bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblast growth factor‐2, derived from cancer‐associated fibroblasts, stimulates growth and progression of human breast cancer cells via FGFR1 signaling
Authors: Suh Jinyoung , Kim Do‐Hee , Lee Yeon‐Hwa , Jang Jeong‐Hoon , Surh Young‐Joon 
Published: June 2020

AbstractCancer‐associated fibroblasts (CAFs) constitute a major compartment of the tumor microenvironment. In the present study, we investigated the role for CAFs in breast cancer progression and underlying molecular mechanisms. Human breast cancer MDA‐MB‐231 cells treated with the CAF‐conditioned media manifested a more proliferative phenotype, as evidenced by enhanced messenger RNA (mRNA) expression of Cyclin D1, c‐Myc, and proliferating cell nuclear antigen. Analysis of data from The Cancer Genome Atlas revealed that fibroblast growth factor‐2 (FGF2) expression was well correlated with the presence of CAFs. We noticed that the mRNA level of FGF2 in CAFs was higher than that in normal fibroblasts. FGF2 exerts its biological effects through interaction with FGF receptor 1 (FGFR1). In the breast cancer tissue array, 42% estrogen receptor‐negative patients coexpressed FGF2 and FGFR1, whereas only 19% estrogen receptor‐positive patients exhibited coexpression. CAF‐stimulated MDA‐MB‐231 cell migration and invasiveness were abolished when FGF2‐neutralizing antibody was added to the conditioned media of CAFs. In a xenograft mouse model, coinjection of MDA‐MB‐231 cells with activated fibroblasts expressing FGF2 dramatically enhanced tumor growth, and this was abrogated by silencing of FGFR1 in cancer cells. In addition, treatment of MDA‐MB‐231 cells with FGF2 enhanced expression of Cyclin D1, a key molecule involved in cell cycle progression. FGF2‐induced cell migration and upregulation of Cyclin D1 were abolished by siRNA‐mediated FGFR1 silencing. Taken together, the above findings suggest that CAFs promote growth, migration and invasion of MDA‐MB‐231 cells via the paracrine FGF2‐FGFR1 loop in the breast tumor microenvironment.
Muskellunge Survival, Interbasin Movement, and Emigration in a Simple and a Complex Interconnected Glacial Lake
Authors: Meerbeek Jonathan R. , Weber Michael J. 
Published: June 2020

Abstract
Glacial lakes can display a wide range of morphometries that may affect fish movements and population dynamics. Muskellunge Esox masquinongy is a popular sportfish that is long-lived and occurs at low densities, making population abundance susceptible to sources of fish loss. Yet, factors influencing Muskellunge survival, movement, and emigration in lakes of different morphometric complexities are unknown. We used capture histories of nearly 5,700 individual adult (age ≥ 3; ≥610 mm) Muskellunge collected from a simple (single shallow lake, bowl-shaped basin with simple shoreline) and a complex (multiple basins with greater habitat diversity) lake basin over 17 years to quantify survival, interbasin movement, and emigration from these systems and evaluate if these parameters were related to population density or water level metrics. Adult Muskellunge annual survival within the interconnected lake chain varied through time and among connected lakes (range = 0.57–0.95), whereas survival was similar among years in the simple lake basin (0.90; 95% CI = 0.85–0.96). Muskellunge movement probabilities within an interconnected lake chain ranged from 0.02 to 0.22 and increased in two systems but decreased in one system with maximum ice-out water level over crest. Similarly, annual Muskellunge emigration ranged from 0.02 to 0.16 from an interconnected lake chain and from 0.00 to 0.28 in a simple lake and increased in both systems with increasing water levels following ice-out. These results demonstrate that Muskellunge movement within and emigration from lakes as a function of ice-out water levels can be an important source of fish loss (either temporary or permanent) from glacial lakes. Information on movement and emigration may help managers mitigate these losses via supplemental stocking or reduced harvest quotas, whereas constructing barriers may be a necessary component of Muskellunge management in other lake systems.
Thermal shock weakening of granite rock under dynamic loading: 3D numerical modeling based on embedded discontinuity finite elements
Authors: Saksala Timo , Ibrahimbegovic Adnan 
Published: June 2020

SummaryThis paper presents a numerical study of thermal shock weakening of granite rock under dynamic loading. A fully 3D numerical scheme based on a combined continuum viscodamage‐embedded discontinuity model and an explicit scheme to solve the underlying thermomechanical problem was developed and validated through numerical examples. First, the dynamic Brazilian disc test is simulated on intact numerical rock. Then, thermal shock‐induced cracking due to a moving external heat flux boundary condition, mimicking experiments based on plasma jet treatment, is numerically predicted. Finally, numerical Brazilian disc test is conducted on the thermal shocked numerical samples. The predicted and experimental weakening effects are in good agreement demonstrating that the present modeling approach has good predictive capabilities. The practical significance of the results is that heat shock pretreatment can substantially enhance rock gravel and rubble crushing.
Vexin is upregulated in cerebral cortical neurons by brain‐derived neurotrophic factor
Authors: Koshimizu Hisatsugu , Suzuki Shingo , Kawai Anna , Miura Ryuichiro , Ohta Ken‐ichi , Miki Takanori , Adachi Naoki , Matsuoka Hidetada 
Published: June 2020

AbstractAimChromosome 8 open reading frame 46 (C8orf46), a human protein‐coding gene, has recently been named Vexin. A recent study indicated that Vexin is involved in embryonic neurogenesis. Additionally, some transcriptomic studies detected changes in the mRNA levels of patients with psychiatric and neurological diseases. In our previous study, we sought for target genes of brain‐derived neurotrophic factor (BDNF) in cultured rat cortical neurons, finding that BDNF potentially leads to the upregulation of Vexin mRNA. However, its underlying mechanisms are unknown. In the present study, we assessed the regulatory mechanisms of the BDNF‐induced gene expression of Vexin in vitro.MethodsWe reanalyzed ChIP‐seq data in various human organs provided by the ENCODE project, evaluating acetylation levels of the 27th lysine residue of the histone H3 (H3K27ac) at the Vexin locus. The transcriptomic effects of BDNF on rat Vexin (RGD1561849) were evaluated by real‐time quantitative PCR (RT‐qPCR) in primary cultures of cerebral cortical neurons, in the presence or absence of inhibitors for signaling molecules activated by BDNF.ResultsThe Vexin locus and its promoter region in the brain angular gyrus show higher acetylation levels of the H3K27 than those in other organs. Stimulation of cultured rat cortical neurons, but not astrocyte, with BDNF, led to marked elevations in the mRNA levels of Vexin, which was inhibited in the presence of K252a and U0126.ConclusionThe upregulated H3K27ac in the brain may be associated with the enriched gene expression of Vexin in the brain. It is indicated that BDNF induces the gene expression of Vexin in the cortical neurons via the TrkB‐MEK signaling pathway.
Partnering with school providers to codesign mental health interventions: An open trial of Act & Adapt in urban public middle schools
Authors: Bearman Sarah K. , Bailin Abby , Rodriguez Erin , Bellevue Alison 
Published: June 2020

AbstractSchools are well positioned to provide access to youth mental health services, but implementing effective programs that promote emotional and behavioral functioning in school settings is complicated by the poor fit of interventions developed in research settings to complex school contexts. The current study formed a research–practice partnership with two urban public schools and mental health providers employed by those schools (N = 6, 100% female, 50% Black/African American, 50% White/Caucasian) in the adaptation of a depression prevention intervention, Act & Adapt. The intervention was modified by decreasing meeting time and streamlining session content, increasing flexibility, making intervention materials more similar to academic curriculum, and increasing the focus on managing disruptive behavior within group sessions. In an open trial, sixth‐grade students (N = 22; 59% boys, 31% Hispanic, 22% Black/African American, 4% Asian, 30% White/Caucasian) at both schools who were identified as clinically “at risk” reported improvements from baseline to postintervention and at 1‐year follow‐up on measures of emotional and behavioral difficulties and coping strategies, with parallel results by caregiver report. The providers reported satisfaction with the intervention, and qualitative analyses of provider focus groups suggested both barriers and facilitators to research‐practice collaborations to implement mental health interventions in schools.
Novel small‐molecule LG1836 inhibits the in vivo growth of castration‐resistant prostate cancer
Authors: Chen Yanhua , Li Xin , Mamouni Kenza , Yang Yang , Danaher Alira , White Joseph , Liu HongYan , Kucuk Omer , Gera Lajos , Wu Daqing 
Published: June 2020

AbstractBackgroundAndrogen deprivation therapy (ADT) is the mainstay of treatment for castration‐resistant prostate cancer (CRPC). Unfortunately, although ADT initially prolongs survival, most patients relapse and develop resistance. Clinical failure of these treatments in CRPC highlights the urgent need to develop novel strategies to more effectively block androgen receptor (AR) signaling and target other oncogenic factors responsible for ADT resistance.MethodsWe developed a small‐molecule compound LG1836 and investigated the in vitro and in vivo activity of LG1836 against CRPC in cellular and animal models.ResultsLG1836 exhibits potent in vitro cytotoxicity in CRPC cells. Mechanistic studies demonstrated that LG1836 inhibits the expression of AR and AR variant 7, partially mediated via proteasome‐dependent protein degradation. LG1836 also suppresses survivin expression and effectively induces apoptosis in CRPC cells. Significantly, as a single agent, LG1836 is therapeutically efficacious in suppressing the in vivo growth of CRPC in the subcutaneous and intraosseous models and extends the survival of tumor‐bearing mice.ConclusionsThese preclinical studies indicate that LG1836 is a promising lead compound for the treatment of CRPC.
An improving approach for failure mode and effect analysis under uncertainty environment: A case study of critical function component
Authors: Huang Guangquan , Xiao Liming , Zhang Wei , Li Jian , Zhang Genbao , Ran Yan 
Published: June 2020

AbstractFailure mode and effect analysis (FMEA) is a powerful risk discerning technique for identifying, evaluating, and reducing possible failures of products or processes. However, the classical FMEA has been criticized for inherent limitations, such as equal weights of risk elements and lack of capability in handling inaccurate information. Although fuzzy‐based modified FMEA methods are frequently utilized to handle vagueness of experts' judgments, they still have some drawbacks, for example, requiring extra assumptions, neglecting experts' bounded rationality and psychological effects, lacking consideration of randomness, and only considering three classical risk elements among most of them. Therefore, this study develops an extended risk assessment method to enhance the performance of FMEA, which integrates the superiority of rough number theory in handling subjective and inaccurate information and the advantage of cloud model theory in reflecting the randomness of qualitative evaluations. Moreover, two synthetic weighting methods are developed to determine the weights of risk elements and handle the experts' individual effects, respectively, which consider both subjective and objective aspects. In addition, maintenance is added into the classical risk elements, and then a hierarchical structure containing four risk dimensions is built to evaluate failures' risk levels comprehensively. Finally, an application case to demonstrate the effectiveness of the developed FMEA model is presented.
A particle filter via constrained sampling for nonlinear dynamic systems
Authors: Hu Chongyang , Liang Yan , Wang Xiaoxu , Xu Linfeng 
Published: June 2020

SummaryThis article is concentrated on the particle filtering problem for nonlinear systems with nonlinear equality constraints. Considering the constraint information incorporated into filters can improve the state estimation accuracy, we propose an adaptive constrained particle filter via constrained sampling. First, in order to obtain particles drawn from the constrained important density function, we construct and solve a general optimization function theoretically fusing equality constraints and the importance density function. Furthermore, to reduce the computation time caused by the number of particles, the constrained Kullback‐Leiler distance sampling method is given to online adapt the number of particles needed for state estimation. A simulation study in the context of road‐confined vehicle tracking demonstrates that the proposed filter outperforms the typical constrained ones for equality constrained dynamic systems.
CO2 emissions and sustainable economic development: New evidence on the role of human capital
Authors: Khan Muhammad 
Published: June 2020

AbstractThe empirical literature testing the Environmental Kuznets Curve hypothesis reports mixed results on the existence of this relationship. This study argues that the effects of economic development on CO2 emissions are contingent upon the level of human capital. In the beginning, when human capital starts increasing from its low levels, more education accelerates the use of non‐renewable resources and increases pollution emissions. However, when certain threshold levels of schooling are traversed, further enrollments reduce CO2 emissions by promoting environmental awareness and facilitating the use of environment friendly technologies. To test these competing possibilities, we rely upon an innovative threshold technique where income–pollution relationship is piecewise linear with human capital serving as regime switching trigger. Our empirical findings using a large sample of 122 economies over the period 1980 to 2014 support the contingency effects of human capital in the income–environment relationship. These results are also supported by our findings from cross‐sectional regressions in the presence of multiplicative interaction term of income and human capital. Based on these results we argue that an increase in education is necessary for reducing the environmental degradation and ensuring the sustainability of economic development.
Quality improvement mechanism for cyber physical systems—An evaluation
Authors: Regan Gilbert , McCaffery Fergal , Paul Pangkaj Chandra , Reich Jan , Armengaud Eric , Kaypmaz Cem , Zeller Marc , Guo Joe Zhensheng , Longo Simone , O'Carroll Eoin , Sorokos Ioannis 
Published: June 2020

AbstractThe future will encompass heavily interconnected, distributed, heterogeneous and intelligent systems which are bound to have a significant economic and social impact. Cyber physical systems (CPS) such as autonomous cars, smart electric grid, implanted medical devices and smart manufacturing are some practical examples of these intelligent systems. However, due to the open and cooperative nature of CPS, assuring their dependability is a challenge. The DEIS project addresses this important and unsolved challenge by developing the concept of a digital dependability identity (DDI). A DDI contains all the information that uniquely describes the dependability characteristics of a CPS or CPS component. DDIs are synthesised at development time and are the basis for the (semi)automated integration of components into systems during development, as well as for the fully automated dynamic integration of systems into systems of systems in the field.
Service offloading oriented edge server placement in smart farming
Authors: Zhang Jie , Li Xiang , Zhang Xuyun , Xue Yuan , Srivastava Gautam , Dou Wanchun 
Published: June 2020

SummaryCurrently, smart farming has been established to realize agriculture automation by leveraging sensors to gather the growth and environmental data for crops, and realizing multiple intelligent controls, such as irrigation, fertilization, and so on, to increase the crop yields. To support real‐time intelligent controls, edge computing is introduced to smart farming by endowing computing and storage capacities to edge devices nearby the geographically distributed sensors. However, the farmers are relatively willing to purchase and deploy a small quantity of edge servers (ESs) in the farm from the perspective of expenditure saving, thereby leading to a key challenge to guarantee the performance of the real‐time controls and the overall edge services. In view of this challenge, a service offloading‐oriented ES placement method for supporting smart farming, called SOP, is proposed to optimize the data transmission delay from sensors to ESs and the load balance among ESs. More precisely, the corresponding service range of a certain ES is ascertained according to the specific analysis of the farming service requirements. Subsequently, the layout policies for the trade‐offs of the ES performance and service efficiency are acquired. Then the most balanced policy is determined as the final ES placement strategy. Eventually, we evaluate the performance of the whole ES system and the service execution efficiency with
SOP.
Accuracy of freely available online GFR calculators using the CKD-EPI equation
Authors: Seiberth Sarah , Terstegen Theresa , Strobach Dorothea , Czock David 
Published: June 2020

Abstract
Purpose
Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is used for detection of chronic kidney disease and drug dose adjustment. The purpose of the present study was to investigate the accuracy of freely available eGFR online calculators.

Methods
All identified CKD-EPI online calculators were run with five reference cases differing in age, sex, serum creatinine, and ethnicity. Conversion from eGFRindexed (unit ml/min per 1.73 m2) to eGFRnon-indexed (unit ml/min) and creatinine unit from milligramme/decilitre to micromole/litre was checked, if available.

Results
Only 36 of 47 calculators (76.6%) produced accurate eGFR results for all reference cases. Eight of 47 (17.0%) calculators were considered as faulty because of errors relating to ethnicity (4 calculators), to conversion of the eGFR unit (2 calculators), to erroneous eGFR values without obvious explanation (2 calculators), to conversion of the creatinine unit (1 calculator), and to an error in the eGFR unit displayed (1 calculator). Overall, 28 errors were found (range 59 to 147% of the correct eGFR value), the majority concerning calculation of eGFRindexed and the conversion to eGFRnon-indexed. Only 7 of 47 (14.9%) calculators offered conversion of the eGFR unit.

Conclusions
Erroneous calculations that might lead to inappropriate clinical decision-making were found in 8 of 47 calculators. Thus, online calculators should be evaluated more thoroughly after implementation. Conversion of eGFR units that might be needed for drug dose adjustments should be implemented more often.
Hybrid-2-Port-23/25-G-Pars-plana-Vitrektomie zur Entfernung von Öl höherer Viskosität
Authors: Priester Lea Donata , Laspas Panagiotis , Stoffelns Bernhard , Pfeiffer Norbert 
Published: June 2020

ZusammenfassungWir stellen eine neue Hybridmethode einer kombinierten 23/25 G-Pars-plana-Vitrektomie (PPV) zur Ölentfernung (5700 Centistokes) vor und vergleichen sie mit einer 25 G PPV. Bei der Hybridmethode erfolgt die Infusion über einen 25-G-Zugang und die Absaugung des Öls über einen 23-G-Zugang. Es wurden die Operationszeit und der postoperative intraokuläre Druck (IOD) ausgewertet. Die Operationszeit konnte mit der Hybrid-Methode signifikant um 32,2 % reduziert werden. Postoperativ bestand kein IOD-Unterschied. Schlussfolgerung: Die Entfernung von Silikonöl durch einen 25-G-Zugang ist generell möglich, wobei die neue Hybridmethode die Operationszeit deutlich reduziert.
Congenic expression of poly-GA but not poly-PR in mice triggers selective neuron loss and interferon responses found in C9orf72 ALS
Authors: LaClair Katherine D. , Zhou Qihui , Michaelsen Meike , Wefers Benedikt , Brill Monika S. , Janjic Aleksandar , Rathkolb Birgit , Farny Daniel , Cygan Mikolaj , de Angelis Martin Hrabe , Wurst Wolfgang , Neumann Manuela , Enard Wolfgang , Misgeld Thomas , Arzberger Thomas , Edbauer Dieter 
Published: June 2020

AbstractExpansion of a (G4C2)n repeat in C9orf72 causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the link of the five repeat-encoded dipeptide repeat (DPR) proteins to neuroinflammation, TDP-43 pathology, and neurodegeneration is unclear. Poly-PR is most toxic in vitro, but poly-GA is far more abundant in patients. To directly compare these in vivo, we created congenic poly-GA and poly-PR mice. 40% of poly-PR mice were affected with ataxia and seizures, requiring euthanasia by 6 weeks of age. The remaining poly-PR mice were asymptomatic at 14 months of age, likely due to an 80% reduction of the transgene mRNA in this subgroup. In contrast, all poly-GA mice showed selective neuron loss, inflammation, as well as muscle denervation and wasting requiring euthanasia before 7 weeks of age. In-depth analysis of peripheral organs and blood samples suggests that peripheral organ failure does not drive these phenotypes. Although transgene mRNA levels were similar between poly-GA and affected poly-PR mice, poly-GA aggregated far more abundantly than poly-PR in the CNS and was also found in skeletal muscle. In addition, TDP-43 and other disease-linked RNA-binding proteins co-aggregated in rare nuclear inclusions in the hippocampus and frontal cortex only in poly-GA mice. Transcriptome analysis revealed activation of an interferon-responsive pro-inflammatory microglial signature in end-stage poly-GA but not poly-PR mice. This signature was also found in all ALS patients and enriched in C9orf72 cases. In summary, our rigorous comparison of poly-GA and poly-PR toxicity in vivo indicates that poly-GA, but not poly-PR at the same mRNA expression level, promotes interferon responses in C9orf72 disease and contributes to TDP-43 abnormalities and neuron loss selectively in disease-relevant regions.
First results of electrode reimplantation and its hypothetical dependence from artificial brain maturation
Authors: Roßberg Willi , Timm Max , Matin Farnaz , Zanoni Alessandra , Krüger Caroline , Giourgas Alexandros , Bültmann Eva , Lenarz Thomas , Kral Andrej , Lesinski-Schiedat Anke 
Published: June 2020

AbstractBackgroundAfter introducing the first Cochlear Implants also in children theses are grown with electrical intracochlear stimulation and subsequent auditory cortical development. Over the meantime the positioning of the electrode was changed orientated on the development of electrode design, ability to insert atraumatic and on the widening of the indications towards highfrequency deafness.MethodsIn this pilot study we analysed five prelingually deafened patients implanted as child in the late 90’s and had a reimplantation 2016 or later. We compared CT and DVT (cone beam CT) scans of the temporal bone and measured the insertion angle, the cochlear coverage, the total length of the electrode in the cochlea and the distance of the first active electrode to the round window. Moreover, we compared their speech understanding before and after reimplantation.ResultsThe results show a lowering in the insertion angle, the cochlear coverage, the total length of the electrode in the cochlea, in the distance of the first active electrode to the round window and in the speech understanding after reimplantation.ConclusionThese results show a difference in the depth of insertion while the speech understanding is not significantly improving in this group—although the technology is advanced. The influence of auditory maturation with CI in these patients will be discussed.