bluuebunny/crossref_metadata_2025_split huggingface dataset:
21st Century Tools for Nanotoxicology: Transcriptomic Biomarker Panel and Precision‐Cut Lung Slice Organ Mimic System for the Assessment of Nanomaterial‐Induced Lung Fibrosis
Authors: Rahman Luna , Williams Andrew , Gelda Krishna , Nikota Jake , Wu Dongmei , Vogel Ulla , Halappanavar Sabina 
Published: April 2020

AbstractThere is an urgent need for reliable toxicity assays to support the human health risk assessment of an ever increasing number of engineered nanomaterials (ENMs). Animal testing is not a suitable option for ENMs. Sensitive in vitro models and mechanism‐based targeted in vitro assays that enable accurate prediction of in vivo responses are not yet available. In this proof‐of‐principle study, publicly available mouse lung transcriptomics data from studies investigating xenobiotic‐induced lung diseases are used and a 17‐gene biomarker panel (PFS17) applicable to the assessment of lung fibrosis is developed. The PFS17 is validated using a limited number of in vivo mouse lung transcriptomics datasets from studies investigating ENM‐induced responses. In addition, an ex vivo precision‐cut lung slice (PCLS) model is optimized for screening of potentially inflammogenic and pro‐fibrotic ENMs. Using bleomycin and a multiwalled carbon nanotube, the practical application of the PCLS method as a sensitive alternative to whole animal tests to screen ENMs that may potentially induce inhalation toxicity is shown. Conditional to further optimization and validation, it is established that a combination of PFS17 and the ex vivo PCLS method will serve as a robust and sensitive approach to assess lung inflammation and fibrosis induced by ENMs.
Direct Fabrication of Freestanding and Patterned Nanoporous Junctions in a 3D Micro‐Nanofluidic Device for Ion‐Selective Transport
Authors: Kim Junhyun , Park Sang Min , Choi Dongwhi , Kim Dong Sung 
Published: April 2020

AbstractIn the field of micro‐nanofluidics, a freestanding configuration of a nanoporous junction is highly demanded to increase the design flexibility of the microscale device and the interfacial area between the nanoporous junction and microchannels, thereby improving the functionality and performance. This work first reports direct fabrication and incorporation of a freestanding nanoporous junction in a microfluidic device by performing an electrolyte‐assisted electrospinning process to fabricate a freestanding nanofiber membrane and subsequently impregnating the nanofiber membrane with a nanoporous precursor material followed by a solidification process. This process also enables to readily control the geometry of the nanoporous junction depending on its application. By these advantages, vertically stacked 3D micro‐nanofluidic devices with complex configurations are easily achieved. To demonstrate the broad applicability of this process in various research fields, a reverse electrodialysis‐based energy harvester and an ion concentration polarization‐based preconcentrator are produced. The freestanding Nafion‐polyvinylidene fluoride nanofiber membrane (F‐NPNM) energy harvester generates a high power (59.87 nW) owing to the enlarged interfacial area. Besides, 3D multiplexed and multi‐stacked F‐NPNM preconcentrators accumulate multiple preconcentrated plugs that can increase the operating sample volume and the degree of freedom of handling. Hence, the proposed process is expected to contribute to numerous research fields related to micro‐nanofluidics in the future.
Nano Assessing Nano: Nanosensor‐Enabled Detection of Cell Phenotypic Changes Identifies Nanoparticle Toxicological Effects at Ultra‐Low Exposure Levels
Authors: Geng Yingying , Chattopadhyay Aritra Nath , Zhang Xianzhi , Jiang Mingdi , Luther David C. , Gopalakrishnan Sanjana , Rotello Vincent M. 
Published: April 2020

AbstractIndustrial use of nanomaterials is rapidly increasing, making the effects of these materials on the environment and human health of critical concern. Standard nanotoxicity evaluation methods rely on detecting cell death or major dysfunction and will miss early signs of toxicity. In this work, the use of rapid and sensitive nanosensors that can efficiently detect subtle phenotypic changes on the cell surface following nanomaterial exposure is reported. Importantly, the method reveals significant phenotypic changes at dosages where other conventional methods show normal cellular activity. This approach holds promise in toxicological and pharmacological evaluations to ensure safer and better use of nanomaterials.
Wnt7b-induced Sox11 functions enhance self-renewal and osteogenic commitment of bone marrow mesenchymal stem cells
Authors: Yu Fanyuan , Wu Fanzi , Li Feifei , Liao Xueyang , Wang Yitian , Li Xin , Wang Chenglin , Shi Yu , Ye Ling 
Published: April 2020

Abstract
As a profoundly anabolic regulator of bone, Wnt7b is well acknowledged to enhance osteoblast activities. Here, we report that bone marrow mesenchymal stem cells (BMSCs) are another important population responding to Wnt7b. In this study, we systematically investigated the in vivo role of Wnt7b in BMSCs using transgenic mice, high-throughput RNA-seq, immunohistochemistry, RT-qPCR, and in situ hybridization. These methods led us to uncover that Sox11 is induced via Wnt7b in BMSCs. Colony formation assay, flow cytometry, EdU incorporation labeling, RT-qPCR, and Western blot were conducted to detect the self-renewal capacity of BMSCs. Alkaline phosphatase staining, alizarin red staining, and ex vivo BMSCs transplantation were utilized to detect the osteogenic ability of BMSCs. ChIP-qPCR, shRNAs, and immunofluorescence staining were utilized to investigate the underlying mechanisms. Consequently, bone-derived Wnt7b was found to decrease in osteoporosis and elevate in bone fracture healing. During bone fracture healing, Wnt7b was particularly expressed in the mesenchymal cells residing within healing frontiers. RNA-seq data of Wnt7b-overexpressed bones uncovered the significant upregulation of Sox11. Histological results further unveiled that Sox11 is specifically increased in BMSCs. Wnt7b-induced Sox11 was demonstrated to reinforce both self-renewal and osteogenic differentiation of BMSCs. Mechanistically, Wnt7b activates the Ca2+-dependent Nfatc1 signaling to directly induce Sox11 transcription, which in turn activates the transcriptions of both proliferation-related transcription factors (Ccnb1 and Sox2) and osteogenesis-related factors (Runx2, Sp7) in BMSCs. It is intriguing that this Wnt7b-Sox11 signaling in BMSCs is β-Catenin-independent. Overall, this study provides brand new insights of Wnt7b in bone formation, namely, Wnt7b can enhance both self-renewal and osteogenic differentiation of BMSCs via inducing Sox11. These findings present a new crosstalk between Wnt and Sox signaling in BMSCs.
Prescription patterns of antidementives in a high income country: A pharmacoepidemiologic study
Authors: Wurm Raphael , Stamm Tanja , Reichardt Berthold , Schwarz Felix , Parvizi Tandis , Silvaieh Sara , König Theresa , Cetin Hakan , Stögmann Elisabeth 
Published: April 2020

AbstractIntroductionDementia is a leading and growing cause of morbidity and mortality. The aim of this study was to investigate real‐world prescription patterns of antidementive medication in one of the largest cohorts published thus far to optimize use in this growing population.MethodsPrescription claims from 2005 to 2016 were provided by Austrian sickness funds, covering 98% of the population of Austria. Patients treated with at least one of the four approved antidementive drugs (ADDs) were included. Prescription prevalence was calculated for 2014 and 2015, and prescription patterns were traced on an individual level during the entire study period.ResultsA total of 127,896 patients were treated with an ADD between 2005 and 2016. The prevalence was 0.93% in 2014 and 1% in 2015. The median age at initiation of treatment was 82.3 years, and 65% were female. Initial therapy was a cholinesterase inhibitor (ChEI) in 80% and memantine in 20%. The median duration of therapy was 13.3 months. Eighteen percent of patients switched medication: two thirds to receive memantine, and one third to a different cholinesterase inhibitor. More than 26% discontinued treatment early.ConclusionWe find that discontinuation of ADDs is more frequent than switching; memantine is a common starting drug and age at the start of treatment is rather high in this population. Interpretation should be cautious, but the data may suggest that treatment guidelines are followed inconsistently. Appropriate provision of the available options should be emphasized to optimize cognitive survival, comorbidity, quality of life, and health care expenditures.
Long‐term changes in extreme air temperature in Nuwara Eliya: a case study from Sri Lanka
Authors: Sonnadara Upul 
Published: April 2020

Long‐term changes in extreme air temperature at Nuwara Eliya (a high‐elevation observatory located in the western slopes of the central mountainous region of Sri Lanka) are examined. The present work is limited to a linear trend analysis of daily maximum and minimum air temperature series of the period 1926–2015. The statistical significance of the trend is estimated using the Mann‐Kendall test. There is a significant reduction in the diurnal temperature range (DTR) in Nuwara Eliya. The magnitude of the reduction is −0.23 degC per decade and is due to the increase in the daily minimum air temperature. No significant increase or decrease in the daily maximum air temperature was evident from the data. There is a strong inverse correlation between the standard deviation (which is related to the temperature variability) and the mean daily minimum air temperature. The increase in minimum temperature is not uniform throughout the year as the minimum temperature of the cold season has increased, while it has remained the same for the warm season, thereby reducing the overall DTR.
Is nutrition science ready for the twenty-first century? Moving towards transdisciplinary impacts in a changing world
Authors: Tufford Adèle R. , Calder Philip C. , Van’t Veer Pieter , Feskens Edith F. , Ockhuizen Theo , Kraneveld Aletta D. , Sikkema Jan , de Vries Jan 
Published: April 2020

AbstractMalnutrition in an obese world was the fitting title of the 13th Federation of European Nutrition Societies (FENS) conference held in October 2019. Many individuals do not eat a healthy, well-balanced diet, and this is now understood to be a major driver of increased disease risk and illness. Moreover, both our current eating patterns and the food system as a whole are environmentally unsustainable, threatening the planetary systems we depend on for survival. As we attempt to feed a growing global population, food systems will increasingly be confronted with their environmental impacts, with the added challenge of climate change-induced threats to food production. As we move into the third decade of the twenty-first century, these challenges demand that the nutrition research community reconsider its scope, concepts, methods, and societal role. At a pre-meeting workshop held at the FENS conference, over 70 researchers active in the field explored ways to advance the discipline’s capacity to address cross-cutting issues of personal, public and planetary health. Using the world cafe method, four themed discussion tables explored (a) the breadth of scientific domains needed to meet the current challenges, (b) the nature and definition of the shifting concepts in nutrition sciences, (c) the next-generation methods required and (d) communication and organisational challenges and opportunities. As a follow-up to earlier work [1], here we report the highlights of the discussions, and propose the next steps to advance responsible research and innovation in the domain of nutritional science.
Brain volumes and dual-task performance correlates among individuals with cognitive impairment: a retrospective analysis
Authors: Longhurst Jason K. , Wise Morgan A. , Krist Daniel J. , Moreland Caitlin A. , Basterrechea Jon A. , Landers Merrill R. 
Published: April 2020

AbstractCognitive impairment (CI) is a prevalent condition characterized by loss of brain volume and changes in cognition, motor function, and dual-tasking ability. To examine associations between brain volumes, dual-task performance, and gait and balance in those with CI to elucidate the mechanisms underlying loss of function. We performed a retrospective analysis of medical records of patients with CI and compared brain volumes, dual-task performance, and measures of gait and balance. Greater cognitive and combined dual-task effects (DTE) are associated with smaller brain volumes. In contrast, motor DTE is not associated with distinct pattern of brain volumes. As brain volumes decrease, dual-task performance becomes more motor prioritized. Cognitive DTE is more strongly associated with decreased performance on measures of gait and balance than motor DTE. Decreased gait and balance performance are also associated with increased motor task prioritization. Cognitive DTE appears to be more strongly associated with decreased automaticity and gait and balance ability than motor DTE and should be utilized as a clinical and research outcome measure in this population. The increased motor task prioritization associated with decreased brain volume and function indicates a potential for accommodative strategies to maximize function in those with CI. Counterintuitive correlations between motor brain volumes and motor DTE in our study suggest a complicated interaction between brain pathology and function.
A New Analytic pdf for Simulations of Premixed Turbulent Combustion
Authors: Pfitzner Michael 
Published: April 2020

AbstractA new reaction rate source term$$\omega _m(c)$$ωm(c)for modelling of premixed combustion with a single progress variablecis proposed.$$\omega _m(c)$$ωm(c)mimics closely the Arrhenius source term$$\omega _A(c)$$ωA(c)for a large range of activation energies and density ratios while admitting analytic evaluation of many quantities of interest. The analytic flame profile$$c_m(\xi )$$cm(ξ)very closely approximates the numerically integrated Arrhenius flame profiles$$c_A(\xi )$$cA(ξ). An important feature of$$c_m(\xi )$$cm(ξ)is that it is analytically invertible into a$$\xi _m(c)$$ξm(c). Analytic estimates of the laminar flame Eigenvalue$$\Lambda$$Λand of theLedependence of the laminar flame speed$$s_L$$sLare derived, which are more accurate than classic results based on asymptotic analyses. The flamelet pdf$$p(c)=1/(\Delta *c*(1-c^m))$$p(c)=1/(Δ∗c∗(1-cm))for a flat laminar flame front in a LES cell of width$$\Delta$$Δis derived. The exact mean of the reaction rate$$\overline{\omega (c)}$$ω(c)¯is compared to a beta pdf result, which is shown to be inaccurate for large ratios of filter width to flame thickness$$\Delta /\delta _f$$Δ/δfand particularly for high activation energy flames. For multidimensional flame wrinkling we derive the exact relationship$$p(c)=p_{1D}(c)I(c)\Xi (c)$$p(c)=p1D(c)I(c)Ξ(c)between the 3D pdfp(c), the 1D flat flame pdf$$p_{1D}(c)$$p1D(c), a correction factorI(c) for change of inner flame structure and a geometrical wrinkling factor$$\Xi (c)$$Ξ(c). We show that thecdependence of these quantities cannot be neglected for small$$\Delta /\delta _f$$Δ/δf. A simple model of a sinusoidally wrinkled flame front qualitatively demonstrates the effect of flame wrinkling onp(c). We show that for large$$\Delta /\delta _f$$Δ/δf, a wrinkling of the reaction zone almost constantly increasesp(c) in the reaction zone by a wrinkling factor$$\Xi ^*$$Ξ∗(defined for the surface of the isosurface of maximum heat release) while reducing it near$$c=0,1$$c=0,1as required for normalisation ofp(c). The 1Dp(c) evaluated using a reduced filter width$$\Delta '=\Delta /\Xi ^*$$Δ′=Δ/Ξ∗may be a good approximation of the wrinkled flame pdf for evaluation of$$\overline{\omega (c)}$$ω(c)¯for such cases.
Analytical solution of the Colombo top problem
Authors: Haponiak J. , Breiter S. , Vokrouhlický D. 
Published: April 2020

AbstractThe Colombo top is a basic model in the rotation dynamics of a celestial body moving on a precessing orbit and perturbed by a gravitational torque. The paper presents a detailed study of analytical solution to this problem. By solving algebraic equations of degree 4, we provide the expressions for the extreme points of trajectories as functions of their energy. The location of stationary points (known as the Cassini states) is found as the function of the two parameters of the problem. Analytical solution in terms of the Weierstrass and the Jacobi elliptic functions is given for regular trajectories. Some trajectories are expressible through elementary functions: not only the homoclinic orbits, as expected, but also a special periodic solution whose energy is equal to that of the first Cassini state (unnoticed in previous studies).
The Pontryagin maximum principle for solving Fokker–Planck optimal control problems
Authors: Breitenbach Tim , Borzì Alfio 
Published: April 2020

AbstractThe characterization and numerical solution of two non-smooth optimal control problems governed by a Fokker–Planck (FP) equation are investigated in the framework of the Pontryagin maximum principle (PMP). The two FP control problems are related to the problem of determining open- and closed-loop controls for a stochastic process whose probability density function is modelled by the FP equation. In both cases, existence and PMP characterisation of optimal controls are proved, and PMP-based numerical optimization schemes are implemented that solve the PMP optimality conditions to determine the controls sought. Results of experiments are presented that successfully validate the proposed computational framework and allow to compare the two control strategies.
Embracing Digital Technology in Science Classrooms—Secondary School Teachers’ Enacted Teaching and Reflections on Practice
Authors: Walan Susanne 
Published: April 2020

AbstractThe aim of this case study was to investigate what happens in science classrooms when teaching is almost entirely based on the use of digital technology. Two secondary school science teachers participated, together with their seventh grade classes. Data were collected through eight observation sessions (altogether about 9.5 h) and 9 h of interviews with the teachers. For analysis, a modified version of the Technological Pedagogical and Content Knowledge framework was used. The results showed the science teachers’ general approach in the classroom and revealed that they were self-confident in using digital technology, and utilised predetermined digital study material and, when it was felt necessary, supplemental materials. The teachers were positive about using digital technology since they thought it motivated their students and made assessment easier. The teachers claimed that digital technology had improved their teaching, providing more breadth because of access to varied digital tools; teaching had also become more individualised. Few differences were identified between different lessons, whether in physics, chemistry or biology, and unfortunately the identified relationship between the use of digital technology and content knowledge was limited. The teachers also reflected on the challenges they faced, especially in supporting low-achieving students and effectively using inquiry-based teaching through digital technology. Despite some acknowledged limitations, the study enhances our knowledge about how the Technological Pedagogical Content Knowledge framework can be used as an analytical tool in authentic teaching, with specific contexts and, above all, when education is largely based on the comprehensive use of digital technology rather than its occasional integration.
Too hot to handle: summer space use shift in a cold-adapted ungulate at the edge of its range
Authors: Borowik Tomasz , Ratkiewicz Mirosław , Maślanko Weronika , Duda Norbert , Kowalczyk Rafał 
Published: April 2020

AbstractContextGlobal warming has been exerting an increasing stress on mammal populations occurring at the bioclimatic edges of their ranges. Moose, as heat-sensitive ungulates, are expected to be increasingly susceptible to thermal stress; however, the behavioral responses of animals could mitigate unfavorable weather conditions.ObjectivesWe aimed to evaluate the temperature-mediated behavioral changes in moose occurring at the southwestern edge of the species’ range in Europe. We predicted that increasing temperature in summer would modify the daily activity pattern of animal and fine-scale utilization of thermal cover.MethodsWe analysed data from 36 moose, who were fitted with GPS collars from two study sites located in Eastern Poland. The distance between moose locations served for assessing moose activity. We applied additive modelling to test the effect of the daily temperature on daily activity patterns and landscape use of moose.ResultsMoose, when exposed to temperatures exceeding thermal comfort, increased their activity during cooler twilight hours. On the hottest days, moose were more likely to use tree canopy cover, especially during midday hours. Finally, with increased temperatures and the risk of thermal stress, at that part of the day, moose utilized denser forest stands which could have provided extra protection against solar radiation.ConclusionsOur observations suggested that under a scenario of further climate warming, moose at the southwestern periphery of their range will be forced to make further behavioral alterations. However, it is not clear whether they will be able to compensate for the negative effects of on-going climate change.
Systemic treatment of breast cancer with leptomeningeal metastases using bevacizumab, etoposide and cisplatin (BEEP regimen) significantly improves overall survival
Authors: Chen Tom Wei-Wu , Jan I-Shiow , Chang Dwang-Ying , Lin Ching-Hung , Chen I-Chun , Chen Ho-Min , Cheng Ann-Lii , Lu Yen-Shen 
Published: April 2020

Abstract
Introduction
Metastatic breast cancer (MBC) with leptomeningeal metastases (LM) has dismal survival. We aim to determine if modern systemic therapy, especially the bevacizumab, cisplatin, and etoposide (BEEP) regimen, is beneficial to MBC LM patients.

Methods
We excerpted data from a prospectively collected cytopathology database for MBC patients who were diagnosed with LM by positive cerebrospinal fluid cytology. The primary outcome was OS from cytologically confirmed LM until death. Univariate and multivariate analyses were performed to elucidate prognostic factors.

Results
We identified 34 patients with cytologically confirmed LM. Treatments after LM diagnosis included: intrathecal methotrexate (82.4%), systemic chemotherapy (68%; BEEP n = 19, others n = 4), and whole brain radiotherapy (n = 5, 14.7%). Three of seven HER2-positive patients (43%) also received intrathecal trastuzumab. OS was improved in 2014–2016 compared with 2011–2013 (13.57 vs 3.20 months, p = 0.004), when 12/17 (71%) versus 7/17 (41%) patients received BEEP, respectively. In the multivariate model including all treatments, BEEP (HR 0.24, p = 0.003) and intrathecal trastuzumab (HR 0.22, p = 0.035), but not intrathecal methotrexate (HR 0.86, p = 0.78), remained significant prognostic factors.

Conclusions
MBC with LM is treatable—systemic BEEP are efficacious and may improve survival.