bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the management and costs of headache disorders in Spain during the period 2011–2016: a retrospective multicentre observational study
Authors: Darbà Josep , Marsà Alicia 
Published: February 2020

ObjectivesTo investigate the number and characteristics of the Spanish population affected by headache disorders and the direct medical cost that these patients represent for the healthcare system.DesignA retrospective multicentre observational study.SettingRecords from all patients admitted with headache in primary and secondary care centres in Spain between 2011 and 2016 that were registered in a Spanish claims database were included in the analysis. Direct medical costs were calculated using the standardised average expenses of medical procedures determined by the Spanish Ministry of Health.ResultsData extraction claimed primary care records from 636 722 patients and secondary care records from 30 077 patients. Women represented 63% and 65% of all patients with headache in primary and secondary care respectively, with the exception of cluster headaches, a group with 60% of male patients. No large shifts were observed over time in patients’ profile; contrarily, the number of cases per 10 000 patients attended in primary care increased 2-folds between 2011 and 2016 for migraine and 1.85-folds for other headaches. Migraine was the cause for 28% of primary care consultations and 50% of secondary care admissions, and it was responsible for the largest portion of healthcare costs in 2016, a total amount of € 7 302 718. The estimated annual direct medical cost of headache disorders was € 10 716 086.ConclusionsMigraine was responsible for half of the secondary care admissions linked to headache disorders. The raise detected in the number of cases registered in primary care is likely to impact the direct medical costs associated to these disorders causing an increase in the total burden they represent for the Spanish National Healthcare System.
Study protocol for a multisite randomised controlled trial of a rehabilitation intervention to reduce participation restrictions among female breast cancer survivors
Authors: Stevens Courtney J , Hegel Mark T , Bakitas Marie Anne , Bruce Martha , Azuero Andres , Pisu Maria , Chamberlin Mary , Keene Kimberly , Rocque Gabrielle , Ellis Daphne , Gilbert Tiffany , Morency Jamme L , Newman Robin M , Codini Megan E , Thorp Karen E , dos Anjos Sarah M , Cloyd Danielle Z , Echols Jennifer , Milford Ashley N , Ingram Stacey A , Davis Jasmine , Lyons Kathleen Doyle 
Published: February 2020

IntroductionMany breast cancer survivors report an inability to fully participate in activities of daily living after completing cancer treatment. Reduced activity participation is linked to negative consequences for individuals (eg, depression, reduced quality of life) and society (reduced workforce participation). There is currently a lack of evidence-based interventions that directly foster cancer survivors’ optimal participation in life roles and activities. Pilot study data suggest rehabilitation interventions based on behavioural activation (BA) and problem-solving treatment (PST) can facilitate post-treatment role resumption among breast cancer survivors.Methods and analysisThis protocol describes a multisite randomised controlled trial comparing a 4-month long, nine-session BA and PST-informed rehabilitation intervention (BA/PS) against a time-matched, attention control condition. The overall objective is to assess the efficacy of BA/PS for enhancing breast cancer survivors’ activity participation and quality of life over time. A total of 300 breast cancer survivors reporting participation restrictions after completing curative treatment for stage 1–3 breast cancer within the past year will be recruited across two sites (Dartmouth-Hitchcock Medical Center and University of Alabama at Birmingham). Assessments are collected on enrolment (T1) and 8 (T2), 20 (T3) and 44 (T4) weeks later.Ethics and disseminationStudy procedures are approved by the Committee for the Protection of Human Subjects at Dartmouth College, acting as the single Institutional Review Board of record for both study sites (STUDY 00031380). Results of the study will be presented at national meetings and submitted for publication in peer-reviewed journals.Trial registration numberNCT03915548; Pre-results.
Laboratory-based Intermountain Validated Exacerbation (LIVE) Score stability in patients with chronic obstructive pulmonary disease
Authors: Blagev Denitza P , Collingridge Dave S , Rea Susan , Carey Kyle A , Mularski Richard A , Zeng Siyang , Arjomandi Mehrdad , Press Valerie G 
Published: February 2020

BackgroundThe Laboratory-based Intermountain Validated Exacerbation (LIVE) Score is associated with mortality and chronic obstructive pulmonary disease (COPD) exacerbation risk across multiple health systems. However, whether the LIVE Score and its associated risk is a stable patient characteristic is unknown.MethodsWe validated the LIVE Score in a fourth health system. Then we determined the LIVE Score stability in a retrospective cohort of 98 766 patients with COPD in four health systems where it was previously validated. We assessed whether LIVE Scores changed or remained the same over time. Stability was defined as a majority of surviving patients having the same LIVE Score 4 years later.ResultsThe LIVE Score separated patients into three LIVE Score risk groups of low, medium, and high mortality and LIVE Score stability. Mortality ranged from 6.2% for low-risk LIVE to 45.8% for high-risk LIVE (p<0.001). We found that low-risk LIVE groups were stable and high-risk LIVE groups were unstable. Low-risk LIVE group patients remained low risk, but few high-risk LIVE group patients remained high risk (79.0% high vs 48.1% medium vs 8.8% low, p<0.001 for all pairwise comparisons).ConclusionThe LIVE Score identifies three major clinically actionable cohorts: a stable low-risk LIVE group, an unstable high-risk LIVE group with high mortality rates, and a medium-risk LIVE group. These observations further our understanding of how existing data used to calculate the LIVE Score may target interventions across risk cohorts of patients with COPD in a health system.
Assessment of home hazards for non-fatal childhood injuries in rural Nepal: a community survey
Authors: Bhatta Santosh , Mytton Julie A , Deave Toity 
Published: February 2020

BackgroundUnintentional injuries in and around the home are important causes of preventable death and disability among young children globally. In Nepal, there is a lack of data regarding home injuries and home hazards to guide the development of effective interventions for preventing childhood home injuries. This study aimed to determine the burden of unintentional home injuries in children <5 years in rural Nepal and quantify the injury hazards in their homes.MethodsA survey was conducted in 740 households in rural areas of the Makwanpur district during February and March 2015. The primary carer reported home injuries which occurred in the previous 3 months and data collector observation identified the injury hazards. Injury incidence, mechanism and the proportion of households with different hazards were described. Multivariable logistic regression explored associations between the number and type of home hazards and injuries.ResultsInjuries severe enough to need treatment, or resulting in non-participation in usual activities for at least a day, were reported in 242/1042 (23.2%) children <5 years. The mean number of injury hazards per household was 14.98 (SD=4.48), range of 3–31. Regression analysis found an estimated increase of 31% in the odds of injury occurrence associated with each additional injury hazard found in the home (adjusted OR 1.31; 95% CI 1.20 to 1.42).ConclusionsA high proportion of young children in rural Nepal sustained injuries severe enough to miss a day of usual activities. Increased frequency of hazards was associated with an increased injury risk.
MiR-21, EGFR and PTEN in non-small cell lung cancer: an in situ hybridisation and immunohistochemistry study
Authors: Marin Irina , Ofek Efrat , Bar Jair , Prisant Nadia , Perelman Marina , Avivi Camila , Lavy-Shahaf Gitit , Onn Amir , Katz Ruth , Barshack Iris 
Published: February 2020

AimsTo analyse microRNA (miR)-21 distribution and expression at the cellular level in non-small cell lung cancer (NSCLC). MiR-21 is an oncogenic microRNA overexpressed in NSCLC. In previous studies, overexpression of miR-21 was evaluated from the tumour bulk by quantitative reverse transcription PCR with results expressed on average across the entire cell population.MethodsWe used in situ hybridisation and immunohistochemistry to assess the correlation between miR-21 levels and the expression of markers that may be possible targets (epidermal growth factor reaction) or may be involved in its upregulation (phosphatase and tensin homolog (PTEN), p53). The Pearson’s χ2tests was used to assess correlation with clinicopathological data and with miR-21 expression both in tumour and tumour stroma.ResultsCytoplasmic staining and expression of Mir-21 were detected in the tumours and in associated stromal cells. Expression was highest in the stroma immediately surrounding the tumour cells and decreased as the distance from the tumour increased. No expression of miR-21 was found in normal lung parenchyma and a significant association was found between tumour localised miR-21 and PTEN.ConclusionsPresence of miR-21 in both cell tumour and stromal compartments of NSCLC and the relationship with PTEN confirms miR-21 as a microenvironment signalling molecule, possibly inducing epithelial mesenchymal transition and invasion by targeting PTEN in the stromal compartment possibly through exosomal transport. In situ immunohistochemical studies such as ours may help shed light on the complex interactions between miRNAs and its role in NSCLC biology.
Role of flavours in vaping uptake and cessation among New Zealand smokers and non-smokers: a cross-sectional study
Authors: Gendall Philip , Hoek Janet 
Published: February 2020

BackgroundConcerns about the effects of vaping have prompted calls to restrict e-cigarette flavours. Vaping proponents have criticised these proposals, which they argue may discourage smokers from taking up vaping or trigger relapse to smoking. We explored the role flavours play in vaping uptake and cessation among New Zealand cigarette smokers and vaping-susceptible never smokers (VSNS), and examined current vapers’ preferred flavours.MethodsWe conducted an online survey of 1005 New Zealanders aged 18–70 years that included 324 current vapers (vaped in the last 30 days) and 302 ‘past’ vapers (reported past vaping, but not within the last month). We asked respondents their reasons for vaping and explored current vapers’ preferred e-cigarette flavours; we analysed the data using descriptive statistics and logistic regression.ResultsIrrespective of smoking status, flavour was one of the main reasons respondents gave for vaping (smokers 83%; former smokers 77%; VSNS 80%). Flavour was less important to former vapers; 47% of smokers, 57% of former smokers and 64% of VSNS cited flavour as a reason for originally taking up vaping. Fruit flavours were most popular among all three groups; smokers also favoured tobacco flavour, while former smokers also favoured mint or menthol, and never smokers also favoured confectionery/sweets/lolly flavours.ConclusionsFlavours play a major role in vaping initiation for current smokers, former smokers and vaping-susceptible non-smokers, and remain important to those who continue vaping. Our findings highlight the need for regulation that allows some flavour diversity without the extravagant marketing currently used to promote vaping and e-liquids.
Fat brane, dark matter and localized kinetic terms in six dimensions
Authors: Landim Ricardo G. 
Published: February 2020

AbstractExtra dimensions (ED) have been used as attempts to explain several phenomena in particle physics over the years. In this paper we investigate the role of an abelian gauge field as mediator of the interaction between dark matter (DM) and Standard Model (SM) particles, in a model with two flat and transverse ED compactified on the chiral square. DM is confined in a thin brane, localized at the origin of the chiral square, while the SM is localized in a finite width brane, lying in the opposite corner of the square. A brane-localized kinetic term is present in the DM brane, while in the fat brane it is not allowed. In this model the kinetic mixing is not required because we assume that the SM particles couple to the mediator through their $$B-L$$B-L charges, while DM couples to it via a dark charge. Assuming a complex scalar field as DM candidate it is possible to obtain the observed DM relic abundance and avoid direct detection constraints for some parameter choices.
Current correlation functions from a bosonized theory in $$3/2+1$$ dimensions
Authors: Fosco C. D. , Schaposnik F. A. 
Published: February 2020

AbstractWithin the context of a bosonized theory, we evaluate the current-current correlation functions corresponding to a massive Dirac field in $$2+1$$2+1 dimensions, which is constrained to a spatial half-plane. The boundary conditions are imposed on the dual theory, and have the form of of perfect-conductor conditions. We also consider, for the sake of comparison, the purely fermionic version of the model and its boundary conditions, in the large-mass limit. We apply the result about the dual theory to the evaluation of induced vacuum currents in the presence of an external field, in a spatial half-plane.
Microfluidic sensor applications by using chiral metamaterial
Authors: Dalgac Sekip , Bakır Mehmet , Karadag Faruk , Karaaslan Muharrem , Akgol Oguzhan , Unal Emin , Sabah Cumali 
Published: February 2020

Chiral metamaterial-based sensor is designed for sensing the change in substance ratio of chemical substances when combined with distilled water. These samples have been prepared with 10%, 50% and 90% volume fraction of methanol, ethanol, acetone, ammonia and isopropyl alcohol. The complex permittivity of the prepared samples has been measured by Agilent 85070E dielectric probe kit and compared with the simulations. In the proposed design, linear shifts with the frequency bands of more than 100 MHz are observed in different measurements. For different material sensing, pure samples have been used and their reflection coefficient measurement results have been presented. Unique side of this study is that the structure provides very clear and sensitive results and presents a new approach to the microfluidic sensor applications by using the sample holder.
Alteration of cardiolipin biosynthesis and remodeling in single right ventricle congenital heart disease
Authors: Garcia Anastacia M. , McPhaul Jessica C. , Sparagna Genevieve C. , Jeffrey Danielle A. , Jonscher Raleigh , Patel Sonali S. , Sucharov Carmen C. , Stauffer Brian L. , Miyamoto Shelley D. , Chatfield Kathryn C. 
Published: February 2020

Despite advances in both medical and surgical therapies, individuals with single ventricle heart disease (SV) remain at high risk for the development of heart failure (HF). However, the molecular mechanisms underlying remodeling and eventual HF in patients with SV are poorly characterized. Cardiolipin (CL), an inner mitochondrial membrane phospholipid, is critical for proper mitochondrial function, and abnormalities in CL content and composition are known in various cardiovascular disease etiologies. The purpose of this study was to investigate myocardial CL content and composition in failing and nonfailing single right ventricle (RV) samples compared with normal control RV samples, to assess mRNA expression of CL biosynthetic and remodeling enzymes, and to quantitate relative mitochondrial copy number. A cross-sectional analysis of RV myocardial tissue from 22 failing SV (SVHF), 9 nonfailing SV (SVNF), and 10 biventricular control samples (BVNF) was performed. Expression of enzymes involved in CL biosynthesis and remodeling were analyzed using RT-qPCR and relative mitochondrial DNA copy number determined by qPCR. Normal phase high-pressure liquid chromatography coupled to electrospray ionization mass spectrometry was used to quantitate total and specific CL species. While mitochondrial copy number was not significantly different between groups, total CL content was significantly lower in SVHF myocardium compared with BVNF controls. Despite having lower total CL content however, the relative percentage of the major tetralinoleoyl CL species is preserved in SVHF samples relative to BVNF controls. Correspondingly, expression of enzymes involved in CL biosynthesis and remodeling were upregulated in SVHF samples when compared with both SVNF samples and BVNF controls. NEW & NOTEWORTHY The mechanisms underlying heart failure in the single ventricle (SV) congenital heart disease population are largely unknown. In this study we identify alterations in cardiac cardiolipin metabolism, composition, and content in children with SV heart disease. These findings suggest that cardiolipin could be a novel therapeutic target in this unique population of patients.
Routine-Dose and High-Dose Icotinib in Patients with Advanced Non–Small Cell Lung Cancer Harboring EGFR Exon 21-L858R Mutation: the Randomized, Phase II, INCREASE Trial
Authors: Li Xi , Zhang Li , Jiang Da , Wang Yan , Zang Aimin , Ding Cuimin , Zhao Min , Su Wuyun , Zhang Yan , Zhong Diansheng , Wu Jin , Zhang Cuiying , An Guangyu , Hu Xingsheng , Cheng Gang , Wang Huaqing , Li Yongqun , He Xiaohui , Liu Junli , Liang Li , Ding Lieming , Mao Li , Zhang Shucai 
Published: February 2020

Abstract

Purpose:
Our primary purpose is to explore safety and efficacy of high-dose icotinib in comparison with routine-dose icotinib in patients with non–small cell lung cancer (NSCLC) harboring 21-L858R mutation.

Patients and Methods:
Patients with treatment-naïve, EGFR-mutant (21-L858R or exon 19 deletion at 2:1) NSCLC were enrolled. Patients with 21-L858R mutation were randomized to receive routine-dose icotinib (125 mg, thrice daily; L858R-RD) or high-dose icotinib (250 mg, thrice daily; L858R-HD), whereas patients with exon 19 deletion received only routine-dose icotinib (19-Del-RD) until progression, death, or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS), assessed by an independent review committee.

Results:
From May 2015 to November 2017, 253 patients (86 in L858R-RD; 90 in L858R-HD; and 77 in 19-Del-RD) were enrolled. The mPFS in L858R-HD group was similar to that in 19-Del-RD group (12.9 months and 12.5 months, respectively) and was significantly longer than that in L858R-RD group [12.9 months vs. 9.2 months, hazard ratio (HR): 0.75; 95% confidence interval (CI), 0.53–1.05]. A longer but statistically nonsignificant mPFS was observed between 19-Del-RD and L858R-RD groups (12.5 months vs. 9.2 months, HR: 0.80; 95% CI, 0.57–1.13). A higher objective response rate (ORR) was observed in L858R-HD group compared with L858R-RD group (73% vs. 48%), also between 19-Del-RD and L858R-RD groups (75% vs. 48%). Similar incidences of grade 3/4 toxicities were observed among the three treatment groups.

Conclusions:
High-dose icotinib improved mPFS and ORR in patients with NSCLC harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population.
The Immune Microenvironment and Neoantigen Landscape of Aggressive Salivary Gland Carcinomas Differ by Subtype
Authors: Linxweiler Maximilian , Kuo Fengshen , Katabi Nora , Lee Mark , Nadeem Zaineb , Dalin Martin G. , Makarov Vladimir , Chowell Diego , Dogan Snjezana , Ganly Ian , Hakimi A. Ari , Wong Richard J. , Riaz Nadeem , Ho Alan L. , Chan Timothy A. , Morris Luc G.T. 
Published: February 2020

Abstract

Purpose:
Salivary gland carcinomas (SGC) are rare, aggressive cancers with high rates of recurrence and distant metastasis. These factors, and a lack of active systemic therapies, contribute to poor clinical outcome. Response rates with immune checkpoint blockade have been low, although clinical data remain sparse. To improve the efficacy of therapies, a more comprehensive understanding of relevant molecular alterations and immunologic processes is needed.

Experimental Design:
To characterize the immune microenvironment and neoantigen landscape of SGCs, we performed RNA sequencing (RNA-seq) in 76 tumors representing the three most lethal histologies: adenoid cystic carcinoma (ACC), myoepithelial carcinoma (MECA), and salivary duct carcinoma (SDC). We analyzed transcriptomic profiles, tumor-infiltrating immune cell populations, and measures of T-cell activation/dysfunction. In 37 cases also undergoing exome sequencing, we analyzed somatic mutations and neoantigens.

Results:
SDCs exhibited high levels of immune infiltration, with corresponding higher levels of T-cell dysfunction, and higher mutational load. In contrast, ACCs were characterized by an immune-excluded microenvironment, the presence of M2-polarized macrophages and myeloid-derived suppressor cells, and very low mutational load. MECAs were more heterogeneous, with both immune-low and immune-high phenotypes represented. Across all SGCs, levels of immune infiltration were associated with mutation- and fusion-derived neoantigens, and with aggressive clinical behavior.

Conclusions:
These findings provide new insights into the immune microenvironment and neoantigen landscape of SGCs, showing that mechanisms of immune escape appear to differ by histology. These data nominate potential immunologic vulnerabilities and may help guide the next steps of investigation in precision immunotherapy for these difficult-to-treat cancers.
Risk Factors for Heart Failure
Authors: Lawson Claire A. , Zaccardi Francesco , Squire Iain , Okhai Hajra , Davies Melanie , Huang Weiting , Mamas Mamas , Lam Carolyn S.P. , Khunti Kamlesh , Kadam Umesh T. 
Published: February 2020

Background:
There are multiple risk factors for heart failure, but contemporary temporal trends according to sex, socioeconomic status, and ethnicity are unknown.

Methods:
Using a national UK general practice database linked to hospitalizations (1998–2017), 108 638 incident heart failure patients were identified. Differences in risk factors among patient groups adjusted for sociodemographic factors and age-adjusted temporal trends were investigated using logistic and linear regression.

Results:

Over time, a 5.3 year (95% CI, 5.2–5.5) age difference between men and women remained. Women had higher blood pressure, body mass index, and cholesterol than men (
P
<0.0001). Ischemic heart disease prevalence increased for all to 2006 before reducing in women by 0.5% per annum, reaching 42.7% (95% CI, 41.7–43.6), but not in men, remaining at 57.7% (95% CI, 56.9–58.6; interaction
P
=0.002). Diabetes mellitus prevalence increased more in men than in women (interaction
P
<0.0001). Age between the most deprived (74.6 years [95% CI, 74.1–75.1]) and most affluent (79.9 [95% CI, 79.6–80.2]) diverged (interaction
P
<0.0001), generating a 5-year gap. The most deprived had significantly higher annual increases in comorbidity numbers (+0.14 versus +0.11), body mass index (+0.14 versus +0.11 kg/m
2
), and lower smoking reductions (−1.2% versus −1.7%) than the most affluent. Ethnicity trend differences were insignificant, but South Asians were overall 6 years and the black group 9 years younger than whites. South Asians had more ischemic heart disease (+16.5% [95% CI, 14.3–18.6]), hypertension (+12.5% [95% CI, 10.5–14.3]), and diabetes mellitus (+24.3% [95% CI, 22.0–26.6]), and the black group had more hypertension (+12.3% [95% CI, 9.7–14.8]) and diabetes mellitus (+13.1% [95% CI, 10.1–16.0]) but lower ischemic heart disease (−10.6% [95% CI, −13.6 to −7.6]) than the white group.

Conclusions:
Population groups show distinct risk factor trend differences, indicating the need for contemporary tailored prevention programs.