bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritisation of water pollutants: the EU Project SOLUTIONS proposes a methodological framework for the integration of mixture risk assessments into prioritisation procedures under the European Water Framework Directive
Authors: Faust Michael , Backhaus Thomas , Altenburger Rolf , Dulio Valeria , van Gils Jos , Ginebreda Antoni , Kortenkamp Andreas , Munthe John , Posthuma Leo , Slobodnik Jaroslav , Tollefsen Knut Erik , van Wezel Annemarie , Brack Werner 
Published: October 2019

Abstract
Current prioritisation procedures under the EU Water Framework Directive (WFD) do not account for risks from chemical mixtures. SOLUTIONS proposes a multiple-lines-of-evidence approach to tackle the problem effectively. The approach merges all available evidence from co-exposure modelling, chemical monitoring, effect-based monitoring, and ecological monitoring. Full implementation of the proposed methodology requires changes in the legal text in adaptation to scientific progress.
Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial
Authors: Pedersen Lene Rørholm , Olsen Rasmus Huan , Anholm Christian , Astrup Arne , Eugen-Olsen Jesper , Fenger Mogens , Simonsen Lene , Walzem Rosemary L. , Haugaard Steen Bendix , Prescott Eva 
Published: October 2019

Abstract
Background
Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD.

Methods
Seventy CAD patients, BMI 28–40 kg/m2 and age 45–75 years were randomised to (1) 12 weeks’ aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks’ AIT twice weekly or (2) a low energy diet (LED) (800–1000 kcal/day) for 8–10 weeks followed by 40 weeks’ weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis.

Results
Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (− 8.4; − 6.1) and waist circumference by 6.6 cm (− 7.7; − 5.5) compared to 1.7 kg (− 0.7; − 2.6) and 3.3 cm (− 5.1; − 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change.

Conclusions
Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients.
Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).
Extracellular and macropinocytosis internalized ATP work together to induce epithelial–mesenchymal transition and other early metastatic activities in lung cancer
Authors: Cao Yanyang , Wang Xuan , Li Yunsheng , Evers Maria , Zhang Haiyun , Chen Xiaozhuo 
Published: October 2019

Abstract

Background
Extracellular ATP (eATP) was shown to induce epithelial–mesenchymal transition (EMT), a very important early process in metastasis, in cancer cells via purinergic receptor signaling. However, the exact induction mechanisms are far from fully known. We previously described that eATP is internalized by cancer cells in vitro and in vivo by macropinocytosis in human non-small cell lung cancer A549 and other cancer cells, drastically elevates intracellular ATP levels, enhances cell proliferation and resistance to anticancer drugs. In this study, we tested the hypothesis that eATP and macropinocytosis-internalized eATP also induces EMT and other early steps of metastasis.

Methods
Floating cells, fencing, and transwell assays were used to show that ATP induces cell detachment, new colony formation, migration and invasion in human A549 and other lung cancer cells. Western blots were used to detect ATP-induced changes in EMT-related proteins; Confocal microscopy was used to demonstrate ATP-induced metastasis-related cell morphological changes. Inhibitors and siRNA knockdowns were used to determine P2X7’s involvement in the ATP-induced EMT. CRISPR–Cas9 knockout of the SNX5 gene was used to identify macropinocytosis’ roles in EMT and cancer cell growth both in vitro and in vivo. Student t-test and one-way ANOVA were used to determine statistical significance, P < 0.05 was considered significant.

Results
eATP potently induces expression of matrix metallopeptidases (MMPs), and detachment, EMT, migration, and invasion of lung cancer cells. The induction was independent of TGF-β and semi-independent of P2X7 activation. eATP performs these functions not only extracellularly, but also intracellularly after being macropinocytically internalized to further enhance P2X7-mediated EMT, filopodia formation and other early steps of metastasis. The knockout of macropinocytosis-associated SNX5 gene significantly reduces macropinocytosis, slows down tumor growth, and changes tumor morphology in nude mice.

Conclusions
Collectively, these results show that eATP's functions in these processes not only from outside of cancer cells but also inside after being macropinocytotically internalized. These findings shed light on eATP’s initiator and effector roles in almost every step in early metastasis, which calls for rethinking and rebalancing energy equations of intracellular biochemical reactions and the Warburg effect, and identifies eATP and macropinocytosis as novel targets for potentially slowing down EMT and preventing metastasis.
Bio-efficacy and wash resistance of MAGNet long-lasting insecticidal net against wild populations of Anopheles funestus in experimental huts in Muheza, Tanzania
Authors: Kweka Eliningaya J. , Tungu Patrick K. , Mahande Aneth M. , Mazigo Humphrey D. , Sayumwe Subira , Msangi Shandala , Lyaruu Lucile , Waweru John , Kisinza William , Wangai James 
Published: October 2019

Abstract

Background
The decline in malaria cases and vectors is major milestone in fighting against malaria. The efficacy of MAGNet long-lasting insecticidal nets (MAGNet LLIN), an alpha-cypermethrin incorporated long-lasting net, with the target dose ± 25% of 5.8 g active ingredient (AI)/kg (4.35–7.25 g AI/kg) was evaluated in six veranda-trap experimental huts in Muheza, Tanzania against freely flying wild population of Anopheles funestus.

Methods
MAGNet LLINs were tested against wild, free-flying, host-seeking An. funestus mosquitoes over a period of 6 weeks (total of 36 nights in the huts). MAGNet LLIN efficacy was determined in terms of mosquito mortality, blood-feeding inhibition, deterrence, induced exiting, personal protection, and insecticidal killing over 20 washes according to WHO standardized procedures. Efficacy was compared with reference to a WHOPES recommended approved LLINs (DuraNet) and to a net conventionally treated (CTN) treated with alpha-cypermethrin at WHO-recommended dose and washed to just before cut-off point. The efficacy of MAGNet was evaluated in experimental huts against wild, free-flying, pyrethroid-resistant An. funestus. The WHO-susceptibility method was used to detect resistance in wild Anopheles exposed to 0.75% permethrin. Mosquito mortality, blood-feeding inhibition and personal protection were compared between untreated nets and standard LLINs. Blood-feeding rates were recorded and compared between the 20 times washed; blood-feeding rates between 20 times washed MAGNet LLIN and 20 times washed WHOPES-approved piperonyl butoxide (PBO)/pyrethroid were not statistically different (p > 0.05).

Results
The results have evidently shown that MAGNet LLIN provides similar blood-feeding inhibition, exophily, mortality, and deterrence to the standard approved LLIN, thus meeting the WHOPES criteria for blood feeding. The significantly high feeding inhibition and personal protection over pyrethroid-resistant An. funestus recorded by both unwashed and 20 times washed MAGNet compared to the unwashed DuraNet, the WHOPES-approved standard pyrethroid-only LLIN provides proof of MAGNet meeting Phase II WHOPES criteria for a LLIN.

Conclusion
Based on this study, MAGNet has been shown to have a promising impact on protection when 20 times washed against a highly resistant population of An. funestus.
Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study
Authors: Ding Xian-Fei , Li Jin-Bo , Liang Huo-Yan , Wang Zong-Yu , Jiao Ting-Ting , Liu Zhuang , Yi Liang , Bian Wei-Shuai , Wang Shu-Peng , Zhu Xi , Sun Tong-Wen 
Published: October 2019

Abstract

Background
To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and laboratory parameters.

Methods
A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission.

Results
All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count.

Conclusions
This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.
Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology
Authors: Frecer Vladimir , Iarossi Giancarlo , Salvetti Anna Paola , Maltese Paolo Enrico , Delledonne Giulia , Oldani Marta , Staurenghi Giovanni , Falsini Benedetto , Minnella Angelo Maria , Ziccardi Lucia , Magli Adriano , Colombo Leonardo , D’Esposito Fabiana , Miertus Jan , Viola Francesco , Attanasio Marcella , Maggio Emilia , Bertelli Matteo 
Published: October 2019

Abstract

Background
Best vitelliform macular dystrophy (BVMD) is an autosomal dominant macular degeneration. The typical central yellowish yolk-like lesion usually appears in childhood and gradually worsens. Most cases are caused by variants in the BEST1 gene which encodes bestrophin-1, an integral membrane protein found primarily in the retinal pigment epithelium.

Methods
Here we describe the spectrum of BEST1 variants identified in a cohort of 57 Italian patients analyzed by Sanger sequencing. In 13 cases, the study also included segregation analysis in affected and unaffected relatives. We used molecular mechanics to calculate two quantitative parameters related to calcium-activated chloride channel (CaCC composed of 5 BEST1 subunits) stability and calcium-dependent activation and related them to the potential pathogenicity of individual missense variants detected in the probands.

Results
Thirty-six out of 57 probands (63% positivity) and 16 out of 18 relatives proved positive to genetic testing. Family study confirmed the variable penetrance and expressivity of the disease. Six of the 27 genetic variants discovered were novel: p.(Val9Gly), p.(Ser108Arg), p.(Asn179Asp), p.(Trp182Arg), p.(Glu292Gln) and p.(Asn296Lys). All BEST1 variants were assessed in silico for potential pathogenicity. Our computational structural biology approach based on 3D model structure of the CaCC showed that individual amino acid replacements may affect channel shape, stability, activation, gating, selectivity and throughput, and possibly also other features, depending on where the individual mutated amino acid residues are located in the tertiary structure of BEST1. Statistically significant correlations between mean logMAR best-corrected visual acuity (BCVA), age and modulus of computed BEST1 dimerization energies, which reflect variations in the in CaCC stability due to amino acid changes, permitted us to assess the pathogenicity of individual BEST1 variants.

Conclusions
Using this computational approach, we designed a method for estimating BCVA progression in patients with BEST1 variants.
A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma
Authors: Krishnan Anitha , Kocab Andrew J. , Zacks David N. , Marshak-Rothstein Ann , Gregory-Ksander Meredith 
Published: October 2019

AbstractBackgroundGlaucoma is a complex, multifactorial disease where apoptosis, microglia activation, and inflammation have been linked to the death of retinal ganglion cells (RGCs) and axon degeneration. We demonstrated previously that FasL-Fas signaling was required for axon degeneration and death of RGCs in chronic and inducible mouse models of glaucoma and that Fas activation triggered RGC apoptosis, glial activation, and inflammation. Here, we investigated whether targeting the Fas receptor with a small peptide antagonist, ONL1204, has anti-inflammatory and neuroprotective effects in a microbead-induced mouse model of glaucoma.MethodsIntracameral injection of microbeads was used to elevate intraocular pressure (IOP) in Fas-deficient (Faslpr) mice and WT C57BL/6J mice that received an intravitreal injection of the Fas inhibitor, ONL1204 (2 μg/1 μl) (or vehicle only), on day 0 or day 7 after microbead injection. The IOP was monitored by rebound tonometry, and at 28 days post-microbead injection, Brn3a-stained RGCs and paraphenylenediamine (PPD)-stained axons were analyzed. The effects of ONL1204 on retinal microglia activation and the expression of inflammatory genes were analyzed by immunostaining of retinal flatmounts and quantitative PCR (qPCR).ResultsRebound tonometry showed equivalent elevation of IOP in all groups of microbead-injected mice. At 28 days post-microbead injection, the RGC and axon counts from microbead-injected Faslprmice were equivalent to saline-injected (no IOP elevation) controls. Treatment with ONL1204 also significantly reduced RGC death and loss of axons in microbead-injected WT mice when compared to vehicle-treated controls, even when administered after IOP elevation. Confocal analysis of Iba1-stained retinal flatmounts and qPCR demonstrated that ONL1204 also abrogated microglia activation and inhibited the induction of multiple genes implicated in glaucoma, including cytokines and chemokines (GFAP, Caspase-8, TNFα, IL-1β, IL-6, IL-18, MIP-1α, MIP-1β, MIP-2, MCPI, and IP10), components of the complement cascade (C3, C1Q), Toll-like receptor pathway (TLR4), and inflammasome pathway (NLRP3).ConclusionsThese results serve as proof-of-principal that the small peptide inhibitor of the Fas receptor, ONL1204, can provide robust neuroprotection in an inducible mouse model of glaucoma, even when administered after IOP elevation. Moreover, Fas signaling contributes to the pathogenesis of glaucoma through activation of both apoptotic and inflammatory pathways.
Social anxiety disorder and emotion regulation problems in adolescents
Authors: Sackl-Pammer Petra , Jahn Rebecca , Özlü-Erkilic Zeliha , Pollak Eva , Ohmann Susanne , Schwarzenberg Julia , Plener Paul , Akkaya-Kalayci Türkan 
Published: October 2019

Abstract

Background
Social anxiety disorder (SAD) in adolescents may be associated with the use of maladaptive emotion regulation (ER) strategies. The present study examined the use of maladaptive and adaptive ER strategies in adolescents with SAD.

Methods
30 adolescents with SAD (CLIN) and 36 healthy adolescents for the control group (CON) aged between 11 and 16 years were assessed with the standardized questionnaires PHOKI (Phobiefragebogen für Kinder und Jugendliche) for self-reported fears as well as FEEL-KJ (Fragebogen zur Erhebung der Emotionsregulation bei Kindern und Jugendlichen) for different emotion regulation strategies.

Results
Compared to controls, adolescents with SAD used adaptive ER strategies significantly less often, but made use of maladaptive ER strategies significantly more often. There was a significant positive correlation between maladaptive ER and social anxiety in adolescents. Examining group differences of single ER strategy use, the CLIN and CON differed significantly in the use of the adaptive ER strategy reappraisal with CLIN reporting less use of reappraisal than CON. Group differences regarding the maladaptive ER strategies withdrawal and rumination, as well as the adaptive ER strategy problem-solving were found present, with CLIN reporting more use of withdrawal and rumination and less use of problem-solving than CON.

Conclusions
Promoting adaptive emotion regulation should be a central component of psychotherapy (cognitive behavioral therapy-CBT) for social anxiety in adolescents from the beginning of the therapy process. These findings provide rationale for special therapy programs concentrating on the establishment of different adaptive ER strategies (including reappraisal). As an increased use of maladaptive ER may be associated with SAD in adolescents, it may be paramount to focus on reduction of maladaptive ER (for example withdrawal and rumination) from the beginning of the psychotherapy process. Incorporating more ER components into psychotherapy (CBT) could increase the treatment efficacy. Further investigations of the patterns of emotion regulation in specific anxiety groups like SAD in adolescents is needed to continue to optimize the psychotherapy (CBT) concept.
Metformin paradoxically worsens insulin resistance in SHORT syndrome
Authors: Lewandowski Krzysztof C. , Dąbrowska Katarzyna , Brzozowska Maria , Kawalec Joanna , Lewiński Andrzej 
Published: October 2019

Abstract

Background
SHORT syndrome is an autosomal dominant condition associated severe insulin resistance (IR) and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), where no clear treatment guidelines are available.

Methods
We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test (OGTT) in a 21-year old patient (BMI 17.5 kg/m2), who presented for endocrine assessment with a history of amenorrhoea.

Results
She had lipid concentrations within the reference range, normal thyroid function tests, prolactin, gonadotropins, estradiol and androgens with Free Androgen Index 4.52. Extended Oral Glucose Tolerance Test was performed and showed severe IR. She was then started on metformin 850 mg twice a day, and had repeated OGTT. This showed dramatic worsening of glucose tolerance (e.g. glucose 96 mg/dl versus 187 mg/dl and 68 mg/dl versus 204 mg/dl at 120 and 150 min of OGTT, respectively). This was accompanied by a massive increase of already high insulin concentrations (e.g. from 488.6 to > 1000 µIU/ml, and from 246.8 to > 1000 µIU/ml at 120 and 150 min of OGTT, respectively). Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 µIU/ml versus 100.6 µIU/ml without metformin).

Conclusions
Metformin treatment may paradoxically lead to deterioration of insulin resistance and to development of glucose intolerance in SHORT syndrome. Hence, metformin treatment might be potentially harmful in these patients. Though, the precise cause of such profound and paradoxical worsening of glucose tolerance post metformin remains unknown, SHORT syndrome might prove to be an interesting model to study the mechanism(s) of metformin action.
Global existence of weak solution for the compressible Navier–Stokes–Poisson system with density-dependent viscosity
Authors: Cui Meiying , Song Wenjing 
Published: October 2019

AbstractIn this paper, we are concerned with the existence of global weak solutions to the compressible Navier–Stokes–Poisson equations with the non-flat doping profile when the viscosity coefficients are density-dependent, the data are large and spherically symmetric, and we focus on the case where those coefficients vanish in vacuum. We construct a suitable approximate system and consider it in annular regions between two balls. The global solutions are obtained as limits of such approximate solutions. Our proofs are mainly based on the energy and entropy estimates.
Random attractors for the stochastic coupled suspension bridge equations of Kirchhoff type
Authors: Xu Ling , Huang Jianhua , Ma Qiaozhen 
Published: October 2019

AbstractThis paper is devoted to the dynamical behavior of stochastic coupled suspension bridge equations of Kirchhoff type. For the deterministic cases, there are many classical results such as existence and uniqueness of a solution and long-term behavior of solutions. To the best of our knowledge, the existence of random attractors for the stochastic coupled suspension bridge equations of Kirchhoff type is not yet considered. We intend to investigate these problems. We first obtain the dissipativeness of a solution in higher-energy spaces$H^{3}(U)\times H_{0}^{1}(U)\times (H^{2}(U)\cap H_{0}^{1}(U))\times H_{0}^{1}(U)$H3(U)×H01(U)×(H2(U)∩H01(U))×H01(U). This implies that the random dynamical system generated by the equation has a random attractor in$(H^{2}(U)\cap H_{0}^{1}(U))\times L^{2}(U) \times H_{0}^{1}(U)\times L^{2}(U)$(H2(U)∩H01(U))×L2(U)×H01(U)×L2(U), which is a tempered random set in the space in$H^{3}(U)\times H_{0}^{1}(U)\times (H^{2}(U)\cap H_{0} ^{1}(U))\times H_{0}^{1}(U)$H3(U)×H01(U)×(H2(U)∩H01(U))×H01(U).
Pathological transition as the arising mechanism for drug resistance in lung cancer
Authors: Chen Yueqing , Tang Waiying Yvonne , Tong Xinyuan , Ji Hongbin 
Published: October 2019

AbstractDespite the tremendous efforts for improving therapeutics of lung cancer patients, its prognosis remains disappointing. This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insufficient development of effective therapeutics in clinic. Based on the current progresses of lung cancer research, we classify drug resistance mechanisms into three different levels: molecular, cellular and pathological level. All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic. Our understanding on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis. In this review, we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.