bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm
Authors: Adam Matti , Kooreman Nigel Geoffrey , Jagger Ann , Wagenhäuser Markus U. , Mehrkens Dennis , Wang Yongming , Kayama Yosuke , Toyama Kensuke , Raaz Uwe , Schellinger Isabel N. , Maegdefessel Lars , Spin Joshua M. , Hamming Jaap F. , Quax Paul H.A. , Baldus Stephan , Wu Joseph C. , Tsao Philip S. 
Published: June 2018

Objective—
Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression.

Approach and Results—

Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE
−/−
infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4
+
/CD25
+
/Foxp3 (forkhead box P3)
+
regulatory T cells, with fewer CD8
+
/GZMB
+
(granzyme B) cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)–positive alternatively activated macrophages. These results concurred with gene expression analysis of lipopolysaccharide-stimulated and Ang II-primed human peripheral blood mononuclear cells.

Conclusions—
Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression.
Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells
Authors: Schillemans Maaike , Karampini Ellie , van den Eshof Bart L. , Gangaev Anastasia , Hofman Menno , van Breevoort Dorothee , Meems Henriët , Janssen Hans , Mulder Aat A. , Jost Carolina R. , Escher Johanna C. , Adam Rüdiger , Carter Tom , Koster Abraham J. , van den Biggelaar Maartje , Voorberg Jan , Bierings Ruben 
Published: June 2018

Objective—
Endothelial cells store VWF (von Willebrand factor) in rod-shaped secretory organelles, called Weibel-Palade bodies (WPBs). WPB exocytosis is coordinated by a complex network of Rab GTPases, Rab effectors, and SNARE (soluble NSF attachment protein receptor) proteins. We have previously identified STXBP1 as the link between the Rab27A-Slp4-a complex on WPBs and the SNARE proteins syntaxin-2 and -3. In this study, we investigate the function of syntaxin-3 in VWF secretion.

Approach and Results—

In human umbilical vein endothelial cells and in blood outgrowth endothelial cells (BOECs) from healthy controls, endogenous syntaxin-3 immunolocalized to WPBs. A detailed analysis of BOECs isolated from a patient with variant microvillus inclusion disease, carrying a homozygous mutation in
STX3
(STX3
−/−
), showed a loss of syntaxin-3 protein and absence of WPB-associated syntaxin-3 immunoreactivity. Ultrastructural analysis revealed no detectable differences in morphology or prevalence of immature or mature WPBs in control versus STX3
−/−
BOECs. VWF multimer analysis showed normal patterns in plasma of the microvillus inclusion disease patient, and media from STX3
−/−
BOECs, together indicating WPB formation and maturation are unaffected by absence of syntaxin-3. However, a defect in basal as well as Ca
2+
- and cAMP-mediated VWF secretion was found in the STX3
−/−
BOECs. We also show that syntaxin-3 interacts with the WPB-associated SNARE protein VAMP8 (vesicle-associated membrane protein-8).

Conclusions—
Our data reveal syntaxin-3 as a novel WPB-associated SNARE protein that controls WPB exocytosis.
Long-Term Prognosis of Patients With Transient Ischemic Attack or Stroke and Symptomatic Vascular Disease in Multiple Arterial Beds
Authors: Heldner Mirjam R. , Li Linxin , Lovett Nicola G. , Kubiak Magdalena M. , Lyons Shane , Rothwell Peter M. ,   for the Oxford Vascular Study
Published: June 2018

Background and Purpose—
Cerebrovascular, coronary, and peripheral vascular disease have common underlying arterial pathology and risk factors, but the clinical significance of multiple-territory disease in patients with transient ischemic attack (TIA)/ischemic stroke is unclear, particularly whether the number of clinically affected territories still predicts long-term outcome on current standard secondary prevention therapies.

Methods—
In a population-based study of 92 728 individuals in Oxfordshire, United Kingdom (Oxford Vascular Study), we studied patients presenting with TIA/ischemic stroke (2002–2014) in relation to the number of other vascular beds (coronary, peripheral) affected by symptomatic (current or previous) disease. We compared the risk factor profile and long-term prognosis in patients with single- versus multiple-territory disease.

Results—

Among 2554 patients with 10 679 patient-years of follow-up, 1842 (72.1%) had single- (TIA/stroke only), 608 (23.8%) double-, and 104 (4.1%) triple-territory symptomatic vascular disease. The number of affected vascular beds increased with the number of atherosclerotic risk factors (
P
trend
<0.0001). Compared with patients with TIA/stroke only, those with multiple-territory disease had more hypertension (age/sex-adjusted odds ratio [OR], 3.43; 95% confidence interval [CI], 2.76–4.27;
P
<0.0001), diabetes mellitus (OR, 2.89; 95% CI, 2.27–3.66;
P
<0.0001), hypercholesterolemia (OR, 4.67; 95% CI, 3.85–5.66;
P
<0.0001), and current or previous smoking (OR, 1.52; 95% CI, 1.26–1.84;
P
<0.0001). Triple-territory disease was particularly strongly associated with hypercholesterolemia (OR, 6.80; 95% CI, 4.39–10.53;
P
<0.0001). Despite more intensive secondary prevention in patients with multiple-territory disease, the 5-year risk of vascular death increased steeply with the number of territories affected (17.2% versus 30.0% versus 42.9%;
P
<0.0001). Compared with patients with single-territory, patients with multiple-territory disease also had higher postacute long-term risks (90 days to 10 years) of recurrent ischemic stroke (age/sex-adjusted hazard ratio, 1.38; 95% CI, 1.04–1.81;
P
=0.02) and nonstroke acute vascular events (hazard ratio, 3.06; 95% CI, 2.23–4.20;
P
<0.0001).

Conclusions—
Number of affected vascular beds appeared to be a simple clinical rule in identifying TIA/ischemic stroke patients who are at high long-term risk of nonstroke vascular events and vascular death.
Similar Outcomes for Contact Aspiration and Stent Retriever Use According to the Admission Clot Burden Score in ASTER
Authors: Zhu François , Lapergue Bertrand , Kyheng Maéva , Blanc Raphael , Labreuche Julien , Ben Machaa Malek , Duhamel Alain , Marnat Gautier , Saleme Suzana , Costalat Vincent , Bracard Serge , Richard Sébastien , Desal Hubert , Mazighi Mikael , Consoli Arturo , Piotin Michel , Gory Benjamin ,   for the ASTER Trial Investigators*
Published: June 2018

Background and Purpose—
The clot burden score (CBS) at admission reliably evaluates the thrombus burden in acute ischemic stroke patients with anterior circulation large vessel occlusion. Mechanical thrombectomy has been diversified, especially with contact aspiration technique, and its efficiency with respect to the thrombus burden is not known. We compared reperfusion, adverse events, neurological recovery, and 90-day functional outcome of stent retriever use versus contact aspiration according to the admission CBS.

Methods—
This is a post hoc analysis of the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) randomized trial. The primary outcome was successful reperfusion after all procedures, defined as modified Thrombolysis in Cerebral Infarction scores 2b/3. Secondary outcomes were 90-day functional outcome, assessed with the modified Rankin Scale. Safety outcomes included 90-day mortality and any intracerebral hemorrhage.

Results—
A total of 231 randomized patients were included in this study: 114 patients had a CBS of 0 to 6 and 117 a CBS ≥7 at admission. Successful reperfusion at procedure end was achieved more frequently in patients with CBS ≥7 (88.9%) than patients with a CBS 0 to 6 (81.6%; fully adjusted risk ratio, 1.09; 95% confidence interval, 1.01–1.28). Favorable outcome (modified Rankin Scale score, 0–2) at 90 days was achieved in significantly more patients with CBS ≥7 (61.9%) than in patients with CBS 0 to 6 (41.8%; fully adjusted risk ratio, 1.19; 95% confidence interval, 1.02–1.40). No outcome differences of first-line mechanical thrombectomy strategy (aspiration versus stent) on any angiographic or clinical outcomes were observed between the 2 groups. We also found no evidence of interaction between first-line mechanical thrombectomy strategy and CBS groups regarding safety.

Conclusions—
First-line mechanical thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful reperfusion rate in acute ischemic stroke patients with large vessel occlusion of the anterior circulation according to the admission CBS. The latter, however, seems to be a reliable prognostic indicator of angiographic and clinical outcome.
Using Evolutionary Programming to Add Deterministic and Probabilistic Skill to Spatial Model Forecasts
Authors: Roebber Paul J. 
Published: June 2018

Abstract
Evolutionary programming is applied to the postpocessing of ensemble forecasts of temperature on a spatial domain. These forecasts are obtained from the 11-member Reforecast V2 ensemble over the region from 24°–53°N to 125°–66°W for the period 1 January 1985–14 May 2011. The evolution is based upon a static ecosystem model that holds constant the number of individuals (algorithms), using a fixed rate of introduction of new algorithms and removal of existing algorithms. Each algorithm adheres to a specific underlying genetic architecture, and the selection pressure on the “species” is according to deterministic performance (root-mean-square error) on a training dataset. On a 2325-case, independent test dataset, the method improved root-mean-square error and ranked probability score relative to the Reforecast ensemble by 0.31°F (8.7%) and 3.3%, respectively, across the domain, with 96% of the grid points showing simultaneous improvements in both measures. The use of input information by the evolutionary programming algorithms varied by region; while the algorithm forecasts at all locations are fundamentally tied to the Reforecast ensemble forecast, northeastern locations found snow cover to be the next most useful input, whereas southwestern locations preferentially employed precipitable water. An adaptive form of the approach, developed to be readily implemented into operations, is tested in the absence of improving inputs but is found to only slightly degrade performance (1.2% in root-mean-square error and 0.6% in ranked probability skill score). A number of future extensions are discussed.
Efficacy, acceptability and tolerability of Zelesse® for the treatment of non-specific vulvovaginitis in paediatric patients: The NINESSE Study
Authors: García Fátima , Rodríguez Carmen-Amparo , Palomo María-Lourdes , Català Pere , Fernández Santiago , Huerta Ibone , Velasco Syra , Nieto Concepción ,   as the writing group of the NINESSE study
Published: June 2018

Objective To evaluate the efficacy, tolerability and acceptability of Zelesse®, an intimate hygiene wash solution, in the relief of the symptoms and signs of non-specific vulvovaginitis in paediatric patients. Methods The NINESSE Study was a prospective, observational, multicentre study involving females aged 2–8 years who attended paediatric offices with symptoms suggestive of non-specific vulvovaginitis. They were administered Zelesse® as a single treatment for 15 ± 5 days. Pruritus, burning, dysuria, erythema, leucorrhoea and oedema were evaluated before and after treatment. Results A total of 71 paediatric patients were enrolled in the study (mean ± SD age, 4.5 ± 1.9 years). The most significant effects were observed for pruritus and burning, where 98.4% (62 of 63) and 96.9% (63 of 65) of the patients improved after treatment, respectively. Zelesse® demonstrated a beneficial effect on dysuria, erythema, leucorrhoea and oedema. The effects on the symptoms and signs were observed within the first week of treatment; although 44.9% (31 of 69) of patients experienced improvements after 2–3 days. Zelesse® was well accepted and tolerated by most patients. No serious adverse events were reported. Conclusions Zelesse® was very effective for the relief of the symptoms and signs of non-specific vulvovaginitis, in particular pruritus, burning and erythema, in females aged 2–8 years.
Onabotulinumtoxin A (BOTOX®) for ProphylaCTIC Treatment of Pediatric Migraine: A Retrospective Longitudinal Analysis
Authors: Shah Shalini , Calderon Michael-David , Wu Wei Der , Grant Jihan , Rinehart Joseph 
Published: June 2018

Background: The use of onabotulinumtoxin A in the pediatric population has not been evaluated for chronic migraine in a longitudinal study. This retrospective study sought to determine the efficacy and safety of onabotulinumtoxin A in prophylactic treatment of chronic migraine in the pediatric population. Methods: The authors retrospectively evaluated pediatric patients who had been treated with onabotulinumtoxin A in the outpatient pain clinic for chronic migraine. Demographic data and pre- and posttreatment migraine days (frequency), pain scores (intensity), and duration of migraine episodes were collected from patient records. Results: Ten patients were included. Median pretreatment to posttreatment headache frequency was 15.5 [8, 29.5] to 4 [2, 10] days/month ( P < .0001), durations were 8 [0, 24] to 1 [0, 7] hours ( P = .025), and intensity was 6 [4, 8] to 4 [2, 5] ( P = .0063). No serious adverse events were reported. Conclusions: This review over a 5-year longitudinal period demonstrates statistically significant improvement from baseline.
Subjective Global Assessment–Dialysis Malnutrition Score and arteriovenous fistula outcome: A comparison with Charlson Comorbidity Index
Authors: Spatola Leonardo , Finazzi Silvia , Calvetta Albania , Angelini Claudio , Badalamenti Salvatore 
Published: June 2018

Introduction: Malnutrition is a well-recognized risk factor for all-cause mortality in hemodialysis patients. However, its role for arteriovenous fistulas outcome has not been exhaustively investigated. Our aim was to point out the impact of Subjective Global Assessment–Dialysis Malnutrition Score as independent predictor of arteriovenous fistulas thrombosis (vascular access thrombosis) and/or significant stenosis (vascular access stenosis). In addition, we compared it with the widespread Charlson Comorbidity Index. Methods: We assessed 57 hemodialysis patients for a 2-year interval and evaluated the incidence of vascular access thrombosis and/or stenosis. Linear regression analysis was used to test the relation of variables with Subjective Global Assessment–Dialysis Malnutrition Score at baseline. Logistic and Cox regression analysis evaluated markers as predictors of both vascular access thrombosis and stenosis. Receiver operating characteristic curve analysis was used to compare area under the curve values of Subjective Global Assessment–Dialysis Malnutrition Score, Charlson Comorbidity Index, and modified Charlson Comorbidity Index. Results: Age and Charlson Comorbidity Index were positively related to Subjective Global Assessment–Dialysis Malnutrition Score: B = 0.06 (95% CI = 0.01; 0.11) and B = 0.31 (95% CI = 0.01; 0.63). Higher albumin and normalized protein catabolic rate levels had a protective role against vascular access failure: OR = 0.67 (95% CI = 0.56; 0.81) and OR = 0.46 (95% CI = 0.32; 0.67), respectively. Higher Subjective Global Assessment–Dialysis Malnutrition Score and Charlson Comorbidity Index values were significant risk factors: HR = 1.42 (95% CI = 1.04; 1.92) and HR = 1.48 (95% CI = 1.01; 2.17), respectively. Area under the curve of Subjective Global Assessment–Dialysis Malnutrition Score was significantly higher than those of both Charlson Comorbidity Index and modified Charlson Comorbidity Index: 0.70 (95% CI = 0.50; 0.88) versus 0.61 (95% CI = 0.41; 0.80) and 0.55 (95CI% = 0.41; 0.70). Conclusion: Subjective Global Assessment–Dialysis Malnutrition Score, as well as Charlson Comorbidity Index, are useful tools to predict vascular access failure and should be carefully and periodically evaluated in order to check significant variations that may compromise vascular access survival.
Agreement between telehealth and face-to-face assessment of intellectual ability in children with specific learning disorder
Authors: Hodge Marie Antoinette , Sutherland Rebecca , Jeng Kelly , Bale Gillian , Batta Paige , Cambridge Aine , Detheridge Jeanette , Drevensek Suzi , Edwards Lynda , Everett Margaret , Ganesalingam Kalaichelvi , Geier Philippa , Kass Carol , Mathieson Susannah , McCabe Michael , Micallef Kay , Molomby Kirsty , Ong Natalie , Pfeiffer Silvia , Pope Sylvia , Tait Francine , Williamsz Marcia , Young-Dwarte Lynne , Silove Natalie 
Published: June 2018

Introduction Access to cognitive assessments for children living remotely is limited. Telehealth represents a potential cost- and time-effective solution. A pilot study was conducted to determine the feasibility of telehealth to assess cognitive function in children with learning difficulties. Methods Thirty-three children (median age = 9 years 11 months), recruited from the New South Wales (NSW) Centre for Effective Reading, underwent assessment of intellectual ability. Comparisons were made between the intellectual ability index scores obtained by a psychologist sitting face-to-face with the children and another psychologist via telehealth using a web-based platform, Coviu. Results The telehealth administration method yielded comparable results to the face-to-face method. Correlation analyses showed high associations between the testing methodologies on the intellectual ability indices (correlation coefficient range = 0.981–0.997). Discussion Findings indicate that telehealth may be an alternative to face-to-face cognitive assessment. Future work in a broader range of cognitive tests and wider range of clinical populations is warranted.
Rescue the child or treat the adult? Understandings among professionals in dual treatment of substance-use disorders and parenting
Authors: Wiig Eli Marie , Halsa Astrid , Bramness Jørgen , Myra Siv Merete , Haugland Bente Storm Mowatt 
Published: June 2018

Aims: Dual treatment of parents with substance-use disorders (SUD) is an approach which aims to meet the needs of both SUD patients and their children. Whereas the parents need to learn to live without substances, the children need a predictable and structured environment with parents who are sensitive and psychologically available. In this study we explore the possibilities and challenges of this joint approach from the perspectives of professionals employed in an in-patient facility for families with parental SUD. Methods: A qualitative design was used comprising three focus-group interviews with 15 professionals: two groups with ward staff and one with therapists, all working at a family ward for parents with SUD and their children. Data were analysed using thematic analysis. Results: Professionals faced difficulties combining the needs of parents and children and seemed to choose to prioritise either the adult with SUD or the wellbeing of the child. However, some professionals described what might be a third and alternative solution by supporting the mothers in everyday life, routines, and care, through exploring present moment situations. This approach seemed to help parents become more conscious of the child, their interaction with the child, and their own feelings. Professionals described working at the family ward as emotionally challenging. Conclusion: Combining treatment of parental SUD, interventions to improve parenting roles and practice, and at the same time focusing on the developmental needs of children, is experienced as a complex and demanding task. Different priorities and treatment aims may enhance tensions between professionals. Even though professionals experience in-patient dual treatment as challenging, they believe this approach facilitates positive development in substance dependent parents and their children.
Clinicopathological significance and diagnostic approach of ROS1 rearrangement in non-small cell lung cancer: a meta-analysis: ROS1 in non-small cell lung cancer
Authors: Yang Jungho , Pyo Jung-Soo , Kang Guhyun 
Published: June 2018

Purpose: The aim of this study was to investigate the rate of ROS1 rearrangement and concordance between ROS1 immunohistochemistry (IHC) and molecular tests in non-small cell lung cancer (NSCLC). Methods: The study included 10,898 NSCLC cases from 21 eligible studies. ROS1 rearrangement rates were evaluated in NSCLC by a meta-analysis, including subgroup analyses. In addition, we performed a concordance analysis and a diagnostic test accuracy review of ROS1 IHC in NSCLC. Results: The estimated overall rate of ROS1 rearrangement and IHC positivity was 2.4% (95% confidence interval (CI) 1.5, 3.7). In the subgroup analysis, which was based on tumor subtype, the rate of ROS1 rearrangement and IHC positivity was 2.9% (95% CI 1.9, 4.5) and 0.6% (95% CI 0.3, 1.2) in adenocarcinoma and non-adenocarcinoma, respectively. The overall concordance rate between ROS1 IHC and molecular tests was 93.4% (95% CI 78.3, 98.2). In ROS1 IHC positive and negative cases, the concordance rates were 79.0% (95% CI 43.3, 94.9) and 97.0% (95% CI 83.3, 99.5), respectively. The pooled sensitivity and the specificity of ROS1 IHC were 0.90 (95% CI 0.70, 0.99) and 0.82 (95% CI 0.79, 0.84), respectively. The diagnostic odds ratio and the area under the curve of the summary receiver operating characteristic curve were 118.01 (95% CI 11.81, 1179.67) and 0.9417, respectively. Conclusion: The rates of ROS1 rearrangement differed by tumor histologic subtype in NSCLC. ROS1 IHC may be useful for the detection of ROS1 rearrangement in NSCLC. Detailed criteria for evaluating ROS1 IHC are needed before it can be applied in daily practice.