bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of age-specific hospital catchment populations to investigate geographical variation in inpatient admissions for children and young people in England: retrospective, cross-sectional study
Authors: Arora Sandeepa , Cheung C Ronny , Sherlaw-Johnson Christopher , Hargreaves Dougal S 
Published: July 2018

ObjectivesTo develop a method for calculating age-specific hospital catchment populations (HCPs) for children and young people (CYP) in England. To show how these methods allow geographical variation in hospital activity to be investigated and addressed more effectively.DesignRetrospective, secondary analysis of existing national datasets.SettingInpatient care of CYP (0-18 years) in England.ParticipantsHospital Episode Statistics (HES) data were accessed for all inpatient admissions (elective and emergency) for CYP from birth to 18 years, 364 days, for 2011/2012–2014/2015. In 2014/2015, 857 112 admissions were analysed, from an eligible population of approximately 11.9 million CYP.Outcome measuresFor each hospital Trust, the catchment population of CYP was calculated; Trust-level admission rates per thousand per year were then calculated for admissions due to (1) any diagnostic code, (2) primary diagnosis of epilepsy and (3) epilepsy listed as primary diagnosis or comorbidity.ResultsEstimated 2014/2015 HCPs for CYP ranged from 268 558 for Barts Health NHS Trust to around 30 000 for the smallest acute general paediatric services and below 10 000 for many Trusts providing specialist services. As expected, the composition of HCPs was fairly consistent for age breakdown but levels of deprivation varied widely. After standardising for population characteristics, admission rates with a primary diagnosis of epilepsy ranged from 14.3 to 157.7 per 100 000 per year (11.0-fold variation) for Trusts providing acute general paediatric services. All-cause admission rates showed less variation, ranging from 4033 to 11 681 per 100 000 per year (2.9-fold variation).ConclusionsUse of age-specific catchment populations allows variation in hospital activity to be linked to specific teams and care pathways. This provides an evidence base for initiatives to tackle unwarranted variation in healthcare activity and health outcomes.
Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis
Authors: Li Maolan , Liu Fatao , Zhang Fei , Zhou Weiping , Jiang Xiaoqing , Yang Yuan , Qu Kai , Wang Yueqi , Ma Qiang , Wang Ting , Bai Lu , Wang Zheng , Song Xiaoling , Zhu Yidi , Yuan Ruiyan , Gao Yuan , Liu Yongchen , Jin Yunpeng , Li Huaifeng , Xiang Shanshan , Ye Yuanyuan , Zhang Yijian , Jiang Lin , Hu Yunping , Hao Yajuan , Lu Wei , Chen Shili , Gu Jun , Zhou Jian , Gong Wei , Zhang Yong , Wang Xuefeng , Liu Xiyong , Liu Chang , Liu Houbao , Liu Yun , Liu Yingbin 
Published: July 2018

ObjectivesPatients with gallbladder carcinoma (GBC) lack effective treatment methods largely due to the inadequacy of both molecular characterisation and potential therapeutic targets. We previously uncovered a spectrum of genomic alterations and identified recurrent mutations in the ErbB pathway in GBC. Here, we aimed to study recurrent mutations of genes and pathways in a larger cohort of patients with GBC and investigate the potential mechanisms and clinical significance of these mutations.DesignWe performed whole-exome sequencing (WES) in 157 patients with GBC. Functional experiments were applied in GBC cell lines to explore the oncogenic roles of ERBB2/ERBB3 hotspot mutations, their correlation with PD-L1 expression and the underlying mechanisms. ERBB inhibitors and a PD-L1 blocker were used to evaluate the anticancer activities in co-culture systems in vitro and in vivo.ResultsWES identified ERBB2 and ERBB3 mutations at a frequency of 7%–8% in the expanded cohort, and patients with ERBB2/ERBB3 mutations exhibited poorer prognoses. A set of in vitro and in vivo experiments revealed increased proliferation/migration on ERBB2/ERBB3 mutation. Ectopic expression of ERBB2/ERBB3 mutants upregulated PD-L1 expression in GBC cells, effectively suppressed normal T-cell-mediated cytotoxicity in vitro through activation of the PI3K/Akt signalling pathway and contributed to the growth and progression of GBC in vivo. Treatment with an ERBB2/ERBB3 inhibitor or a PD-L1 monoclonal antibody reversed these immunosuppressive effects, and combined therapy revealed promising therapeutic activities.ConclusionsERBB2/ERBB3 mutations may serve as useful biomarkers in identifying patients who are sensitive to ERBB2/ERBB3 inhibitors and PD-L1 monoclonal antibody treatment.Trial registration numberNCT02442414;Pre-results.
Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016
Authors: Adderley Nicola Jaime , Ryan Ronan , Nirantharakumar Krishnarajah , Marshall Tom 
Published: July 2018

ObjectiveAtrial fibrillation (AF) is the most common cardiac arrhythmia and an important risk factor for stroke. Treatment with anticoagulants substantially reduces risk of stroke. Current prevalence and treatment rates of AF in the UK as well as changes in recent years are not known. The aim of this analysis was to determine trends in age–sex specific prevalence and treatment of AF in the UK from 2000 to 2016.Methods17 sequential cross-sectional analyses were carried out between 2000 and 2016 using a large database of electronic primary care records of patients registered with UK general practitioners. These determined the prevalence of patients diagnosed with AF, the stroke risk of those with AF and the proportion of AF patients currently receiving anticoagulants. Stroke risk was assessed using CHA2DS2-VASc score.ResultsAge–sex standardised AF prevalence increased from 2.14% (95% CI 2.11% to 2.17%) in 2000 to 3.29% (95% CI 3.27% to 3.32%) in 2016. Between 2000 and 2016, the proportion of patients with AF prescribed anticoagulants increased from 35.4% (95% CI 34.7% to 36.1%) to 75.5% (95% CI 75.1% to 75.8%) in those with high stroke risk (p for change over time <0.001) and from 32.8% (95% CI 30.5% to 35.2%) to 47.1% (95% CI 45.4% to 48.7%) in those with moderate stroke risk (p<0.001). In patients with low risk of stroke, the proportion decreased from 19.9% (95% CI 17.8% to 22.2%) to 9.7% (95% CI 8.4% to 11.1%) (p<0.001). Anticoagulant prescribing performance varied between practices; in 2016, the proportion of eligible patients treated was 82.9% (95% CI 82.2% to 83.7%) and 62.0% (95% CI 61.0% to 63.0%) in the highest-performing and lowest-performing practice quintiles, respectively. There was poor agreement in individual practice performance over time from 2006 to 2016: linear-weighted κ=0.10 (95% CI 0.02 to 0.19).ConclusionsFrom 2000 to 2016, the prevalence of recorded AF has increased in all age groups and both sexes. Anticoagulant treatment of eligible patients with AF has more than doubled, with marked improvements since 2011, alongside a reduction in the use of anticoagulants in ineligible patients with AF.
Respiratory symptoms among search and rescue workers who responded to the 2016 Taiwan earthquake
Authors: Wu Chen-Long , Lan Fan-Yun , Chen Bo-Lei , Chang Ray Hsienho , Chang Wei Hung , Pan Shih-Tien , Fang Pin-Hui , Lu Chien-Hsin , Lin Chih-Hao 
Published: July 2018

ObjectivesHigh respiratory hazards among search and rescue workers (SRWs) emerged after the World Trade Center attacks on 11 September 2001. There have been limited studies on respiratory symptoms among earthquake SRWs. We investigated the respiratory symptoms and the use of respiratory protective equipment among the SRWs who responded to the 2016 Taiwan earthquake.MethodsOn 6 February 2016, a 6.4-magnitude earthquake struck southern Taiwan and caused 513 injuries and 117 deaths. During the 9-day field operation, 519 firefighters affiliated with the Tainan City Government Fire Bureau participated in the search and rescue response. A standardised, self-completed questionnaire was used to collect data on demographics, dust exposures, personal protective measures and health outcomes 3 weeks after the earthquake. Descriptive and multivariate analyses adjusting for demographics and exposure variables were performed for new or worsened outcomes.ResultsOf the 519 SRWs, 414 (80%) responded to the questionnaire. Of these SRWs, 153 (37%) reported new or worsened respiratory symptoms, with cough (23%) as the leading symptom, followed by rhinorrhoea or nasal congestion (22%) and chest tightness (6%). More than 90% of the symptoms persisted to the third week after the earthquake. The prevalence of new or worsened respiratory symptoms was significantly higher among SRWs with a higher level of exposure to dust. Prior training in response to respiratory pollutants was only 5%.ConclusionsThere were significant respiratory hazards among earthquake SRWs. The persistent symptoms and low coverage of training warrant further regular examination and occupational health programmes.
NOTCH3 contributes to rhinovirus-induced goblet cell hyperplasia in COPD airway epithelial cells
Authors: Jing Yaxun , Gimenes Joao Antonio , Mishra Rahul , Pham Duc , Comstock Adam T , Yu Daohai , Sajjan Umadevi 
Published: July 2018

RationaleGoblet cell hyperplasia (GCH) is one of the cardinal features of chronic obstructive pulmonary disease (COPD) and contributes to airways obstruction. Rhinovirus (RV), which causes acute exacerbations in patients with COPD, also causes prolonged airways obstruction. Previously, we showed that RV enhances mucin gene expression and increases goblet cell number in a COPD mouse model. This study examines whether RV causes sustained GCH in relevant models of COPD.MethodsMucociliary-differentiated COPD and normal airway epithelial cell cultures and mice with normal or COPD phenotype were infected with RV or sham and examined for GCH by immunofluorescence and/or mucin gene expression. In some experiments, RV-infected COPD cells and mice with COPD phenotype were treated with γ-secretase inhibitor or interleukin-13 neutralising antibody and assessed for GCH. To determine the contribution of NOTCH1/3 in RV-induced GCH, COPD cells transduced with NOTCH1/3 shRNA were used.ResultsRV-infected COPD, but not normal cell cultures, showed sustained GCH and increased mucin genes expression. Microarray analysis indicated increased expression of NOTCH1, NOTCH3 and HEY1 only in RV-infected COPD cells. Blocking NOTCH3, but not NOTCH1, attenuated RV-induced GCH in vitro. Inhibition of NOTCH signalling by γ-secretase inhibitor, but not neutralising antibody to IL-13, abrogated RV-induced GCH and mucin gene expression.ConclusionsRV induces sustained GCH via NOTCH3 particularly in COPD cells or mice with COPD phenotype. This may be one of the mechanisms that may contribute to RV-induced prolonged airways obstruction in COPD.
Regulating the local availability of tobacco retailing in Madrid, Spain: a GIS study to evaluate compliance
Authors: Valiente Roberto , Sureda Xisca , Bilal Usama , Navas-Acien Ana , Pearce Jamie , Franco Manuel , Escobar Francisco 
Published: July 2018

BackgroundIn Spain, tobacco sales are limited to tobacco-exclusive stores and associated vending machines. A minimum of 150 m between stores is required, unless they exceed a legal sales threshold. Minimum distances to schools are recommended but not defined. We evaluated compliance with these regulations in Madrid, Spain.MethodsInformation about tobacco-exclusive stores and their sales volume was obtained in 2014. We used geographic information system to identify stores closer than 150 m between them and examine whether they exceeded the sales threshold. We estimated distances between stores and schools, considering different distance intervals (<150 m, 150–300 m and >300 m) and calculations (crow flies and street network). We assessed the association of area-level demographic and socioeconomic characteristics with the distribution of tobacco stores.Results5.3% (34/638) of tobacco stores were within 150 m of each other. Among those, 76% (26/34) did not meet the regulation sales threshold. These stores were in areas with lower proportion of young population (<15 years) and higher proportion of people with university-level education. 75% (476/638) of stores were situated closer than 300 m to schools. No differences were identified in sociodemographic and economic characteristics by the store distance to schools.ConclusionMost tobacco stores are compliant with the regulations in Spain. However, these regulations are insufficient to reduce tobacco availability. More restrictive regulations are needed to limit the geographic distribution of tobacco retailers, and health criteria should also be considered in the current legislation. The evaluation of the Spanish regulatory model may provide useful insights for other jurisdictions looking to decrease the tobacco retail availability.
Acute perceptions of preferred cigarettes when blinded to brand
Authors: Perkins Kenneth A , Karelitz Joshua L 
Published: July 2018

BackgroundMarketing claims often have promoted specific perceptions that users should expect from acutely smoking that cigarette brand. Yet, little controlled study has determined the degree to which actual perceptions are based on the cigarette’s tobacco constituents in the absence of knowledge about the brand’s identity.Methods194 adult dependent smokers rated their perceptions on ‘liking’, ‘satisfying’, ‘strong’ and perceived amount of ‘nicotine’ after smoking ad lib one of their preferred brands of cigarettes. All did so either when blinded (n=118) or unblinded (n=76) to the brand they were given, with the blinding conditions from separate studies. These between-groups secondary analyses determined differences in perceptions based on blinding to brand, controlling for age and cigarettes/day.ResultsAll perceptions were lower for those smoking own brand under blinded versus unblinded conditions, as hypothesised. Consistent with lowered perceptions for smoking one’s own brand obtained from the 118 blinded to brand, their ‘somewhat’ ratings for a ‘how similar to own brand’ item indicated uncertainty, just mid-way between ‘not at all’ and ‘very much’ on the 0–100 visual analogue scale. (The 76 unblinded were already informed it was their own brand.)ConclusionsAcute perceptions of one’s own cigarette are substantially lower when smokers are simply unaware of brand, relative to those aware it is their preferred brand. Results support the notion that perceptions of smoking own brand are enhanced by marketing efforts to associate brands with expectations of pleasurable subjective effects, beyond the impact due solely to the cigarette’s manufactured product constituents.
Soil fertility increases rapidly during the 6–10 yr following conversion of cropland to grassland in China’s Loess Plateau region
Authors: Zhang Qingyin , Shao Ming’an 
Published: July 2018

Change in land use causes changes in soil properties and soil fertility, with long-term effects on ecosystem and crop productivity. This study determined soil fertility along sequential conversion of cropland to grassland in China’s Loess Plateau. Soil samples were collected in 2015 at two sites in the semiarid region, following the conversion of cropland to grassland. Soil particle-size distribution, bulk density, pH, organic carbon (OC), total nitrogen (TN), total phosphorus (TP), available potassium, and available phosphorus were measured in this study. In addition, we analysed the changes of soil OC, TN, and TP, and evaluated soil fertility after the conversion from cropland to grassland. The establishment of grassland significantly increased soil OC, N, and P content, especially in the 0–10 cm soil layer. The highest change in soil OC, N, and P content occurred 6–10 yr after land conversion. The measured soil variables did not change significantly after 10 yr of land conversion. The overall increase in soil fertility after the land conversion was 13% at one site and 26% at the other site. The results suggested that establishing grassland could enhance soil fertility in the semiarid Loess Plateau region of China, and this enhancement is optimal 6–10 yr after the establishment of grassland.
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conditions of symplectite formation in the eclogites from the Western Gneiss Region (Norway)
Authors: Martin Céline 
Published: July 2018

Abstract

Symplectite, defined as plagioclase + Ca-pyroxene (±amphibole) intergrowths after omphacite, and kelyphite, defined as amphibole + plagioclase coronas around garnet, are common features of retrogressed eclogites. These textures are related to exhumation under (ultra) high pressure towards the surface, but the estimation of the pressure–temperature (
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) of symplectite formation is difficult because of the narrowness of pyroxene and plagioclase lamellas, and the compositional variability of the phases. Retrogressed eclogites from Norwegian localities with different eclogite peak conditions have been chosen to investigate the formation of symplectite and associated kelyphite. Thermobarometry calculations show that symplectite crystallizes as soon as the rocks enter the stability field of plagioclase and continues crystallizing until they have reached amphibolite facies. Symplectite yields a pressure range from 18 to 10 kbar, and a temperature range from 700 to 550°C. Amphibole found in the symplectite assemblage crystallizes later, at lower pressures and temperatures (10–4 kbar, 680–420°C). Kelyphite is always associated with well-developed symplectite, when the former omphacite is totally transformed into symplectite. These features likely testify to the influence of an external fluid during retrogression. Samples with limited symplectite and no kelyphite are likely retrogressed with an internal fluid.
Remission of Spontaneous Canine Tumors after Systemic Cellular Viroimmunotherapy
Authors: Cejalvo Teresa , Perisé-Barrios Ana Judith , del Portillo Isabel , Laborda Eduardo , Rodriguez-Milla Miguel A. , Cubillo Isabel , Vázquez Fernando , Sardón David , Ramirez Manuel , Alemany Ramon , del Castillo Noemí , García-Castro Javier 
Published: July 2018

AbstractDogs with spontaneous tumors treated in veterinary hospitals offer an excellent opportunity for studying immunotherapies, including oncolytic viruses. Oncolytic viruses have advanced into the clinic as an intratumorally administered therapeutic; however, intravenous delivery has been hindered by neutralization in the blood. To circumvent this hurdle, mesenchymal stem cells have been used as a "Trojan horse." Here, we present the treatment of 27 canine patients with cancer with canine mesenchymal stem cells infected with ICOCAV17, a canine oncolytic adenovirus. No significant adverse effects were found. The response rate was 74%, with 14.8% showing complete responses, including total remissions of lung metastasis. We detected virus infection, stromal degeneration, and immune cell infiltration in tumor biopsies after 4 weeks of treatment. The increased presence of antiadenoviral antibodies in the peripheral blood of treated dogs did not appear to prevent the clinical benefit of this therapy. These data indicate that oncolytic viruses loaded in mesenchymal stem cells represent an effective cancer immunotherapy.Significance: The classical clinical limitations of antitumoral viroimmunotherapy can be overcome by use of mesenchymal stem cells.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/4891/F1.large.jpg. Cancer Res; 78(17); 4891–901. ©2018 AACR.
LINC00152 Promotes Invasion through a 3′-Hairpin Structure and Associates with Prognosis in Glioblastoma
Authors: Reon Brian J. , Takao Real Karia Bruno , Kiran Manjari , Dutta Anindya 
Published: July 2018

Abstract
Long noncoding RNAs (lncRNA) are increasingly implicated in oncogenesis. Here, it is determined that LINC00152/CYTOR is upregulated in glioblastoma multiforme (GBM) and aggressive wild-type IDH1/2 grade 2/3 gliomas and upregulation associates with poor patient outcomes. LINC00152 is similarly upregulated in over 10 other cancer types and associates with a poor prognosis in 7 other cancer types. Inhibition of the mostly cytoplasmic LINC00152 decreases, and overexpression increases cellular invasion. LINC00152 knockdown alters the transcription of genes important to epithelial-to-mesenchymal transition (EMT). PARIS and Ribo-seq data, together with secondary structure prediction, identified a protein-bound 121-bp stem-loop structure at the 3′ end of LINC00152 whose overexpression is sufficient to increase invasion of GBM cells. Point mutations in the stem-loop suggest that stem formation in the hairpin is essential for LINC00152 function. LINC00152 has a nearly identical homolog, MIR4435-2HG, which encodes a near identical hairpin, is equally expressed in low-grade glioma (LGG) and GBM, predicts poor patient survival in these tumors, and is also reduced by LINC00152 knockdown. Together, these data reveal that LINC00152 and its homolog MIR4435-2HG associate with aggressive tumors and promote cellular invasion through a mechanism that requires the structural integrity of a hairpin structure.
Implications: Frequent upregulation of the lncRNA, LINC00152, in glioblastoma and other tumor types combined with its prognostic potential and ability to promote invasion suggests LINC00152 as a potential biomarker and therapeutic target. Mol Cancer Res; 16(10); 1470–82. ©2018 AACR.
Sex-Specific Association between Family History of Diabetes and Risk of Colorectal Cancer: Two Prospective Cohort Studies
Authors: Ma Wenjie , Song Mingyang , Kværner Ane Sørlie , Prescott Jennifer , Chan Andrew , Giovannucci Edward , Zhang Xuehong 
Published: July 2018

Abstract
Type 2 diabetes (T2D) is associated with increased risk of colorectal cancer. It remains unclear whether family history of diabetes influences colorectal cancer risk and relevant biomarkers. We followed 101,323 women from the Nurses’ Health Study (1982–2012) and 48,542 men from the Health Professionals Follow-up Study (1988–2012), free of cancer and inflammatory bowel disease at baseline. Participants reported whether any of their first-degree family members ever had diabetes in multiple questionnaires administered biennially. Plasma levels of colorectal cancer–related biomarkers were measured in subsets of participants from previous nested case–control studies. We documented 1,950 colorectal cancer cases in women and 1,173 colorectal cancer cases in men. After adjustment for potential confounders including obesity and diabetes, the hazard ratio (HR) for colorectal cancer among men who had family history of diabetes was 1.19 [95% confidence interval (CI), 1.04–1.36) as compared with those who did not. The corresponding HR was 1.06 among women (95% CI, 0.96–1.17). Interestingly, for individuals younger than 60 years, these associations appeared stronger among men (HR, 1.65; 95% CI, 1.15–2.38) and possibly among women (HR, 1.23; 95% CI, 0.99–1.54). Moreover, family history of diabetes was related to reduced levels of estradiol, sex hormone binding globulin (SHBG), and adiponectin in men, with a greater reduction of SHBG for those younger than 60 years (P for interaction = 0.03). In conclusion, family history of diabetes was associated with increased colorectal cancer risk in men, which may be partly mediated by altered sex hormones and adiponectin. The possible positive association in younger women needs further confirmation. Cancer Prev Res; 11(9); 535–44. ©2018 AACR.