bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ponatinib Combined With Rapamycin Causes Regression of Murine Venous Malformation
Authors: Li Xian , Cai Yuqi , Goines Jillian , Pastura Patricia , Brichta Lars , Lane Adam , Le Cras Timothy D. , Boscolo Elisa 
Published: January 2019

Objective—
Venous malformations (VMs) arise from developmental defects of the vasculature and are characterized by massively enlarged and tortuous venous channels. VMs grow commensurately leading to deformity, obstruction of vital structures, bleeding, and pain. Most VMs are associated with the activating mutation L914F in the endothelial cell (EC) tyrosine kinase receptor TIE2. Therapeutic options for VM are limited and ineffective while therapy with the mammalian target of rapamycin inhibitor rapamycin shows moderate efficacy. Here, we investigated novel therapeutic targets promoting VM regression.

Approach and Results—

We performed an unbiased screen of Food and Drug Administration–approved drugs in human umbilical vein ECs expressing the TIE2-L914F mutation (HUVEC-TIE2-L914F). Three ABL (Abelson) kinase inhibitors prevented cell proliferation of HUVEC-TIE2-L914F. Moreover, c-ABL, common target of these inhibitors, was highly phosphorylated in HUVEC-TIE2-L914F and VM patient–derived ECs with activating TIE2 mutations. Knockdown of
c-ABL/ARG
in HUVEC-TIE2-L914F reduced cell proliferation and vascularity of murine VM. Combination treatment with the ABL kinase inhibitor ponatinib and rapamycin caused VM regression in a xenograft model based on injection of HUVEC-TIE2-L914F. A reduced dose of this drug combination was effective in this VM murine model with minimal side effects. The drug combination was antiproliferative, enhanced cell apoptosis and vascular channel regression both in vivo and in a 3-dimensional fibrin gel assay.

Conclusions—
This is the first report of a combination therapy with ponatinib and rapamycin promoting regression of VM. Mechanistically, the drug combination enhanced AKT inhibition compared with single drug treatment and reduced PLCγ (phospholipase C) and ERK (extracellular signal-regulated kinase) activity.
Multicenter Study of the Validity of Additional Freeze Cycles for Cryoballoon Ablation in Patients With Paroxysmal Atrial Fibrillation
Authors: Miyamoto Koji , Doi Atsushi , Hasegawa Kanae , Morita Yoshiaki , Mishima Tsuyoshi , Suzuki Ippei , Kaseno Kenichi , Nakajima Kenzaburo , Kataoka Naoya , Kamakura Tsukasa , Wada Mitsuru , Yamagata Kenichiro , Ishibashi Kohei , Inoue Yuko Y. , Nagase Satoshi , Noda Takashi , Aiba Takeshi , Asakura Masanori , Izumi Chisato , Noguchi Teruo , Tada Hiroshi , Takagi Masahiko , Yasuda Satoshi , Kusano Kengo F. 
Published: January 2019

Background:
Pulmonary vein isolation (PVI) is a cornerstone of catheter ablation in patients with paroxysmal atrial fibrillation, and balloon-based ablation has been recently performed worldwide. The second-generation cryoballoon (CB2) ablation has proven to be highly effective in achieving freedom from paroxysmal atrial fibrillation. However, there are some debatable questions, including the ideal number of freeze cycles.

Methods:
The AD-Balloon study (Multicenter Study of the Validity of Additional Freeze Cycles for Cryoballoon Ablation) was designed as a prospective, multicenter, and randomized clinical trial for investigation of the optimal strategy of freeze cycles for the CB2 ablation. One hundred and ten consecutive patients (aged 64±11 years) were randomly assigned to 2 groups after achieving a PVI by the CB2 ablation: 3-minute freeze cycles were added to each pulmonary vein (AD group: n=55) or not (non-AD group: n=55). Delayed-enhancement magnetic resonance imaging was also performed 1 to 2 months after the PVI to assess the ablation lesions.

Results:

The patient characteristics did not differ between the 2 groups. A complete PVI was achieved in all patients. The total number of freeze cycles and durations for all pulmonary veins were significantly shorter in the non-AD group than in the AD group (5.7±1.6 versus 9.1±1.6 cycles,
P
<0.0001, and 932±244 versus 1483±252 seconds,
P
<0.0001). The cumulative freedom from any atrial tachyarrhythmia at 1 year was 87.3% in the AD group and 89.1% in the non-AD group (log-rank test
P
=0.78). There was no significant difference in the frequency of gaps on the PVI lines in the delayed-enhancement magnetic resonance imaging (46% in the AD group versus 36% in the non-AD group;
P
=0.38).

Conclusions:
No benefit was found in the patients receiving additional 3-minute freeze cycles after the complete PVI with the CB2 ablation, suggesting that an insurance freeze after achieving a PVI with the CB2 may be unnecessary and time consuming.
Impact of Stent Retriever Size on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry
Authors: Zaidat Osama O. , Haussen Diogo C. , Hassan Ameer E. , Jadhav Ashutosh P. , Mehta Brijesh P. , Mokin Maxim , Mueller-Kronast Nils H. , Froehler Michael T. 
Published: January 2019

Background and Purpose—
The safety and efficacy of mechanical thrombectomy in patients with acute ischemic stroke has been demonstrated. However, the impact of stent retriever size on clinical and angiographic outcomes is not well established.

Methods—
This was a retrospective ad hoc analysis of data from the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) registry—a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever. An independent core laboratory, blinded to clinical outcomes, reviewed all procedures and angiographic data to classify stent retriever size, targeted clot location, recanalization after each pass, and the number of stent retriever passes. The primary angiographic end point was first-pass effect (FPE) as determined by a core laboratory and defined as achieving near-complete revascularization (modified Thrombolysis in Cerebral Infarction ≥2c) after the first pass without the use of rescue therapy. Rates of modified FPE were also assessed, defined as meeting all criteria for FPE but achieving modified Thrombolysis in Cerebral Infarction ≥2b after first pass. The primary clinical end point was functional independence (modified Rankin Scale, 0–2) at 3 months as determined on-site. Outcome comparisons were made across the stent retriever size groups and adjusted for baseline characteristics.

Results—

Of 715 patients, a 4×20 stent retriever was used in 201 (28%) patients, 4×40 was used in 270 (38%) patients, and 6×30 was used in 244 (34%) patients. The 4×40 group had the highest rate of FPE (
P
=0.003 versus 6×30) and modified FPE (
P
=0.038 versus 4×20;
P
=0.0001 versus 6×30). Final revascularization was not significantly different across the groups, and there were no significant differences in functional dependence or mortality at 90 days post-procedure. Use of the longer stent retriever (4×40) was an independent predictor of achieving modified FPE (
P
=0.037 versus 6×30;
P
=0.037 versus 4×20).

Conclusions—
The longer stent retriever (4×40) demonstrated the highest rate FPE and modified FPE compared with larger diameter or shorter stent retrievers, suggesting that their routine use may improve early revascularization success.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02239640.
AP-1 (Activated Protein-1) Transcription Factor JunD Regulates Ischemia/Reperfusion Brain Damage via IL-1β (Interleukin-1β)
Authors: Diaz-Cañestro Candela , Reiner Martin F. , Bonetti Nicole R. , Liberale Luca , Merlini Mario , Wüst Patricia , Amstalden Heidi , Briand-Schumacher Sylvie , Semerano Aurora , Giacalone Giacomo , Sessa Maria , Beer Jürg H. , Akhmedov Alexander , Lüscher Thomas F. , Camici Giovanni G. 
Published: January 2019

Background and Purpose—
Inflammation is a major pathogenic component of ischemia/reperfusion brain injury, and as such, interventions aimed at inhibiting inflammatory mediators promise to be effective strategies in stroke therapy. JunD—a member of the AP-1 (activated protein-1) family of transcription factors—was recently shown to regulate inflammation by targeting IL (interleukin)-1β synthesis and macrophage activation. The purpose of the present study was to assess the role of JunD in ischemia/reperfusion-induced brain injury.

Methods—
WT (wild type) mice randomly treated with either JunD or scramble (control) siRNA were subjected to 45 minutes of transient middle cerebral artery occlusion followed by 24 hours of reperfusion. Stroke size, neurological deficit, plasma/brain cytokines, and oxidative stress determined by 4-hydroxynonenal immunofluorescence staining were evaluated 24 hours after reperfusion. Additionally, the role of IL-1β was investigated by treating JunD siRNA mice with an anti–IL-1β monoclonal antibody on reperfusion. Finally, JunD expression was assessed in peripheral blood monocytes isolated from patients with acute ischemic stroke.

Results—
In vivo JunD knockdown resulted in increased stroke size, reduced neurological function, and increased systemic inflammation, as confirmed by higher neutrophil count and lymphopenia. Brain tissue IL-1β levels were augmented in JunD siRNA mice as compared with scramble siRNA, whereas no difference was detected in IL-6, TNF-α (tumor necrosis factor-α), and 4-hydroxynonenal levels. The deleterious effects of silencing of JunD were rescued by treating mice with an anti–IL-1β antibody. In addition, JunD expression was decreased in peripheral blood monocytes of patients with acute ischemic stroke at 6 and 24 hours after onset of stroke symptoms compared with sex- and age-matched healthy controls.

Conclusions—
JunD blunts ischemia/reperfusion-induced brain injury via suppression of IL-1β.
An Analysis of the Reliability of a New Dataset of Transmission Line Icing Thickness in Southern China
Authors: Lu Jiazheng , Li Li , Xu Xunjian , Feng Tao 
Published: January 2019

AbstractBased on ERA-Interim data, gauge observations, transmission line icing observational data, and hindcasted predictors from a numerical forecast system of transmission line icing, a new transmission line icing thickness (TLIT) dataset was constructed to solve the problem of limited historical data. The reliability of the dataset was analyzed using case studies and climate data. The results showed that the descriptions of three icing events in southern China by the TLIT were consistent with the actual observational data, and the icing thickness differences were less than 2 mm. The spatial distribution of annual icing days and icing thickness calculated using meteorological observation station icing data (OIT) and the TLIT data had a similar pattern, with small differences in the numerical values. A rotated empirical orthogonal function (REOF) decomposition was conducted for 67 transmission line icing events. It was found that the spatial distributions of the first three characteristic vectors of the TLIT and OIT data were similar, and the correlation coefficients for the time coefficients of the first three characteristic vectors were 0.801, −0.443, and 0.576, respectively. Three key areas were identified based on the first three patterns of REOF, and the average icing thickness of 67 events in southern China and the three key areas was calculated. The correlation coefficients of icing thickness calculated by the TLIT and OIT data for these areas were 0.648, 0.384, 0.565, and 0.599, respectively. The results illustrate that the TLIT data can reflect the temporal and spatial variations of ice thickness in southern China.
The Empirical Dependence of Tornadogenesis on Elevation Roughness: Historical Record Analysis Using Bayes’s Law in Arkansas
Authors: Hua Zhanxiang , Chavas Daniel R. 
Published: January 2019

AbstractRecent research suggests that surface elevation variability may influence tornado activity, though separating this effect from reporting biases is difficult to do in observations. Here we employ Bayes’s law to calculate the empirical joint dependence of tornado probability on population density and elevation roughness in the vicinity of Arkansas for the period 1955–2015. This approach is based purely on data, exploits elevation and population information explicitly in the vicinity of each tornado, and enables an explicit test of the dependence of results on elevation roughness length scale. A simple log-link linear regression fit to this empirical distribution yields an 11% decrease in tornado probability per 10-m increase in elevation roughness at fixed population density for large elevation roughness length scales (15–20 km). This effect increases by at least a factor of 2 moving toward smaller length scales down to 1 km. The elevation effect exhibits no time trend, while the population bias effect decreases systematically in time, consistent with the improvement of reporting practices. Results are robust across time periods and the exclusion of EF1 tornadoes and are consistent with recent county-level and gridded analyses. This work highlights the need for a deeper physical understanding of how elevation heterogeneity affects tornadogenesis and also provides the foundation for a general Bayesian tornado probability model that integrates both meteorological and nonmeteorological parameters.
A pilot study of radon levels in certified passive house buildings
Authors: McCarron Barry , Meng Xianhai , Colclough Shane 
Published: January 2019

The international Passive House Standard delivers high thermal comfort based on the principles of excellent building fabric and balanced mechanical heat recovery ventilation. Considering that the typical person in industrial countries (such as the UK) spends ∼90% of their time indoors, there are surprisingly few academic studies on air quality in the home. Indoor air quality and the prevalence of overheating are attracting an increasing amount of research attention across Europe, but post occupancy monitoring of indoor radon concentrations is severely underrepresented, especially in Ireland and the UK. Radon is a naturally occurring radioactive gas and known carcinogen that presents a potential risk to occupier health. This pilot study investigates measured radon levels in certified Passive House buildings in Northern Ireland and presents an overview of technical radon prevention design options for new builds and mitigation measures for existing buildings. Initial findings indicate that buildings built to the Passive House Standard correspond with reduced indoor radon gas concentrations. Practical application: This Technical Note addresses an issue pertinent to the industry at this time. The growth of energy-efficient standards (such as Passive House) and common principles (such as increased airtightness levels and mechanical ventilation systems) has accelerated the need for research data on indoor radon concentrations. This research bridges the knowledge gap between the fields of indoor air quality (specifically radon), health, sustainability and the built environment.
The treatment of Fatigue and Damage Accumulation in Composite Design
Authors: Kedward K T , Beaumont P W R 
Published: January 2019

SUMMARY The process of design has traditionally involved a specialized treatment of damage accumulation and associated fatigue phenomena, e.g. Miners Rule. The treatment of such phenomena for the case of advanced composites tends to be complicated by the existence of a multiplicity of competing failure modes. The subject assumes even greater importance when the ever expanding types of composite systems are considered, i.e. Polymer Matrix Composites (PMC's), Ceramic Matrix Composites (CMC's) and Metal Matrix Composites (MMC's) to name the broader categories. All composite systems are considered herein to comprise continuous fiber reinforcements.
A multi-objective evaluation method based on connection numbers theory of hazardous chemical accidents emergency medical rescue capability
Authors: Wang Yapeng , Zhang Jinguo , Wang Yundou , Xiong Xiaowen , Zhao Xin 
Published: January 2019

Background: An objective, comprehensive and scientific evaluation of emergency medical rescue capability (EMRC) is of great realistic significance in assisting the health administrative department to grasp the overall response capability of all emergency medical rescue teams, enabling each team to have a full understanding of its own strengths and weakness and improve itself accordingly. At present, the research on the evaluation of EMRC in Hazardous Chemicals Accidents (HCA) is not systematic and in-depth, and the existing research results also have some shortcomings, such as, the lack of strong theoretical support for the evaluation index system, the relatively single function of evaluation methods, and so on. Objectives: The objective of this article is to research the evaluation index system and a new evaluation method of EMRC in HCA to overcome the above shortcomings. Methods: It establishes an emergency medical rescue capability model by employing the competency model and then constructs the evaluation index system on the basis of the analysis of all the factors of emergency medical rescue capability in hazardous chemical accidents and sets up an evaluation model based on the theory of connection numbers and partial connection numbers. It determines the competence ranking of several emergency medical rescue teams and the competence state of an individual emergency medical rescue team by calculating the connection principal value, and it also predicts how the emergency medical rescue capability will develop based on the values of partial connection numbers. Results: The example shows that the calculation process of this model is relatively simple, and its assessment results are objective and authentic, and moreover, its multi-functions can make up for the deficiency of the simplified function of other evaluation models. Conclusion: This method is scientific and rational to some extent and can provide reference for evaluation problems of the same kind.
The Elimination of Dental Crowding and Development of a Proper Dental Arch by Maxillary Anterior Segmental Distraction Osteogenesis for a Patient With UCLP
Authors: Tanikawa Chihiro , Lee Donghoon , Oonishi Yuri Yamamoto , Haraguchi Seiji , Aikawa Tomonao , Kogo Mikihiko , Iida Seiji , Yamashiro Takashi 
Published: January 2019

Objective: This report describes the case of a male patient with a complete unilateral cleft lip and palate who presented with midface deficiency and an anteroposteriorly constricted maxilla. Design: Case report Interventions: Correction involved anterior distraction of the segmented maxilla. Results: The present case demonstrates that elongation of the maxilla with anterior distraction is an effective way to develop a proper dental arch, correct anterior and posterior crowding, and improve a midface deficiency.
Vitamin D Level and Supplementation in Pediatric Atopic Dermatitis: A Randomized Controlled Trial
Authors: Lara-Corrales Irene , Huang Christina M. , Parkin Patricia C. , Rubio-Gomez Gustavo A. , Posso-De Los Rios Claudia J. , Maguire Jonathon , Pope Elena 
Published: January 2019

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by a pruritic eczematous rash. Evidence surrounding the role of serum vitamin D (VD) in modifying disease severity is inconsistent. Objectives: To determine whether VD levels are correlated with AD severity and the effects of VD supplementation on disease modification. Methods: This was a 2-phase study, using a cross-sectional design to evaluate the relationship between VD level and severity, as well as a double-blinded, randomized control trial to elucidate the effects of VD supplementation. Patients aged 0 to 18 years with AD were included in phase 1, and disease severity and serum VD levels were determined. Those with renal, liver, or other dermatologic conditions were excluded. Patients with abnormal (<72.7 nmol/L) VD levels were eligible for phase 2 and to be randomized to either VD supplementation of 2000 IU/d or placebo. VD level and severity were assessed at baseline and 3 months. Results: The 77 patients included in phase 1 had a mean (SD) age of 7.4 (4.5) years, and 45.5% (33/77) were female. Increased severity was significantly correlated with lower VD levels ( P = .015). Of the 45 patients included in phase 2, 21 and 24 were assigned to the supplementation and placebo arm, respectively. The mean (SD) change in severity did not differ significantly between the supplementation (15.35 [9.71]) and placebo (15.13 [8.97]) groups after 3 months of intervention ( P = .7). Conclusion: Although VD levels correlated with AD severity, VD supplementation did not significantly improve disease severity.
Evaluating Patients for Elective Outpatient Foot and Ankle Surgery: Insurance as a Predictor of Patient Outcomes
Authors: Bakhsh Wajeeh , Childs Sean , Oh Irvin , Flemister Sam , Baumhauer Judy , Ketz John 
Published: January 2019

Background. Elective surgical procedures necessitate careful patient selection. Insurance level has been associated with postoperative outcomes in trauma patients. This study evaluates the relationship insurance level has with outcomes from elective foot and ankle surgery. Methods. Retrospective chart review was performed on patients who underwent elective surgery at a single center with 1-year follow-up. Patients were classified by insurance: under-/uninsured (Medicaid, Option plans) versus fully insured. Outcomes included narcotic refills, patient-reported outcomes (PROMIS) of pain, function, and mood, and compliance with follow-up visits. Statistical analysis involved mean comparison and multivariate regression modeling, with significance P < .05. Results. Cohort groups included 220 insured and 47 under-/uninsured. Outcomes between the insured and under-/uninsured groups differed significantly in narcotic refills (0.72 vs 1.74 respectively, P < .01), missed appointments (0.13 vs 0.62, P < .01), and PROMIS results (pain 54.5 vs 60.2; function 44.3 vs 39.5; mood 44.6 vs 51.3; P < .01). The change in PROMIS scores from preoperative to 1-year postoperative were different in pain (−7.3 vs −2.5, P = .03) and function (+6.3 vs +1.3, P = .04). Regression results confirm insurance as a significant factor (coefficient 0.27, P < .01). Conclusion. These results establish that under-/uninsured patients have worse pain, patient-reported outcomes, and functional outcomes after elective foot and ankle surgery, which may inform patient selection. Levels of Evidence: Level III: Retrospective cohort study