bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the asylum process on mental health: a longitudinal study of unaccompanied refugee minors in Norway
Authors: Jakobsen Marianne , Meyer DeMott Melinda Ashley , Wentzel-Larsen Tore , Heir Trond 
Published: June 2017

ObjectivesTo examine the mental health of unaccompanied refugee minors prospectively during the asylum-seeking process, with a focus on specific stages in the asylum process, such as age assessment, placement in a supportive or non-supportive facility and final decision on the asylum applications.DesignThis was a2½ year follow-up study of unaccompanied minors (UM) seeking asylum in Norway. Data were collected within three weeks (n=138) and at 4 months (n=101), 15 months (n=84) and 26 months (n=69) after arrival.SettingInitially in an observation and orientation centre for unaccompanied asylum-seeking adolescents, and subsequently wherever the UM were located in other refugee facilities in Norway.ParticipantsMale UM from Afghanistan, Somalia, Algeria and Iran.Main outcome measuresMental health symptoms assessed by Hopkins Symptom Checklist-25 and Harvard Trauma Questionnaire.ResultsAt the group level, the young asylum seekers reported high levels of psychological distress on arrival and symptom levels that stayed relatively unchanged over time. According to age-assessment procedures, 56% of the population were not recognised as minors. Subsequent placement in a low-support facility was associated with higher levels of psychological distress in the follow-up period. Those who were placed in a reception centre for adults had higher levels of psychological distress symptoms both after 15 months and 26 months compared with the remaining participants who were placed in reception centres for youth. Refusal of asylum was highly associated with higher levels of psychological distress.ConclusionMental health trajectory of young asylum seekers appears to be negatively affected by low support and refusal of asylum.
Outpatient percutaneous native renal biopsy: safety profile in a large monocentric cohort
Authors: Roccatello Dario , Sciascia Savino , Rossi Daniela , Naretto Carla , Bazzan Mario , Solfietti Laura , Baldovino Simone , Menegatti Elisa 
Published: June 2017

ObjectivesWe aim to evaluate the safety of performing percutaneous native kidney biopsy (PKB) as an outpatient procedure (implying an observation period of 6 hours) compared with the traditional inpatient policy.Design, setting, participants and measurementsGroup I, in whom PKB was performed in the outpatient department (2012–2016) and followed by 6 hours’ observation period and then by regular outpatient visits and group II, in whom PKB was performed and followed by at least 1 day hospital admission. Group II included retrospectively retrieved patients who underwent PKB in our Institution between January 2000 and November 2012 as an inpatient procedure. All biopsies were performed by a single nephrologist following a structured protocol.Results462 biopsies were reviewed, 210 (45.5%) of patients were women and the mean age was 54.7±17.9 years. One hundred and twenty-nine (27.9%) of these biopsies were performed in outpatients. A total of 36 (7.8%) of patients developed a complication, and of those, 9 (1.9%) suffered for a major complication (arteriovenous fistula (six cases, 1.2%), ischaemic stroke (2; 0.4%), thromboembolic pulmonary embolism (1; 0.2%)) and 27 (5.8%) for minor(macroscopic haematuria (12 cases, 2.6%), haematomas on sonography not requiring intervention (15 cases, 3.2%)). When comparing the complication rate between groups I and II, no statical difference was observed. When analysing together both groups, after multivariate analysis, serum creatinine >3 mg/dL (OR 2.03, 95% CI 1.18 to 6.81) and known severe hypertension (OR 2.01, 95% CI 1.2 to 4.7) were found to be independent risk factors for minor and major complications, respectively. Conversely, we found no association of risk with the number of biopsy passes, gender, age, diagnosis, presence of haematuria before the kidney biopsy nor the degree of proteinuria.ConclusionsOutpatient biopsy could be a valuable, safe and perhaps cost-effective method of obtaining diagnostic renal tissue in the majority of patients.
The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial
Authors: Neubert Antje , Baarslag Manuel Alberto , Dijk Monique van , Rosmalen Joost van , Standing Joseph F , Sheng Yucheng , Rascher Wolfgang , Roberts Deborah , Winslade Jackie , Rawcliffe Louise , Hanning Sara M , Metsvaht Tuuli , Giannuzzi Viviana , Larsson Peter , Pokorná Pavla , Simonetti Alessandra , Tibboel Dick 
Published: June 2017

IntroductionSedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation.Methods and analysisThe CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points.EthicsWritten informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.Trial RegistrationEudraCT: 2014-003582-24; Clinicaltrials.gov:NCT02509273; pre-results.
Heritability of resting heart rate and association with mortality in middle-aged and elderly twins
Authors: Jensen Magnus T , Wod Mette , Galatius Søren , Hjelmborg Jacob B , Jensen Gorm B , Christensen Kaare 
Published: June 2017

ObjectiveResting heart rate (RHR) possibly has a hereditary component and is associated with longevity. We used the classical biometric twin study design to investigate the heritability of RHR in a population of middle-aged and elderly twins and, furthermore, studied the association between RHR and mortality.MethodsIn total, 4282 twins without cardiovascular disease were included from the Danish Twin Registry, hereof 1233 twin pairs and 1816 ‘single twins’ (twins with a non-participating co-twin); mean age 61.7 (SD 11.1) years; 1334 (31.2%) twins died during median 16.3 (IQR 13.8–16.5) years of follow-up assessed through Danish national registers. RHR was assessed by palpating radial pulse.ResultsWithin pair correlations for RHR adjusted for sex and age were 0.23 (95% CI 0.14 to 0.32) and 0.10 (0.03 to 0.17) for RHR in monozygotic (MZ) and dizygotic (DZ) twin pairs, respectively. Overall, heritability estimates were 0.23 (95% CI 0.15 to 0.30); 0.27 (0.15 to 0.38) for males and 0.17 (0.06 to 0.28) for females. In multivariable models adjusting for age, gender, body mass index, diabetes, hypertension, pulmonary function, smoking, physical activity and zygosity, RHR was significantly associated with mortality (eg, RHR >90 vs 61–70 beats per min: all-cause HR 1.56 (95% CI 1.21 to 2.03); cardiovascular 2.19 (1.30 to 3.67). Intrapair twin comparison revealed that the twin with the higher RHR was significantly more likely to die first and the probability increased with increase in intrapair difference in RHR.ConclusionsRHR is a trait with a genetic influence in middle-aged and elderly twins free of cardiovascular disease. RHR is independently associated with longevity even when familial factors are controlled for in a twin design.
Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma
Authors: Kawanishi Aya , Hirabayashi Kenichi , Yamada Misuzu , Takanashi Yumi , Hadano Atsuko , Kawaguchi Yoshiaki , Nakagohri Toshio , Nakamura Naoya , Mine Tetsuya 
Published: June 2017

AimsThe loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsImmunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained.ResultsNecl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p<0.001). Negative Necl-4 expression was significantly associated with a larger tumour size of >30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB–IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, p<0.001).ConclusionsThe results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.
Measuring the distribution of adolescent births among 15–19-year-olds in Chile: an ecological study
Authors: Velarde Marissa , Zegers-Hochschild Fernando 
Published: June 2017

BackgroundAlthough within Latin America Chile has one of the lowest birth rates among adolescents, it has a high rate in comparison to other developed nations.AimTo explore trends in birth rates among adolescents by selected demographics in Chile.MethodsThe national trend in birth rates was examined for women aged 15–19 years between 1992 and 2012. The birth rates for regions and communes were calculated using birth and census data and were analysed to determine its relationship to the regional or communal poverty rate, which were obtained from the Casen Survey. Differences in educational attainment were explored among adolescents with first-order and second-order or higher births using the Chi-square test.ResultsThe birth rate among adolescents has experienced a 25% decline in the past 20 years. Cross-regional variance in birth rates could not be explained by poverty rates. Within the Metropolitan Region, there is a positive correlation between poverty and adolescent birth rates. Among adolescents giving birth, 67% had completed 10–12 years of school at birth, but there is a significant difference in educational attainment between girls with a first-order and those with a higher-order birth.ConclusionsIn Chile, the adolescent birth rate varies greatly among regions and communes. This study found that urban and wealthy areas had lower birth rates than poor and rural ones, and that girls with a first-order birth had completed more years of school than girls with higher-order births.
Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China): results from a prospective double-blind randomised clinical trial
Authors: Zhao Ying , Yang Wanyong , Tan Zefeng , Wang Wenmin , Xiao Weimin , Zeng Jinsheng , Xu Anding 
Published: June 2017

AimThe role of clopidogrel in treating patients with acute ischaemic stroke is unclear. We have conducted the clinical trial in order to evaluate the efficacy and safety of clopidogrel with a loading dose in treating patients with non-cardiogenic acute ischaemic stroke.MethodClopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China) was a prospective, randomised, double-blind and placebo-controlled clinical trial in China. Patients with acute ischaemic stroke of non-cardiogenic origin within 48 hours of onset were enrolled and those received thrombolysis were excluded. Enrolled patients were divided into two treatment groups: loading dose and routine dose. The primary outcome was the incidence of stroke recurrence or progression within 7 days. Primary safety outcome was measured by life-threatening haemorrhage. An intent-to-treat analysis was used for the statistical analysis.ResultsFrom March 2008 to March 2010, a total of 303 patients from 16 centres were recruited into this study; six were excluded because of lack of basic information. Since the enrolment was slow and the study drug expired in March 2010, this clinical trial was stopped earlier than planned. No significant baseline and demographic differences were seen between the two groups. There was no difference in primary outcome between the loading dosage group 16.1% (24/149) and control group 14.9% (22/148), respectively (p=0.782). The mortality and disability rate within 90 days in loading dose group (19.6%) was slightly lower than that in controlled group (23.4%), p=0.444. Loading dose group had two (1.3%) cases of fatal haemorrhage and control group had four (2.7%) within 90 days, p=0.674. No significant difference was detected in other adverse events between the groups.ConclusionIn our study stopped early due to slow enrolment, loading dose of clopidogrel does not reduce the risk of recurrent stroke. Future trials with sufficient number of patients enrolled are needed to re-examine this hypothesis.
Comments on “Casimir effect in the Kerr spacetime with quintessence”
Authors: Toshmatov Bobir , Stuchlík Zdeněk , Ahmedov Bobomurat 
Published: June 2017

This comment is devoted to the recalculation of the Casimir energy of a massless scalar field in the Kerr black hole surrounded by quintessence derived in [B. Toshmatov, Z. Stuchlík and B. Ahmedov, Eur. Phys. J. Plus 132, 98 (2017)] and its comparison with the results recently obtained in [V. B. Bezerra, M. S. Cunha, L. F. F. Freitas and C. R. Muniz, Mod. Phys. Lett. A 32, 1750005 (2017)] in the spacetime [S. G. Ghosh, Eur. Phys. J. C 76, 222 (2016)]. We have shown that in the more realistic spacetime which does not have the failures illustrated here, the Casimir energy is significantly bigger than that derived in [V. B. Bezerra, M. S. Cunha, L. F. F. Freitas and C. R. Muniz, Mod. Phys. Lett. A 32, 1750005 (2017)], and the difference becomes crucial especially in the regions of near horizons of the spacetime.
Analysis of Performance Indicators for Optimization of Noninteger-Order Controllers
Authors: Zagorowska Marta 
Published: June 2017

Tuning noninteger-order controllers using parametric optimization remains a subject of ongoing research. One of the areas of focus concerns analysis of performance indicators ensuring desired behavior. In this paper we analyze linear, quadratic and quartic performance indicators as tools for finding parameters of PD[Formula: see text] and PI[Formula: see text] controllers in [Formula: see text] ladder system of fourth order. Proposed optimization method uses the Laguerre Impulse Response Approximation (LIRA) method and ensures the stability of noninteger closed-loop system. The results were compared with classic PID controllers.
p120-Catenin Downregulation and PIK3CA Mutations Cooperate to Induce Invasion through MMP1 in HNSCC
Authors: Kidacki Michal , Lehman Heather L. , Green Michelle V. , Warrick Joshua I. , Stairs Douglas B. 
Published: June 2017

Abstract
Despite recent improvements in treatment for head and neck squamous cell carcinoma (HNSCC), half of all patients with a regional or advanced disease will die within 5 years from diagnosis. Therefore, identification of mechanisms driving the aggressive behavior of HNSCC is of utmost importance. Because p120-catenin (CTNND1/P120CTN) downregulation and PIK3CA mutations are commonly found in HNSCC, the objective of this study was to identify their impact on fundamental processes of metastasis, specifically, migration and invasion. Furthermore, this study aimed to identify the key effector proteins regulated by P120CTN downregulation and PIK3CA mutations. Studies using oral keratinocytes demonstrated that P120CTN downregulation and PIK3CA mutations increased migration and invasion. In addition, P120CTN downregulation and PIK3CA mutations resulted in elevated matrix metallopeptidase 1 (MMP1) levels. Inhibition of MMP1 resulted in decreased invasion, suggesting that MMP1 plays a critical role in HNSCC invasion. Moreover, analysis of HNSCC patient specimens from The Cancer Genome Atlas confirmed these findings. Tumors with low P120CTN and PI3K pathway mutations have higher levels of MMP1 compared to tumors with high P120CTN and no PI3K pathway mutations. In conclusion, this study demonstrates that P120CTN downregulation and PIK3CA mutations promote MMP1-driven invasion, providing a potential novel target for limiting metastasis in HNSCC.
Implications: Because of its role in invasion, MMP1 represents a novel, potential target for limiting metastasis in a subset of HNSCCs with P120CTN downregulation and PIK3CA mutations. Mol Cancer Res; 15(10); 1398–409. ©2017 AACR.
Lys 42/43/44 and Arg 12 of thrombin-activable fibrinolysis inhibitor comprise a thrombomodulin exosite essential for its antifibrinolytic potential
Authors: Wu Chengliang , Stafford Alan , Fredenburgh James , Weitz Jeffrey , Gils Ann , Declerck Paul , Kim Paul 
Published: June 2017

SummaryThe thrombin-thrombomodulin (TM) complex activates thrombin-activable fibrinolysis inhibitor (TAFI) more efficiently than thrombin alone. The exosite on TAFI required for its TM-dependent activation by thrombin has not been identified. Based on previous work by us and others, we generated TAFI variants with one or more of residues Lys 42, Lys 43, Lys 44 and Arg 12 within the activation peptide mutated to alanine. Mutation of one, two, or three Lys residues or the Arg residue alone decreased the catalytic efficiency of TAFI activation by thrombin-TM by 2.4-, 3.2-, 4.7-, and 15.0-fold, respectively, and increased the TAFI concentrations required for half-maximal prolongation of clot lysis times (K1/2) by 3-, 4,- 15-, and 24-fold, respectively. Mutation of all four residues decreased the catalytic efficiency of TAFI activation by 45.0-fold, increased the K1/2 by 130-fold, and abolished antifibrinolytic activity in a clot lysis assay at physiologic levels of TAFI. Similar trends in the antifibrinolytic activity of the TAFI variants were observed when plasma clots were formed using HUVECs as the source of TM. When thrombin was used as the activator, mutation of all four residues reduced the rate of activation by 1.1-fold compared with wild-type TAFI, suggesting that these mutations only impacted activation kinetics in the presence of TM. Surface plasmon resonance data suggest that mutation of the four residues abrogates TM binding with or without thrombin. Therefore, Lys 42, Lys 43, Lys 44 and Arg 12 are critical for the interaction of TAFI with the thrombin-TM complex, which modulates its antifibrinolytic potential.
New paradigms in venous thromboprophylaxis of medically ill patients
Authors: Spyropoulos Alex C. , Raskob Gary E. 
Published: June 2017

SummaryAcutelly-ill hospitalised medical patients are at risk of venous thromboembolism (VTE), both in-hospital and in the immediate post-discharge period, and mortality from VTE is thought to be particularly high in this patient population. However, despite previous mandates from international antithrombotic guidelines such as those of the American College of Chest Physicians (ACCP) for the “universal” use of thromboprophylaxis in hospitalised medical patients, global audits suggest that implementation of thromboprophylaxis continues to be challenging because of the perceived higher risk of bleeding and lower risk of VTE than that reported in clinical trials. Recent population-based studies also reveal that a “universal” hospital-only thromboprophylactic strategy does not reduce the community burden of VTE from this population, which may constitute nearly one quarter of the attributable risk of VTE. Lastly, four large randomised placebo-controlled trials of extended thromboprophylaxis have failed to show a definitive net clinical benefit in hospitalised medical patients. Recent large-scale efforts in deriving and validating scored VTE and bleed risk assessment models (RAMs) have been completed in the medically-ill population. In addition, an elevated D-dimer as a new biomarker to identify at-VTE risk medically ill patients has also undergone prospective evaluation. This paper will review current concepts of VTE and bleed risk in hospitalised medical patients, both in the hospital as well as the post-hospital discharge period, and will discuss new paradigms of thromboprophylaxis in this population using an individualised, patient-centered approach.
Platelets Express Activated P2Y
12
Receptor in Patients With Diabetes Mellitus
Authors: Hu Liang , Chang Lin , Zhang Yan , Zhai Lili , Zhang Shenghui , Qi Zhiyong , Yan Hongmei , Yan Yan , Luo Xinping , Zhang Si , Wang Yiping , Kunapuli Satya P. , Ye Hongying , Ding Zhongren 
Published: June 2017

Background:
Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood.

Methods:

We measured P2Y
12
expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus. We also assayed platelet P2Y
12
activation by measuring cAMP and VASP phosphorylation. The antiplatelet and antithrombotic effects of AR-C78511 and cangrelor were compared in rats. Finally, we explored the role of the nuclear factor-κB pathway in regulating P2Y
12
receptor expression in megakaryocytes.

Results

Platelet P2Y
12
levels are 4-fold higher in patients with type 2 diabetes mellitus compared with healthy subjects. P2Y
12
expression correlates with ADP-induced platelet aggregation (r=0.89,
P
<0.01). P2Y
12
in platelets from patients with diabetes mellitus is constitutively activated. Although both AR-C78511, a potent P2Y
12
inverse agonist, and cangrelor have similar antiplatelet efficacy on platelets from healthy subjects, AR-C78511 exhibits more powerful antiplatelet effects on diabetic platelets than cangrelor (aggregation ratio 36±3% versus 49±5%, respectively,
P
<0.05). Using a FeCl
3
-injury mesenteric arteriole thrombosis model in rats and an arteriovenous shunt thrombosis model in rats, we found that the inverse agonist AR-C78511 has greater antithrombotic effects on GK rats with diabetes mellitus than cangrelor (thrombus weight 4.9±0.3 mg versus 8.3±0.4 mg, respectively,
P
<0.01). We also found that a pathway involving high glucose-reactive oxygen species-nuclear factor-κB increases platelet P2Y
12
receptor expression in diabetes mellitus.

Conclusions

Platelet P2Y
12
receptor expression is significantly increased and the receptor is constitutively activated in patients with type 2 diabetes mellitus, which contributes to platelet hyperactivity and limits antiplatelet drug efficacy in type 2 diabetes mellitus.