bluuebunny/crossref_metadata_2025_split huggingface dataset:
Café nation? Exploring the growth of the UK café industry
Authors: Ferreira Jennifer 
Published: October 2016

The UK café industry has experienced significant growth over the last decade. With over 18 800 outlets, and a turnover of £7.2 billion recorded in 2014, the industry represents an important component of the retail sector. Industry commentators forecast that the industry will continue to grow and that there will be 27 000 outlets by 2020. This article provides an overview of the UK café industry and highlights the key drivers of it's rapid growth. It explores the ways that a new economic geography is quietly made as the café industry refashions our high streets. The article culminates by presenting an illustrative typology of café types which comprise the café industry in the UK, highlighting the need for greater research into the landscape of the café industry as it develops, and the roles that café spaces play in different communities.
Restoration of tropical forests requires more than just planting trees, a lot more…
Authors: Mayfield Margaret M. 
Published: October 2016

AbstractForest restoration is an important tool for combating climate change and protecting biodiversity. In this issue of Applied Vegetation Science, Garcia et al. show that alone, planting trees is insufficient for fully restoring rain forest complexity. This study highlights the need for longer‐term restoration plans, including enrichment plantings that speed the recovery of non‐tree forest components once planted trees have established.
Efficacy of bisphosphonate as an adjunct to nonsurgical periodontal therapy in the management of periodontal disease: a systematic review
Authors: Akram Zohaib , Abduljabbar Tariq , Kellesarian Sergio Varela , Abu Hassan Mohamed Ibrahim , Javed Fawad , Vohra Fahim 
Published: October 2016

AimsThe aim of this systematic review was to assess the efficacy of bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the management of periodontitis.MethodsDatabases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched up to and including July 2016. The primary outcome was probing depth (PD), and the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill. The mean differences (MD) of outcomes and 95% confidence intervals (CI) for each variable were calculated using random effect model.ResultsEight clinical studies were included. Seven studies used alendronate as an adjunct to SRP; of these, four studies used topical application and three used oral alendronate. Considering the effects of adjunctive bisphosphonates as compared to SRP alone, a high degree of heterogeneity for PD (Q value = 39.6, P < 0.0001, I2 = 87.38%), CAL (Q value = 13.65, P = 0.008, I2 = 70.71%), and BD fill (Q value = 53.26, P < 0.0001, I2 = 92.49%) was noticed among both the groups. Meta‐analysis showed a statistically significant PD reduction (MD = –1.18, 95% CI = –1.91 to –0.44, P = 0.002), CAL gain (MD = –0.69, 95% CI = –1.20 to –0.18, P = 0.008) and BD fill (MD = –2.36, 95% CI = –3.64 to –1.08, P < 0.001) for SRP + bisphosphonate treatment vs. SRP alone.ConclusionsAdjunctive bisphosphonate therapy appears to be effective in managing periodontitis, however, due to the potential risk of osteonecrosis of the jaws and short‐term follow‐up of the studies, their clinical application is debatable.
Biomarker‐guided clinical development of the first‐in‐class anti‐inflammatory FPR2/ALX agonist ACT‐389949
Authors: Stalder Anna K. , Lott Dominik , Strasser Daniel S. , Cruz Hans G. , Krause Andreas , Groenen Peter M.A. , Dingemanse Jasper 
Published: October 2016

AimsThe main objectives of these two phase I studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective formyl peptide receptor type 2 (FPR2)/Lipoxin A4 receptor (ALX) agonist ACT‐389949. A challenge model was used to assess the drug's anti‐inflammatory potential, with the aim of selecting a dosing regimen for future patient studies.MethodsTwo double‐blind, randomized phase I studies investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of ACT‐389949 at different doses and dosing regimens. Drug exposure was correlated with target engagement markers such as receptor internalization and cytokine measurements. The effect of FPR2/ALX agonism on neutrophil migration was studied in a lipopolysaccharide (LPS) inhalation model.ResultsACT‐389949 was well tolerated. Maximum concentrations were reached around 2 h after dosing, with a mean terminal half‐life of 29.3 h [95% confidence interval (CI) 25.5, 33.7]. After multiple‐dose administration, exposure increased by 111% (95% CI 89, 136), indicating drug accumulation.Administration of ACT‐389949 resulted in a dose‐dependent, long‐lasting internalization of FPR2/ALX into leukocytes. Pro‐ and anti‐inflammatory cytokines were dose‐dependently but transiently upregulated only after the first dose. No pharmacological effect on neutrophil count was observed in the LPS challenge test performed at steady state.ConclusionsFPR2/ALX agonism with ACT‐389949 was shown to be safe and well tolerated in healthy subjects. Receptor internalization and downstream mediators pointed towards a desensitization of the system, which may explain the lack of effect on neutrophil recruitment in the LPS challenge model.
Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation
Authors: Quan‐Jun Yang , Jian‐Ping Zhang , Jian‐Hua Zhang , Yong‐Long Han , Bo Xin , Jing‐Xian Zhang , Bona Dai , Yuan Zhang , Cheng Guo 
Published: October 2016

AbstractInhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high‐resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction–partial least squares using SIMCA‐P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high‐resolution NMR‐based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4‐hydroxybutyrate, lactate, cis‐aconitate, 5‐hydroxyindoleacetate, taurine, trans‐4‐hydroxy‐l‐proline, tiglylglycine, 3‐hydroxybutyrate, 3‐methylhistidine, glucose, cis‐aconitate, 2‐deoxyinosine and 2‐aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2‐hydroxy‐3‐methylvalerate, creatine, citrulline, glutamate, asparagine, 2‐hydroxyvalerate, citrate, homoserine, histamine, sn‐glycero‐3‐phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N‐oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic reprogramming associated with a combination treatment of inhaled budesonide and salbutamol in asthmatic children.
Lipid‐soluble Cigarette Smoke Particles Induced Vascular Endothelin Type A Receptor Up‐Regulation through Activation of ERK1/2 Signal Pathways
Authors: Zhang Yaping , Zhang Wei , Edvinsson Lars , Xu Cang‐Bao 
Published: October 2016

AbstractAbnormal contraction of vessels termed ‘vasospasm’ is associated with various cardiovascular diseases. Smoking is a well‐known risk factor that increases vasospasm. However, the molecular mechanisms by which smoking leads to vasospasm and cardiovascular disease are not fully understood. This study was designed to examine whether DMSO‐extracted cigarette smoke particles (DSP) could induce up‐regulation of vascular endothelin type A (ETA) receptors, and whether ETA receptor is up‐regulated through activation of extracellular regulated protein kinases 1 and 2 (ERK1/2) signal pathways. Mesenteric arterial segments from rats were cultured in the presence of DSP, water‐extracted cigarette smoke particles (WSP) or equivalent concentration of nicotine for up to 24 hr. The results showed that DSP, but not WSP or nicotine, induced ETA receptor up‐regulation with increased ETA receptor‐mediated contraction (myograph, p < 0.001). Simultaneously, the expression of ETA receptor mRNA (real‐time PCR, p < 0.001) and protein (immunohistochemistry) were enhanced in the smooth muscle cells, suggesting that the lipid‐soluble substances contained in cigarette smoke were responsible for the effects of DSP. Actinomycin D (a general transcriptional inhibitor) decreased ETA receptor mRNA expression and attenuated receptor‐mediated contraction (p < 0.001), while DSP accelerated ETA receptor mRNA degradation (p < 0.01) and promoted the translation of ETA receptor mRNA into protein. Furthermore, the up‐regulation of ETA receptors was significantly attenuated by inhibition of ERK1/2 signal pathways (p < 0.001). In conclusion, DSP most likely activate ERK1/2 signal pathway‐mediated transcriptional and post‐transcriptional (translational) mechanisms that lead to vascular ETA receptor up‐regulation, which might contribute to vasospasm and the development of smoking‐associated cardiovascular diseases.
MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB
Authors: Li Yanming , Zhang Qian , Du Zhenglin , Lu ZhiChao , Liu Shuge , Zhang Lu , Ding Nan , Bao Binghao , Yang Yadong , Xiong Qian , Wang Hai , Zhang Zhaojun , Qu Hongzhu , Jia Haibo , Fang Xiangdong 
Published: October 2016

SummaryPrevious studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid‐inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF‐1 cells confirmed its inhibitory role in erythroid differentiation. Further in vivo study indicated that overexpression of mir200a inhibited primitive erythropoiesis of zebrafish. Transcriptome analyses after MIR200A overexpression in TF‐1 cells indicated a significant role in regulating erythroid function and revealed potential regulation networks. Additionally, bioinformatics and experimental analyses confirmed that PDCD4 (programmed cell death 4) and THRB (thyroid hormone receptor, beta) are both targets of MIR200A‐3p. Gain‐ and loss‐of‐function studies of PDCD4 and THRB revealed that the two targets were capable of promoting erythroid gene expression. Overall, our results revealed that microRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.
Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation
Authors: Loeys Tom , Talloen Wouter , Goubert Liesbet , Moerkerke Beatrijs , Vansteelandt Stijn 
Published: October 2016

It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others’ pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break‐up.
Trastuzumab cardiotoxicity: from clinical trials to experimental studies
Authors: Nemeth Balazs T , Varga Zoltan V , Wu Wen Jin , Pacher Pal 
Published: October 2016

Epidermal growth factor receptor‐2 (HER‐2) is overexpressed in 20 to 25% of human breast cancers, which is associated with aggressive tumour growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER‐2, the first highly selective form of therapy targeting HER‐2 overexpressing tumours. Although initial trials indicated high efficacy and a favourable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in earlier trials utilizing trastuzumab. There has been ongoing debate on the cardiac safety of trastuzumab ever since, initiating numerous clinical and preclinical investigations to better understand the background of trastuzumab cardiotoxicity and evaluate its effects on patient morbidity. Here, we have given a comprehensive overview of our current knowledge on the cardiotoxicity of trastuzumab, primarily focusing on data from clinical trials and highlighting the main molecular mechanisms proposed.Linked ArticlesThis article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc
Macroecology of parental care in arthropods: higher mortality risk leads to higher benefits of offspring protection in tropical climates
Authors: Santos Eduardo S. A. , Bueno Pedro P. , Gilbert James D. J. , Machado Glauco 
Published: October 2016

ABSTRACTThe intensity of biotic interactions varies around the world, in such a way that mortality risk imposed by natural enemies is usually higher in the tropics. A major role of offspring attendance is protection against natural enemies, so the benefits of this behaviour should be higher in tropical regions. We tested this macroecological prediction with a meta‐regression of field experiments in which the mortality of guarded and unguarded broods was compared in arthropods. Mortality of unguarded broods was higher, and parental care was more beneficial, in warmer, less seasonal environments. Moreover, in these same environments, additional lines of defence further reduced offspring mortality, implying that offspring attendance alone is not enough to deter natural enemies in tropical regions. These results help to explain the high frequency of parental care among tropical species and how biotic interactions influence the occurrence of parental care over large geographic scales. Finally, our findings reveal that additional lines of defences – an oftentimes neglected component of parental care – have an important effect on the covariation between the benefits of parental care and the climate‐mediated mortality risk imposed by natural enemies.
Comparison of tumor‐infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients
Authors: Ogiya Rin , Niikura Naoki , Kumaki Nobue , Bianchini Giampaolo , Kitano Shigehisa , Iwamoto Takayuki , Hayashi Naoki , Yokoyama Kozue , Oshitanai Risa , Terao Mayako , Morioka Toru , Tsuda Banri , Okamura Takuho , Saito Yuki , Suzuki Yasuhiro , Tokuda Yutaka 
Published: October 2016

The presence of tumor‐infiltrating lymphocytes (TILs) is associated with favorable long‐term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor‐2 (HER2+, n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin–eosin‐stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD‐L1), PD‐L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t‐test, P = 0.004) and that of CD8+ and CD4+ T cells significantly decreased from primary to metastatic tumors (paired t‐test, P = 0.008 and P = 0.026, respectively). The PD‐L1, PD‐L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2+ and TN breast cancers have a lower percentage of TILs and CD8+ and CD4+ T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.
Metacognition in Early Childhood: Fertile Ground to Understand Memory Development?
Authors: Geurten Marie , Willems Sylvie 
Published: October 2016

AbstractMetacognition is a critical factor that appears to be involved in improving episodic memory during childhood. However, as metacognitive abilities emerge relatively late in development, they have not been expected to influence children's memory performance before age 7. Nevertheless, in recent studies, as early as age 3, children rely on basic metacognitive abilities to evaluate their memory and use the result of this evaluation to regulate their memory performance. In this article, we consider evidence for the early development of metacognitive skills. We then review studies indicating that children can use inference rules based on the results of their introspection (monitoring) to regulate their memory decisions, demonstrating the early use of several metacognitive heuristics. Finally, we discuss preliminary findings indicating that changes in how children use metacognitive heuristics can account for changes in episodic memory throughout childhood.
Survey of glaucoma surgical preferences and post‐operative care in the United Kingdom
Authors: Rodriguez‐Una Ignacio , Azuara‐Blanco Augusto , King Anthony J 
Published: October 2016

AbstractBackgroundTo evaluate the spectrum of glaucoma surgery and the post‐operative follow‐up regimes undertaken among glaucoma specialists in the United Kingdom.DesignNational survey.ParticipantsSeventy‐five glaucoma specialists (consultants and fellows).MethodsAn eight‐question survey was emailed to all glaucoma subspecialists members of the United Kingdom and Eire Glaucoma Society.Main Outcome MeasuresSurgery undertaken, post‐operative management, awareness of intervention tariff and handling of the follow‐up burden generated through surgery.ResultsAlmost all the participants (74/75: 99%) routinely performed trabeculectomy, 54 responders (72%) undertook tube surgery and Minimally Invasive Glaucoma Surgery (MIGS) was more frequently undertaken (33.0%) than non‐penetrating surgery (23%).In general, for patients with advanced glaucoma requiring a low target intraocular pressure (IOP), the most frequent primary intervention was trabeculectomy (99%), followed by tubes (64%). Similarly, in patients with less advanced glaucoma requiring moderate target IOP, participants preferred trabeculectomy (99%), followed by MIGS (60%). By the first 6 months after the procedure, trabeculectomy and Baerveldt tube implant required a larger number of postoperative visits (9 and 7, respectively), than iStent® and non‐penetrating deep sclerectomy (3 and 5, respectively).The majority of participants were not aware of the costs of their interventions.ConclusionsA wide variety of glaucoma surgery techniques are undertaken. Post‐operative follow‐up regimes are variable between techniques and for surgeons using the same technique. Trabeculectomy requires more follow‐up than any other intervention. For patients requiring low IOP, trabeculectomy is the operation of choice for most surgeons.
Supporting Conservation: The Roles of Flagship Species and Identifiable Victims
Authors: Thomas‐Walters Laura , J Raihani Nichola 
Published: October 2016

AbstractPsychological insights into human behavior can have enormous applied value for promoting charitable giving. Nevertheless, the application of these insights to conservation appeals featuring nonhuman animals has scarcely been explored. Although people often donate more when presented with single “identifiable” victims, whether this effect also extends to nonhumans is not known. Similarly, although many conservation appeals feature flagship species, it is unclear whether flagship species generate increased donations. We experimentally investigated how (1) identifiable versus statistical beneficiaries and (2) flagship versus nonflagship species affected donations to a conservation charity. Unexpectedly, subjects did not donate more when presented with single identifiable beneficiaries rather than groups of beneficiaries. Flagship species, on the other hand, increased donation amounts relative to appeals featuring nonflagship species. We discuss how these findings can inform and improve the effectiveness of conservation fundraising appeals.
Zinc sulfate improved the unbalanced T cell profiles in Der p‐allergic asthma: An ex vivo study
Authors: Tsai Yu Lin , Ko Wang‐Sheng , Hsiao Jung‐Lung , Pan Hsin‐Hung , Chiou Ya‐Ling 
Published: October 2016

AbstractIntroductionIn the pathogenesis of asthma, an imbalance between helper T (Th) 1/Th2 and Th17/Treg cells is believed to play a key role in asthmatic inflammatory responses. Some studies indicated that zinc deficiency increases inflammatory factor production and worsens asthma. However, the effects of zinc on T cell profiles to reduce inflammatory response remain unclear.ObjectivesWe investigated the beneficial effects of zinc on isolated cell populations and cytokine levels from patients with asthma.MethodsThirty‐six individuals Dermatophagoides pteronyssinus (Der p)‐allergic and 31 healthy subjects were enrolled in the study, and peripheral blood mononuclear cells (PBMCs) were collected. Harvested PBMCs were stimulated with recombinant Der p antigen in the presence or absence of zinc sulfate (25 μM or 50 μM) for 48 h. Cell surface markers and intracellular cytokine levels were examined by flow cytometry. The pro‐inflammatory factors in plasma and culture supernatants were measured by commercial enzyme‐linked immunosorbent assay.ResultsZinc sulfate dramatically reduced the proportions of Th2 and Th17 cells, but increased that of Th1 and Treg cells. Zinc sulfate also markedly reduced the levels of interleukin (IL)‐4 and IL‐17, but increased the levels of IFN‐γ.ConclusionsZinc ameliorates the imbalance in T cell profiles and could be a potential adjuvant therapy for Der p‐induced allergic hypersensitivity.