bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review with meta‐analysis: placebo rates in induction and maintenance trials of Crohn's disease
Authors: Jairath V. , Zou G. , Parker C. E. , MacDonald J. K. , Mosli M. H. , AlAmeel T. , Al Beshir M. , AlMadi M. , Al‐Taweel T. , Atkinson N. S. S. , Biswas S. , Chapman T. P. , Dulai P. S. , Glaire M. A. , Hoekman D. , Kherad O. , Koutsoumpas A. , Minas E. , Restellini S. , Samaan M. A. , Khanna R. , Levesque B. G. , D'Haens G. , Sandborn W. J. , Feagan B. G. 
Published: February 2017

SummaryBackgroundMinimising placebo response is essential for drug development.AimTo conduct a meta‐analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates.MethodsMEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo‐controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random‐effects and mixed‐effects meta‐regression models to evaluate effects of study‐level characteristics on these rates.ResultsIn 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16–21%] and 28% (95% CI 24–32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25–39%) and 26% (95% CI 19–35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics.ConclusionsPlacebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.
Effect of ezetimibe on plasma adipokines: a systematic review and meta‐analysis
Authors: Dolezelova Eva , Stein Evan , Derosa Giuseppe , Maffioli Pamela , Nachtigal Petr , Sahebkar Amirhossein 
Published: February 2017

AimsStatins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add‐on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta‐analysis of controlled trials.MethodsA systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed‐ or random‐effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI).ResultsMeta‐analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI –0.28, 0.96; P = 0.288), leptin (SMD –0.75, 95% CI: –2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD –1.06, 95% CI: –2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: –0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF‐α) (SMD –0.48, 95% CI –0.87, −0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy.ConclusionsThe results suggested that ezetimibe add‐on to statin therapy is associated with an enhanced TNF‐α‐lowering effect compared with statin monotherapy. Owing to the emerging role of TNF‐α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF‐α‐lowering effect.
Significant disparities in allergy prevalence and microbiota between the young people in Finnish and Russian Karelia
Authors: Ruokolainen L. , Paalanen L. , Karkman A. , Laatikainen T. , von Hertzen L. , Vlasoff T. , Markelova O. , Masyuk V. , Auvinen P. , Paulin L. , Alenius H. , Fyhrquist N. , Hanski I. , Mäkelä M. J. , Zilber E. , Jousilahti P. , Vartiainen E. , Haahtela T. 
Published: February 2017

SummaryBackgroundAtopic allergy has been more common among schoolchildren in Finland, as compared to Russian Karelia. These adjacent regions show one of the most contrasting socio‐economical differences in the world.ObjectiveWe explored changes in allergy from school age to young adulthood from 2003 to 2010/2012 in these two areas. The skin and nasal microbiota were also compared.MethodsRandomly selected children from Finnish (n = 98) and Russian Karelia (n = 82) were examined in 2003, when the children were 7–11 years of age, and again in 2010 (Finnish Karelia) and 2012 (Russian Karelia). We analysed self‐reported allergy symptoms and sensitization to common allergens by serum sIgE values. The skin (volar forearm) and nasal mucosa microbiota, collected in 2012 (aged 15–20 years), identified from DNA samples, were compared with multivariate methods.ResultsAsthma, hay fever, atopic eczema, self‐reported rhinitis, as well as atopic sensitization, were threefold to 10‐fold more common in Finland, as compared to Russian Karelia. Hay fever and peanut sensitization were almost non‐existent in Russia. These patterns remained throughout the 10‐year follow‐up. Skin microbiota, as well as bacterial and fungal communities in nasal mucosa, was contrastingly different between the populations, best characterized by the diversity and abundance of genus Acinetobacter; more abundant and diverse in Russia. Overall, diversity was significantly higher among Russian subjects (Pskin < 0.0001, Pnasal‐bacteria < 0.0001 and Pnasal‐fungi < 0.01). Allergic diseases were not associated with microbial diversity in Finnish subjects.Conclusions and Clinical RelevanceDifferences in allergic phenotype, developed in early life, remain between populations. A parallel difference in the composition of skin and nasal microbiota suggests a potential underlying mechanism. Our results also suggest that high abundance and diversity of Acinetobacter might contribute to the low allergy prevalence in Russia. Implications of early‐life exposure to Acinetobacter should be further investigated.
Patient with a novel purine‐rich element binding protein A mutation
Authors: Okamoto Nobuhiko , Nakao Hideto , Niihori Tetsuya , Aoki Yoko 
Published: February 2017

AbstractThere have been several reports on 5q31.3 microdeletion syndrome. The overlapping deleted region includes purine‐rich element binding protein A (PURA), which encodes transcriptional activator protein Pur‐α. Patients withPURAmutations show moderate to severe neurodevelopmental delay and learning disability. Neonatal hypotonia, respiratory insufficiency, feeding difficulties, and seizures are often seen. Dysmorphic features including myopathic faces are helpful as clinical signs of the diagnosis. We report a patient with a novelPURAmutation detected by whole‐exome sequencing. We suggest that PURA abnormality is a recognizable syndrome.
Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross‐sectional study with cluster analysis
Authors: Frejo L. , Martin‐Sanz E. , Teggi R. , Trinidad G. , Soto‐Varela A. , Santos‐Perez S. , Manrique R. , Perez N. , Aran I. , Almeida‐Branco M.S. , Batuecas‐Caletrio A. , Fraile J. , Espinosa‐Sanchez J.M. , Perez‐Guillen V. , Perez‐Garrigues H. , Oliva‐Dominguez M. , Aleman O. , Benitez J. , Perez P. , Lopez‐Escamez J.A. ,   the Meniere's disease Consortium (MeDiC)
Published: February 2017

ObjectivesTo define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD.DesignA cross‐sectional study with a two‐step cluster analysis.SettingsA tertiary referral multicenter study.ParticipantsNine hundred and eighty‐eight adult patients with unilateral MD. Main outcome measures: best predictors to define clinical subgroups with potential different aetiologies.ResultsWe established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni‐ and bilateral MD.ConclusionsCluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.
Quantification of walking‐based physical activity and sedentary time in individuals with Rett syndrome
Authors: Downs Jenny , Leonard Helen , Wong Kingsley , Newton Nikki , Hill Kylie 
Published: February 2017

AimTo quantify, in individuals with Rett syndrome with the capacity to walk, walking‐based activity and sedentary time, and to analyse the influences of age, walking ability, scoliosis, and the severity of epilepsy.MethodSixty‐four participants with a mean age of 17 years and 7 months (standard deviation [SD] 9y) were recruited from the Australian Rett Syndrome Database for this cross‐sectional study. Each participant wore a StepWatch Activity Monitor for at least 4 days. Linear regression models were used to assess relationships between daily step count and the proportion of waking hours spent in sedentary time with the covariates of age group, walking ability, presence of scoliosis, and frequency of seizures.ResultsOn average, 62% (SD 19%) of waking hours were sedentary and 20% (SD 8%) was at cadences lower than or equal to 20 steps in a minute. The median daily steps count was 5093 (interquartile range 2026–8602). Compared with females younger than 13 years of age and accounting for the effects of covariates, adults took fewer steps, and both adolescents and adults had more sedentary time.InterpretationAdolescents and adults led the least active lives and would appear to be in particular need of interventions aiming to optimize slow walking‐based physical activity and reduce sedentary time.
Shared‐use mining infrastructure: Why it matters and how to achieve it
Authors: Collier Paul , Ireland Glen 
Published: February 2017

AbstractThis article considers the cases for and against ‘open access’ regulation of rail and port logistics infrastructure used by ‘bulk’ mining operations, arguing that host governments should proactively impose and then enforce such regulation in almost all cases. The logistics infrastructure needed for this type of mining activity is of critical importance. The costs and potential inefficiencies involved in duplicating such infrastructure confer a significant competitive advantage on its owner in the absence of effective access regulation. In particular, where a first mover develops an ‘integrated’ project incorporating a mine and associated infrastructure, a failure to impose access regulation discourages third‐party investment in mineral exploration and development in the region serviced by the infrastructure, due to the risk of hold‐up by the first mover. An unregulated first mover can also use its infrastructure advantage to capture the state's share of resource rents from the mineral endowment of the region. Open access regulation further benefits host countries by enabling broad‐based economic development through the shared‐use of mining infrastructure with other sectors (e.g., agribusiness). The article highlights contrasting experience with access regulation in Australia: the Pilbara iron ore region has seen protracted disputes involving mining firms and policy‐makers and very few examples of third‐party access, while in the coal region of central Queensland an extensive multi‐user, multi‐purpose railway network operates independently of mining firms. The authors urge governments in sub‐Saharan Africa (in particular) not to underestimate the internal capacity and other challenges associated with developing and enforcing open access regulation of mining infrastructure in a manner that protects their national interests.
Indigenous peoples, the city and inclusive urban development policies in Latin America: Lessons from Bolivia and Ecuador
Authors: Horn Philipp 
Published: February 2017

AbstractThe historical construction of indigeneity as essentially rural policy category represents a key cause for the ongoing exclusion of urban indigenous peoples and blocks progress in delivering Agenda 2030 in Latin American cities. Even in Bolivia and Ecuador, where urban indigeneity is recognized through constitutional reforms, there are obstacles to the delivery of policies shaped to urban indigenous interests. By reviewing experiences from these countries, this article highlights that policy delivery problems are a result of multiple factors, including (1) rural constructions of indigeneity, (2) conflicting development priorities, and (3) difficulties in promoting universal rights while simultaneously guaranteeing indigenous rights. The article concludes with policy recommendations for more inclusive urban development approaches which leave no indigenous person behind.
Integration between the London and New York Stock Exchanges, 1825–1925
Authors: Campbell Gareth , Rogers Meeghan 
Published: February 2017

AbstractIn this article the integration between the London and New York Stock Exchanges is analysed during the era when they were still developing as asset markets. The domestic securities on both exchanges showed little sustained integration, even when controlling for the different characteristics of stocks, which implies that the pricing of securities in the US and UK was still being driven by local factors. These results place a limit on the view that the pre‐First World War period was the first era of globalization in terms of capital markets. However, there was considerable integration between New York and those listings on London that operated internationally. This suggests that the listing of foreign securities may be one of the primary mechanisms driving asset market integration.
Challenging the de‐industrialization thesis: gender and indigenous textile production in Java under Dutch colonial rule, c. 1830–1920
Authors: van Nederveen Meerkerk Elise 
Published: February 2017

AbstractMany dependency theorists as well as economic historians have contended that nineteenth‐century imperial policies and economic globalization de‐industrialized the global ‘periphery’. European metropoles extracted raw materials and tropical commodities from their overseas territories, and in turn indigenous consumers bought their industrial products, textiles in particular. This article investigates three of the assumptions of Ricardian trade theory that are often behind the de‐industrialization narrative. In this article it is argued that, at least for colonial Java's textile industry, these assumptions should be reconsidered. Adverse trade policies imposed by the Dutch and a prolonged terms‐of‐trade boom in favour of primary commodities make colonial Java a unique case for exploring the merits of the de‐industrialization thesis. Here it is demonstrated that Javanese households resourcefully responded to changing market circumstances, in the first place by flexible allocation of female labour. Moreover, indigenous textile producers specialized in certain niches that catered for local demand. Because of these factors, local textile production in Java appears to have been much more resilient than most of the historical literature suggests. These findings not only shed new light on the social and economic history of colonial Indonesia, but also contribute to the recent literature on alternative, labour‐intensive paths of industrialization in the non‐western world.
Interrater agreement in the interpretation of neonatal electroencephalography in hypoxic‐ischemic encephalopathy
Authors: Wusthoff Courtney J. , Sullivan Joseph , Glass Hannah C. , Shellhaas Renée A. , Abend Nicholas S. , Chang Taeun , Tsuchida Tammy N. 
Published: February 2017

SummaryObjectiveResearch using neonatal electroencephalography (EEG) has been limited by a lack of a standardized classification system and interpretation terminology. In 2013, the American Clinical Neurophysiology Society (ACNS) published a guideline for standardized terminology and categorization in the description of continuous EEG in neonates. We sought to assess interrater agreement for this neonatal EEG categorization system as applied by a group of pediatric neurophysiologists.MethodsA total of 60 neonatal EEG studies were collected from three institutions. All EEG segments were from term neonates with hypoxic‐ischemic encephalopathy. Three pediatric neurophysiologists independently reviewed each record using the ACNS standardized scoring system. Unweighted kappa values were calculated for interrater agreement of categorical data across multiple observers.ResultsInterrater agreement was very good for identification of seizures (κ = 0.93, p < 0.001), with perfect agreement in 95% of records (57 of 60). Interrater agreement was moderate for classifying records as normal or having any abnormality (κ = 0.49, p < 0.001), with perfect agreement in 78% of records (47 of 60). Interrater agreement was good in classifying EEG backgrounds on a 5‐category scale (normal, excessively discontinuous, burst suppression, status epilepticus, or electrocerebral inactivity) (κ = 0.70, p < 0.001), with perfect agreement in 72% of records (43 of 60). Other specific background features had lower agreement, including voltage (κ = 0.41, p < 0.001), variability (κ = 0.35, p < 0.001), symmetry (κ = 0.18, p = 0.01), presence of abnormal sharp waves (κ < 0.20, p < 0.05), and presence of brief rhythmic discharges (κ < 0.20, p < 0.05).SignificanceWe found good or very good interrater agreement applying the ACNS system for identification of seizures and classification of EEG background. Other specific EEG features showed limited interrater agreement. Of importance to both clinicians and researchers, our findings support using the ACNS system in identifying seizures and classifying backgrounds of neonatal EEG recordings, but also suggest limited reproducibility for certain other EEG features.
Toll‐like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of SE‐induced epilepsy in mice
Authors: Gross Adi , Benninger Felix , Madar Ravit , Illouz Tomer , Griffioen Kathleen , Steiner Israel , Offen Daniel , Okun Eitan 
Published: February 2017

SummaryObjectiveEpilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll‐like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE).MethodsTo test the involvement of TLR3 in epileptogenesis, we used the pilocarpine model for SE in TLR3‐deficient mice and their respective wild‐type controls. In this model, a single SE event leads to spontaneous recurrent seizures (SRS). Two weeks after SE, mice were implanted with wireless electroencephalography (EEG) transmitters for up to 1 month. The impact of TLR3 deficiency on SE was assessed using separate cohorts of mice regarding EEG activity, seizure progression, hippocampal microglial distribution, and expression of the proinflammatory cytokines tumor necrosis factor (TNF)α and interferon (IFN)β.ResultsOur data indicate that TLR3 deficiency reduced SRS, microglial activation, and the levels of the proinflammatory cytokines TNFα and IFNβ, and increased survival following SE.SignificanceThis study reveals novel insights into the pathophysiology of epilepsy and the contribution of TLR3 to disease progression. Our results identify the TLR3 pathway as a potential future therapeutic target in SE.
Plasticity in gene transcription explains the differential performance of two invasive fish species
Authors: Wellband Kyle W. , Heath Daniel D. 
Published: February 2017

AbstractPhenotypic plasticity buffers organisms from environmental change and is hypothesized to aid the initial establishment of nonindigenous species in novel environments and postestablishment range expansion. The genetic mechanisms that underpin phenotypically plastic traits are generally poorly characterized; however, there is strong evidence that modulation of gene transcription is an important component of these responses. Here, we use RNA sequencing to examine the transcriptional basis of temperature tolerance for round and tubenose goby, two nonindigenous fish species that differ dramatically in the extent of their Great Lakes invasions despite similar invasion dates. We used generalized linear models of read count data to compare gene transcription responses of organisms exposed to increased and decreased water temperature from those at ambient conditions. We identify greater response in the magnitude of transcriptional changes for the more successful round goby compared with the less successful tubenose goby. Round goby transcriptional responses reflect alteration of biological function consistent with adaptive responses to maintain or regain homeostatic function in other species. In contrast, tubenose goby transcription patterns indicate a response to stressful conditions, but the pattern of change in biological functions does not match those expected for a return to homeostatic status. Transcriptional plasticity plays an important role in the acute thermal tolerance for these species; however, the impaired response to stress we demonstrate in the tubenose goby may contribute to their limited invasion success relative to the round goby. Transcriptional profiling allows the simultaneous assessment of the magnitude of transcriptional response as well as the biological functions involved in the response to environmental stress and is thus a valuable approach for evaluating invasion potential.