bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution mass spectrometry to complement monitoring and track emerging chemicals and pollution trends in European water resources
Authors: Brack Werner , Hollender Juliane , de Alda Miren López , Müller Christin , Schulze Tobias , Schymanski Emma , Slobodnik Jaroslav , Krauss Martin 
Published: October 2019

Abstract
Currently, chemical monitoring based on priority substances fails to consider the majority of known environmental micropollutants not to mention the unexpected and unknown chemicals that may contribute to the toxic risk of complex mixtures present in the environment. Complementing component- and effect-based monitoring with wide-scope target, suspect, and non-target screening (NTS) based on high-resolution mass spectrometry (HRMS) data is recommended to support environmental impact and risk assessment. This will allow for detection of newly emerging compounds and transformation products, retrospective monitoring efforts, and the identification of possible drivers of toxicity by correlation with effects or modelling of expected effects for future and abatement scenarios. HRMS is becoming increasingly available in many laboratories. Thus, the time is right to establish and harmonize screening methods, train staff, and record HRMS data for samples from regular monitoring events and surveys. This will strongly enhance the value of chemical monitoring data for evaluating complex chemical pollution problems, at limited additional costs. Collaboration and data exchange on a European-to-global scale is essential to maximize the benefit of chemical screening. Freely accessible data platforms, inter-laboratory trials, and the involvement of international partners and networks are recommended.
A holistic approach is key to protect water quality and monitor, assess and manage chemical pollution of European surface waters
Authors: Posthuma Leo , Munthe John , van Gils Jos , Altenburger Rolf , Müller Christin , Slobodnik Jaroslav , Brack Werner 
Published: October 2019

Abstract
Chemical pollution of surface waters is a societal concern around the globe. Key problems in current water quality protection, assessment and management are the narrow focus on a small fraction of the chemicals in commerce, concerns for increasingly diverse chemical emissions, and lack of effective diagnosis and management approaches. In reply, three key concepts to address these challenges were developed and tested. The approaches were developed in the context of the European Union Water Framework Directive, based on principles such as the DPSIR-causal framework (Drivers, Pressure, Status, Impact and Response) and the basic feature that water protection and management should be based on a water-system level approach. Collaborative actions of researchers and stakeholders resulted in: (1) an operationalization and implementation of the solution-focused risk assessment paradigm as proposed in 2009, to improve the utility of risk assessments, (2) the provision of a large set of tools and services to prevent, monitor, assess and manage complex mixture pollution problems, and (3) a strategy and a database on intervention options. These three elements were recognized as core elements to help protecting and improving water quality. Although the methods were developed in the context of water quality problems in Europe, the three elements can be applied globally in water quality protection and management.
The RiBaTox web tool: selecting methods to assess and manage the diverse problem of chemical pollution in surface waters
Authors: Kramer Kees J. M. , Sleeuwaert Frank , Engelen Guy , Müller Christin , Brack Werner , Posthuma Leo 
Published: October 2019

Abstract
Chemical pollution of water bodies is a complex problem around the globe. When described by the extremes of the range of problem definitions, water bodies can be chemically polluted by a single compound that is emitted from a point source or an incidental spill, or by chronic diffuse emissions from local and upstream land uses. The resulting mixture exposures can vary in space and time, e.g. due to the use of pesticides in the crop growing season. The environmental management objectives are commonly to protect and restore surface waters against human influences. Currently, chemical pollution is globally judged for a selected set of compounds, by judging each of these individually in comparison with protective environmental quality standards. Research has provided a novel assessment paradigm (solution-focused risk assessment) and novel data, measurement methods and models to improve on current practices. Their adoption and application require establishing novel linkages between the diverse problem definitions and the novel approaches. That would assist water quality professionals to select the most effective option or options to protect and restore water quality. The present paper introduces the RiBaTox (River Basin Specific Toxicants assessment and management) web tool. It consists of short descriptions of the novel approaches (made available as Additional file 1) and a decision tree for end-users to select those. The overview of novel approaches collated in RiBaTox is relevant for end-users ranging from local water quality experts up till strategic policy developers. Although RiBaTox was developed in the context of European water quality problems, the methods provided by RiBaTox are relevant for users from (inter)national to local scales. This paper is part of a series of Policy Briefs from the EU-FP7 project SOLUTIONS (http://www.solutions-project.eu), which provide backgrounds on chemical pollution of surface waters and policy practices and proposed improvements.
Improved component-based methods for mixture risk assessment are key to characterize complex chemical pollution in surface waters
Authors: Posthuma Leo , Altenburger Rolf , Backhaus Thomas , Kortenkamp Andreas , Müller Christin , Focks Andreas , de Zwart Dick , Brack Werner 
Published: October 2019

Abstract
The present monitoring and assessment of water quality problems fails to characterize the likelihood that complex mixtures of chemicals affect water quality. The European collaborative project SOLUTIONS suggests that this likelihood can be estimated, amongst other methods, with improved component-based methods (CBMs). The use of CBMs is a well-established practice in the WFD, as one of the lines of evidence to evaluate chemical pollution on a per-chemical basis. However, this is currently limited to a pre-selection of 45 and approximately 300 monitored substances (priority substances and river basin-specific pollutants, respectively), of which only a few actually co-occur in relevant concentrations in real-world mixtures. Advanced CBM practices are therefore needed that consider a broader, realistic spectrum of chemicals and thereby improve the assessment of mixture impacts, diagnose the causes of observed impacts and provide more useful water management information. Various CBMs are described and illustrated, often representing improvements of well-established methods. Given the goals of the WFD and expanding on current guidance for risk assessment, these improved CBMs can be applied to predicted or monitored concentrations of chemical pollutants to provide information for management planning. As shown in various examples, the outcomes of the improved CBMs allow for the evaluation of the current likelihood of impacts, of alternative abatement scenarios as well as the expected consequences of future pollution scenarios. The outputs of the improved CBMs are useful to underpin programmes of measures to protect and improve water quality. The combination of CBMs with effect-based methods (EBMs) might be especially powerful to identify as yet underinvestigated emerging pollutants and their importance in a mixture toxicity context. The present paper has been designed as one in a series of policy briefs to support decisions on water quality protection, monitoring, assessment and management under the European Water Framework Directive (WFD).
The European Collaborative Project SOLUTIONS developed models to provide diagnostic and prognostic capacity and fill data gaps for chemicals of emerging concern
Authors: van Gils Jos , Posthuma Leo , Cousins Ian T. , Lindim Claudia , de Zwart Dick , Bunke Dirk , Kutsarova Stela , Müller Christin , Munthe John , Slobodnik Jaroslav , Brack Werner 
Published: October 2019

Abstract
The European Union Water Framework Directives aims at achieving good ecological status in member states’ water bodies. Insufficient ecological status could be the result of different interacting stressors, among them the presence of many thousands of chemicals. The diagnosis of the likelihood that these chemicals negatively affect the ecological status of surface waters or human health, and the subsequent development of abatement measures usually relies on water quality monitoring. This gives an incomplete picture of chemicals’ contamination, due to the limited number of monitoring stations, samples and substances. Information gaps thus limit the possibilities to protect against and effectively manage chemicals in aquatic ecosystems. The EU FP7 SOLUTIONS project has developed and validated a collection of integrated models (“Model Train”) to increase our understanding of issues related to emerging chemicals in Europe’s river basins and to complement information and knowledge derived from field data. Unlike pre-existing models, the Model Train is suitable to model mixtures of thousands of chemicals, to better approach a “real-life” mixture exposure situation. It can also be used to model new chemicals at a stage where not much is known about them. The application of these models on a European scale provides temporally and spatially variable concentration data to fill gaps in the space, time and substance domains left open by water quality monitoring, and it provides homogeneous data across Europe where water quality data from monitoring are missing. Thus, it helps to avoid overlooking candidate chemicals and possible hot spots for management intervention. The application of the SOLUTIONS Model Train on a European scale presents a relevant line of evidence for water system level prognostic and diagnostic impact assessment related to chemical pollution. The application supports the design of cost-effective programmes of measures by helping to identify the most affected sites and the responsible substances, by evaluating alternative abatement options and by exploring the consequences of future trends.
The impact of body weight and diabetes on new-onset atrial fibrillation: a nationwide population based study
Authors: Kim Yun Gi , Han Kyung-Do , Choi Jong-Il , Boo Ki Yung , Kim Do Young , Oh Suk-Kyu , Lee Kwang-No , Shim Jaemin , Kim Jin Seok , Kim Young-Hoon 
Published: October 2019

Abstract

Background
Being obese or underweight, and having diabetes are important risk factors for new-onset atrial fibrillation (AF). However, it is unclear whether there is any interaction between body weight and diabetes in regard to development of new-onset AF. We aimed to evaluate the role of body weight status and various stage of diabetes on new-onset AF.

Methods
This was a nationwide population based study using National Health Insurance Service (NHIS) data. A total of 9,797,418 patients who underwent national health check-ups were analyzed. Patients were classified as underweight [body mass index (BMI) < 18.5], normal reference group (18.5 ≤ BMI < 23.0), upper normal (23.0 ≤ BMI < 25.0), overweight (25.0 ≤ BMI < 30.0), or obese (BMI ≥ 30.0) based on BMI. Diabetes were categorized as non-diabetic, impaired fasting glucose (IFG), new-onset diabetes, diabetes < 5 years, and diabetes ≥ 5 years. Primary outcome end point was new-onset AF. New-onset AF was defined as one inpatient or two outpatient records of International Classification of Disease, Tenth Revision (ICD-10) codes in patients without prior AF diagnosis.

Results
During 80,130,161 patient*years follow-up, a total of 196,136 new-onset AF occurred. Obese [hazard ration (HR) = 1.327], overweight (HR = 1.123), upper normal (HR = 1.040), and underweight (HR = 1.055) patients showed significantly increased risk of new-onset AF compared to the normal reference group. Gradual escalation in the risk of new-onset AF was observed along with advancing diabetic stage. Body weight status and diabetes were independently associated with new-onset AF and at the same time, had synergistic effects on the risk of new-onset AF with obese diabetic patients having the highest risk (HR = 1.823).

Conclusions
Patients with obesity, overweight, underweight, and diabetes had significantly increased risk of new-onset AF. Body weight status and diabetes had synergistic effects on the risk of new-onset AF. The risk of new-onset AF increased gradually with advancing diabetic stage. This study suggests that maintaining optimal body weight and glucose homeostasis might prevent new-onset AF.
CircRNA expression profiles in human dental pulp stromal cells undergoing oxidative stress
Authors: Zhang Jingying , Li Dan , Wang Dan , Man Kenny , Yang Xuebin 
Published: October 2019

Abstract

Background
Oxidative stress has a determinantal effect on human dental pulp stromal cells (hDPSCs), including affecting their longevity and functionality. Circular RNAs (circRNAs) play an essential role in stromal cell behavior; however, the exact mechanism in which circRNAs functions within hDPSCs were undergoing oxidative stress remains unclear. The purpose of this study is to assess the global changes and characteristics of circRNAs in hDPSCs undergoing oxidative stress.

Methods
Using an oxidative stress model of hDPSCs, we applied microarray analysis to examine the circRNAs profiles. We confirmed the changes in circRNAs by quantitative Real-Time PCR (qRT-PCR). Furthermore, bioinformatics tools, including a miRcode map, TargetScan, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were reconstructed for further assessment. SIRT1 gene and protein expression were tested by qRT-PCR and In Cell-Western analysis.

Results
We revealed 330 upregulated, and 533 downregulated circRNAs undergoing oxidative stress in hDPSCs and confirmed three circRNAs distinct expressions (hsa_circ_0000257, hsa_circ_0087354, and hsa_circ_0001946) in hDPSCs undergoing oxidative stress by qRT-PCR. GO, and KEGG pathway enrichment revealed the differentially expressed circRNAs might participate in p53 and cell cycle signaling networks associated with oxidative stress. SIRT1 gene and protein expression was reduced in the oxidatively stressed cells (OSC) group compared to untreated cells (UC).

Conclusions
The findings of this study has provided new insights into circRNAs and a basis for further studies assessing the potential functions of hsa_circ_0000257, hsa_circ_0087354, and hsa_circ_0001946 in oxidatively stressed hDPSCs.
90-gene signature assay for tissue origin diagnosis of brain metastases
Authors: Zheng Yulong , Ding Yongfeng , Wang Qifeng , Sun Yifeng , Teng Xiaodong , Gao Qiqi , Zhong Weixiang , Lou Xiaofeng , Xiao Cheng , Chen Chengshu , Xu Qinghua , Xu Nong 
Published: October 2019

Abstract

Background
Brain metastases (BM) are the most common intracranial tumors. 2–14% of BM patients present with unknown primary site despite intensive evaluations. This study aims to evaluate the performance of a 90-gene expression signature in determining the primary sites for BM samples.

Methods
The sequence-based gene expression profiles of 708 primary brain tumors (PBT) collected from The Cancer Genome Atlas (TCGA) database were analyzed by the 90-gene expression signature, with a similarity score for each of 21 common tumor types. We then used Optimal Binning algorithm to generate a threshold for separating PBT from BM. Eighteen PBT samples were analyzed to substantiate the reliability of the threshold. In addition, the performance of the 90-gene expression signature for molecular classification of metastatic brain tumors was validated in a cohort of 48 BM samples with the known origin. For each BM sample, the tumor type with the highest similarity score was considered tissue of origin. When a sample was diagnosed as PBT, but the similarity score below the threshold, the second prediction was considered as the primary site.

Results
A threshold of the similarity score, 70, was identified to discriminate PBT from BM (PBT: > 70, BM: ≤ 70) with an accuracy of 99% (703/708, 95% CI 98–100%). The 90-gene expression signature was further validated with 18 PBT and 44 BM samples. The results of 18 PBT samples matched reference diagnosis with a concordance rate of 100%, and all similarity scores were above the threshold. Of 44 BM samples, the 90-gene expression signature accurately predicted primary sites in 89% (39/44, 95% CI 75–96%) of the cases.

Conclusions
Our findings demonstrated the potential that the 90-gene expression signature could serve as a powerful tool for accurately identifying the primary sites of metastatic brain tumors.
Serial plasma DNA levels as predictors of outcome in patients with acute traumatic cervical spinal cord injury
Authors: Wang Hung-Chen , Lin Yu-Tsai , Hsu Shih-Yuan , Tsai Nai-Wen , Lai Yun-Ru , Su Ben Yu-Jih , Kung Chia-Te , Lu Cheng-Hsien 
Published: October 2019

AbstractBackgroundAcute traumatic cervical spinal cord injury (SCI) is a leading cause of disability in adolescents and young adults worldwide. Evidence from previous studies suggests that circulating cell-free DNA is associated with severity following acute injury. The present study determined whether plasma DNA levels in acute cervical SCI are predictive of outcome.MethodsIn present study, serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were obtained from 44 patients with acute traumatic cervical SCI at five time points from day 1 to day 180 post-injury. Control blood samples were obtained from 66 volunteers.ResultsData showed a significant increase in plasma nDNA and mtDNA concentrations at admission in SCI patients compared to the control group. Plasma nDNA levels at admission, but not plasma mtDNA levels, were significantly associated with the Japanese Orthopaedic Association (JOA) score and Injury Severity Score in patients with acute traumatic cervical SCI. In patients with non-excellent outcomes, plasma nDNA increased significantly at days 1, 14 and 30 post-injury. Furthermore, its level at day 14 was independently associated with outcome. Higher plasma nDNA levels at the chosen cutoff point (> 45.6 ng/ml) predicted poorer outcome with a sensitivity of 78.9% and a specificity of 78.4%.ConclusionsThese results indicate JOA score performance and plasma nDNA levels reflect the severity of spinal cord injury. Therefore, the plasma nDNA assays can be considered as potential neuropathological markers in patients with acute traumatic cervical SCI.
Performance and trend for quality of service in a large HIV/AIDS treatment program in Nigeria
Authors: Aliyu Ahmad , El-Kamary Samer , Brown Jessica , Agins Bruce , Ndembi Nicaise , Aliyu Gambo , Jumare Jibreel , Adelekan Babatunde , Dakum Patrick , Abimiku Alash’le , Charurat Manhattan 
Published: October 2019

Abstract

Background
As antiretroviral therapy (ART) programs expand access, there is an increase in burden to a healthcare system. These results are reduced provider-patient contact time and poor programmatic and patient outcomes. Quality management offers providers a standardized approach for addressing the appropriateness of care to be applied in resource-limited settings. This study aimed to determine the trend of performance on HIV/AIDS quality management indicators of health facilities providing ART over a period of 5 years.

Methods
The annual performance scores of quality of care (QoC) indicators of 31 health facilities providing ART was extracted from a database covering a period of 5 years (from October 2008 to September 2012). The data are percentages that indicate scores of each health facility assessed based on compliance to National ART guidelines categorized into several indicator domains. A Chi square statistic for the trend, as well as test for departure from the trend line was determined. The p value associated with each indicator provides the significant level for testing an alternative hypothesis that the rate of change over the period considered for that indicator does not equal to zero. The slope of the regression line also gives the magnitude of the rate of change for each indicator by healthcare level across the review period.

Results
Generally, performance trends showed improvement across most indicator domains. The highest improvement occurred for “3 month loss to follow-up” and “1 year no-visit”, with scores declining from 37 to 3%, and 42% to 12% respectively. However, there was a sharp decline in performance between 2010 and 2012 in weight monitoring of patients (p < 0.01), adherence assessment to ARVs (p < 0.01) and hematocrit measurements (p = 0.01). The aggregate rate of change β, as obtained from the slope of the trend line is highly significant (p < 0.01) for all the quality of care indicators considered, whether improving or declining.

Conclusion
Periodic assessment to determine HIV/AIDS quality of care can guide rapid scale-up of services to achieve universal coverage in resource-limited settings. Determining trends to understand patterns is very useful for improving programmatic and patient outcomes.
Efficient production of d-lactate from methane in a lactate-tolerant strain of Methylomonas sp. DH-1 generated by adaptive laboratory evolution
Authors: Lee Jong Kwan , Kim Sujin , Kim Wonsik , Kim Sungil , Cha Seungwoo , Moon Hankyeol , Hur Dong Hoon , Kim Seon-Young , Na Jeong-Geol , Lee Jin Won , Lee Eun Yeol , Hahn Ji-Sook 
Published: October 2019

Abstract

Background
Methane, a main component of natural gas and biogas, has gained much attention as an abundant and low-cost carbon source. Methanotrophs, which can use methane as a sole carbon and energy source, are promising hosts to produce value-added chemicals from methane, but their metabolic engineering is still challenging. In previous attempts to produce lactic acid (LA) from methane, LA production levels were limited in part due to LA toxicity. We solved this problem by generating an LA-tolerant strain, which also contributes to understanding novel LA tolerance mechanisms.

Results
In this study, we engineered a methanotroph strain Methylomonas sp. DH-1 to produce d-lactic acid (d-LA) from methane. LA toxicity is one of the limiting factors for high-level production of LA. Therefore, we first performed adaptive laboratory evolution of Methylomonas sp. DH-1, generating an LA-tolerant strain JHM80. Genome sequencing of JHM80 revealed the causal gene watR, encoding a LysR-type transcription factor, whose overexpression due to a 2-bp (TT) deletion in the promoter region is partly responsible for the LA tolerance of JHM80. Overexpression of the watR gene in wild-type strain also led to an increase in LA tolerance. When d form-specific lactate dehydrogenase gene from Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 was introduced into the genome while deleting the glgA gene encoding glycogen synthase, JHM80 produced about 7.5-fold higher level of d-LA from methane than wild type, suggesting that LA tolerance is a critical limiting factor for LA production in this host. d-LA production was further enhanced by optimization of the medium, resulting in a titer of 1.19 g/L and a yield of 0.245 g/g CH4.

Conclusions
JHM80, an LA-tolerant strain of Methylomonas sp. DH-1, generated by adaptive laboratory evolution was effective in LA production from methane. Characterization of the mutated genes in JHM80 revealed that overexpression of the watR gene, encoding a LysR-type transcription factor, is responsible for LA tolerance. By introducing a heterologous lactate dehydrogenase gene into the genome of JHM80 strain while deleting the glgA gene, high d-LA production titer and yield were achieved from methane.