bluuebunny/crossref_metadata_2025_split huggingface dataset:
Setting the international standard for longitudinal follow-up of patients with systemic sclerosis: a Delphi-based expert consensus on core clinical features
Authors: Hoffmann-Vold Anna-Maria , Distler Oliver , Murray Baron , Kowal-Bielecka Otylia , Khanna Dinesh , Allanore Yannick 
Published: March 2019

BackgroundSystemic sclerosis (SSc) is a severe, progressive multiorgan disease but to date, there are no established standardised international guidelines for follow-up of patients with SSc. The goal of this project was to develop an expert consensus for annual systematic investigations in patients with SSc to enhance their standard-of-care.Material and methodsThe Delphi method was applied. All SSc experts from the European Scleroderma Trials and Research group network and the Scleroderma Clinical Trial Consortium were invited to participate. All experts were asked to answer questionnaires in five Delphi steps to determine the domains of interest and tools for each domain for an annual systematic assessment of patients with SSc. Each item was rated on a scale between 0% and 100% (not and very important), and parameters rated >80% by more than 75% of the experts were regarded as acceptable.ResultsIn total, 157 experts worldwide participated with 71.3% experts seeing >50 patients with SSc annually. In the first round, 23 domains and 204 tools were suggested. After five Delphi steps, experts agreed on 10 domains including (1) Raynaud’s phenomenon; (2) Digital ulcers; (3) Skin and mucosa; (4) Lung; (5); Heart; (6) GI domain, (7) Renal; (8) Musculoskeletal; (9) Laboratory and (10) Treatment. Overall, 55 tools were identified including clinical assessments, laboratory measurements and imaging or functional investigations.ConclusionThrough five Delphi steps with world leading experts, a consensus was established on strongly suggested tools for a minimum annual systemic assessment of organ involvement in SSc. This work should enhance the standardisation and homogenisation of the practices.
Effect of moisture absorption and fiber orientation on electrical conductivity and electromagnetic interference shielding of carbon fiber reinforced bioplastic composites
Authors: Solafide Wahyu , Murakami Ri-Ichi 
Published: March 2019

The aim of this study is to discuss the effect of moisture absorption on electrical conductivity and electromagnetic interference of the carbon fiber (CF) reinforced bioplastic composite. The composites were prepared by the hot press machine, and immersed in water for 20 and 40 days. The electrical conductivity measurements were carried out as a function immersed time. The electrical conductivity of CF with two layers is greater than that of one layer, because the electrical conductivity increases with increasing the volume filler of CF. The electrical conductivity slightly increases with increasing the immersion time. The EMI SE (electromagnetic interference shielding effectiveness) of the composite was examined with the frequency from 500 MHz to 2000 MHz. The EMI SE of the CF increases with increasing the content of the CF, and the EMI SE result of composite is around 50 dB to 60 dB. There is scarcely significant effect of orientation on composite on the EMI SE.
Somatic Hypermutation of the YAP Oncogene in a Human Cutaneous Melanoma
Authors: Zhang Xiaomeng , Tang Jian Zhong , Vergara Ismael A. , Zhang Youfang , Szeto Pacman , Yang Lie , Mintoff Christopher , Colebatch Andrew , McIntosh Lachlan , Mitchell Katrina A. , Shaw Evangeline , Rizos Helen , Long Georgina V. , Hayward Nicholas , McArthur Grant A. , Papenfuss Anthony T. , Harvey Kieran F. , Shackleton Mark 
Published: March 2019

Abstract

Melanoma is usually driven by mutations in BRAF or NRAS, which trigger hyperactivation of MAPK signaling. However, MAPK-targeted therapies are not sustainably effective in most patients. Accordingly, characterizing mechanisms that co-operatively drive melanoma progression is key to improving patient outcomes. One possible mechanism is the Hippo signaling pathway, which regulates cancer progression via its central oncoproteins YAP and TAZ, although is thought to be only rarely affected by direct mutation. As YAP hyperactivation occurs in uveal melanoma, we investigated this oncogene in cutaneous melanoma. YAP protein expression was elevated in most benign nevi and primary cutaneous melanomas but present at only very low levels in normal melanocytes. In patient-derived xenografts and melanoma cell lines, we observed variable reliance of cell viability on Hippo pathway signaling that was independent of TAZ activity and also of classical melanoma driver mutations such as BRAF and NRAS. Finally, in genotyping studies of melanoma, we observed the first ever hyperactivating YAP mutations in a human cancer, manifest as seven distinct missense point mutations that caused serine to alanine transpositions. Strikingly, these mutate four serine residues known to be targeted by the Hippo pathway and we show that they lead to hyperactivation of YAP.

Implications:
Our studies highlight the YAP oncoprotein as a potential therapeutic target in select subgroups of melanoma patients, although successful treatment with anti-YAP therapies will depend on identification of biomarkers additional to YAP protein expression.
The Pioneering Role of GATA2 in Androgen Receptor Variant Regulation Is Controlled by Bromodomain and Extraterminal Proteins in Castrate-Resistant Prostate Cancer
Authors: Chaytor Lewis , Simcock Matthew , Nakjang Sirintra , Heath Richard , Walker Laura , Robson Craig , Jones Dominic , Gaughan Luke 
Published: March 2019

Abstract

The androgen receptor (AR) is a key driver of prostate cancer development. Antiandrogens effectively inactivate the AR, but subsequent AR reactivation progresses the disease to castrate-resistant prostate cancer (CRPC). Constitutively active AR splice variants (AR-V) that function unchallenged by current AR-targeted therapies are key drivers of CRPC. Currently, very little is known about the regulation of AR-Vs at the chromatin level. Here, we show that the pioneer factor GATA2 is a critical regulator of AR-Vs. Furthermore, we demonstrate that the GATA2 cistrome in CRPC shares considerable overlap with bromodomain and extraterminal (BET) proteins and is codependent for DNA binding. GATA2 activity is compromised by BET inhibitors, which attenuates the pioneering role of GATA2 in CRPC. In all, this study indicates that GATA2 is a critical regulator of AR-V–mediated transactivation and is sensitive to BET inhibitors, signifying these agents may be efficacious in patients with CRPC which overexpress GATA2.

Implications:
We have defined novel mechanisms of AR-V and GATA2 regulation in advanced prostate cancer that could be therapeutically exploited.
Association between Trimetazidine and Parkinsonism: A Population-Based Study
Authors: Kwon Jeongyoon , Yu Yun Mi , Kim Seungyeon , Jeong Kyeong Hye , Lee Euni 
Published: March 2019

<b><i>Background:</i></b> The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. <b><i>Objectives:</i></b> To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. <b><i>Methods:</i></b> A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. <b><i>Results:</i></b> Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06–1.81; <i>p</i> = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13– 3.74; <i>p</i> = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87–5.61; <i>p</i> &#x3c; 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. <b><i>Conclusions:</i></b> Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.
Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0–5
Authors: Kaesmacher Johannes , Chaloulos-Iakovidis Panagiotis , Panos Leonidas , Mordasini Pasquale , Michel Patrik , Hajdu Steven D. , Ribo Marc , Requena Manuel , Maegerlein Christian , Friedrich Benjamin , Costalat Vincent , Benali Amel , Pierot Laurent , Gawlitza Matthias , Schaafsma Joanna , Mendes Pereira Vitor , Gralla Jan , Fischer Urs 
Published: March 2019

Background and Purpose—
If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients.

Methods—

Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI.

Results—
Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results.

Conclusions—
In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.
A New Normal for Interest Rates? Evidence from Inflation-Indexed Debt
Authors: Christensen Jens H. E. , Rudebusch Glenn D. 
Published: March 2019

Abstract
The downtrend in U.S. interest rates over the past two decades may partly reflect a decline in the longer-run equilibrium real rate of interest. We examine this issue using dynamic term structure models that account for time-varying term and liquidity risk premiums and are estimated directly from prices of individual inflation-indexed bonds. Our finance-based approach avoids two potential pitfalls of previous macroeconomic analyses: structural breaks at the zero lower bound and misspecification of output and inflation dynamics. We estimate that the longer-run equilibrium real rate has fallen about 2 percentage points and appears unlikely to rise quickly.
Relationship between the elbow joint valgus instability and forearm flexor muscle strength in high school pitchers with and without symptom
Authors: Tajika Tsuyoshi , Oya Noboru , Ichinose Tsuyoshi , Shimoyama Daisuke , Sasaki Tsuyoshi , Hamano Noritaka , Shitara Hitoshi , Yamamoto Atsushi , Takagishi Kenji , Chikuda Hirotaka 
Published: March 2019

Objectives: Earlier reports describe forearm flexor muscles as active stabilizers of the elbow to valgus stress during throwing motion. Given high school pitchers’ history of elbow symptoms, this study assesses its relation to elbow valgus joint instability and forearm flexor muscle strength. Methods: Ultrasound examination was made for 132 high school baseball pitchers with and without valgus stress of the medial aspect of the bilateral elbows. They had completed a self-administered questionnaire related to self-satisfaction score (0–100) for pitching performance and throwing-related elbow joint pain sustained during the prior year. Using a digital manual muscle strength meter, we examined the grip strength and muscle strength of the flexor carpi ulnaris (FCU). For participants with and without a history of elbow symptom, we compared differences of ulnohumeral joint space width with and without valgus stress and grip and FCU muscle strength. Results: For ulnohumeral joint width difference with and without valgus stress, pitchers with an elbow symptom and those without elbow symptom history on the throwing side were not significantly different. No difference was found in the grip strength or FCU muscle strength of the throwing side for each group. Positive significant association was found between FCU muscle strength on the pitching side and the self-evaluation score for pitching performance ( r = 0.27, p = 0.002). However, no association was found between the elbow valgus instability and the forearm flexor muscle strength. Conclusion: FCU muscle strength might influence high school baseball pitching performance.
Stabilization of chevron osteotomy with a capsuloperiosteal flap: Results in 15 years of follow-up
Authors: Koken Murat , Basat H Cagdas , Kara A Hakan , Us A Kemal , Guclu Berk 
Published: March 2019

Purpose: Distal chevron osteotomy (DCO) is used more frequently than other methods for the correction of mild-to-moderate hallux valgus deformity because it is markedly more stable. Here, we evaluated the use of a capsuloperiosteal flap to stabilize DCO and presented our last longer follow-up. Methods: This study included a total of 57 patients (86 feet) made up of 50 women (79 feet) and 7 men (7 feet) with a mean age of 37.8 years who were diagnosed with hallux valgus and met the inclusion criteria. These patients received treatment using a capsuloperiosteal flap to stabilize DCO from 1994 to 2000. Clinical outcomes of the patients were assessed using the American Orthopaedic Foot and Ankle Society hallux scale. Results: The mean follow-up duration was 14.8 years. The score increased from a preoperative mean of 52 points to a mean of 90.5 points at last follow-up. The mean hallux valgus angle changed from 30.3° preoperatively to 14.4° postoperatively at the last follow-up. The first to second intermetatarsal angle changed from 13.6° preoperatively to 10.5° postoperatively. The correction in the range of motion proved to be consistent with only an average of 1° correction loss and 5.5° loss. Eighty-four feet (97.6%) were pain-free. Discomfort with shoe wear was absent in 82 feet (95.3%) postoperatively, and 23 of 24 (95.8%) patients were fascinated cosmetically. Conclusion: Correction of mild-to-moderate hallux valgus deformity with the use of capsuloperiosteal flap for stabilization of DCO provided findings comparable with the literature regarding clinical and radiological outcomes at long-term follow-up. Level of Evidence: IV, Retrospective Case Series.
Substitution mechanisms in In-, Au-, and Cu-bearing sphalerites studied by X-ray absorption spectroscopy of synthetic compounds and natural minerals
Authors: Filimonova Olga N. , Trigub Alexander L. , Tonkacheev Dmitriy E. , Nickolsky Max S. , Kvashnina Kristina O. , Chareev Dmitriy A. , Chaplygin Ilya V. , Kovalchuk Elena V. , Lafuerza Sara , Tagirov Boris R. 
Published: March 2019

AbstractSphalerite is the main source of In – a ‘critical’ metal widely used in high-tech electronics. In this mineral the concentration of In is commonly correlated directly with Cu content. Here we use X-ray absorption spectroscopy of synthetic compounds and natural crystals in order to investigate the substitution mechanisms in sphalerites where In is present, together with the group 11 metals. All the admixtures (Au, Cu, In) are distributed homogeneously within the sphalerite matrix, but their structural and chemical states are different. In all the samples investigated In3+replaces Zn in the structure of sphalerite. The In ligand distance increases by 0.12 Å and 0.09–0.10 Å for the 1st and 2nd coordination shells, respectively, in comparison with pure sphalerite. The In–S distance in the 3rd coordination shell is close to the one of pure sphalerite. Gold in synthetic sphalerites is coordinated with sulfur (NS= 2.4–2.5,RAu–S= 2.35 ± 0.01 Å). Our data suggest that at high Au concentrations (0.03–0.5 wt.%) the Au2S clusters predominate, with a small admixture of the Au+solid solution with an Au–S distance of 2.5 Å. Therefore, the homogeneous character of a trace-element distribution, which is commonly observed in natural sulfides, does not confirm formation of a solid solution. In contrast to Au, the presence of Cu+with In exists only in the solid-solution state, where it is tetrahedrally coordinated with S atoms at a distance of 2.30 ± 0.03 Å. The distant coordination shells of Cu are disordered. These results demonstrate that the group 11 metals (Cu, Ag and Au) can exist in sphalerite in the metastable solid-solution state. The solid solution forms at high temperature via the charge compensation scheme 2Zn2+↔Me++Me3+. The final state of the trace elements at ambient temperature is governed by the difference in ionic radii with the main component (Zn), and concentration of admixtures.
Dysregulated alveolar function and complications in smokers following oesophagectomy
Authors: Lugg Sebastian T. , Alridge Kerrie A. , Howells Phillip A. , Parekh Dhruv , Scott Aaron , Mahida Rahul Y. , Park Daniel , Tucker Olga , Gao Fang , Perkins Gavin D. , Thickett David R. , Dancer Rachel C.A. 
Published: March 2019

Acute respiratory distress syndrome (ARDS) has a significant impact on post-operative morbidity and mortality following oesophagectomy. Smoking is a risk factor for the development of ARDS, although the mechanism is unclear. We examined the effect of smoking on alveolar and systemic inflammation, in addition to alveolar–capillary permeability, leading to ARDS in patients undergoing oesophagectomy.We compared clinical, biomarker and PiCCO system data between current smokers (n=14) and ex-smokers (n=36) enrolled into a translational substudy of the BALTI-P (Beta Agonist Lung Injury Trial Prevention) trial.Current smokers compared with ex-smokers had significantly higher numbers of circulating neutrophils, elevated bronchoalveolar lavage (BAL) interleukin (IL)-1 receptor antagonist (IL-1ra), soluble tumour necrosis factor receptor-1 and pre-operative plasma soluble intercellular adhesion molecule-1, and lower BAL vascular endothelial growth factor and post-operative plasma IL-17 (p<0.05). On post-operative day 1, current smokers had higher extravascular lung water index (9.80versus7.90; p=0.026) and pulmonary vascular permeability index (2.09versus1.70; p=0.013). Current smokers were more likely to develop ARDS (57%versus25%; p=0.031) and had a significantly reduced post-operative median survival (421versus771 days; p=0.023).Smoking prior to oesophagectomy is associated with dysregulated inflammation, with higher concentrations of inflammatory mediators and lower concentrations of protective mediators. This translates into a higher post-operative inflammatory alveolar oedema, greater risk of ARDS and poorer long-term survival.
Association between diuretic use and the risk of vertebral fracture after stroke: a population-based retrospective cohort study
Authors: Lin Shu-Man , Yang Shih-Hsien , Wang Chih-Yung , Huang Huei-Kai 
Published: March 2019

Abstract
Background
Stroke is a major risk factor for osteoporosis and fractures. No study has evaluated the association between diuretic use and risk of vertebral fracture in stroke patients, although a considerable proportion of stroke patients are prescribed diuretics for hypertension. Our study aimed to investigate whether treatment with thiazides or loop diuretics affects the risk of vertebral fracture after stroke.

Methods
A population-based propensity score-matched retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients with a new diagnosis of stroke between 2000 and 2011 were included. After propensity score matching, 9468 patients were included in the analysis of the effect of thiazides, of who 4734 received thiazides within 2 years after stroke. To analyze the loop diuretic effect, 4728 patients were included, of who 2364 received loop diuretics. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) of vertebral fractures among patients according to thiazide or loop diuretic use within 2 years following stroke. Sensitivity analyses based on the duration of thiazide or loop diuretic use were further conducted.

Results
There was no significant difference in vertebral fracture risk between thiazide users and non-users (adjusted HR [aHR] = 1.14, 95% confidence interval [CI] = 0.88–1.47, p = 0.316). Loop diuretic users had a significantly higher vertebral fracture risk than non-users (aHR = 1.45, 95% CI = 1.06–1.98, p = 0.019). However, the sensitivity analysis revealed that short-term thiazide use (exposure duration < 90 days within 2 years after stroke) significantly increased the risk of vertebral fracture versus non-use (aHR = 1.38, 95% CI = 1.02–1.88, p = 0.039). Only short-term loop diuretic users had significantly higher risk of vertebral fracture (aHR = 1.56, 95% CI = 1.11–2.20, p = 0.011). The other two subgroups with longer exposure duration in analyses for both thiazides and loop diuretics revealed no significant effect.

Conclusions
Short-term thiazide or loop diuretic use was associated with an increased risk of vertebral fracture after stroke. Further prospective clinical trials are required to confirm this finding.