bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inequalities in the dental health needs and access to dental services among looked after children in Scotland: a population data linkage study
Authors: McMahon Alex D , Elliott Lawrie , Macpherson Lorna MD , Sharpe Katharine H , Connelly Graham , Milligan Ian , Wilson Philip , Clark David , King Albert , Wood Rachael , Conway David I 
Published: August 2017

BackgroundThere is limited evidence on the health needs and service access among children and young people who are looked after by the state. The aim of this study was to compare dental treatment needs and access to dental services (as an exemplar of wider health and well-being concerns) among children and young people who are looked after with the general child population.MethodsPopulation data linkage study utilising national datasets of social work referrals for ‘looked after’ placements, the Scottish census of children in local authority schools, and national health service’s dental health and service datasets.Results633 204 children in publicly funded schools in Scotland during the academic year 2011/2012, of whom 10 927 (1.7%) were known to be looked after during that or a previous year (from 2007–2008). The children in the looked after children (LAC) group were more likely to have urgent dental treatment need at 5 years of age: 23%vs10% (n=209/16533), adjusted (for age, sex and area socioeconomic deprivation) OR 2.65 (95% CI 2.30 to 3.05); were less likely to attend a dentist regularly: 51%vs63% (n=5519/388934), 0.55 (0.53 to 0.58) and more likely to have teeth extracted under general anaesthesia: 9%vs5% (n=967/30253), 1.91 (1.78 to 2.04).ConclusionsLAC are more likely to have dental treatment needs and less likely to access dental services even when accounting for sociodemographic factors. Greater efforts are required to integrate child social and healthcare for LAC and to develop preventive care pathways on entering and throughout their time in the care system.
Keratopigmentation with micronised mineral pigments: complications and outcomes in a series of 234 eyes
Authors: Alio Jorge L , Al-Shymali Olena , Amesty Maria A , Rodriguez Alejandra E 
Published: August 2017

AimTo report the complications observed in a consecutive large series of cases treated with keratopigmentation (KTP).MethodsKTP was performed in 234 eyes of 204 patients for therapeutic and cosmetic reasons. From them, 50 eyes of 29 patients suffered complications. Different KTP techniques and three generations of pigments (GP) were used. The follow-up period ranged from 4 months to 12 years. Light sensitivity (LS), visual field (VF) limitations and MRI alterations were considered functional complications. Organic complications were described as change in colour, colour fading and neovascularisation.ResultsThe percentage of complications was 12.82%. Most patients complained of LS (49%), then colour fading and change in colour (19%). Neovascularisation, VF limitations and MRI complications constituted 7%, 4% and 2%, respectively. Organic complications were observed with the previous GP but resolved with the latest third GP with CE mark certification (Conformité Européene). Although LS remained with the corneal-specific pigments, it gradually disappeared in most of the patients (81.81%) 6 months postoperatively.ConclusionTo the best of our knowledge this is the first time a study systematically and comprehensively approaches and reports KTP complications. KTP with third GP provides better results and fewer complications than previous ones. It is a modern, minimally invasive technique that helps solve several functional ocular problems and improves cosmetic appearance of the patients. Dermatological pigments should not be used as they lead to complications; instead pigments specifically tested for the eye in terms of toxicity and teratogenicity should be used.
Antenatal corticosteroids for women at risk of imminent preterm birth in low-resource countries: the case for equipoise and the need for efficacy trials
Authors: Vogel Joshua P , Oladapo Olufemi T , Pileggi-Castro Cynthia , Adejuyigbe Ebunoluwa A , Althabe Fernando , Ariff Shabina , Ayede Adejumoke Idowu , Baqui Abdullah H , Costello Anthony , Chikamata Davy M , Crowther Caroline , Fawole Bukola , Gibbons Luz , Jobe Alan H , Kapasa Monica Lulu , Kinuthia John , Kriplani Alka , Kuti Oluwafemi , Neilson James , Patterson Janna , Piaggio Gilda , Qureshi Rahat , Qureshi Zahida , Sankar Mari Jeeva , Stringer Jeffrey S A , Temmerman Marleen , Yunis Khalid , Bahl Rajiv , Metin Gülmezoglu A 
Published: August 2017

The scientific basis for antenatal corticosteroids (ACS) for women at risk of preterm birth has rapidly changed in recent years. Two landmark trials—the Antenatal Corticosteroid Trial and the Antenatal Late Preterm Steroids Trial—have challenged the long-held assumptions on the comparative health benefits and harms regarding the use of ACS for preterm birth across all levels of care and contexts, including resource-limited settings. Researchers, clinicians, programme managers, policymakers and donors working in low-income and middle-income countries now face challenging questions of whether, where and how ACS can be used to optimise outcomes for both women and preterm newborns.In this article, we briefly present an appraisal of the current evidence around ACS, how these findings informed WHO’s current recommendations on ACS use, and the knowledge gaps that have emerged in the light of new trial evidence. Critical considerations in the generalisability of the available evidence demonstrate that a true state of clinical equipoise exists for this treatment option in low-resource settings. An expert group convened by WHO concluded that there is a clear need for more efficacy trials of ACS in these settings to inform clinical practice.
PREDICT prioritisation study: establishing the research priorities of paediatric emergency medicine physicians in Australia and New Zealand
Authors: Deane Heather Carol , Wilson Catherine L , Babl Franz E , Dalziel Stuart R , Cheek John Alexander , Craig Simon S , Oakley Ed , Borland Meredith , Cheng Nicholas G , Zhang Michael , Cotterell Elizabeth , Schuster Tibor , Krieser David 
Published: August 2017

BackgroundThe Paediatric Research in Emergency Departments International Collaborative (PREDICT) performs multicentre research in Australia and New Zealand. Research priorities are difficult to determine, often relying on individual interests or prior work.ObjectiveTo identify the research priorities of paediatric emergency medicine (PEM) specialists working in Australia and New Zealand.MethodsOnline surveys were administered in a two-stage, modified Delphi study. Eligible participants were PEM specialists (consultants and senior advanced trainees in PEM from 14 PREDICT sites). Participants submitted up to 3 of their most important research questions (survey 1). Responses were collated and refined, then a shortlist of refined questions was returned to participants for prioritisation (survey 2). A further prioritisation exercise was carried out at a PREDICT meeting using the Hanlon Process of Prioritisation. This determined the priorities of active researchers in PEM including an emphasis on the feasibility of a research question.ResultsOne hundred and six of 254 (42%) eligible participants responded to survey 1 and 142/245 (58%) to survey 2. One hundred and sixty-eight (66%) took part in either or both surveys. Two hundred forty-six individual research questions were submitted in survey 1. Survey 2 established a prioritised list of 35 research questions. Priority topics from both the Delphi and Hanlon process included high flow oxygenation in intubation, fluid volume resuscitation in sepsis, imaging in cervical spine injury, intravenous therapy for asthma and vasopressor use in sepsis.ConclusionThis prioritisation process has established a list of research questions, which will inform multicentre PEM research in Australia and New Zealand. It has also emphasised the importance of the translation of new knowledge.
Economic insecurity during the Great Recession and metabolic, inflammatory and liver function biomarkers: analysis of the UK Household Longitudinal Study
Authors: Niedzwiedz Claire L , Katikireddi Srinivasa Vittal , Reeves Aaron , McKee Martin , Stuckler David 
Published: August 2017

BackgroundEconomic insecurity correlates with adverse health outcomes, but the biological pathways involved are not well understood. We examine how changes in economic insecurity relate to metabolic, inflammatory and liver function biomarkers.MethodsBlood analyte data were taken from 6520 individuals (aged 25–59 years) participating in Understanding Society. Economic insecurity was measured using an indicator of subjective financial strain and by asking participants whether they had missed any bill, council tax, rent or mortgage payments in the past year. We investigated longitudinal changes in economic insecurity (remained secure, increase in economic insecurity, decrease in economic insecurity, remained insecure) and the accumulation of economic insecurity. Linear regression models were calculated for nine (logged) biomarker outcomes related to metabolic, inflammatory, liver and kidney function (as falsification tests), adjusting for potential confounders.ResultsCompared with those who remained economically stable, people who experienced consistent economic insecurity (using both measures) had worsened levels of high-density lipoprotein (HDL)-cholesterol, triglycerides, C reactive protein (CRP), fibrinogen and glycated haemoglobin. Increased economic insecurity was associated with adverse levels of HDL-cholesterol (0.955, 95% CI 0.929 to 0.982), triglycerides (1.077, 95% CI 1.018 to 1.139) and CRP (1.114, 95% CI 1.012 to 1.227), using the measure of financial strain. Results for the other measure were generally consistent, apart from the higher levels of gamma-glutamyl transferase observed among those experiencing persistent insecurity (1.200, 95% CI 1.110 to 1.297).ConclusionEconomic insecurity is associated with adverse metabolic and inflammatory biomarkers (particularly HDL-cholesterol, triglycerides and CRP), heightening risk for a range of health conditions.
The neural basis of temporal individuation and its capacity limits in the human brain
Authors: Naughtin Claire K. , Tamber-Rosenau Benjamin J. , Dux Paul E. 
Published: August 2017

Individuation refers to individualsʼ use of spatial and temporal properties to register objects as distinct perceptual events relative to other stimuli. Although behavioral studies have examined both spatial and temporal individuation, neuroimaging investigations have been restricted to the spatial domain and at relatively late stages of information processing. Here, we used univariate and multivoxel pattern analyses of functional MRI data to identify brain regions involved in individuating temporally distinct visual items and the neural consequences that arise when this process reaches its capacity limit (repetition blindness, RB). First, we found that regional patterns of blood-oxygen-level-dependent activity across the cortex discriminated between instances where repeated and nonrepeated stimuli were successfully individuated—conditions that placed differential demands on temporal individuation. These results could not be attributed to repetition suppression or other stimulus-related factors, task difficulty, regional activation differences, other capacity-limited processes, or artifacts in the data or analyses. Contrary to current theoretical models, this finding suggests that temporal individuation is supported by a distributed set of brain regions, rather than a single neural correlate. Second, conditions that reflect the capacity limit of individuation—instances of RB—lead to changes in the spatial patterns within this network, as well as amplitude changes in the left hemisphere premotor cortex, superior medial frontal cortex, anterior cingulate cortex, and bilateral parahippocampal place area. These findings could not be attributed to response conflict/ambiguity and likely reflect the core brain regions and mechanisms that underlie the capacity-limited process that gives rise to RB.NEW & NOTEWORTHY We present novel findings into the neural bases of temporal individuation and repetition blindness (RB)—the perceptual deficit that arises when this process reaches its capacity limit. Specifically, we found that temporal individuation is a widely distributed process in the brain and identified a number of candidate brain regions that appear to underpin RB. These findings enhance our understanding of how these fundamental perceptual processes are reflected in the human brain.
Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587
Authors: Figueroa Javier , Phillips Lynette M. , Shahar Tal , Hossain Anwar , Gumin Joy , Kim Hoon , Bean Andrew J. , Calin George A. , Fueyo Juan , Walters Edgar T. , Kalluri Raghu , Verhaak Roel G. , Lang Frederick F. 
Published: August 2017

AbstractTumor–stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC–derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808–19. ©2017 AACR.
CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy
Authors: Turcotte Martin , Allard David , Mittal Deepak , Bareche Yacine , Buisseret Laurence , José Vinu , Pommey Sandra , Delisle Vincent , Loi Sherene , Joensuu Heikki , Kellokumpu-Lehtinen Pirkko-Liisa , Sotiriou Christos , Smyth Mark J. , Stagg John 
Published: August 2017

Abstract
Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 were associated with improved clinical outcome. In immunocompetent mouse models of HER2/ErbB2–driven breast cancer, CD73 expression by tumor cells and host cells significantly suppressed immune-mediated responses mediated by anti-ErbB2 mAb. Furthermore, anti-CD73 mAb therapy enhanced the activity of anti-ErbB2 mAb to treat engrafted or spontaneous tumors as well as lung metastases. Gene ontology enrichment analysis from gene-expression data revealed a positive association of CD73 expression with extracellular matrix organization, TGFβ genes, epithelial-to-mesenchymal transition (EMT) transcription factors and hypoxia-inducible-factor (HIF)-1 gene signature. Human mammary cells treated with TGFβ or undergoing EMT upregulated CD73 cell-surface expression, confirming roles for these pathways. In conclusion, our findings establish CD73 in mediating resistance to trastuzumab and provide new insights into how CD73 is regulated in breast cancer. Cancer Res; 77(20); 5652–63. ©2017 AACR.
Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases
Authors: Ross Michael H. , Esser Alison K. , Fox Gregory C. , Schmieder Anne H. , Yang Xiaoxia , Hu Grace , Pan Dipanjan , Su Xinming , Xu Yalin , Novack Deborah V. , Walsh Thomas , Colditz Graham A. , Lukaszewicz Gabriel H. , Cordell Elizabeth , Novack Joshua , Fitzpatrick James A. J. , Waning David L. , Mohammad Khalid S. , Guise Theresa A. , Lanza Gregory M. , Weilbaecher Katherine N. 
Published: August 2017

Abstract
Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells, but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n = 42). Mechanistic investigations revealed that TGFβ signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle-based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3-MPs of ∼12.5 nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared with equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3-MP-docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared with free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site. Cancer Res; 77(22); 6299–312. ©2017 AACR.
Shrimp miR-S8 Suppresses the Stemness of Human Melanoma Stem-like Cells by Targeting the Transcription Factor YB-1
Authors: Yang Fan , Wei Jun , Zhang Song , Zhang Xiaobo 
Published: August 2017

Abstract
Cross-species regulation of gene expression by microRNA is a possible untapped opportunity for miRNA-based therapy. In this study, we report a novel approach to ablate melanoma stem-like cells by targeting the transcription factor YB-1, which is significantly and selectively upregulated in these cells in melanoma. Silencing YB-1 expression was sufficient to significantly inhibit the stemness of melanoma stem-like cells. In exploring YB-1 targeting, we discovered that the shrimp microRNA miR-S8 could suppress human YB-1 expression in melanoma stem-like cells. Mechanistic investigations revealed that miR-S8 recognized the 3′UTR of YB-1 mRNA and mediated its degradation. In tumor cell and xenograft experiments, miR-S8 suppressed the tumorigenic capacity of melanoma stem-like cells by targeting human YB-1. Overall, our results illuminated a novel aspect of miRNA-mediated cross-species gene expression and its use in regulating cancer stem-like cells. Cancer Res; 77(20); 5543–53. ©2017 AACR.
Chemogenomic Landscape of RUNX1-mutated AML Reveals Importance of RUNX1 Allele Dosage in Genetics and Glucocorticoid Sensitivity
Authors: Simon Laura , Lavallée Vincent-Philippe , Bordeleau Marie-Eve , Krosl Jana , Baccelli Irène , Boucher Geneviève , Lehnertz Bernhard , Chagraoui Jalila , MacRae Tara , Ruel Réjean , Chantigny Yves , Lemieux Sébastien , Marinier Anne , Hébert Josée , Sauvageau Guy 
Published: August 2017

Abstract
Purpose: RUNX1-mutated (RUNX1mut) acute myeloid leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Toward this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup.
Experimental Design: RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML.
Results: We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the glucocorticoid receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that coassociating mutations as well as GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells.
Conclusions: Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Clin Cancer Res; 23(22); 6969–81. ©2017 AACR.
Follicle‐Stimulating Hormone, Its Association with Cardiometabolic Risk Factors, and 10‐Year Risk of Cardiovascular Disease in Postmenopausal Women
Authors: Wang Ningjian , Shao Hongfang , Chen Yi , Xia Fangzhen , Chi Chen , Li Qin , Han Bing , Teng Yincheng , Lu Yingli 
Published: August 2017

Background

Cardiovascular disease is the leading cause of mortality in postmenopausal women. Follicle‐stimulating hormone (
FSH
) shows negative associations with obesity and diabetes mellitus in postmenopausal women. We aimed to study the associations between
FSH
and 10‐year risk of atherosclerotic cardiovascular disease (
ASCVD
) in postmenopausal women.

Methods and Results

SPECT
‐China (the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors) is a 22‐site, population‐based study conducted during 2014–2015. This study included 2658 postmenopausal women. A newly developed effective tool for 10‐year
ASCVD
risk prediction among Chinese was adopted. Regression analyses were performed to assess the relationship among
FSH
, 10‐year
ASCVD
risk, and multiple cardiometabolic risk factors. With the increase in
FSH
quartiles, the mean 10‐year
ASCVD
risk in postmenopausal women decreased from 4.9% to 3.3%, and most metabolic parameters were significantly ameliorated (all
P
for trend <0.05). In regression analyses, a 1‐
SD
increment in ln‐
FSH
was negatively associated with continuous (B −0.12, 95% confidence interval, −0.16, −0.09,
P
<0.05) and categorical (odds ratio 0.65, 95% confidence interval, 0.49, 0.85,
P
<0.05) 10‐year
ASCVD
risk. These significant associations existed in subgroups with or without medication use, obesity, diabetes mellitus, hypertension, and dyslipidemia. Body mass index and waist circumference (both B −0.35, 95% confidence interval, −0.40, −0.30,
P
<0.05) had the largest associations of all metabolic measures, and blood pressure had the smallest association.

Conclusions

Serum
FSH
levels were negatively associated with 10‐year
ASCVD
risk in postmenopausal women. Among cardiometabolic factors, obesity indices had the largest associations with
FSH
. These results indicated that a low
FSH
might be a risk factor or a biomarker for cardiovascular disease risk in postmenopausal women.