bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study of suicide attempt in a Mexican population: a study protocol
Authors: González-Castro Thelma Beatriz , Genis-Mendoza Alma Delia , Tovilla-Zárate Carlos Alfonso , Martínez-Magaña José Jaime , Juárez-Rojop Isela Esther , Sarmiento Emmanuel , Nicolini Humberto 
Published: April 2019

IntroductionSuicidality is a complex behaviour and a major health problem; the speciﬁc features that could predispose to suicidal behaviour have been extensively investigated, most frequently in European and Asian populations. Therefore, our aim is to present a protocol that will explore suicide attempt in Mexican individuals diagnosed with psychiatric disorders, through a genome-wide association study (GWAS).Method and analysisWe will perform a GWAS by comparing 700 individuals who have suicide attempt history, with control subjects without suicide attempt history (n=500). The genotyping will be conducted using the Infinium PsychArray BeadChip and quality controls will be applied to single nucleotides (SNPs) genotyped. After that, we will perform the imputation using reference panels provided by the Haplotype Reference Consortium. We will perform two different workflows: (A) the classic GWAS analysis applying the same weight to all the variants and (B) an algorithm with prediction of deleteriousness of variants.Ethics and disseminationThis study was approved by the ethics and investigation committees of the National Institute of Genomic Medicine on 22 July 2015, No CEI 215/13. We plan to disseminate research findings in scientific conferences and as a manuscript in peer-reviewed journals.Trial registration numberCEI 215/13.
Patients’ and health professionals’ attitudes and perceptions towards the initiation of preventive drugs for primary prevention of cardiovascular disease: protocol for a systematic review of qualitative studies
Authors: Qadi Olla , Marshall Tom , Adderley Nicola , Bem Danai 
Published: April 2019

IntroductionLipid-lowering drugs and antihypertensive agents can be prescribed for the primary prevention of cardiovascular disease. In some cases, patients eligible for primary prevention of cardiovascular disease according to the European guidelines are not always started on preventive drugs. Existing research explores the attitudes of health professionals and patients towards cardiovascular preventive drugs but does not always differentiate between the attitudes towards drug initiation for primary or secondary prevention. We aim to systematically review qualitative studies assessing health professionals’ and patients’ attitudes and perceptions towards drug initiation for primary prevention of cardiovascular disease.Methods and analysisMEDLINE, MEDLINE In Process, EMBASE, PsycINFO, CINAHL, Applied Social Sciences Index and Abstracts, Conference Proceedings Citation Index (Web of Science), Healthcare Management Information Consortium, and Open Grey will be searched without restrictions on date or language of publication. Searches will be limited to studies of qualitative design, standalone or in the context of a mixed-method design, focusing on cardiovascular drug initiation for primary prevention. The primary outcome is the attitudes of health professionals and patients towards drug initiation for primary prevention of cardiovascular disease. Two reviewers will independently carry out the study selection, data extraction and quality assessment. The Critical Appraisal Skills Programme Qualitative Research Checklist will be used to assess the quality of included studies. The findings will be analysed using Thomas and Harden’s thematic synthesis approach.Ethics and disseminationThis systematic review does not require ethical approval as primary data will not be collected. The results of the study will be published in a peer-reviewed journal and presented at relevant conferences.PROSPERO registration numberCRD42018095346.
Labour market attachment after mild traumatic brain injury: nationwide cohort study with 5-year register follow-up in Denmark
Authors: Graff Heidi Jeannet , Siersma Volkert , Møller Anne , Kragstrup Jakob , Andersen Lars L , Egerod Ingrid , Malá Rytter Hana 
Published: April 2019

ObjectivesSickness absence after mild traumatic brain injury (mTBI) is frequent due to postconcussive symptoms. We examined labour market attachment following mTBI up to 5 years postinjury.Design and settingNationwide cohort study with register follow-up.ParticipantsPatients between 18 and 60 years with mTBI (International Classification of Diseases, version 10 diagnosis S06.0) were extracted from the Danish National Patient Register (n=19 732). Controls were matched on sex, age and municipality (n=18 640). Patients with spinal cord and column injuries, traumatic brain injury and concussions 5 years preinjury or as secondary diagnosis to the concussion in the inclusion period were excluded.Primary and secondary outcome measuresData were extracted from the Danish Register for Evaluation of Marginalization. Primary outcome was ‘not attending ordinary work’ defined as receiving any social transfer payment. Secondary outcomes were health-related benefits, limited attachment to the labour market, permanent lack of attachment to the labour market and death.Results5 years after diagnosis, 43% of patients were not attending ordinary work. The odds increased from 6 months (OR 1.30, 95% CI 1.24 to 1.36) to 5 years (OR 1.54, 95% CI 1.45 to 1.63). The odds of health-related benefits were 32% (OR 1.32, 95% CI 1.22 to 1.42) at 6 months and 22% (OR 1.22, 95% CI 1.12 to 1.33) at 5 years. Limited attachment to the labour market showed increased odds at 5 years (OR 1.38, 95% CI 1.27 to 1.51) and the odds of permanent lack of attachment to the labour market were higher for patients compared with controls (OR 2.59, 95% CI 2.30 to 2.92). Death was more than two times higher at 5 years postinjury (OR 2.62, 95% CI 2.10 to 3.26).Conclusions43% of concussed patients were not attending ordinary work 5 years postinjury and received health and social transfer benefits. We conclude that mTBI has a long-term impact on labour market attachment. Prevention and treatment of persisting postconcussive symptoms should be considered.Trial registration numberNCT03214432; Results
Advance care planning and place of death, hospitalisation and actual place of death in lung, heart and cancer disease: a randomised controlled trial
Authors: Skorstengaard Marianne Hjorth , Jensen Anders Bonde , Andreassen Pernille , Brogaard Trine , Brendstrup Elisabeth , Løkke Anders , Aagaard Susanne , Wiggers Henrik , Neergaard Mette Asbjoern 
Published: April 2019

ObjectivesAdvance care planning (ACP) can be a way to meet patients’ end-of-life preferences and enhance awareness of end-of-life care. Thereby it may affect actual place of death (APOD) and decrease the rate of hospitalisations. The aim was to investigate if ACP among terminally ill patients with lung, heart and cancer diseases effects fulfilment of preferred place of death (PPOD), amount of time spent in hospital and APOD.MethodsThe study was designed as a randomised controlled trial. Patients were assessed using general and disease-specific criteria and randomised into groups: one received usual care and one received usual care plus ACP. The intervention consisted of a discussion between a healthcare professional, the patient and their relatives about preferences for end-of-life care. The discussion was documented in the hospital file.ResultsIn total, 205 patients were randomised, of which 111 died during follow-up. No significant differences in fulfilment of PPOD (35% vs 52%, p=0.221) or in amount of time spent in hospital among deceased patients (49% vs 23%, p=0.074) were found between groups. A significant difference in APOD was found favouring home death in the intervention group (17% vs 40%, p=0.013).ConclusionConcerning the primary outcome, fulfilment of PPOD, and the secondary outcome, time spent in hospital, no differences were found. A significant difference concerning APOD was found, as more patients in the intervention group died at home, compared with the usual care group.Trial registration numberNCT01944813.
Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration
Authors: Menon Bijoy K , Hill Michael D , Davalos Antoni , Roos Yvo B W E M , Campbell Bruce C V , Dippel Diederik W J , Guillemin Francis , Saver Jeffrey L , van der Lugt Aad , Demchuk Andrew M , Muir Keith , Brown Scott , Jovin Tudor , Mitchell Peter , White Phil , Bracard Serge , Goyal Mayank 
Published: April 2019

BackgroundThe Society of Neurointerventional Surgery revised its operational definition of emergent large vessel occlusion (ELVO) recently to include proximal M2 segment middle cerebral artery (MCA) occlusions. We sought to assess the benefit of endovascular thrombectomy (EVT) over best medical care for M2 segment MCA occlusion.MethodsPatient level data from trials in the HERMES Collaboration were included. The HERMES core laboratory identified patients with M2 segment MCA occlusions and further classified them as proximal versus distal, anterior versus posterior division, and dominant versus co-dominant versus non-dominant. Primary outcome was modified Rankin Scale (mRS) score 0–2 at 90 days. Secondary outcomes were modified Thrombolysis in Cerebral Infarction (mTICI) rates at end of procedure, 90-day mRS shift, 90-day mRS 0–1, 24 hours National Institute of Health Stroke Scale (NIHSS) score 0–2, symptomatic intracerebral hemorrhage (ICH), and death.Results130 patients with M2 MCA (proximal location n=116 vs distal n=14, anterior division n=72 vs posterior n=58, dominant n=73 vs co-dominant n=50 vs non-dominant n=7) were included. Successful reperfusion (mTICI 2b or 3) among those undergoing EVT was seen in 59.2% of patients. Treatment effect favored EVT (adjusted OR 2.39, 95% CI 1.08 to 5.28, p=0.03) for 90-day mRS 0–2 (58.2% EVT vs 39.7% control). Direction of benefit favored EVT for other outcomes. Treatment effect favoring EVT was maximal in patients with proximal M2 segment MCA occlusions (n=116, adjusted OR 2.68, 95% CI 1.13 to 6.37) and in dominant M2 segment MCA occlusions (n=73, adjusted OR 4.08, 95% CI 1.08 to 15.48). No sICH (0%) was observed in patients treated with EVT compared with five (7.9%) in the control arm.ConclusionPatients with proximal M2 segment MCA occlusions eligible for EVT trial protocols benefited from EVT.
Progressive thrombosis of unruptured aneurysms after coil embolization: analysis of 255 consecutive aneurysms
Authors: Funakoshi Yusuke , Imamura Hirotoshi , Tani Shoichi , Adachi Hidemitsu , Fukumitsu Ryu , Sunohara Tadashi , Omura Yoshihiro , Matsui Yuichi , Sasaki Natsuhi , Fukuda Tatsumaru , Akiyama Ryo , Horiuchi Kazufumi , Kajiura Shinji , Shigeyasu Masashi , Sakai Nobuyuki 
Published: April 2019

IntroductionWe have observed that aneurysms treated by insufficient coil embolization and filled with contrast agent immediately after the procedure are often completely occluded at follow-up. However, there are limited studies showing progressive thrombosis of aneurysms after coil embolization. Herein, we describe our experience with coil embolization for aneurysms, and discuss the factors involved in progressive thrombosis.MethodsA total of 255 aneurysms treated by coil embolization in our institute between January 2011 and June 2017 and observed >6 months were included. ‘Progressive thrombosis’ indicated that aneurysms that were neck remnant (NR) or dome filling (DF) immediately after coil embolization changed to complete obliteration (CO) at the 6-month follow-up digital subtraction angiography. The factors involved in progressive thrombosis were assessed.ResultsIn all aneurysms (n=255), 24 (9.4%) were CO, 82 (32.2%) were NR, and 149 (58.4%) were DF immediately after the procedure. At 6-month digital subtraction angiography, 123 (48.2%) were CO, 95 (37.3%) were NR, and 37 (14.5%) were DF. Retreatment for major recanalization was performed in eight cases (3.1%). One hundred and three aneurysms showed progressive thrombosis. There were significant differences in aneurysm location (P=0.0002), aneurysm dome diameter (P=0.0015), aneurysm neck diameter (P=0.0068), volume embolization ratio (P=0.0054), and endovascular procedure with stent (P=0.0264) between the progressive thrombosis and no thrombosis groups.ConclusionsProgressive thrombosis can occur in aneurysms after coil embolization depending on aneurysm location and size, and stent use. Thus, the degree of coil embolization and combination with a stent should be adjusted depending on aneurysm type.
Assessment of ceftiofur residues in cow milk using commercial screening test kits
Authors: Durel Luc , Gallina Guglielmo , Pellet Terence 
Published: April 2019

Ceftiofur, a third‐generation cephalosporin, is one of the most used antibiotics in dairy industry. Intramuscular injection of 1 mg/kgBW ceftiofur hydrochloride (HCl) generally results in 0 hour withdrawal time for the milk in dairy cows. Nevertheless, farmers and dairy processors occasionally complain about ceftiofur‐based products in case of positive result to a commercial rapid screening test for the presence of violative residues of antimicrobials (inhibitors) in the bulk milk tank. Six lactating cows were injected with a 50 mg/ml ceftiofur HCl‐based product at the dosage regimen of 1 mg/kg, intramuscularly, once a day, for five consecutive days, as per label. Milk samples were then collected just before the very last injection (T0) and then at 12, 24, 36, 48, 60, 72, 84 and 96 hours after the last injection. Individual milk samples were tested using three commercial screening test kits for inhibitor residues: DelvotestSP NT, SNAP Beta‐Lactam ST Plus and ROSA MRL Beta‐Lactam Test. Since bulk tank is screened in real operating conditions, samples were also diluted to 1:4, 1:10 and tested again. For the Delvotest SP NT, which lowest detected concentration is close the MRL of the ceftiofur (100 µg/kg), all results were negative. For the ROSA MRL Beta‐Lactam Test and the SNAP Beta‐Lactam ST Plus, several samples yielded positive and doubtful results at T0and T12. However, after dilution to 1:10, all results were negative. Consequently, when used as officially instructed, the tested 50 mg/ml ceftiofur HCl‐based injectable veterinary products are safe, and milk should be free of violative residues of ceftiofur. With consideration to the low specificity and the low positive predictive value of commercial screening tests, positive reactions of the bulk milk should be interpreted as false positive or another risky usage of β‐lactam‐based medicines in the farm must be investigated.
A Framework for Governance of Sustainability Indicator Systems in Strategic Environmental Assessment Processes
Authors: da Silva Antonio Waldimir Leopoldino , Netto Marinilse , Selig Paulo Maurício , de Ávila Lerípio Alexandre 
Published: April 2019

Sustainability indicators (SIs) are considered an important tool in Strategic Environmental Assessment (SEA), but their choice and management present shortcomings and must be improved. This work aimed to develop a governance model of SI systems for SEA. The study was carried out by means of documentary research on SEA reports and interviews with leaders of Brazilian SEA working teams, through the application of Content Analysis. The resulting framework, called G-SINDS, is composed of six phases and three transverse elements. Each phase represents a stage of construction of the SI system, with methodological procedures adaptable to the specificity of each SEA process. The transverse elements are factors that affect each phase, in order to perfect them. The G-SINDS represents an innovative model, since it involves the “life cycle of the indicators”, is directed to the SEA and is based on principles and techniques of knowledge management, constituting a means of improving the execution of SEA processes.
High Serum Uric Acid Is Associated with Tubular Damage and Kidney Inflammation in Patients with Type 2 Diabetes
Authors: Guarda Naiara S. , Bollick Yãnaí S. , de Carvalho José Antonio M. , Premaor Melissa O. , Comim Fabio V. , Moresco Rafael N. 
Published: April 2019

Background. Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). Methods. Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. Results. Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations≥6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). Conclusions. High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.
Hypoxia Triggers Osteochondrogenic Differentiation of Vascular Smooth Muscle Cells in an HIF-1 (Hypoxia-Inducible Factor 1)–Dependent and Reactive Oxygen Species–Dependent Manner
Authors: Balogh Enikő , Tóth Andrea , Méhes Gábor , Trencsényi György , Paragh György , Jeney Viktória 
Published: April 2019

Objective—
Vascular calcification is associated with high risk of cardiovascular events and mortality. Osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) is the major cellular mechanism underlying vascular calcification. Because tissue hypoxia is a common denominator in vascular calcification, we investigated whether hypoxia per se triggers osteochondrogenic differentiation of VSMCs.

Approach and Results—

We studied osteochondrogenic differentiation of human aorta VSMCs cultured under normoxic (21% O
2
) and hypoxic (5% O
2
) conditions. Hypoxia increased protein expression of HIF (hypoxia-inducible factor)-1α and its target genes GLUT1 (glucose transporter 1) and VEGFA (vascular endothelial growth factor A) and induced mRNA and protein expressions of osteochondrogenic markers, that is, RUNX2 (runt-related transcription factor 2), SOX9 (Sry-related HMG box-9), OCN (osteocalcin) and ALP (alkaline phosphatase), and induced a time-dependent calcification of the extracellular matrix of VSMCs. HIF-1 inhibition by chetomin abrogated the effect of hypoxia on osteochondrogenic markers and abolished extracellular matrix calcification. Hypoxia triggered the production of reactive oxygen species, which was inhibited by chetomin. Scavenging reactive oxygen species by
N
-acetyl cysteine attenuated hypoxia-mediated upregulation of HIF-1α, RUNX2, and OCN protein expressions and inhibited extracellular matrix calcification, which effect was mimicked by a specific hydrogen peroxide scavenger sodium pyruvate and a mitochondrial reactive oxygen species inhibitor rotenone. Ex vivo culture of mice aorta under hypoxic conditions triggered calcification which was inhibited by chetomin and
N
-acetyl cysteine. In vivo hypoxia exposure (10% O
2
) increased RUNX2 mRNA levels in mice lung and the aorta.

Conclusions—
Hypoxia contributes to vascular calcification through the induction of osteochondrogenic differentiation of VSMCs in an HIF-1–dependent and mitochondria-derived reactive oxygen species–dependent manner.
Proinflammatory Effect of Endothelial Microparticles Is Mitochondria Mediated and Modulated Through MAPKAPK2 (MAPK-Activated Protein Kinase 2) Leading to Attenuation of Cardiac Hypertrophy
Authors: Tripathi Dipti , Biswas Bharti , Manhas Amit , Singh Abhinav , Goyal Dipika , Gaestel Matthias , Jagavelu Kumaravelu 
Published: April 2019

Objective—
This study investigates the functional significance of mitochondria present in endothelial microparticles (EMP) and how MK2 (MAPKAPK2 [MAPK-activated protein kinase 2]) governs EMP production and its physiological effect on cardiac hypertrophy.

Approach and Results—
Flow cytometric analysis, confocal imaging, oxygen consumption rate measurement through Seahorse were used to confirm the presence of functionally active mitochondria in nontreated EMP (EMP derived from untreated control cells), lipopolysaccharide, and oligomycin treatment increased mitochondrial reactive oxygen species activity in EMP (EMP derived from cells treated with lipopolysaccharide and EMP derived from cells treated with oligomycin, respectively). The dysfunctional mitochondria contained in EMP derived from cells treated with lipopolysaccharide and EMP derived from cells treated with oligomycin induced the expression of proinflammatory mediators in the target endothelial cells leading to the augmented adhesion of human monocytic cell line on EA.hy926 cells. Multiphoton real-time imaging detected the increased adherence of EMP derived from cells treated with oligomycin at the site of carotid artery injury as compared to EMP derived from untreated control cells. MK2 regulates EMP generation during inflammation by reducing E-selectin expression and regulating the cytoskeleton rearrangement through ROCK-2 (Rho-associated coiled-coil containing protein kinase 2) pathway. MK2-deficient EMP reduced the E-selectin and ICAM-1 (intracellular adhesion molecule-1) expression on target endothelial cells leading to reduced monocyte attachment and reduced cardiac hypertrophy in mice.

Conclusions—
MK2 promotes the proinflammatory effect of EMP mediated through dysfunctional mitochondria. MK2 modulates the inflammatory effect induced during cardiac hypertrophy through EMP.