bluuebunny/crossref_metadata_2025 huggingface dataset:
How prolonged mechanical ventilation is a neglected disease in chest medicine: a study of prolonged mechanical ventilation based on 6 years of experience in Taiwan
Authors: Huang Chienhsiu
Published: October 2019

Background:

An increasing number of patients require prolonged mechanical ventilation (PMV) to survive recovery from critical care. It should be emphasized that PMV is a neglected disease in chest medicine. We investigated 6 years of clinical outcomes and long-term survival rates of patients who required PMV.

Methods:

We analyzed retrospectively data from patients in respiratory care center (RCC) to investigate the main causes of respiratory failure leading patients to require PMV. We also studied the factors that influence the ventilator weaned rate, factors that influence the long-term ventilator dependence of patients who require PMV, as well as patients’ hospital mortality and long-term survival rates.

Results:

A total of 574 patients were admitted to RCC during the 6 years. Of these, 428 patients (74.6%) were older than 65 years. A total of 391 patients (68.1%) were successfully weaned from the ventilator while 83 patients (14.4%) were unsuccessfully weaned. A total of 95 patients (16.6%) died during RCC hospitalization. The most common cause of acute respiratory failure leading to patients requiring PMV was pneumonia. The factor that affected whether patients were successfully weaned from the ventilator was the cause of the respiratory failure that lead patients to require PMV. Our hospital mortality rate was 32.4%; the 1-year survival rate was 24.3%. There was a strong correlation between higher patient age and higher hospital mortality rate and poor 1-year survival rate. Patients with no comorbidity demonstrated good 1-year survival rates. Patients with four comorbidities and patients with end-stage renal disease requiring hemodialysis comorbidity showed poor 1-year survival rates.

Conclusions:

The factor that affected whether patients were successfully weaned from the ventilator was the cause of the respiratory failure that lead patients to require PMV. Older patients, patients with renal failure requiring hemodialysis, and those with numerous comorbidities demonstrated poor long-term survival. The reviews of this paper are available via the supplemental material section.
Global transcriptional regulation of STAT3- and MYC-mediated sepsis-induced ARDS
Authors: Zhang Jianfeng , Luo Yifeng , Wang Xiaoling , Zhu Jieyun , Li Qian , Feng Jihua , He Dan , Zhong Zhimei , Zheng Xiaowen , Lu Junyu , Zou Donghua , Luo Jiefeng
Published: October 2019

Background:

In recent years, sepsis-induced acute respiratory distress syndrome (ARDS) has remained a major clinical challenge for patients in intensive care units. While some progress has been reported over the years, the pathogenesis of ARDS still needs to be further expounded.

Methods:

In the present study, gene set enrichment analysis, differentially expressed genes analysis, short time-series expression miner, protein–protein interaction (PPI) networks, module analysis, hypergeometric test, and functional enrichment analysis were performed in whole blood gene expression profiles of sepsis and induced-sepsis ARDS to explore the molecular mechanism of sepsis-induced ARDS.

Results:

Further dysregulated genes in the process evolving from healthy control through sepsis to sepsis-induced ARDS were identified and organized into 10 functional modules based on their PPI networks. These functional modules were significantly involved in cell cycle, ubiquitin mediated proteolysis, spliceosome, and other pathways. MYC, STAT3, LEF1, and BRCA1 were potential transcription factors (TFs) regulating these modules. A TF-module-pathway global regulation network was constructed. In particular, our findings suggest that MYC and STAT3 may be the key regulatory genes in the underlying dysfunction of sepsis-induced ARDS. Receiver operating characteristic curve analysis showed the core genes in the global regulation network may be biomarkers for sepsis or sepsis-induced ARDS.

Conclusions:

We found that MYC and STAT3 may be the key regulatory genes in the underlying dysfunction of sepsis-induced ARDS. The reviews of this paper are available via the supplementary material section.
Oct-4: a prognostic biomarker of urinary bladder cancer in North India
Authors: Siddiqui Zainab , Srivastava Anand N. , Sankhwar Satya N. , Zaidi Noorin , Fatima Naseem , Singh Shivangi , Yusuf Mohd.
Published: October 2019

Background:

The objective of this study was to evaluate Octamer-binding transcription factor 4 (Oct-4), neutrophil to lymphocyte ratio (NLR) and body mass index (BMI) as independent prognostic biomarkers for prediction of urinary bladder cancer (UBC) outcomes. With the advancement in prognostic biomarker discovery, tumor recurrence is difficult to accurately predict in UBC. UBC is costly to treat due to the requirement of frequent invasive follow-up sessions. Therefore, it is of utmost importance to evaluate good prognostic biomarkers for UBC surveillance.

Methods:

We studied 39 UBC tissue samples. Oct-4 protein expression was evaluated semiquantitatively by immunohistochemistry (IHC). Complete blood count data and body weight as well as the height of the patients were retrieved and recorded before the date of the first transurethral resection of bladder tumor (TURBT). The follow-up period was 48 months for recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS).

Results:

Oct-4 expression profile was found to be significantly associated with gender ( p = 0.028), tumor grade ( p = 0.038), tumor stage ( p = 0.003), lymph node status ( p = 0.029), recurrence ( p = 0.004), progression ( p = 0.011), and treatment modality ( p = 0.016). Tumor grade and progression were found significant with NLR values (tumor grade, p = 0.006; progression, p = 0.038) and BMI (tumor grade, p = 0.036; progression, p = 0.014). Moreover, BMI was also significantly associated with UBC recurrence ( p = 0.014). Kaplan–Meier survival analysis showed poor prognosis with both high Oct-4 expression (RFS, p = 0.001; PFS, p = 0.004; OS, p = 0.014) and high NLR values (RFS, p = 0.049; PFS, p = 0.004; OS, p = 0.005). Patients with high BMI too had poor RFS ( p = 0.025) and poor PFS ( p = 0.032). Furthermore, multivariate Cox regression analysis, indicated Oct-4 as an independent prognostic biomarker for RFS (HR = 0.240, 95% CI, 0.072–0.804, p = 0.021).

Conclusions:

We conclude that the expression profile of Oct-4 will be beneficial in prediction of UBC recurrence, and could have profound implications on the development of new therapeutic targets for UBC treatment.
Effectiveness of surgical management with an adjustable sling versus an artificial urinary sphincter in patients with severe urinary postprostatectomy incontinence: a systematic review and network meta-analysis
Authors: Guachetá Bomba Pedro Luis , Ocampo Flórez Ginna Marcela , Echeverría García Fernando , García-Perdomo Herney Andrés
Published: October 2019

Background:

The purpose of this study was to determine the effectiveness of an adjustable sling compared with an artificial urinary sphincter (AUS) in patients with severe urinary incontinence (SUI) postprostatectomy (PP).

Methods:

This review was carried out following the Cochrane Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration. We searched Medline, Embase, LILACS, and CENTRAL databases. Studies with patients older than 18 years of age with SUI PP who underwent sling or AUS intervention and had been monitored for longer than 12 months were included.

Results:

Seven studies were included, yielding a sample size of 420. Pads were reportedly dry or improved in 70% of the sling group compared with 74% in the AUS group. The Incontinence Impact Questionnaire, Short Form (IIQ-7) was the most frequently used scale and showed improvement, with a score of 82.8% in the AUS group compared with 86.1% in the sling group. When comparing interventions with nonintervention, relative risks (RRs) of 35.37 (95% confidence interval [CI]: 7.17–174.35) and 45.14 (95% CI: 11.09–183.70) were found for the adjustable sling and AUS, respectively, which were statistically significant. No significant differences were found when AUS versus adjustable sling were compared, with an RR of 0.78 (95% CI: 0.09–6.56). We found a low risk of bias in most studies.

Conclusions:

Both interventions can reduce incontinence and improve the quality of life of patients with SUI PP. The published literature is substantially limited as no randomized clinical trials are available, no consensus has been reached regarding the definition of severity of incontinence, and considerable heterogeneity exists across the outcome variables measured.
Cytokines trigger disruption of endothelium barrier function and p38 MAP kinase activation in BMPR2‐silenced human lung microvascular endothelial cells
Authors: Tielemans Birger , Stoian Leanda , Gijsbers Rik , Michiels Annelies , Wagenaar Allard , Farre Marti Ricard , Belge Catharina , Delcroix Marion , Quarck Rozenn
Published: October 2019

The bone morphogenetic protein receptor II (BMPRII) signaling pathway is impaired in pulmonary arterial hypertension and mutations in the BMPR2 gene have been observed in both heritable and idiopathic pulmonary arterial hypertension. However, all BMPR2 mutation carriers do not develop pulmonary arterial hypertension, and inflammation could trigger the development of the disease in BMPR2 mutation carriers. Circulating levels and/or lung tissue expression of cytokines such as tumor necrosis factor‐α or interleukin‐18 are elevated in patients with pulmonary arterial hypertension and could be involved in the pathogenesis of pulmonary arterial hypertension. We consequently hypothesized that cytokines could trigger endothelial dysfunction in addition to impaired BMPRII signaling. Our aim was to determine whether impairment of BMPRII signaling might affect endothelium barrier function and adhesiveness to monocytes, in response to cytokines. BMPR2 was silenced in human lung microvascular endothelial cells (HLMVECs) using lentiviral vectors encoding microRNA‐based hairpins. Effects of tumor necrosis factor‐α and interleukin‐18 on HLMVEC adhesiveness to the human monocyte cell line THP‐1, adhesion molecule expression, endothelial barrier function and activation of P38MAPK were investigated in vitro. Stable BMPR2 silencing in HLMVECs resulted in impaired endothelial barrier function and constitutive activation of P38MAPK. Adhesiveness of BMPR2‐silenced HLMVECs to THP‐1 cells was enhanced by tumor necrosis factor‐α and interleukin‐18 through ICAM‐1 adhesion molecule. Interestingly, tumor necrosis factor‐α induced activation of P38MAPK and disrupted endothelial barrier function in BMPR2‐silenced HLMVECs. Altogether, our findings showed that stable BMPR2 silencing resulted in impaired endothelial barrier function and activation of P38MAPK in HLMVECs. In BMPR2‐silenced HLMVECs, cytokines enhanced adhesiveness capacities, activation of P38MAPK and impaired endothelial barrier function suggesting that cytokines could trigger the development of pulmonary arterial hypertension in a context of impaired BMPRII signaling pathway.
Effects of preoperative anti‐tumour necrosis factor alpha infusion timing on postoperative surgical site infection in inflammatory bowel disease: A systematic review and meta‐analysis
Authors: Qiu YuJie , Zheng ZiCheng , Liu Gang , Zhao XinYu , He AnQi
Published: October 2019

Background

Anti‐tumour necrosis factor alpha agents (anti‐TNF‐α) have been widely used in patients with inflammatory bowel disease (IBD). However, few published meta‐analyses have focused on timing of the last infusion before surgery. We evaluated the relationship between preoperative anti‐TNF‐α timing and postoperative surgical site infection to provide additional evidence for surgeons to choose appropriate dates for surgery.

Methods

We searched from inception until January 2019 for studies that documented postoperative complications of adults with IBD who underwent preoperative anti‐TNF‐α treatment. Primary outcomes of included studies were the odds ratios of preoperative anti‐TNF‐α time frames (4, 8 and 12 weeks). In addition, surgical site infection and its subtypes (anastomotic leakage, abscesses and wound infection) were analysed.

Results

Twenty‐seven publications were included. No significant difference between anti‐TNF‐α and control cohorts was observed for most postoperative surgical site infections (or its subtypes) when the preoperative anti‐TNF‐α infusion time window was within 4, 8 or 12 weeks. Additionally, no significant difference in postoperative complications was observed between preoperative anti‐TNF‐α windows of within four weeks and more than four weeks.

Conclusions

In terms of surgical site infection and its subtypes, anti‐TNF‐α may be safe for ulcerative colitis and Crohn's disease patients who receive their last infusion of anti‐TNF‐α more than four weeks before surgery. We also found no evidence that anti‐TNF‐α was a risk factor when administered within four weeks, with the exception of subgroup results from a single study. Stratified by time window, use of anti‐TNF‐α until surgery has the potential to become a more considered strategy in clinical practice.
Data out of place: Toxic traces and the politics of recycling
Authors: Thylstrup Nanna Bonde
Published: October 2019

It has become increasingly common to talk about “digital traces”. The idea that we leak, drop and leave traces wherever we go has given rise to a culture of traceability, and this culture of traceability, I argue, is intimately entangled with a socio-economics of data disposability and recycling. While the culture of traceability has often been theorised in terms of, and in relation to, privacy, I offer another approach, framing digital traces instead as a question of waste. This perspective, I argue, allows us to connect to, extend and nuance existing discussions of digital traces. It shows us that data traces raise questions about not only how data capitalism tracks individual and multiple data behaviours, but also how it links to social and environmental toxicities in the form of abuse and environmental pollution, which follow gendered and colonial structures of violence.
Institutions, infrastructures, and data friction – Reforming secondary use of health data in Finland
Authors: Aula Ville
Published: October 2019

New data-driven ideas of healthcare have increased pressures to reform existing data infrastructures. This article explores the role of data governing institutions during a reform of both secondary health data infrastructure and related legislation in Finland. The analysis elaborates on recent conceptual work on data journeys and data frictions, connecting them to institutional and regulatory issues. The study employs an interpretative approach, using interview and document data. The results show the stark contrast between the goals of open and Big Data inspired reforms and the existing institutional realities. The multiple tensions that emerged during the process indicate how data frictions emanate to the institutional level, and how mundane data practices and institutional dynamics are intertwined. The article argues that in the Finnish case, public institutions acted as sage-guards of public interest, preventing more controversial parts from passing. Finally, it argues that initiating regulatory and infrastructural reforms simultaneously was beneficial for solving the tensions of the initiative and analysing either side separately would have produced misleading accounts of the overall initiative. The results highlight the benefits of analysing institutional dynamics and data practices as connected issues.
Game of text: Bruce Lee’s media legacies
Authors: Bowman Paul
Published: October 2019

This article situates Bruce Lee at the heart of the emergence of ‘martial arts’. It argues that the notion ‘martial arts’, as we now know it, is a discursive entity that emerged in the wake of media texts, and that the influence of Bruce Lee films of the early 1970s was both seminal and structuring of ‘martial arts’, in ways that continue to be felt. Using the media theory proposition that a limited range of ‘key visuals’ structure the aesthetic terrain of the discursive entity ‘martial arts’, the article assesses the place, role and status of images of Bruce Lee as they work intertextually across a wide range of media texts. In so doing, the article demonstrates the enduring media legacy of Bruce Lee – one that has always overflowed the media realm and influenced the lived, embodied lifestyles of innumerable people the world over, who have seen Bruce Lee and other martial arts texts and gone on to study Chinese and Asian martial arts because of them.
Bruce Lee as director and the star as author
Authors: Pellerin Eric
Published: October 2019

This article examines Bruce Lee’s films as a director as well as his influence on films in which he starred. Using Richard Dyer’s “star studies” framework in conjunction with Patrick McGilligan’s notion of the “actor as auteur,” this article analyzes Bruce Lee’s star persona and his authorial power and contends that a case can be made for Lee’s authorship even in films for which he did not serve as the director. Against the backdrop of Golden Harvest and the New Hollywood–modeled Hong Kong production context in which Lee worked, Lee’s fight scenes as a director are juxtaposed with his fight scenes as a star in the interest of identifying similarities and differences toward the goal of identifying greater similarities than critics and scholars have hitherto realized. Ultimately, this article proposes that so overpowering was Lee’s stardom that, whether as “merely” a star or as a “true” auteur, every Bruce Lee film bears his irrepressible signature.
Bruce Lee as gladiator: Celebrity, vernacular stoicism and cinema
Authors: Steenberg Lindsay
Published: October 2019

This article situates Bruce Lee’s films and star persona in the context of wider patterns in global genre cinema of the 1960s and 1970s. I argue for a connection between the Western reception of Lee’s films and those of the mid-century Italian sword and sandal films, beginning with the Colosseum fight between Bruce Lee and Chuck Norris that concludes Way of the Dragon (1972). From the dojo fights of Fist of Fury (1972), through the tournament structure in Enter the Dragon (1973), to his statistically led re-animation in the EA Sports UFC 3 (2018) videogame, Bruce Lee can be usefully considered as a gladiator. Bruce Lee, as fighter, performer and star persona, contributes to the enduring gladiatorial archetype that is an embedded feature in the Western visual imaginary. Furthermore, I argue that the gladiator archetype itself shifted because of Lee’s onscreen roles and the discourse that surrounds his star persona. In order to map these shifts and patterns of confluence, I chart three main points of impact that Lee has had on the gladiatorial archetype using his Western-facing roles on film and television, namely the television series Longstreet (1971–1972) and Enter the Dragon (1973). First, I consider the inclusion of martial arts and, second, the opening up of the field of representation to different models of masculinity, including a leaner body type and a non-White – in this case, ethnically Chinese – gladiator. The third point is the emphasis on a popular, or vernacular, stoicism. Ultimately, I elucidate the relationship between the gladiator, Bruce Lee, and philosophy, arguing that Lee embodies a vernacular stoicism that has become one of the defining features of the post-millennial gladiator and notions of heroic masculinity in popular culture more widely.
New National Initiatives of Modernizing Education in China
Authors: Zhu Yiming
Published: October 2019

Purpose:

This article aims to shed light on a latest education policy blueprint in China, titled China’s education modernization 2035, which was issued by the Central Government of China in February of 2019.

Design/Approach/Methods:

This is an analytical policy review.

Findings:

The author argues that this new Chinese educational policy was driven by three factors: UN 2030 Agenda, China’s national strategy, and Chinese educational reform and improvement. In China’s education modernization 2035, eight key principles were rooted in the Chinese context and also recognized by international society. According to this policy initiative, 10 specific strategical tasks are outlined to reform Chinese education toward 2035.

Originality/Value:

The article will be useful to learn and understand the new directions and the future approaches of Chinese education development and reform toward 2035.
Failure Pressures of Dural Repairs in a Porcine Ex Vivo Model: Novel Use of Titanium Clips Versus Tissue Glue
Authors: Chorath Kevin , Krysinski Mason , Bunegin Leonid , Majors Jacob , Weitzel Erik Kent , McMains Kevin Christopher , Chen Philip G.
Published: October 2019

Objective

Endoscopic skull base surgery is advancing, and it is important to have reliable methods to repair the resulting defect. The objective of this study was to determine the failure pressures of 2 commonly used methods to repair large dural defects: collagen matrix underlay with fibrin glue and collagen matrix underlay with polyethylene glue, as well as a novel repair method: fascia lata with nonpenetrating titanium vascular clips.

Methods

The failure pressure of the 3 dural repairs was determined in a closed testing apparatus. Defects in porcine dura were created and collagen matrix grafts were used as an underlay followed by either fibrin glue (FG/CMG) or polyethylene glycol glue (PEG/CMG). A third condition using a segment of fascia lata was positioned flush with the edges of the dural defect and secured with titanium clips (TC/FL). Saline was infused to simulate increasing intracranial pressure (ICP) applied to the undersurface of the grafts until the repairs failed.

Results

The mean failure pressure of the PEG/CMG repair was 34.506 ± 14.822 cm H2O, FG/CMG was 12.413 ± 5.114 cm H2O, and TC/FL was 8.330 ± 3.483 cm H2O. There were statistically significant differences in mean failure pressures among the 3 repair methods.

Conclusion

In this ex vivo model comparing skull base repairs’ ability to withstand cerebrospinal fluid leak, the repairs that utilized PEG/CMG tolerated the greatest amount of pressure and was the only repair that exceeded normal physiologic ICP’s. Repair methods utilizing glues generally tolerated higher pressures compared to the novel repair using clips alone.
Fuzzy Torque Control of the Bionic Flexible Manipulator Actuated by Pneumatic Muscle Actuators
Authors: Liu Kai , Chen Yining , Xu Jiaqi , Wu Yang , Lu Yonghua , Zhao Dongbiao
Published: October 2019

A bionic flexible manipulator driven by pneumatic muscle actuator (PMA) can better reflect the flexibility of the mechanism. Current research on PMA mainly focuses on the modeling and control strategy of the pneumatic manipulator system. Compared with traditional electro-hydraulic actuators, the structure of PMA is simple but possesses strong nonlinearity and flexibility, which leads to the difficulty in improving the control accuracy. In this paper, the configuration design of a bionic flexible manipulator is performed by human physiological map, the kinematic model of the mechanism is established, and the dynamics is analyzed by Lagrange method. A fuzzy torque control algorithm is designed based on the computed torque method, where the fuzzy control theory is applied. The hardware experimental system is established. Through the co-simulation contrast test on MATLAB and ADAMS, it is found that the fuzzy torque control algorithm has better tracking performance and higher tracking accuracy than the computed torque method, and is applied to the entity control test. The experimental results show that the fuzzy torque algorithm can better control the trajectory tracking movement of the bionic flexible manipulator. This research proposes a fuzzy torque control algorithm which can compensate the error more effectively, and possesses the preferred trajectory tracking performance.
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

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

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

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

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

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

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

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

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

Background

Acute 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.

Methods

In 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.

Results

Data 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%.

Conclusions

These 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

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

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.