bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relapse in teenage and young adult patients treated on a paediatric minimal residual disease stratified ALL treatment protocol is associated with a poor outcome: results from UKALL2003
Authors: Sellar Rob S. , Rowntree Clare , Vora Ajay J. , Furness Caroline L. , Goulden Nicholas , Mitchell Chris , Moorman Anthony V. , Hough Rachael 
Published: April 2018

AbstractOutcomes for teenage and young adult (TYA) patients with acute lymphoblastic leukaemia (ALL) who relapse on contemporary risk‐adapted paediatric protocols are largely unknown and there is no consensus on optimal salvage strategies. We assessed the treatment and outcome of TYA patients (aged 16–24 years) recruited to the UKALL2003 trial, who relapsed following attainment of complete morphological remission. Forty‐two of 223 patients (18·8%) relapsed, the majority (n = 26, 62%) on treatment. Thirty‐eight (90%) patients received salvage treatment, with 22 (58%) achieving second remission (CR2) and 21 patients receiving an allogeneic haematopoietic cell transplant (alloHSCT). Post‐relapse outcomes were poor with a 5‐year overall survival (OS) of 23% (95% confidence interval; 11–37%). Outcomes for patients relapsing on active treatment were inferior to those relapsing after completing treatment (5‐year OS 9% vs. 52%, log‐rank P = 0·001). No patient with B cell ALL relapsing on treatment was alive at the end of the study period. TYA patients with ALL who relapse on the UK paediatric protocol, UKALL2003, are largely unsalvageable with conventional approaches aimed at achieving CR2 followed by alloHSCT. Future efforts should be aimed at identifying those patients who are destined to relapse and exploring novel treatment approaches for this high‐risk group and for those who do relapse.
The Role of Design and Training in Artifact Expertise: The Case of the Abacus and Visual Attention
Authors: Srinivasan Mahesh , Wagner Katie , Frank Michael C. , Barner David 
Published: April 2018

AbstractPrevious accounts of how people develop expertise have focused on how deliberate practice transforms the cognitive and perceptual representations and processes that give rise to expertise. However, the likelihood of developing expertise with a particular tool may also depend on the degree to which that tool fits pre‐existing perceptual and cognitive abilities. The present studies explored whether the abacus—a descendent of the first human computing devices—may have evolved to exploit general biases in human visual attention, or whether developing expertise with the abacus requires learning special strategies for allocating visual attention to the abacus. To address this question, we administered a series of visual search tasks to abacus experts and subjects who had little to no abacus experience, in which search targets and distractors were overlaid atop abacus “beads.” Across three studies, we found that both experts and naïve subjects were faster to detect targets in semantically relevant components of the abacus, suggesting that abacus training is not required to exhibit attentional biases toward these components of the abacus. This finding suggests that the attentional biases that scaffold numerical processing of the abacus may emerge from general properties of visual attention that are exploited by the design of the abacus itself.
Association between dental hygiene, gingivitis and overweight or the risk of overweight in primary teeth of 4‐ and 5‐year‐old preschoolers in México
Authors: Patiño‐Marín N , Zavala‐Alonso NV , Martínez‐Castañón GA , Alegría‐Torres JA , Medina‐Solís CE , Laredo‐Naranjo MA , Orellana‐Centeno JE , Lemus‐Rojero O 
Published: April 2018

AbstractObjectiveTo determine the association between dental hygiene, gingivitis and overweight or the risk of overweight according to body mass index (BMI).MethodsA cross‐sectional study was performed with 1527 preschoolers. The children were divided into 4 groups: (i) absence of visible plaque and normal weight; (ii) absence of visible plaque and risk of overweight or overweight; (iii) presence of visible plaque and normal weight; and (iv) presence of visible plaque and risk of overweight or overweight. The clinical parameters evaluated were as follows: body mass index, degree of urban marginalization, dental caries, the simplified oral hygiene index and gingival status. Bivariate analysis and multivariate binary logistic regression models were used to identify associations between variables.ResultsThe highest mean of gingivitis (0.28) was observed in the groups with visible plaque with normal weight and with overweight and risk of overweight. The presence of visible plaque and risk of overweight or overweight were positively associated (P = .0001) with the mean of gingivitis (OR = 8.28, 95% CI = 3.30‐19.8). The absence of visible plaque and risk of overweight or overweight (P = .0001) were also positively associated with the presence of gingivitis (OR = 2.44, 95% CI = 0.68‐8.06). This is after both models were adjusted by gender and degree of marginalization.ConclusionsThe professionals should develop interdisciplinary approaches to (i) propose appropriate interventions to improve oral health in overweight preschoolers; and (ii) propose interventions to decrease the overweight with the possibility of also reducing its association with gingivitis.
Clinical complications in renal biopsy using two different needle gauges: The impact of large hematomas, a random clinical trial study
Authors: Antunes Paulo Ramos Botelho , Prado Fabiano Franco Monteiro , de Souza Fabrício Tinôco Alvim , de Siqueira Elisa Carvalho , de Campos Marcos Álvares , Álvares Maria Carolina Barbosa , Neto Rene Berindoague 
Published: April 2018

ObjectiveTo compare complications of ultrasound‐guided percutaneous renal biopsy using two needle gauges (16‐G and 18‐G).MethodsA total of 238 individuals with renal biopsy indication were included and randomly separated into two groups: ultrasound‐guided percutaneous renal biopsy procedure carried out with a 16‐G or 18‐G needle. The adequacy of biopsy samples and post‐procedure complications were compared between the two groups.ResultsThe procedures carried out with a 16‐G needle collected fragments with a mean of 22.1 ± 10.8 glomeruli, and those carried out with an 18‐G needle had a mean of 17.5 ± 9.4 glomeruli. Patients submitted to renal biopsies with a 16‐G needle had a higher likelihood of having a complication (OR5.1, 95% CI 1.7–15.4, P = 0.001). The overall mean volume of post‐biopsy hematoma in patients with complications was significantly larger than those without complications (44 ± 56.1 mL vs 5.9 ± 6.6 mL; P < 0.001).ConclusionsRenal biopsies carried out by ultrasonography using an 18‐G needle provide adequate histological analysis, showing a lower amount of glomeruli but with similar clinical quality as a 16‐G needle. Furthermore, it is associated with a lower risk of procedure‐related complications.
Compensation modes of border effects in cross‐border regions
Authors: Capello Roberta , Caragliu Andrea , Fratesi Ugo 
Published: April 2018

AbstractBoth international and regional economics discuss borders as barriers to economic growth. They hamper trade flows between areas sharing an international border (a demand effect), as well as causing firms’ inefficiency because of the increase in production costs (supply side). In the theoretical and empirical discussions, no question has been raised on whether regional economies are able to set up compensation mechanisms, by replacing low endowments with high efficiency in the use of existing assets, or by compensating an inefficient use of internal assets with an efficient use of external ones. The reply to this question has normative implications. Empirical evidence on the universe of 1,398 European NUTS3 regions is presented and policy suggestions elaborated.
Increasing incidence of type 2 diabetes in New Zealand children <15 years of age in a regional‐based diabetes service, Auckland, New Zealand
Authors: Sjardin Natalia , Reed Peter , Albert Ben , Mouat Fran , Carter Phillipa J , Hofman Paul , Cutfield Wayne , Gunn Alistair , Jefferies Craig 
Published: April 2018

AimIt is important to understand whether type 2 diabetes mellitus (T2DM) is increasing in childhood for health‐care planning and clinical management. The aim of this study is to examine the incidence of T2DM in New Zealand children, aged <15 years from a paediatric diabetes centre, Auckland, New Zealand.MethodsRetrospective analysis of prospectively collected data from a population‐based referral cohort from 1995 to 2015.ResultsHundred and four children presented with T2DM over the 21‐year period. The female:male ratio was 1.8:1, at mean (standard deviation) age 12.9 (1.9) years, body mass index standard deviation score +2.3 (0.5), blood sugar 15.3 (8.5) mmol/L, HbA1c 76 (28) mmol/mol. At diagnosis, 90% had acanthosis nigricans and 48% were symptomatic. In all, 33% were Maori, 46% Pacific Island, 15% Asian/Middle Eastern and 6% European. There was a progressive secular increase of 5% year on year in incidence. The overall annual incidence of T2DM <15 years of age was 1.5/100 000 (1.2–1.9) (95% confidence interval), with higher rates in Pacific Island (5.9/100 000) and Maori (4.1/100 000).ConclusionsThe incidence of T2DM in children <15 years of age in New Zealand has increased progressively at 5%/year over the last 21 years. The risk was disproportionately associated with girls and children from high‐risk ethnic groups.
Pro‐osteogenic properties of hydrophilic and hydrophobic titanium surfaces: Crosstalk between signalling pathways in in vivo models
Authors: Calciolari E. , Hamlet S. , Ivanovski S. , Donos N. 
Published: April 2018

BackgroundIt is now generally accepted that the response to a particular signal, such as the surgical trauma following implant placement, is not the result of a single linear signalling pathway, but rather reflects pathway integration, which can occur at multiple levels. Although it is well documented that both SLA and SLActive surfaces are able to promote bone formation and osseointegration, it is still unclear which are the key signalling pathways involved and how surface hydrophilicity/hydrophobicity might affect pathway integration.ObjectiveTo combine gene and protein data from in vivo studies applying titanium hydrophobic (Sandblasting, Large‐grit, Acid‐etching, SLA) and hydrophilic (SLActive) surfaces to understand the molecular mechanisms responsible for the pro‐osteogenic properties of these surfaces.MethodsThe Kyoto Encyclopedia of Genes and Genomes (KEGG®) pathway database and the Ingenuity® Pathway Analysis (IPA®) software were applied to the genomic and proteomic data of previous in vivo studies applying SLA and SLActive surfaces, with the specific aim to focus on bone formation‐related signalling pathways. While gene data were derived from a human study on osseointegration, protein data originated from a preclinical study in rabbits. Data were available for the 4, 7 and 14 days of healing periods.ResultsBoth genomic and proteomic data showed that the osteogenesis process takes place mainly at 7 and 14 days of healing on both SLA and SLActive surfaces. Surface hydrophilicity enhances bone formation at multiple levels, by directly promoting an earlier expression of pathways involved in cell proliferation and osteoblast precursor differentiation (eg, mitogen‐activated protein kinase, phosphoinositide‐3 kinase‐AKT, Wnt, Notch, transforming growth factor‐β), but also by positively regulating angiogenesis, bone mineralization and bone remodelling.ConclusionThis study combined, for the first time, different ‘omics’ outputs to get new insights on the molecular mechanisms behind the influence of surface hydrophilicity on osseointegration/bone formation. Specific signalling pathways, such as Wnt, vascular endothelial growth factor and mitogen‐activated protein kinase, were identified as differentially modulated by titanium surface hydrophilicity both at a genomic and proteomic level. These findings may be used in the future to monitor/predict the bone formation/osseointegration process, or as a screening tool towards the manufacture of new pro‐osteogenic implant surfaces. In order to take into account the full complexity and interplay of cell signalling during bone formation, powerful bioinformatics tools integrating different ‘omics’ data and predicting signalling pathways trends should be applied by future studies.
Peptidylarginine deiminase is involved in maintaining the cornified oral mucosa of rats
Authors: Arita S. , Hatta M. , Uchida K. , Kita T. , Okamura K. , Ryu T. , Murakami H. , Sakagami R. , Yamazaki J. 
Published: April 2018

Background and ObjectiveEpithelial cells derived from different regions exhibit marked differences in their differentiation capacity, allowing them to provide a suitable protective barrier. We aimed to clarify the role of peptidylarginine deiminase (PAD) in modifying the key epidermal proteins filaggrin (FLG) and keratin 1 (K1) during stratification of the rat palate and buccal mucosa.Material and MethodsWe performed immunofluorescence, immunoblotting, PAD activity assays and 2‐dimensional electrophoresis, and developed an organotypic culture model.ResultsPAD1 expression was highest in the palate, whereas PAD2, PAD3 and PAD4 expression was highest in the skin, suggesting the tissue‐specific expression of PAD isozymes that leads to differences in calcium dependency. Immunoblotting showed that the FLG monomer, as well as its degradation products and precursor (proFLG), were most abundantly expressed in the skin but had low expression in the palate, whereas only faint proFLG expression was detected in the buccal mucosa. FLG and K1 were colocalized with PAD1 and were likely to be citrullinated in the cornified layers of the skin; this colocalization was not detected on the palatal surface, and dot‐like presence of proFLG that might be citrullinated and that of PAD1 were found in the granules of the palate. Organotypic models derived from the rat palate revealed that PAD inhibition reduced the breakdown of FLG, increased its association with K1 together with epithelial compaction, and decreased permeability in a dye permeability assay. Conversely, PAD stimulation had the opposite effects.ConclusionCitrullination is likely a protein modification that plays an important role in maintaining the structure and function of oral cornified mucosa in a way that is distinctly different from that of the skin.
“Mobile (nomadic) cultures” and the politics of mobility: Insights from Indigenous Australia
Authors: Prout Quicke Sarah , Green Charmaine 
Published: April 2018

The recent “mobility turn” in the social sciences has emphasised the increasing scale and speed of movement in our modern world. It also invites critical analyses of the politics of mobility: how movement is conceptualised and regulated and what these processes reveal about power and marginalisation within societies. However, within this literature to date, there have been relatively few empirical, geographical analyses of mobile (or nomadic) cultures: those peoples whose identities and lived experience are often contested through the interplay of population (im)mobilities and state regulation. Though these mobile cultures – including pastoral nomads, Indigenous hunter‐gatherer peoples and Gypsy/Traveller peoples – are vastly different in many ways, they share a set of common experiences which suggests that an analysis of the politics of mobility for one is likely to have relevance to others. As a call to future comparative efforts, this paper begins by setting out four commonalities across diverse mobile cultures, related to: experiences of oppression; disciplining discourses; forced confinement/sedentarism; and contemporary socio‐economic marginalisation. We then present a set of empirical findings that elaborate the related experiences of one mobile culture in situ. Here, we examine the politics of mobility regulation in the context of Indigenous Australians and state housing policy. The findings reveal how state practices that ignore or attempt to regulate the spatial/population mobilities of mobile cultures have questionable efficacy, and can further entrench the marginal status of mobile cultures. They also show how mobile cultures challenge sedentarist policy parameters that insist on fixity in household tenure and composition. These observed struggles with respect to cultural identity and movement regulation constitute important empirical challenges to the nomadic metaphysics within the mobility turn.
Antimicrobial peptides: an effective approach to prevent bacterial biofilm formation in platelet concentrates
Authors: Alabdullatif Meshari , Atreya Chintamani D. , Ramirez‐Arcos Sandra 
Published: April 2018

BACKGROUNDThe safety of platelet concentrates (PCs) is a major concern in transfusion medicine due to contamination mainly with skin Gram‐positive bacteria. The predominant contaminant, Staphylococcus epidermidis, forms bacterial cell aggregates (biofilms) in PCs posing a safety risk for transfusion patients. Combinations of synthetic antimicrobial peptides (AMPs) have demonstrated bactericidal activity in PCs. Herein, we have evaluated the ability of a mix of AMPs to inhibit biofilm formation and/or eradicate S. epidermidis biofilms.STUDY DESIGN AND METHODSThree synthetic AMPs, the platelet‐derived peptide (PD4) and two arginine‐tryptophan repeats (RW3 and RW4), were used for bactericidal and antibiofilm experiments in glucose‐supplemented trypticase soy broth (TSBg) and PCs spiked with three biofilm‐forming strains of S. epidermidis. Time‐killing assays were performed to evaluate the bactericidal capability of the peptides. Inhibition of biofilm formation was assayed by seeding S. epidermidis into TSBg or PC cultures supplemented with the AMPs. Biofilm eradication assays were performed after AMP treatment of preformed biofilms with and without mechanical dislodging. Biofilms were measured using a crystal violet assay.RESULTSTime‐killing assays demonstrated that all S. epidermidis strains were eliminated after 24 hours of AMP treatment. While inhibition of biofilm formation was observed for all S. epidermidis strains in TSBg and PCs, the AMP treatment was only effective to reduce the bacterial load of mechanically dislodged biofilms.CONCLUSIONThe combination of three synthetic AMPs (PD4‐RW3‐RW4) can be used to inhibit biofilm formation by S. epidermidis to enhance PC safety. However, further investigation is needed to improve their activity against mature S. epidermidis biofilms.
A Complex Mechanism Involving LysR and TetR/AcrR That Regulates Iron Scavenger Biosynthesis in Pseudomonas donghuensis HYS
Authors: Chen Min , Wang Panning , Xie Zhixiong 
Published: April 2018

ABSTRACT

7-Hydroxytropolone (7-HT) is a symmetrical seven-membered heteroatomic ring with a carboxyl group and two hydroxyl groups and was recently reported to be an iron scavenger of
Pseudomonas donghuensis
HYS. Cluster 1 includes 12 genes related to the synthesis of 7-HT; among these genes, those for two regulators, Orf1 and Orf12, were predicted to regulate 7-HT biosynthesis and to be LysR-type transcriptional regulators (LTTRs) and TetR/AcrR family transcriptional regulators, respectively. Data from real-time quantitative PCR and β-galactosidase and classical siderophore assays indicated that the transcription levels of
orf1
and
orf12
, as well as those of crucial genes
orf6
to
orf9
, were repressed under high-iron conditions. The deletion of
orf1
and
orf12
led to an absence of 7-HT and a decrease in
orf6-orf9
expression. Orf1 and Orf12 were essential for the production of 7-HT through
orf6-orf9
. These two regulators are regulated by the Gac/Rsm system; Orf1 facilitates the expression of Orf12, and Orf12 concomitantly stimulates the expression of
orf6-orf9
to synthesize 7-HT. The overexpression of Orf12 decreased 7-HT yields, possibly through decreased
orf6-orf9
expression. This work thus outlines a complex mechanism regulating the biosynthesis of the iron scavenger 7-HT in
P. donghuensis
HYS. The synergy between Orf1 and Orf12 ensures that 7-HT acts as an iron chelator despite being toxic to bacteria and provides new ideas for the novel regulation of dual-functional secondary metabolism and research on 7-HT and its derivates in other bacteria.

IMPORTANCE
A complex regulation mechanism including two regulators, LysR and TetR/AcrR, in the biosynthesis of the novel iron scavenger 7-hydroxytropolone (7-HT) was verified in
Pseudomonas donghuensis
HYS. The coaction of LysR Orf1 and TetR/AcrR Orf12 may balance the toxicity and iron chelation of 7-HT in
P. donghuensis
HYS to overcome iron deficiency, as well as improve the bacterial competitiveness under iron-scarce conditions because of the toxicity of 7-HT toward other bacteria, making the accurate regulation of 7-HT biosynthesis indispensable. This regulation mechanism may be ubiquitous in the
Pseudomonas putida
group but may better explain the group's strong adaptability.
Domains within RbpA Serve Specific Functional Roles That Regulate the Expression of Distinct Mycobacterial Gene Subsets
Authors: Prusa Jerome , Jensen Drake , Santiago-Collazo Gustavo , Pope Steven S. , Garner Ashley L. , Miller Justin J. , Ruiz Manzano Ana , Galburt Eric A. , Stallings Christina L. 
Published: April 2018

ABSTRACT

The RNA polymerase (RNAP) binding protein A (RbpA) contributes to the formation of stable RNAP-promoter open complexes (RP
o
) and is essential for viability in mycobacteria. Four domains have been identified in the RbpA protein, i.e., an N-terminal tail (NTT) that interacts with RNAP β′ and σ subunits, a core domain (CD) that contacts the RNAP β′ subunit, a basic linker (BL) that binds DNA, and a σ-interaction domain (SID) that binds group I and group II σ factors. Limited
in vivo
studies have been performed in mycobacteria, however, and how individual structural domains of RbpA contribute to RbpA function and mycobacterial gene expression remains mostly unknown. We investigated the roles of the RbpA structural domains in mycobacteria using a panel of
rbpA
mutants that target individual RbpA domains. The function of each RbpA domain was required for
Mycobacterium tuberculosis
viability and optimal growth in
Mycobacterium smegmatis
. We determined that the RbpA SID is both necessary and sufficient for RbpA interaction with the RNAP, indicating that the primary functions of the NTT and CD are not solely association with the RNAP. We show that the RbpA BL and SID are required for RP
o
stabilization
in vitro
, while the NTT and CD antagonize this activity. Finally, RNA-sequencing analyses suggest that the NTT and CD broadly activate gene expression, whereas the BL and SID activate or repress gene expression in a gene-dependent manner for a subset of mycobacterial genes. Our findings highlight specific outcomes for the activities of the individual functional domains in RbpA.

IMPORTANCE
Mycobacterium tuberculosis
is the causative agent of tuberculosis and continues to be the most lethal infectious disease worldwide. Improved molecular understanding of the essential proteins involved in
M. tuberculosis
transcription, such as RbpA, could provide targets for much needed future therapeutic agents aimed at combatting this pathogen. In this study, we expand our understanding of RbpA by identifying the RbpA structural domains responsible for the interaction of RbpA with the RNAP and the effects of RbpA on transcription initiation and gene expression. These experiments expand our knowledge of RbpA while also broadening our understanding of bacterial transcription in general.