the ‘inverse care law’ is seen in both countries, access to publicly funded hip arthroplasties in Brazil is worse than in Scotland; the distribution of specialists and higher treatment rates in Brazil is highly skewed towards wealthier areas, perpetuating historical regional inequalities.
Maternal microchimerism protects hemophilia A patients from inhibitor development
Authors: Lu Yeling , Chen Zhenping , Dai Jing , Wu Xi , Gu Hao , Li Zekun , Li Jian , Ding Qiulan , Wu Wenman , Wu Runhui , Wang Xuefeng 
Published: May 2020

Key Points
Deleterious F8 mutations do not necessarily lead to the incidence of inhibitors in hemophilia A patients receiving replacement therapy. Maternal chimeric cells migrated into a fetus with hemophilia A during pregnancy could induce tolerance toward FVIII.
The SP1-12LOX axis promotes chemoresistance and metastasis of ovarian cancer
Authors: Zhang Qi , Yan Guifang , Lei Juan , Chen Yu , Wang Ting , Gong Juan , Zhou Yong , Zhao Huakan , Chen Hao , Zhou Yu , Wu Lei , Zhang Jiangang , Zhang Xiao , Wang Jingchun , Li Yongsheng 
Published: May 2020

Abstract
Background
Ovarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer.

Methods
Cisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells.

Results
SKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo.

Conclusion
Our results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer.
Water-Soluble Fullerenol with Hydroxyl Group Dependence for Efficient Two-Photon Excited Photodynamic Inactivation of Infectious Microbes
Authors: Kuo Wen-Shuo , Wang Jiu-Yao , Chang Chia-Yuan , Liu Jui-Chang , Shao Yu-Ting , Lin Yen-Sung , So Edmund Cheung , Wu Ping-Ching 
Published: May 2020

AbstractWe successfully prepared water-soluble fullerenol [C60(OH)46] that exhibited a high singlet oxygen quantum yield and efficiently generated reactive oxygen species. Additionally, the water-soluble C60(OH)46 with a higher composition of exposed hydroxyl groups had superior two-photon stability and characteristics compared with that with a lower composition of such groups. Therefore, the prepared fullerenol can be an effective two-photon photosensitizer. The water-soluble C60(OH)46 had favorable two-photon properties. During two-photon photodynamic therapy, the water-soluble C60(OH)46 had substantial antimicrobial activity against Escherichia coli at an ultralow-energy level of 211.2 nJ pixel−1 with 800 scans and a photoexcited wavelength of 760 nm.
Exploring the recycling of bioleaching functional bacteria and sulfur substrate using the sulfur-covered biochar particles
Authors: Wu Chuncheng , Jiang Mengying , Ye Zhe , Cai Yuchen , Shen Yutao , Wang Haizhen , Lin Qi , Shen Chaofeng , Hu Baolan , Lou Liping 
Published: May 2020

Abstract
Background
Bioleaching has been attracting attention in the recent years as an emerging sediment heavy metal pollution remediation technology. However, the use of sulfur powder as sulfur substrate causes the problem of “post-acidification”, and the free bioleaching functional bacteria which are susceptible to environmental impact during reactor operation cannot be used efficiently for multiple rounds. These problems can be solved if the sulfur substrate and the bioleaching functional bacteria can be recycled simultaneously after bioleaching. A new kind of sulfur substrate, the laboratory-made sulfur-covered biochar particles, was used in the bioleaching experiment, compared with sulfur powder and sulfur powder mixed with the surfactant rhamnolipid.

Results
The sulfur-covered biochar particles exhibited superior bioleaching performance, including faster acidification rate, SO42− production rate and heavy metal bioleaching rate, and higher heavy metal solubilization percentage (Ni 33.76%; Cu 66.16%; Zn 65.494%), which resulted from the acceleration of bioleaching reaction by the bioleaching functional bacteria immobilized on the biochar surface. Otherwise, the sulfur-covered biochar particles could be reused in the second round, and the heavy metal solubilization percentage (Ni 32.84%, Cu 69.93%, Zn 67.17%) was comparable with that of the first round. Nevertheless, the sulfur content became the main limiting factor causing poor bioleaching performance during the third round. Sulfur mixed with the surfactant rhamnolipid did not show significant effect in promoting acidification and heavy metal solubilization due to high levels of organic matter and the impact of the low pH value.

Conclusion
The research indicated the laboratory-made sulfur-covered biochar particles could realize the dual immobilization of the bioleaching functional bacteria and the sulfur substrate to support their recycling and reuse in the second bioleaching round. In the future research, the way to maintain the reuse of the sulfur-covered biochar particles for more rounds will be explored.
Identification of functional mutations associated with environmental variance of litter size in rabbits
Authors: Casto-Rebollo Cristina , Argente María José , García María Luz , Pena Romi , Ibáñez-Escriche Noelia 
Published: May 2020

Abstract
Background
Environmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience. Unravelling the genetic background of the VE of complex traits could help to improve resilience of livestock and stabilize their production across farming systems. The objective of this study was to identify genes and functional mutations associated with variation in VE of litter size (LS) in rabbits. To achieve this, we combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low VE of LS. These lines differ in terms of biomarkers of immune response and mortality. Moreover, rabbits with a lower VE of LS were found to be more resilient to infections than animals with a higher VE of LS.

Results
By using two GWAS approaches (single-marker regression and Bayesian multiple-marker regression), we identified four genomic regions associated with VE of LS, on chromosomes 3, 7, 10, and 14. We detected 38 genes in the associated genomic regions and, using WGS, we identified 129 variants in the splicing, UTR, and coding (missense and frameshift effects) regions of 16 of these 38 genes. These genes were related to the immune system, the development of sensory structures, and stress responses. All of these variants (except one) segregated in one of the rabbit lines and were absent (n = 91) or fixed in the other one (n = 37). The fixed variants were in the HDAC9, ITGB8, MIS18A, ENSOCUG00000021276 and URB1 genes. We also identified a 1-bp deletion in the 3′UTR region of the HUNK gene that was fixed in the low VE line and absent in the high VE line.

Conclusions
This is the first study that combines GWAS and WGS analyses to study the genetic basis of VE. The new candidate genes and functional mutations identified in this study suggest that the VE of LS is under the control of functions related to the immune system, stress response, and the nervous system. These findings could also explain differences in resilience between rabbits with homogeneous and heterogeneous VE of litter size.
A single amino acid substitution in aromatic hydroxylase (HpaB) of Escherichia coli alters substrate specificity of the structural isomers of hydroxyphenylacetate
Authors: Kim Hanseol , Kim Sinyeon , Kim Dohyeon , Yoon Sung Ho 
Published: May 2020

AbstractBackgroundA broad range of aromatic compounds can be degraded by enteric bacteria, and hydroxyphenylacetic acid (HPA) degrading bacteria are the most widespread. Majority ofEscherichia colistrains can use both the structural isomers of HPA, 3HPA and 4HPA, as the sole carbon source, which are catabolized by the same pathway whose associated enzymes are encoded byhpagene cluster. Previously, we observed thatE. coliB REL606 grew only on 4HPA, whileE. coliB BL21(DE3) grew on 3HPA as well as 4HPA.ResultsIn this study, we report that a single amino acid in 4-hydroxyphenylacetate 3-hydroxylase (HpaB) ofE. colidetermines the substrate specificity of HPA isomers. Alignment of protein sequences encoded inhpagene clusters of BL21(DE3) and REL606 showed that there was a difference of only one amino acid (position 379 in HpaB) between the two, viz., Arg in BL21(DE3) and Cys in REL606. REL606 cells expressing HpaB having Arg379 could grow on 3HPA, whereas those expressing HpaB with Gly379 or Ser379 could not. Structural analysis suggested that the amino acid residue at position 379 of HpaB is located not in the active site, but in the vicinity of the 4HPA binding site, and that it plays an important role in mediating the entrance and stable binding of substrates to the active site.ConclusionsThe arginine residue at position 379 of HpaB is critical for 3HPA recognition. Information regarding the effect of amino acid residues on the substrate specificity of structural isomers can facilitate in designing hydoxylases with high catalytic efficiency and versatility.
The model cyanobacteria Anabaena sp. PCC 7120 possess an intact but partially degenerated gene cluster encoding gas vesicles
Authors: Cai Kun , Xu Bo-Ying , Jiang Yong-Liang , Wang Ying , Chen Yuxing , Zhou Cong-Zhao , Li Qiong 
Published: May 2020

AbstractBackgroundBacterial gas vesicles, composed of two major gas vesicle proteins and filled with gas, are a unique class of intracellular bubble-like nanostructures. They provide buoyancy for cells, and thus play an essential role in the growth and survival of aquatic and soil microbes. Moreover, the gas vesicle could be applied to multimodal and noninvasive biological imaging as a potential nanoscale contrast agent. To date, cylinder-shaped gas vesicles have been found in several strains of cyanobacteria. However, whether the functional gas vesicles could be produced in the model filamentous cyanobacteriaAnabaenasp. PCC 7120 remains controversial.ResultsIn this study, we found that an intactgvpgene cluster indeed exists in the model filamentous cyanobacteriaAnabaenasp. PCC 7120. Real-time PCR assays showed that thegvpAgene is constitutively transcribed in vivo, and its expression level is upregulated at low light intensity and/or high growth temperature. Functional expression of this intactgvpgene cluster enables the recombinantEscherichia colito gain the capability of floatation in the liquid medium, thanks to the assembly of irregular gas vesicles. Furthermore, crystal structure of GvpF in combination with enzymatic activity assays of GvpN suggested that these two auxiliary proteins of gas vesicle are structurally and enzymatically conserved, respectively.ConclusionsOur findings show that the laboratory strain of model filamentous cyanobacteriaAnabaenasp. PCC 7120 possesses an intact but partially degenerated gas vesicle gene cluster, indicating that the natural isolate might be able to produce gas vesicles under some given environmental stimuli for better floatation.
The sucrose transporter MdSUT4.1 participates in the regulation of fruit sugar accumulation in apple
Authors: Peng Qian , Cai Yaming , Lai Enhui , Nakamura Masayoshi , Liao Liao , Zheng Beibei , Ogutu Collins , Cherono Sylvia , Han Yuepeng 
Published: May 2020

Abstract
Background
Sugar content is an important determinant of fruit sweetness, but details on the complex molecular mechanism underlying fruit sugar accumulation remain scarce. Here, we report the role of sucrose transporter (SUT) family in regulating fruit sugar accumulation in apple.

Results
Gene-tagged markers were developed to conduct candidate gene-based association study, and an SUT4 member MdSUT4.1 was found to be significantly associated with fruit sugar accumulation. MdSUT4.1 encodes a tonoplast localized protein and its expression level had a negative correlation with fruit sugar content. Overexpression of MdSUT4.1 in strawberry and apple callus had an overall negative impact on sugar accumulation, suggesting that it functions to remobilize sugar out of the vacuole. In addition, MdSUT4.1 is located on chromosomal region harboring a previously reported QTL for sugar content, suggesting that it is a candidate gene for fruit sugar accumulation in apple.

Conclusions
MdSUT4.1 is involved in the regulation of fruit sugar accumulation in apple. This study is not only helpful for understanding the complex mechanism of fruit sugar accumulation, but it also provides molecular tools for genetic improvement of fruit quality in breeding programs of apple.
Genome-wide identification of the peptide transporter family in rice and analysis of the PTR expression modulation in two near-isogenic lines with different nitrogen use efficiency
Authors: Yang Xinghai , Xia Xiuzhong , Zeng Yu , Nong Baoxuan , Zhang Zongqiong , Wu Yanyan , Tian Qinglan , Zeng Weiying , Gao Ju , Zhou Weiyong , Liang Haifu , Li Danting , Deng Guofu 
Published: May 2020

Abstract
Background
Nitrogen (N) is a major nutrient element for crop growth. In plants, the members of the peptide transporter (PTR) gene family may involve in nitrate uptake and transport. Here, we identified PTR gene family in rice and analyzed their expression profile in near-isogenic lines.

Results
We identified 96, 85 and 78 PTR genes in Nipponbare, R498 and Oryza glaberrima, and the phylogenetic trees were similar in Asian cultivated rice and African cultivated rice. The number of PTR genes was higher in peanut (125) and soybean (127). The 521 PTR genes in rice, maize, sorghum, peanut, soybean and Arabidopsis could be classified into 4 groups, and their distribution was different between monocots and dicots. In Nipponbare genome, the 25 PTR genes were distributed in 5 segmental duplication regions on chromosome 1, 2, 3, 4, 5, 7, 8, 9, and 10. The PTR genes in rice have 0–11 introns and 1–12 exons, and 16 of them have the NPF (NRT1/PTR family) domain. The results of RNA-seq showed that the number of differentially expressed genes (DEGs) between NIL15 and NIL19 at three stages were 928, 1467, and 1586, respectively. Under low N conditions, the number of differentially expressed PTR genes increased significantly. The RNA-seq data was analyzed using WGCNA to predict the potential interaction between genes. We classified the genes with similar expression pattern into one module, and obtained 25 target modules. Among these modules, three modules may be involved in rice N uptake and utilization, especially the brown module, in which hub genes were annotated as protein kinase that may regulate rice N metabolism.

Conclusions
In this study, we comprehensively analyzed the PTR gene family in rice. 96 PTR genes were identified in Nippobare genome and 25 of them were located on five large segmental duplication regions. The Ka/Ks ratio indicated that many PTR genes had undergone positive selection. The RNA-seq results showed that many PTR genes were involved in rice nitrogen use efficiency (NUE), and protein kinases might play an important role in this process. These results provide a fundamental basis to improve the rice NUE via molecular breeding.
Prognostic values of the SYNTAX score II and the erythrocyte sedimentation rate on long-term clinical outcomes in STEMI patients with multivessel disease: a retrospective cohort study
Authors: Li Chuang , Zhang Qian , Wang Qianhui , Zhong Jiuchang , Wang Lefeng , Li Kuibao , Yang Xinchun 
Published: May 2020

Abstract
Background
There is a paucity of evidence on the combination of the SYNTAX score II (SSII) and erythrocyte sedimentation rate (ESR) in assessing the long-term prognosis of patients with ST-elevated myocardial infarction (STEMI) and multivessel disease. The objective of this study was to investigate whether the ESR could enhance the predictive value of SSII on the long-term prognosis of STEMI patients.

Methods
A retrospective cohort study involving 483 STEMI and multivessel disease subjects receiving primary percutaneous coronary intervention was conducted. Major adverse cardiovascular events (MACE) included cardiovascular death, acute heart failure, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predicted values of different models were estimated by a likelihood ratio test, Akaike’s information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results
During the follow-up period of up to 52 months, both the SSII and ESR were independently associated with MACE (hazard ratio [HR] = 1.032, p < 0.001; and HR = 1.021, p < 0.001, respectively). The likelihood test indicated that ESR could improve the prognostic model containing SSII (p < 0.001), while the combined model of SSII and ESR attained a lower AIC (p < 0.001). The area under the ROC curve of the combined model containing SSII and ESR increased by 0.05 (p = 0.04) compared to that of the model with SSII alone. The net reclassification and integrated discrimination of the SSII alone model improved significantly with ESR (NRI = 0.0319, p < 0.001; IDI = 0.0334, p < 0.001).

Conclusions
The prognostic model containing SSII, which is an independent risk factor of MACE, had a significantly enhanced predictive probability with the addition of ESR.