bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remote care technologies, older people and the social care crisis in the United Kingdom: a Multiple Streams Approach to understanding the ‘silver bullet’ of telecare policy
Authors: Eccles Andrew 
Published: February 2020

AbstractThe policy announcement in November 2018 by the Secretary of State for Health and Social Care that: ‘from today, let this be clear: tech transformation is coming’ indicates that confidence in care technologies, so apparent over the past decade in policy circles, remains unabated. This article suggests, based on evidence of significant limitations in technological solutions to care needs, that this confidence is misplaced. The focus is on remote care technologies – primarily telecare – which involve the passive or real-time monitoring of recipients, the majority of whom will be older people. These information and communication technologies (ICT) have been heralded by politicians, policy makers and industry interests alike as a solution to the challenges of demographic change and social care demand. While the research evidence suggests telecare works well for some people, in some circumstances, there are also significant complexities in its use, challenges presented to care relationships, and conflicting interpretations around its efficacy and cost-effectiveness. These critical issues have been marginalised in the mainstream discourse around telecare policy. This article explores the dissonance between this policy and the available evidence, drawing on a Multiple Streams Approach to analyse the emergence of, and continued confidence in, telecare policy based on a congruence of views across policy interests. To the extent that social care for older people is now in crisis, the article argues that the discourse around telecare represents an example of ‘silver bullet’ thinking: that is, too much focus on a single policy solution to address complex problems. Accordingly, the crisis in social care has deepened, without alternative policy proposals being available to address it. The renewed push for ICT-based solutions to this crisis in social care ought therefore to be viewed with some concern.
Snow Mechanics Near the Ductile‐Brittle Transition: Compressive Stick‐Slip and Snow Microquakes
Authors: Löwe H. , Zaiser M. , Mösinger S. , Schleef S. 
Published: February 2020

AbstractThe rate‐dependent mechanical response of snow is commonly believed to directly inherit the ductile‐to‐brittle transition (DBT) from the viscoplastic ice matrix. Recent work has however stressed the impact of microstructure evolution by rapid sintering during deformation. To understand these phenomena we have conducted deformation‐controlled compression experiments in an X‐ray tomography stage. By varying the strain rate over 3 orders of magnitude, we find an intermediate regime where the stress response changes from smooth to serrated behavior. This regime is accompanied by microstructure quakes associated with strain localization bands in the sample interior. To interpret the results we developed a minimal, scalar model with a rate‐dependent, elastoplastic constitutive law and healing which falls into the general class of rate‐and‐state models. The model correctly predicts the range of the instability as well as amplitude and frequency of the serrations and reveals a formal equivalence of the observed (compressive) stick‐slip with seismic faults.
Logarithmic Growth of Dikes From a Depressurizing Magma Chamber
Authors: Grossman‐Ponemon Benjamin E. , Heimisson Elías R. , Lew Adrian J. , Segall Paul 
Published: February 2020

AbstractDike propagation is an intrinsically multiphase problem, where deformation and fluid flow are intricately coupled in a fracture process. Here we perform the first fully coupled simulations of dike propagation in two dimensions, accounting for depressurization of a circular magma chamber, dynamic fluid flow, fracture formation, and elastic deformation. Despite the complexity of the governing equations, we observe that the lengthening is well explained by a simple model
, where
is the dike length,
is time, and
and
are constants. We compare the model to seismic data from eight dikes in Iceland and Ethiopia, and, in spite of the assumption of plane strain, we find good agreement between the data and the model. In addition, we derive an approximate model for the depressurization of the chamber with the dike length. These models may help forecast the growth of lateral dikes and magma chamber depressurization.
Electrically controlled white laser emission through liquid crystal/polymer multiphases
Authors: Adamow Alina , Szukalski Adam , Sznitko Lech , Persano Luana , Pisignano Dario , Camposeo Andrea , Mysliwiec Jaroslaw 
Published: February 2020

AbstractWhite lasers are becoming increasingly relevant in various fields since they exhibit unprecedented properties in terms of beam brightness and intensity modulation. Here we introduce a white laser based on a polymer matrix encompassing liquid crystals and multiple organic chromophores in a multifunctional phase-separation system. The separation of the hydrophilic matrix and the hydrophobic liquid crystals leads to the formation of a complex optically active layer, featuring lasing emission tuneable from blue to red. White laser emission is found with an optical excitation threshold of approximately 12 mJ/cm2. Importantly, an external electric field can be used to control the device emission intensity. White lasers with low-voltage (≤10 V) controllable emission might pave the way for a new generation of broadband light sources for analytical, computational, and communication applications.
Chemopreventive targeted treatment of head and neck precancer by Wee1 inhibition
Authors: van Harten Anne M. , de Boer D. Vicky , Martens-de Kemp Sanne R. , Buijze Marijke , Ganzevles Sonja H. , Hunter Keith D. , Leemans C. René , van Beusechem Victor W. , Wolthuis Rob M. F. , de Menezes Renée X. , Brakenhoff Ruud H. 
Published: February 2020

AbstractHPV-negative head and neck squamous cell carcinomas (HNSCCs) develop in precancerous changes in the mucosal lining of the upper-aerodigestive tract. These precancerous cells contain cancer-associated genomic changes and cause primary tumors and local relapses. Therapeutic strategies to eradicate these precancerous cells are very limited. Using functional genomic screens, we identified the therapeutic vulnerabilities of premalignant mucosal cells, which are shared with fully malignant HNSCC cells. We screened 319 previously identified tumor-lethal siRNAs on a panel of cancer and precancerous cell lines as well as primary fibroblasts. In total we identified 147 tumor-essential genes including 34 druggable candidates. Of these 34, 13 were also essential in premalignant cells. We investigated the variable molecular basis of the vulnerabilities in tumor and premalignant cell lines and found indications of collateral lethality. Wee1-like kinase (WEE1) was amongst the most promising targets for both tumor and precancerous cells. All four precancerous cell lines were highly sensitive to Wee1 inhibition by Adavosertib (AZD1775), while primary keratinocytes tolerated this inhibitor. Wee1 inhibition caused induction of DNA damage during S-phase followed by mitotic failure in (pre)cancer cells. In conclusion, we uncovered Wee1 inhibition as a promising chemopreventive strategy for precancerous cells, with comparable responses as fully transformed HNSCC cells.
Outcome of facial contour asymmetry after conventional two-dimensional versus computer-assisted three-dimensional planning in cleft orthognathic surgery
Authors: Hsu Po-Jung , Denadai Rafael , Pai Betty C. J. , Lin Hsiu-Hsia , Lo Lun-Jou 
Published: February 2020

AbstractComputer-assisted 3D planning has overcome the limitations of conventional 2D planning-guided orthognathic surgery (OGS), but difference for facial contour asymmetry outcome has not been verified to date. This comparative study assessed the facial contour asymmetry outcome of consecutive patients with unilateral cleft lip and palate who underwent 2D planning (n = 37)- or 3D simulation (n = 38)-guided OGS treatment for correction of maxillary hypoplasia and skeletal Class III malocclusion between 2010 and 2018. Normal age-, gender-, and ethnicity-matched individuals (n = 60) were enrolled for comparative analyses. 2D (n = 60, with 30 images for each group) and 3D (n = 43, with 18 and 25 images for 2D planning and 3D simulation groups, respectively) photogrammetric-based facial contour asymmetry-related measurements were collected from patients and normal individuals. The facial asymmetry was further verified by using subjective perception of a panel composed of 6 blinded raters. On average, the facial contour asymmetry was significantly (all p < 0.05) reduced after 3D virtual surgery planning for all tested parameters, with no significant differences between post-OGS 3D simulation-related values and normal individuals. No significant differences were observed for pre- and post-OGS values in conventional 2D planning-based treatment, with significant (all p < 0.05) differences for all normal individuals-related comparisons. This study suggests that 3D planning presents superior facial contour asymmetry outcome than 2D planning.
Effects of a solid lipid curcumin particle formulation on chronic activation of microglia and astroglia in the GFAP-IL6 mouse model
Authors: Ullah Faheem , Asgarov Rustam , Venigalla Madhuri , Liang Huazheng , Niedermayer Garry , Münch Gerald , Gyengesi Erika 
Published: February 2020

AbstractChronic glial activation is characterized by increased numbers of activated glial cells, secreting free radicals and cytotoxic cytokines, subsequently causing neuronal damage. In order to investigate the anti-inflammatory activity of Longvida® Optimised Curcumin (LC), we fed 500 ppm of LC to 2-month-old wild type and GFAP-IL6 mice for 6 months. LC feeding led to a significant reduction in the number of Iba-1+ microglia by 26% in the hippocampus and by 48% in the cerebellum, GFAP+ astrocytes by 30%, and TSPO+ cells by 24% in the hippocampus and by 31% in the cerebellum of the GFAP-IL6 mice. The morphology of the cells was assessed and LC significantly decreased the dendritic length of microglia and the convex area, convex perimeter, dendritic length, nodes and number of processes of astrocytes in the hippocampus while decreasing the soma area and perimeter in the cerebellum, in LC-fed GFAP-IL6 mice. In addition, LC feeding increased pre- and postsynaptic protein levels and improved balance measured by Rotarod. Together, these data suggest that LC is able to attenuate the inflammatory pathology and ameliorate neurodegeneration and motor deficits in GFAP-IL6 mice. For patients with neuro-inflammatory disorders, LC might potentially reverse the detrimental effects of chronic glial activation.
Bacterial dominance is due to effective utilisation of secondary metabolites produced by competitors
Authors: Morgan Benjamin G. , Warren Paul , Mewis Ryan E. , Rivett Damian W. 
Published: February 2020

AbstractInteractions between bacteria govern the progression of respiratory infections; however, the mechanisms underpinning these interactions are still unclear. Understanding how a bacterial species comes to dominate infectious communities associated with respiratory infections has direct relevance to treatment. In this study, Burkholderia, Pseudomonas, and Staphylococcus species were isolated from the sputum of an individual with Cystic Fibrosis and assembled in a fully factorial design to create simple microcosms. Measurements of growth and habitat modification were recorded over time, the later using proton Nuclear Magnetic Resonance spectra. The results showed interactions between the bacteria became increasingly neutral over time. Concurrently, the bacteria significantly altered their ability to modify the environment, with Pseudomonas able to utilise secondary metabolites produced by the other two isolates, whereas the reverse was not observed. This study indicates the importance of including data about the habitat modification of a community, to better elucidate the mechanisms of bacterial interactions.
Early decrease in erector spinae muscle area and future risk of mortality in idiopathic pulmonary fibrosis
Authors: Nakano Akiko , Ohkubo Hirotsugu , Taniguchi Hiroyuki , Kondoh Yasuhiro , Matsuda Toshiaki , Yagi Mitsuaki , Furukawa Taiki , Kanemitsu Yoshihiro , Niimi Akio 
Published: February 2020

AbstractComputed tomography (CT) assessment of the cross-sectional area of the erector spinae muscles (ESMCSA) can be used to evaluate sarcopenia and cachexia in patients with lung diseases. This study aimed to confirm whether serial changes in ESMCSA are associated with survival in patients with idiopathic pulmonary fibrosis (IPF). Data from consecutive patients with IPF who were referred to a single centre were retrospectively reviewed. We measured the ESMCSA at the level of the 12th thoracic vertebra on CT images at referral and 6 months later (n = 119). The follow-up time was from 817–1633 days (median, 1335 days) and 59 patients (49.6%) died. A univariate Cox regression analysis showed that the decline in % predicted forced vital capacity (FVC) (Hazard ratios [HR] 1.041, 95% confidence interval [CI] 1.013–1.069, P = 0.004), the decline in body mass index (BMI) (HR 1.084, 95% CI 1.037–1.128; P < 0.001) and that in ESMCSA (HR 1.057, 95% CI 1.027–1.086; P < 0.001) were prognostic factors. For multivariate analyses, the decline in ESMCSA (HR 1.039, 95% CI 1.007–1.071, P = 0.015) was a significant prognostic factor, while those in % FVC and BMI were discarded. Early decrease in ESMCSA may be a useful predictor of prognosis in patients with IPF.
High pressure inhibits signaling protein binding to the flagellar motor and bacterial chemotaxis through enhanced hydration
Authors: Hata Hiroaki , Nishihara Yasutaka , Nishiyama Masayoshi , Sowa Yoshiyuki , Kawagishi Ikuro , Kitao Akio 
Published: February 2020

AbstractHigh pressure below 100 MPa interferes inter-molecular interactions without causing pressure denaturation of proteins. In Escherichia coli, the binding of the chemotaxis signaling protein CheY to the flagellar motor protein FliM induces reversal of the motor rotation. Using molecular dynamics (MD) simulations and parallel cascade selection MD (PaCS-MD), we show that high pressure increases the water density in the first hydration shell of CheY and considerably induces water penetration into the CheY-FliM interface. PaCS-MD enabled us to observe pressure-induced dissociation of the CheY-FliM complex at atomic resolution. Pressure dependence of binding free energy indicates that the increase of pressure from 0.1 to 100 MPa significantly weakens the binding. Using high-pressure microscopy, we observed that high hydrostatic pressure fixes the motor rotation to the counter-clockwise direction. In conclusion, the application of pressure enhances hydration of the proteins and weakens the binding of CheY to FliM, preventing reversal of the flagellar motor.
Track and dose-average LET dependence of Gafchromic EBT3 and MD-V3 films exposed to low-energy photons
Authors: Massillon-JL G. 
Published: February 2020

AbstractGafchromic films are widely used in radiotherapy using photons, electrons and protons. Dosimetric characteristics of the films in terms of beam-quality is of great importance for a better evaluation of the absorbed-dose in the clinic. In proton-therapy, film’s response has been reported in terms of track-average, LΔ,T, or dose-average, LΔ,D, linear energy transfer (LET), concluding that LΔ,D is a more reliable parameter than LΔ,T. Nonetheless, in photon-beams, the film’s response is generally scrutinised in terms of photon-energy. This work aimed at investigating, the total (TEF) and secondary (SE) electron fluence produced in EBT3 and MD-V3 films exposed to 20 kV-160 kV x-ray and 60Co beams and their corresponding LΔ,T and LΔ,D to determine their influence on the film’s relative-efficiency, REFilm. Regardless the film-model, at energies below 100 keV, LΔ,D for TEF are about 1.7 to 2.5 times those of LΔ,T while for SE they are relatively similar (8–29%). For 60Co-gamma, LΔ,D for TEF and SE are approximately 9 and 4 times LΔ,T, respectively, which implies that LΔ,D is more important for high-photon energies. Independent of the electron-fluence and film-model, REFilm is almost constant at low average-LET, rapidly increases and thereafter steadily rises with average-LET. The REFilm−LET curve indicated that LΔ,D is more sensitive to small change than LΔ,T and if it is evaluated for SE, it would even be more appropriate to better describing the dosimeter response induced by photons in terms of ionization-density instead of LΔ,T for TEF, as generally done. Based on these results, once can conclude that the effect of the average-LET on the film’s response should be considered when use for clinical-dosimetry using photons and not only the energy.
TRPM7 contributes to progressive nephropathy
Authors: Suzuki Sayuri , Penner Reinhold , Fleig Andrea 
Published: February 2020

AbstractTRPM7 belongs to the Transient Receptor Potential Melastatin family of ion channels and is a divalent cation-conducting ion channel fused with a functional kinase. TRPM7 plays a key role in a variety of diseases, including neuronal death in ischemia, cancer, cardiac atrial fibrillation, malaria invasion. TRPM7 is aberrantly over-expressed in lung, liver and heart fibrosis. It is also overexpressed after renal ischemia-reperfusion, an event that induces kidney injury and fibrosis. However, the role of TRPM7 in kidney fibrosis is unclear. Using the unilateral ureteral obstruction (UUO) mouse model, we examined whether TRPM7 contributes to progressive renal damage and fibrosis. We find that TRPM7 expression increases in UUO kidneys. Systemic application of NS8593, a known TRPM7 inhibitor, prevents kidney atrophy in UUO kidneys, retains tubular formation, and reduces TRPM7 expression to normal levels. Cell proliferation of both tubular epithelial cells and interstitial cells is reduced by NS8593 treatment in UUO kidneys, as are TGF-β1/Smad signaling events. We conclude that TRPM7 is upregulated during inflammatory renal damage and propose that pharmacological intervention targeting TRPM7 may prove protective in progressive kidney fibrosis.
Bacterial DNA promotes Tau aggregation
Authors: Tetz George , Pinho Michelle , Pritzkow Sandra , Mendez Nicolas , Soto Claudio , Tetz Victor 
Published: February 2020

AbstractA hallmark feature of Alzheimer’s disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.
Peripheral inflammation promotes brain tau transmission via disrupting blood–brain barrier
Authors: Liu Yanchao , Zhang Shujuan , Li Xiaoguang , Liu Enjie , Wang Xin , Zhou Qiuzhi , Ye Jinwang , Wang Jian-Zhi 
Published: February 2020

Abstract
Abnormal aggregation of pathological tau protein is a neuropathological feature of Alzheimer’s disease (AD). In the AD patients, the abnormal tau accumulation first appeared in entorhinal cortex (EC) and then propagated to the hippocampus with microglia activation and inflammation, but the mechanism is elusive. Here, we studied the role and mechanisms underlying periphery inflammation on brain tau transmission. By intraperitoneal injection of lipopolysaccharide (LPS) with brain medial entorhinal cortex (MEC)-specific overexpressing P301L human tau (P301L-hTau), we found that both acute and chronic administration of LPS remarkably promoted P301L-hTau transmission from MEC to the hippocampal subsets. Interestingly, the chronic LPS-induced P301L-hTau transmission was still apparent after blocking microglia activation. Further studies demonstrated that LPS disrupted the integrity of blood–brain barrier (BBB) and simultaneous intraperitoneal administration of glucocorticoid (GC) attenuated LPS-promoted P301L-hTau transmission. These data together suggest that a non-microglia-dependent BBB disruption contributes to peripheral LPS-promoted brain P301L-hTau transmission, therefore, maintaining the integrity of BBB can be a novel strategy for preventing pathological tau propagation in AD and other tauopathies.
Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study
Authors: Thomann Anne Kerstin , Schulte Lucas-Alexander , Globig Anna-Maria , Hoffmann Peter , Klag Thomas , Itzel Timo , Teufel Andreas , Schreiner Rupert , Scheffe Nina , Ebert Matthias Philip , Wehkamp Jan , Gauss Annika , Hasselblatt Peter , Klaus Jochen , Reindl Wolfgang 
Published: February 2020

Abstract
Background and aim The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn’s disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16.
Methods Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration.
Results Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001).
Conclusion Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.