bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Onset of Efficacy With Fremanezumab for the Preventive Treatment of Chronic Migraine
Authors: Winner Paul K. , Spierings Egilius L. H. , Yeung Paul P. , Aycardi Ernesto , Blankenbiller Tricia , Grozinski‐Wolff Melissa , Yang Ronghua , Ma Yuju 
Published: November 2019

ObjectiveTo assess the onset of efficacy for fremanezumab in chronic migraine by evaluating pain‐related clinical measures at different time points.BackgroundFaster onset of efficacy of preventive treatments could benefit patients with migraine. Fremanezumab is a fully humanized monoclonal antibody that selectively targets calcitonin gene‐related peptide, a neuropeptide involved in the pathophysiology of migraine. In 12‐week clinical trials, subcutaneous fremanezumab significantly reduced the frequency of migraine headaches, headache hours, and headaches in general, without serious treatment‐related adverse events. New drug classes of migraine preventive treatment demonstrate markedly different clinical profiles from standard‐of‐care treatments.MethodsIn this double‐blind phase III study, eligible patients were randomized 1:1:1 to receive subcutaneous injections of fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline, 225 mg at weeks 4 and 8), or placebo at each time point. This study included secondary, exploratory, and post hoc analyses of the primary trial, evaluating the change in headache days of at least moderate severity or migraine days during the first 4 weeks of the trial.ResultsA total of 1130 patients were randomized (fremanezumab quarterly, n = 376; fremanezumab monthly, n = 379; or placebo, n = 375). During the 4‐week period after the first dose, the mean number of monthly headache days of at least moderate severity was reduced for the all‐fremanezumab group (mean reduction [95% confidence interval]: −4.6 days [−5.1, −4.1]) compared with the placebo group (−2.3 days [−2.9, −1.6]; P < .0001). Treatment effects were observed at Week 1 for the all‐fremanezumab group (−1.1 days [−1.3, −1.0]) vs placebo (−0.5 days [−0.7, −0.3]; P < .0001), with separation from placebo by Day 2 (P = .003). Similar effects were observed for the monthly average number of migraine days and mean number of monthly headache hours.ConclusionsThe early onset of efficacy of fremanezumab may have the potential to improve patient compliance and clinical outcomes.
The regulation of CD4+ T cells during malaria
Authors: Kumar Rajiv , Loughland Jessica R. , Ng Susanna S. , Boyle Michelle J. , Engwerda Christian R. 
Published: November 2019

AbstractMalaria is a major global health problem. Despite decades of research, there is still no effective vaccine to prevent disease in the majority of people living in malaria‐endemic regions. Additionally, drug treatment options are continually threatened by the emergence of drug‐resistant parasites. Immune responses generated against Plasmodium parasites that cause malaria are generally not sufficient to prevent the establishment of infection and can even contribute to the development of disease, unless individuals have survived multiple infections. Research conducted in experimental models, controlled human malaria infection studies, and with malaria patients from disease‐endemic areas indicate the rapid development of immunoregulatory pathways in response to Plasmodium infection. These “imprinted” immune responses limit inflammation, and likely prevent progression to severe disease manifestations. However, they also cause slow acquisition of immunity and possibly hamper the development of vaccine‐mediated protection against disease. A major target for and mediator of the immunoregulatory pathways established during malaria are CD4+ T cells that play critical roles in priming phagocytic cells to capture and kill malaria parasites, as well as helping B cells produce functional anti‐parasitic antibodies. In this review, we describe mechanisms of CD4+ T cell activation during malaria and discuss the immunoregulatory mechanisms that develop to dampen their anti‐parasitic and pathological functions. We also offer some ideas about how host‐directed approaches might be applied to modulate CD4+ T cell functions to improve vaccine responses and enhance development of natural immunity.
Influence of Zr dopant on polarization in rutile (In0.5Nb0.5)0.005(Ti1‐xZrx)0.995O2 ceramics
Authors: Guo Baochun , Liu Peng , Cui Xiulei , Song Yuechan 
Published: November 2019

Abstract(In0.5Nb0.5)0.005(Ti1‐xZrx)0.995O2 (INZT, x = 0‐0.10) ceramics were synthesized using a conventional sintering method, and the effects of Zr content on the microstructures, dielectric properties and electron‐pinned defect‐dipoles (EPDD) polarization of the resultant products were investigated. The solubility limit of INZT was x = 0.075, and a secondary ZrTiO4 phase appeared at x = 0.10. Ceramics with x = 0‐0.10 exhibited excellent dielectric properties, ie, colossal permittivity (CP, εʹ > 103) and low dielectric loss (tanδ < 0.1), over a wide range of frequencies (100‐106 Hz at 300 K) and temperatures (50‐350 K at 1 kHz). The dielectric spectra and XPS results confirmed that the CP property of the ceramics could be ascribed to their EPDD polarization. The activation energy (Ea) for EPDD polarization was continuously enhanced by increasing x values. EPDD relaxation parameters at different x values were revealed using Cole‐Cole equation fitting. Moreover, α, which characterize the relaxation time τ distribution, increased with x values, thus indicating that Zr was involved in and affected electron localized states. The high Ea, temperature Tp of the peak εʹʹ at 1 kHz, and dielectric relaxation time τp at 30 K were related to increases in hopping distance of electrons among defect clusters with Zr addition.
Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury
Authors: Lin Jialiang , Pan Xiangxiang , Huang Chongan , Gu Mingbao , Chen Ximiao , Zheng Xuanqi , Shao Zhenxuan , Hu Sunli , Wang Ben , Lin Hao , Wu Yaosen , Tian Naifeng , Wu Yan , Gao Weiyang , Zhou Yifei , Zhang Xiaolei , Wang Xiangyang 
Published: November 2019

AbstractInflammation and neuronal apoptosis contribute to the progression of secondary injury after spinal cord injury (SCI) and are targets for SCI therapy; autophagy is reported to suppress apoptosis in neuronal cells and M2 polarization may attenuate inflammatory response in microglia, while both are negatively regulated by mTORC1 signalling. We hypothesize that mTORC1 suppression may have dual effects on inflammation and neuronal apoptosis and may be a feasible approach for SCI therapy. In this study, we evaluate a novel inhibitor of mTORC1 signalling, Astragaloside IV (AS‐IV), in vitro and in vivo. Our results showed that AS‐IV may suppress mTORC1 signalling both in neuronal cells and microglial cells in vitro and in vivo. AS‐IV treatment may stimulate autophagy in neuronal cells and protect them against apoptosis through autophagy regulation; it may also promote M2 polarization in microglial cells and attenuate neuroinflammation. In vivo, rats were intraperitoneally injected with AS‐IV (10 mg/kg/d) after SCI, behavioural and histological evaluations showed that AS‐IV may promote functional recovery in rats after SCI. We propose that mTORC1 suppression may attenuate both microglial inflammatory response and neuronal apoptosis and promote functional recovery after SCI, while AS‐IV may become a novel therapeutic medicine for SCI.
Collective Identities, European Solidarity: Identification Patterns and Preferences for European Social Insurance
Authors: Nicoli Francesco , Kuhn Theresa , Burgoon Brian 
Published: November 2019

AbstractA degree of collective identity is often perceived to be a requirement for integration of core state powers, and even more so when redistributive measures are at stake. Existing research has shown that European identity is an important correlate of support for European social policy in general. This article explores the ways in which collective identities relate to the multidimensional nature of social policy at the European level. We explore in particular the features of European social policy that receive the most support from European publics, and how local, national and European identity moderates these preferences. We expect that people who have primarily sub‐national or national attachments are less supportive of generous schemes and schemes that involve greater cross‐country redistribution, and are more in favour of decentralized schemes administered by the member states than those with stronger European identities. We find support for these expectations in a conjoint survey experiment fielded in autumn 2018 in 13 EU member states.
Juncker's Curse? Identity, Interest, and Public Support for the Integration of Core State Powers
Authors: Bremer Björn , Genschel Philipp , Jachtenfuchs Markus 
Published: November 2019

AbstractIn this study we analysed the patterns and covariates of public support for the European integration of core state powers based on an original new survey. We found considerable variation across integration instruments, member states and policy issues. Horizontal transfers are supported more than vertical capacity building; member states from the EU's South‐East are more supportive than states from the North‐West; and support increases from debt relief to unemployment assistance, sharing the burdens of refugees, and military defence to disaster aid. Identity is a strong and fairly consistent predictor for individual variations in support. The association with respondents’ interest is less consistent, but can be quite strong with respect to specific policy issues such as debt and unemployment. Overall, support for the integration of core state powers is higher and more variable than expected. This suggests there is considerable room for political agency rather than a general constraining dissensus.
Losing Faith: Religion and Attitudes toward the European Union in Uncertain Times
Authors: Nelsen Brent F. , Guth James L. 
Published: November 2019

AbstractThis paper explores the changing role of religion in forming public attitudes toward integration. We first outline the complex relationship of religion to the development of the European Union, and then use the 2009 and 2014 European Parliamentary Election Studies to examine the changes taking place in those historic patterns. In 2009 traditional religious patterns persisted, with Catholics more positive toward the EU than Protestants, with religiosity reinforcing the respective tendencies. By 2014, however, traditional divisions had virtually disappeared, as the economic crisis (and perhaps the growing refugee problem) had a powerful effect on Catholic majorities in EU countries. Nevertheless, when economic and other assessments are accounted for, Catholic confessional culture still provides ‘deep’ support for the EU. Finally, we discover that EU expansion has not changed old religious patterns as much as we expected, but find those traditional relationships to be virtually absent among millennials.
Akkermansia muciniphila reduces Porphyromonas gingivalis‐induced inflammation and periodontal bone destruction
Authors: Huck Olivier , Mulhall Hannah , Rubin George , Kizelnik Zev , Iyer Radha , Perpich John D. , Haque Nasreen , Cani Patrice D. , de Vos Willem M. , Amar Salomon 
Published: November 2019

AbstractAimAkkermansia muciniphila is a beneficial gut commensal, whose anti‐inflammatory properties have recently been demonstrated. This study aimed to evaluate the effect of A. muciniphila on Porphyromonas gingivalis elicited inflammation.Material and MethodsIn lean and obese mice, A. muciniphila was administered in P. gingivalis‐induced calvarial abscess and in experimental periodontitis model (EIP). Bone destruction and inflammation were evaluated by histomorphometric analysis. In vitro, A. muciniphila was co‐cultured with P. gingivalis, growth and virulence factor expression was evaluated. Bone marrow macrophages (BMMϕ) and gingival epithelial cells (TIGK) were exposed to both bacterial strains, and the expression of inflammatory mediators, as well as tight junction markers, was analysed.ResultsIn a model of calvarial infection, A. muciniphila decreased inflammatory cell infiltration and bone destruction. In EIP, treatment with A. muciniphila resulted in a decreased alveolar bone loss. In vitro, the addition of A. muciniphila to P. gingivalis‐infected BMMϕ increased anti‐inflammatory IL‐10 and decreased IL‐12. Additionally, A. muciniphila exposure increases the expression of junctional integrity markers such as integrin‐β1, E‐cadherin and ZO‐1 in TIGK cells. A. muciniphila co‐culture with P. gingivalis reduced gingipains mRNA expression.DiscussionThis study demonstrated the protective effects of A. muciniphila administration and may open consideration to its use as an adjunctive therapeutic agent to periodontal treatment.
Seasonal dynamics of riverine fish communities using eDNA
Authors: Milhau Tristan , Valentini Alice , Poulet Nicolas , Roset Nicolas , Jean Pauline , Gaboriaud Coline , Dejean Tony 
Published: November 2019

AbstractAs fish communities are a major concern in rivers ecosystems, we investigated if their environmental (e)DNA signals vary according to the sampling period or hydromorphological conditions. Three rivers were studied over a year using eDNA metabarcoding approach. The majority of the species (c. 80%) were detected all year round in two rivers having similar hydromorphological conditions, whereas in the river affected by an upstream lake waterflow, more species were detected sporadically (42%). For all the rivers, in more than 98% of the occasional detections, the reads abundance represented <0.4% of the total reads per site and per sampling session. Even if the majority of the fish communities remained similar over the year for each of the three rivers, specific seasonal patterns were observed. We studied if the waterflow or the reproduction period had an effect on the observed dynamics. Waterflow, which influences eDNA downstream transportation, had a global influence in taxonomic richness, while the fishes' reproductive period had only an influence on certain species. Our results may help selecting the best sampling strategy according to research objectives. To study fish communities at local scale, seasons of low waterflow periods are recommended. This particularly helps to restraint effects of external eDNA coming from connections with other aquatic environment (tributaries, lakes, wetlands, sewage effluents, etc.). To obtain a more integrative overview of the fish community living in a river basin, high waterflow or breeding seasons are preferable for enhancing species detection probability, especially for rare species.
Managing muddy floods: Balancing engineered and alternative approaches
Authors: Boardman John , Vandaele Karel 
Published: November 2019

AbstractMuddy runoff from agricultural fields is widespread across Europe causing damage to properties, transport, and freshwater systems. Clean‐up costs are high and include making water fit for drinking. Mitigation against muddy flooding (MF) includes standard soil conservation and flood protection measures. MF occurs during intense localised storms, for example, in Flanders, northern Belgium, but can also result from longer duration rainfall events, for example, in southern England. MF occurs in catchments with large areas of arable land, adjacent to property or freshwater systems. Early experience with mitigation measures favoured engineered approaches. On their own, these have frequently failed to achieve adequate protection or been ruled out on economic or safety grounds: a combination of engineered and land‐use approaches is necessary. We illustrate this with reference to the Molenbeek catchment in Flanders where monitoring shows a significant decline in erosion and damage to adjacent properties. Cost–benefit analysis of mitigation measures shows them to pay for themselves over short periods of time. Protecting freshwater systems from MF damage should focus on interrupting flow from field to streams, ditches and roads which act to convey muddy runoff to the main river channels.
The role of antibiotics in upper gastrointestinal bleeding among cirrhotic patients without major complications after endoscopic hemostasis
Authors: Wu Cheng‐Kun , Yang Shih‐Cheng , Liang Chih‐Ming , Li Yu‐Chi , Yeh Wen‐Shuo , Tai Wei‐Chen , Lee Chen‐Hsiang , Yang Yao‐Hsu , Hsu Chien‐Ning , Tsai Tzu‐Hsien , Chuah Seng‐Kee 
Published: November 2019

AbstractBackground and aimAntibiotic prophylaxis should be instituted for cirrhotic patients with upper gastrointestinal bleeding (UGIB), but the benefit on compensated patients remains undetermined. We aimed to compare the clinical outcomes between cirrhotic patients without major complications with UGIB with and without antibiotic prophylaxis.MethodsWe conducted this population‐based cohort study by using Taiwanese Longitudinal Health Insurance Database 2000 (LHID2000, between 1997 to 2013), aged 18 years or older with a hospital discharge diagnosis of cirrhosis (n = 64,506), UGIB (n = 7,784), and endoscopic therapy (n = 2,292). After strict exclusions, 1205 patients were enrolled and were divided into antibiotic exposure (n = 558) and non‐exposure (n = 647) groups. The outcomes were rebleeding and mortality.ResultsAfter completing the analysis adjusted by death, the rebleeding rates within 4 weeks were significantly lower in patients with antibiotic prophylaxis (3.05% versus 6.03%, P = 0.0142) and those with endoscopic therapy (0.72% vs 3.09%, P = 0.0033) but not significant after 3 months and onwards. Male patients aged > 55, high CCI score ≧ 4, and UGIB of variceal etiologies were benefited from rebleeding. The use of antibiotics did not significantly impact 6‐week mortality (adjusted hazard ratio: 1.07, 95%CI: 0.41~2.75; P = 0.8943). Old age, multiple comorbidities, and UGIB of variceal etiologies were risk factors of all‐cause mortality.ConclusionsThe current study suggested that cirrhotic patients without major complications who suffered from UGIB were benefited by the use of antibiotics to prevent rebleeding within 4 weeks after endoscopic treatment of UGIB especially for those with age > 55, high CCI score ≧ 4, and UGIB of variceal etiologies.
Attachment, emotion regulation, and well‐being in couples: Intrapersonal and interpersonal associations
Authors: Brandão Tânia , Matias Marisa , Ferreira Tiago , Vieira Joana , Schulz Marc S. , Matos Paula Mena 
Published: November 2019

AbstractObjectiveThere is a well‐established link in the literature between secure romantic attachment orientation and psychological well‐being. The underlying processes of this link and the couple interplay between attachment and well‐being are notably less explored. Using a dyadic framework, this study examines both couple members' emotion regulation strategies as potential mediators of this link.MethodOne hundred and nineteen heterosexual couples completed self‐report measures on attachment style, psychological well‐being, tendency to suppress emotions, and emotion expression. Analyses were performed using the actor–partner interdependence mediation model that distinguishes between intrapersonal and interpersonal influences.ResultsResults showed that controlling for relationship length, there was an intrapersonal indirect effect of attachment avoidance on psychological well‐being through emotion suppression. Moreover, interpersonal indirect effects were found (a) with individual attachment avoidance being associated with partner's psychological well‐being through own emotion expression and (b) individual's attachment anxiety being associated with partner's psychological well‐being through both own's emotion expression and partner's emotion suppression.ConclusionsThese findings highlight the complex associations among attachment, emotion regulation, and well‐being and point out the role of emotion regulation as a potential underlying pathway explaining these associations. The results suggest the importance of considering the relational nature of emotional and attachment dynamics in couples.
Racial Disparities in the Criminal Justice System: Prevalence, Causes, and a Search for Solutions
Authors: Kovera Margaret Bull 
Published: November 2019

AbstractRacial disparities in the criminal justice system are well documented and widespread. The present review examines racial disparities in three areas of the system: policing, prison populations, and participation on juries. Some, but not all, of these disparities may be the result of implicit racial bias. Even if the disparities are caused by implicit racial bias, given the number of people involved in the decision making that results in these disparities and the difficulty in training people to overcome implicit bias, interventions designed to eliminate disparities by reducing implicit racial bias may fail. Instead, policies designed to constrain the operation of implicit and/or explicit bias or that eliminate (or at a minimum reduce) problematic outcomes for everyone, regardless of race, may be more effective at reducing racial disparities than are interventions designed to eliminate implicit bias.
Predictors of urinary or fecal incontinence in dogs with thoracolumbar acute non‐compressive nucleus pulposus extrusion
Authors: Mari Lorenzo , Behr Sebastien , Shea Anita , Dominguez Elisabet , Ricco Cristoforo , Alcoverro Emili , Ekiri Abel , Sanchez‐Masian Daniel , De Risio Luisa 
Published: November 2019

AbstractBackgroundUrinary (UI) and fecal (FI) incontinence occur in up to 7.5% and 32% of dogs, respectively, after thoracolumbar acute noncompressive nucleus pulposus extrusion (ANNPE).Hypotheses/ObjectivesTo investigate clinical, diagnostic, and therapeutic predictors of UI and FI in dogs with ANNPE affecting the T3‐L3 spinal cord segments.AnimalsHundred and eighty‐seven dogs with T3‐L3 ANNPE diagnosed based on clinical and MRI findings.MethodsMulticenter retrospective study. Data were obtained from medical records and telephone questionnaires and analyzed by logistic regression.ResultsUI and FI were reported in 17 (9.1%) and 44 (23.5%) dogs, respectively. Paraplegic dogs were 3 times (95% CI = 1.25, 10.87) more likely to develop UI (P = .018) and 4 times (95% CI = 1.94, 12.56) more likely to develop FI (P = .001) compared to nonparaplegic dogs. Dogs with an intramedullary hyperintensity greater than 40% of the cross‐sectional area of the spinal cord at the same level on transverse T2‐weighted MRI images were 4 times more likely to develop UI (95% CI = 1.04, 21.72; P = .045) and FI (95% CI = 1.56, 10.39; P = .004) compared to dogs with smaller lesions. FI was 3 times (95% CI = 1.41, 7.93) more likely in dogs that were not treated with nonsteroidal anti‐inflammatory drugs (NSAIDs) after diagnosis compared to dogs administered NSAIDs (P = .006) and 2 times (95% CI = 1.12, 5.98) more likely in dogs presented with clinical signs compatible with spinal shock compared to dogs without (P = .026).Conclusion and Clinical ImportanceThe identification of clinical, diagnostic, and therapeutic predictors of UI and FI in dogs with T3‐L3 ANNPE can help to approach these autonomic dysfunctions occurring after spinal cord injury.