bluuebunny/crossref_metadata_2025_split huggingface dataset:
VLA-2 blockade in vivo by vatelizumab induces CD4+FoxP3+ regulatory T cells
Authors: Breuer Johanna , Schneider-Hohendorf Tilman , Ostkamp Patrick , Herich Sebastian , Rakhade Sanjay , Antonijevic Irina , Klotz Luisa , Wiendl Heinz , Schwab Nicholas 
Published: February 2019

Abstract
Integrin α2β1, also known as very late antigen (VLA)-2, is a collagen-binding molecule expressed constitutively on platelets. Vatelizumab, a monoclonal antibody targeting the α2 subunit (CD49b) of VLA-2, was recently investigated for its safety and efficacy during a Phase 2 clinical study in multiple sclerosis patients, as integrin-mediated collagen binding at the site of inflammation is central to a number of downstream pro-inflammatory events. In the course of this study, we could show that VLA-2 is expressed ex vivo on platelets, platelet–T-cell aggregates, as well as a small population of highly activated memory T cells. Even though the clinical trial did not meet its primary clinical end-point (reduction in the cumulative number of new contrast-enhancing lesions on magnetic resonance imaging (MRI)), we observed enhanced frequencies of regulatory T cells (TREG) following vatelizumab treatment. Elevated TREG frequencies might be explained by the inhibition of p38 mitogen-activated protein kinase (MAPK) signaling, which is critically involved in the polarization of T helper 17 (TH17) cells and is activated by the α2 integrin cytoplasmic domain. Our findings suggest that blockade of VLA-2 might be a way to safely shift the TH17/TREG balance by inducing TREGin vivo.
Effect of PlzD, a YcgR homologue of c-di-GMP-binding protein, on polar flagellar motility in Vibrio alginolyticus
Authors: Kojima Seiji , Yoneda Takuro , Morimoto Wakako , Homma Michio 
Published: February 2019

AbstractYcgR, a cyclic diguanylate (c-di-GMP)-binding protein expressed in Escherichia coli, brakes flagellar rotation by binding to the motor in a c-di-GMP dependent manner and has been implicated in triggering biofilm formation. Vibrio alginolyticus has a single polar flagellum and encodes YcgR homologue, PlzD. When PlzD or PlzD-GFP was highly over-produced in nutrient-poor condition, the polar flagellar motility of V. alginolyticus was reduced. This inhibitory effect is c-di-GMP independent as mutants substituting putative c-di-GMP-binding residues retain the effect. Moderate over-expression of PlzD-GFP allowed its localization at the flagellated cell pole. Truncation of the N-terminal 12 or 35 residues of PlzD abolished the inhibitory effect and polar localization, and no inhibitory effect was observed by deleting plzD or expressing an endogenous level of PlzD-GFP. Subcellular fractionation showed that PlzD, but not its N-terminally truncated variants, was precipitated when over-produced. Moreover, immunoblotting and N-terminal sequencing revealed that endogenous PlzD is synthesized from Met33. These results suggest that an N-terminal extension allows PlzD to localize at the cell pole but causes aggregation and leads to inhibition of motility. In V. alginolyticus, PlzD has a potential property to associate with the polar flagellar motor but this interaction is too weak to inhibit rotation.
Collecting French art in the late 1800s at the Art Gallery of New South Wales
Authors: O’Reilly Chiara 
Published: February 2019

Abstract
From the nineteenth century, Sydney’s Art Gallery of New South Wales has been a marker of cultural ambition in Australia. This paper critically considers five large French paintings purchased at the end of the nineteenth century at significant expense by the gallery. Feted by contemporaries as examples of the French academic style, they formed part of plans to develop a representative collection to further understanding of art in the colony and, over time, they have taken on a rich role in the collective cultural memory. Through close examination of these paintings, their historical reception, criticism, reproduction and traces in the gallery’s archives this article reveals a history of taste, class and the formation of the cultural value of art. Using an object-based approach, it positions these works as evidence of changing cultural ideas within the context of a state collection to offer new insight into their status, the gallery itself, and the multiple roles of public art collections.
Adults are more efficient in creating and transmitting novel signalling systems than children
Authors: Kempe Vera , Gauvrit Nicolas , Gibson Alison , Jamieson Margaret 
Published: February 2019

Abstract
Iterated language learning experiments have shown that meaningful and structured signalling systems emerge when there is pressure for signals to be both learnable and expressive. Yet, such experiments have mainly been conducted with adults using language-like signals. Here we explore whether structured signalling systems can also emerge when signalling domains are unfamiliar and when the learners are children with their well-attested cognitive and pragmatic limitations. In Experiment 1, we compared iterated learning of binary auditory sequences denoting small sets of meanings in chains of adults and 5- to 7-year-old children. Signalling systems became more learnable even though iconicity and structure did not emerge despite applying a homonymy filter designed to keep the systems expressive. When the same types of signals were used in referential communication by adult and child dyads in Experiment 2, only the adults, but not the children, were able to negotiate shared iconic and structured signals. Referential communication using their native language by 4- to 5-year-old children in Experiment 3 showed that only interaction with adults, but not with peers resulted in informative expressions. These findings suggest that emergence and transmission of communication systems are unlikely to be driven by children, and point to the importance of cognitive maturity and pragmatic expertise of learners as well as feedback-based scaffolding of communicative effectiveness by experts during language evolution.
Posaconazole therapy in children with cystic fibrosis and Aspergillus-related lung disease
Authors: Patel Deepa , Popple Sarah , Claydon Alison , Modha Deborah E , Gaillard Erol A 
Published: February 2019

Abstract
There is emerging evidence for the role of posaconazole in the management of Aspergillus-related cystic fibrosis (CF) lung disease. The tolerability and efficacy of posaconazole in paediatric CF is not well established. We report a prospective study over a fifty-three month period evaluating the safety, tolerability, and efficacy of posaconazole in pediatric CF. Fourteen children (seven males, median age 13 years, range 3–17 years) received a total of twenty-three courses of posaconazole (13 oral suspension and 10 tablet formulation). Of these patient episodes, nine received posaconazole for emerging or active allergic bronchopulmonary aspergillosis (ABPA) and two required a combination of posaconazole and systemic corticosteroids for difficult-to-treat ABPA. A subgroup of patients (n = 12) with persistent isolates of Aspergillus fumigatus, in the absence of serological markers of ABPA, received posaconazole monotherapy for pulmonary exacerbations not responding to conventional broad-spectrum antibiotic treatment. Posaconazole levels, full blood count, electrolytes, and liver function were monitored on day 7 of treatment and then monthly. Posaconazole was well tolerated in all but three patients. Therapeutic plasma levels &gt;1 mg/l were achieved in all receiving the tablet formulation in comparison to 60% on the liquid preparation. There was a modest but significant improvement in FEV1 (% predicted) demonstrated for the cohort as a whole (p = 0.015) following posaconazole therapy. Posaconazole is well tolerated in children as young as six years old, improvements in lung function are observed, and therapeutic plasma levels are readily achieved in patients taking the tablet formulation and in adherent patients taking the liquid formulation.
Examining inequality of opportunity in the use of maternal and reproductive health interventions in Sierra Leone
Authors: Tsawe Mluleki , Susuman A Sathiya 
Published: February 2019

Abstract

Background
Poor countries, such as Sierra Leone, often have poor health outcomes, whereby the majority of the population cannot access lifesaving health services. Access to, and use of, maternal and reproductive health services is crucial for human development, especially in developing regions. However, inequality remains a persistent problem for many developing countries. Moreover, we have not found empirical studies, which have examined inequalities in maternal and reproductive health in Sierra Leone.

Method
We used data collected from the Sierra Leone Demographic and Health Surveys (DHS) conducted in 2008 and 2013. Five maternal and reproductive health indicators were selected for this study, including four or more antenatal care visits, skilled antenatal care provider, births delivered in a facility, births assisted by a skilled birth attendant, and any method of contraception. To measure inequalities, we adopted the Human Opportunity Index (HOI). Using this measure, we measured differentials over the two periods, and decomposed it to measure the contribution of the selected circumstance variables to inequality.

Results
Inequalities declined over time, as shown by the decrease in the dissimilarity index. Due to the drop in the dissimilarity index, the HOI increased for all the selected maternal and reproductive health indicators. Moreover, antenatal services were closer to equality compared to the other selected services. Overall, we found that household wealth status, maternal education and place of residence, are the most important factors contributing to the inequality in the use of maternal and reproductive health services.

Conclusions
Even though there are improvements in inequalities over time, there are variations in the way in which inequality within the different indicators has improved. In order to improve the use of maternal and reproductive health services, and to reduce inequalities in these services, the government will have to invest in: (i) increasing the educational levels of women, (ii) improving the standard of living, as well as (iii) bringing maternal and reproductive health services closer to rural populations.
Clinical practices: Epilepsy at the National Hospital for the Paralysed and Epileptic, London, from 1860 to 1870
Authors: Vieyra Alejandra , Barahona Ana 
Published: February 2019

Summary
In the nineteenth century, epilepsy was established as a curable and treatable condition at the National Hospital for the Paralysed and Epileptic, in London, England. Since its inception, the National Hospital (NH) hosted the work of many physicians who tried to characterise and define epilepsy as a nosological entity. During the first decade of this Institution, different medical traditions, clinical practices, staff, physicians (among them, John Hughlings Jackson, Charles-Édouard Brown-Séquard, Jabez Spence Ramskill, and Charles Bland Radcliffe), patients, remedies, devices and publications, began to grant the National Hospital a place in London society as a special medical community. The delimitation of epilepsy at the National Hospital would have an impact on the study and description of the human nervous system at the end of the nineteenth century.
Nutritional Treatment of a Young Infant with Cystic Fibrosis Presenting with Severe Kwashiorkor Dermatosis
Authors: Sandy Natascha Silva , Nogueira Roberto José Negrão 
Published: February 2019

Abstract
Kwashiorkor in infancy is typically associated to an underlying disease. Edema, a striking feature of this type of malnutrition, can be difficult to assess in this age group. The typical dermatosis of Kwashiorkor is not fully explained the deficiency of one isolated vitamin or micronutrient. This article presents an infant with cystic fibrosis, who developed Kwashiorkor in the third month of life with extensive cutaneous manifestations. An early, individualized and aggressive nutritional intervention with optimized supplementationof sulfur amino acids, vitamins and micronutrients was established, with impressively recovery of overall nutrition and skin manifestations in a relatively short period of time.
Big data: the end of the scientific method?
Authors: Succi Sauro , Coveney Peter V. 
Published: February 2019

For it is not the abundance of knowledge, but the interior feeling and taste of things, which is accustomed to satisfy the desire of the soul.
(Saint Ignatius of Loyola).

We argue that the boldest claims of big data (BD) are in need of revision and toning-down, in view of a few basic lessons learned from the science of complex systems. We point out that, once the most extravagant claims of BD are properly discarded, a synergistic merging of BD with big theory offers considerable potential to spawn a new scientific paradigm capable of overcoming some of the major barriers confronted by the modern scientific method originating with Galileo. These obstacles are due to the presence of nonlinearity, non-locality and hyperdimensions which one encounters frequently in multi-scale modelling of complex systems.
This article is part of the theme issue ‘Multiscale modelling, simulation and computing: from the desktop to the exascale’.
Search for early pancreatic cancer blood biomarkers in five European prospective population biobanks using metabolomics
Authors: Fest Jesse , Vijfhuizen Lisanne S. , Goeman Jelle J. , Veth Olga , Joensuu Anni , Perola Markus , Männistö Satu , Ness-Jensen Eivind , Hveem Kristian , Haller Toomas , Tonisson Neeme , Mikkel Kairit , Metspalu Andres , van Duijn Cornelia M. , Ikram Arfan , Stricker Bruno H. , Ruiter Rikje , van Eijck Casper H.J. , van Ommen Gertjan B. , ’t Hoen Peter A.C. 
Published: February 2019

AbstractBackground and aimMost patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer.MethodsThe low incidence rate complicates prospective biomarker studies. Here, we took advantage of the availability of biobanked samples from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian biobank, Rotterdam Study) and identified prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between one month and seventeen years after blood sampling, and compared these with age- and gender-matched controls from the same cohorts. We applied1H-NMR-based metabolomics on the Nightingale platform on these samples and applied logistic regression to assess the predictive value of individual metabolite concentrations, with gender, age, body mass index, smoking status, type 2 diabetes mellitus status, fasting status, and cohort as covariates.ResultsAfter quality assessment, we retained 356 cases and 887 controls. We identified two interesting hits, glutamine (p=0.011) and histidine (p=0.012), and obtained Westfall-Young family-wise error rate adjusted p-values of 0.43 for both. Stratification in quintiles showed a 1.5x elevated risk for the lowest 20% of glutamine and a 2.2x increased risk for the lowest 20% of histidine. Stratification by time to diagnosis (<2 years, 2-5 years, >5 years) suggested glutamine to be involved in an earlier process, tapering out closer to onset, and histidine in a process closer to the actual onset. Lasso-penalized logistic regression showed a slight improvement of the area under the Receiver Operator Curves when including glutamine and histidine in the model. Finally, our data did not support the earlier identified branched-chain amino acids as potential biomarkers for pancreatic cancer in several American cohorts.ConclusionWhile identifying glutamine and histidine as early biomarkers of potential biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically usefulper seas prognostic biomarkers.
Glutathionylation primes soluble GAPDH for late collapse into insoluble aggregates
Authors: Zaffagnini M. , Marchand C.H. , Malferrari M. , Murail S. , Bonacchi S. , Genovese D. , Montalti M. , Venturoli G. , Falini G. , Baaden M. , Lemaire S.D. , Fermani S. , Trost P. 
Published: February 2019

ABSTRACTProtein aggregation is a complex physiological process, primarily determined by stress-related factors revealing the hidden aggregation propensity of proteins that otherwise are fully soluble. Here we report a mechanism by which glycolytic glyceraldehyde-3-phosphate dehydrogenase of Arabidopsis thaliana (AtGAPC1) is primed to form insoluble aggregates by the glutathionylation of its catalytic cysteine (Cys149). Following a lag phase, glutathionylated AtGAPC1 initiates a self-aggregation process resulting in the formation of branched chains of globular particles made of partially misfolded and totally inactive proteins. GSH molecules within AtGAPC1 active sites are suggested to provide the initial destabilizing signal. The following removal of glutathione by the formation of an alternative disulfide bond between Cys149 and Cys153 reinforces the aggregation process. Besides acting as a protective mechanism against overoxidation, S-glutathionylation of AtGAPC1 triggers an unexpected aggregation pathway with completely different and still unexplored physiological implications.
Mapping of long-term impact of conventional and organic soil management on resident and active fractions of rhizosphere communities of barley
Authors: Harkes Paula , Suleiman Afnan K.A. , van den Elsen Sven J.J. , Haan Janjo J. de , Holterman Martijn , Kuramae Eiko E. , Helder Johannes 
Published: February 2019

AbstractSoil biota plays an essential role in ecosystem services such as carbon fixation, nitrogen and phosphorous cycling, and disease suppressiveness. Conventional soil management with large inputs of mineral fertilizers and pesticides have a significant impact on primary decomposer communities (bacteria and fungi), as well as on protists and metazoa, representatives of the next trophic level. Organic soil management is thought to contribute to a more diverse and stable soil food web. However, information to pinpoint this supposed beneficial effect is sparse and fragmented. Keeping in mind that a substantial fraction of the soil biota is dormant, we set out to map both the resident and the active the bacterial, fungal, protozoan and metazoan communities under various soil management regimes in two distinct soil types with barley as main crop. For all four organismal groups, the contrast between resident (rDNA-based) and active (rRNA-based) was the most important explanatory variable explaining 22%, 14%, 21% and 25% of the variance among bacterial, fungal, protozoan, and metazoan communities. Less prominent were the effects of soil management and soil type, however significant as well for all four organismal groups. LEfSe was used to identify indicator taxa for both the contrasts between resident and active communities, and the effects of soil management. Our results suggest that - next to DNA-based community characterisation - mapping of the active microbial community could provide essential insights in the effects of variables such as crop and soil management on the soil living community.
Treatment utilization and medical problems in a community sample of adult women with anorexia nervosa
Authors: Brodrick Brooks , Harper Jessica A. , Van Enkevort Erin , McAdams Carrie J. 
Published: February 2019

ABSTRACTAnorexia nervosa has a prolonged course of illness, making both defining recovery and determining optimal outpatient treatments difficult. Here, we report the types of treatments utilized in a naturalistic sample of adult women with anorexia nervosa in Texas. Participants were recruited from earlier studies of women with anorexia nervosa (AN-C, n = 28) and in weight recovery following anorexia nervosa (AN-WR, n = 18). Participants provided information about both their illness and treatments during their most severe period (severe period) as well as during the two to six years following original assessments (follow-up period). New follow-up groups were defined based on current clinical status (continued eating disorder, AN-CC; newly in recovery, AN-CR; sustained weight-recovery, AN-WS), and clinical utilization was compared across groups. There were no differences in groups related to symptoms or treatments utilized during the severe-period. During the follow-up period, intensive outpatient programs were utilized significantly more by the AN-CC group than the other groups, and dietitians were seen significantly less by the AN-WS group. Medical complications related to the ED were significantly more common in the AN-CC group. All groups maintained similar levels of contact with outpatient psychiatrists, therapists, and primary care physicians.
Trends of Hospitalization in Acute Pancreatitis in Patients in the United States from 2001-2014
Authors: Casey Kevin , Argo Roberto , Bianco Albert 
Published: February 2019

ABSTRACTBackground & PurposeThe prevalence of acute pancreatitis(AP) has increased over time and is one of the most important gastrointestinal causes of frequent admissions to hospital in the United States. The cost burden of AP has been steadily increasing. The primary objective of our study was to analyze patient demographics, cost burden, mortality and length of stay associated with AP hospital admissions.MethodsNationwide inpatient sample (NIS) database was used to identify AP admissions in all patients from ≥18 years of age from 2001 to 2014 using ICD-9-CM code 577.0 as the principal discharge diagnosisResultsThe number of hospitalizations increased from 215,238 in 2001 to 279,145 in 2014. Inhospital mortality decreased from 1.74% in 2001 to 0.66% in 2014. Mean length of hospital stay has decreased from 6.1 days to 4.6 days during the same period, but the mean hospital charges increased from $19,303 in 2001 to $35,728 in 2014. The proportion of males to females with acute pancreatitis is slowly trending up from 2001 to 2014.ConclusionThe number of hospitalizations due to acute pancreatitis has been steadily increasing, and further research needs to be done on finding out the reasons for increased causes of hospitalization and ways to decrease the cost burden on patients and hospitals.