bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Therapeutic Synergy of MEK1/2 and CDK4/6 Inhibition in Neuroblastoma
Authors: Hart Lori S. , Rader JulieAnn , Raman Pichai , Batra Vandana , Russell Mike R. , Tsang Matthew , Gagliardi Maria , Chen Lucy , Martinez Daniel , Li Yimei , Wood Andrew , Kim Sunkyu , Parasuraman Sudha , Delach Scott , Cole Kristina A. , Krupa Shiva , Boehm Markus , Peters Malte , Caponigro Giordano , Maris John M. 
Published: October 2016

Abstract
Purpose: Neuroblastoma is treated with aggressive multimodal therapy, yet more than 50% of patients experience relapse. We recently showed that relapsed neuroblastomas frequently harbor mutations leading to hyperactivated ERK signaling and sensitivity to MEK inhibition therapy. Here we sought to define a synergistic therapeutic partner to potentiate MEK inhibition.
Experimental Design: We first surveyed 22 genetically annotated human neuroblastoma-derived cell lines (from 20 unique patients) for sensitivity to the MEK inhibitor binimetinib. After noting an inverse correlation with sensitivity to ribociclib (CDK4/6 inhibitor), we studied the combinatorial effect of these two agents using proliferation assays, cell-cycle analysis, Ki67 immunostaining, time-lapse microscopy, and xenograft studies.
Results: Sensitivity to binimetinib and ribociclib was inversely related (r = −0.58, P = 0.009). MYCN amplification status and expression were associated with ribociclib sensitivity and binimetinib resistance, whereas increased MAPK signaling was the main determinant of binimetinib sensitivity and ribociclib resistance. Treatment with both compounds resulted in synergistic or additive cellular growth inhibition in all lines tested and significant inhibition of tumor growth in three of four xenograft models of neuroblastoma. The augmented growth inhibition was attributed to diminished cell-cycle progression that was reversible upon removal of drugs.
Conclusions: Here we demonstrate that combined binimetinib and ribociclib treatment shows therapeutic synergy across a broad panel of high-risk neuroblastoma preclinical models. These data support testing this combination therapy in relapsed high-risk neuroblastoma patients, with focus on cases with hyperactivated RAS–MAPK signaling. Clin Cancer Res; 23(7); 1785–96. ©2016 AACR.
Prognostic Benefit of Cardiac Magnetic Resonance Over Transthoracic Echocardiography for the Assessment of Ischemic and Nonischemic Dilated Cardiomyopathy Patients Referred for the Evaluation of Primary Prevention Implantable Cardioverter–Defibrillator Therapy
Authors: Pontone Gianluca , Guaricci Andrea I. , Andreini Daniele , Solbiati Anna , Guglielmo Marco , Mushtaq Saima , Baggiano Andrea , Beltrama Virginia , Fusini Laura , Rota Cristina , Segurini Chiara , Conte Edoardo , Gripari Paola , Dello Russo Antonio , Moltrasio Massimo , Tundo Fabrizio , Lombardi Federico , Muscogiuri Giuseppe , Lorenzoni Valentina , Tondo Claudio , Agostoni Piergiuseppe , Bartorelli Antonio L. , Pepi Mauro 
Published: October 2016

Background—
The aim of this study was to determine the prognostic benefit of cardiac magnetic resonance (CMR) over transthoracic echocardiography (TTE) in ischemic cardiomyopathy and nonischemic dilated cardiomyopathy patients evaluated for primary prevention implantable cardioverter–defibrillator therapy.

Methods and Results—

We enrolled 409 consecutive ischemic and dilated cardiomyopathy patients (mean age: 64±12 years; 331 men). All patients underwent TTE and CMR, and left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricle ejection fraction (LVEF) were evaluated. In addition, late gadolinium enhancement was also assessed. All patients were followed up for major adverse cardiac events (MACE) defined as a composite end point of long runs of nonsustained ventricular tachycardia, sustained ventricular tachycardia, aborted sudden cardiac death, or sudden cardiac death. The median follow-up was 545 days. CMR showed higher left ventricle end-diastolic volume (mean difference: 43±22.5 mL), higher left ventricle end-systolic volume (mean difference: 34±20.5 mL), and lower LVEF (mean difference: −4.9±10%) as compared to TTE (
P
<0.01). MACE occurred in 103 (25%) patients. Patients experiencing MACE showed higher left ventricle end-diastolic volume, higher left ventricle end-systolic volume, and lower LVEF with both imaging modalities and higher late gadolinium enhancement per-patient prevalence as compared to patients without MACE. At multivariable analysis, CMR-LVEF ≤35% (hazard ratio=2.18 [1.3–3.8]) and the presence of late gadolinium enhancement (hazard ratio=2.2 [1.4–3.6]) were independently associated with MACE (
P
<0.01). A model based on CMR-LVEF ≤35% or CMR-LVEF ≤35% plus late gadolinium enhancement detection showed a higher performance in the prediction of MACE as compared to TTE-LVEF resulting in net reclassification improvement of 0.468 (95% confidence interval, 0.283–0.654;
P
<0.001) and 0.413 (95% confidence interval, 0.23–0.63;
P
<0.001), respectively.

Conclusions—
CMR provides additional prognostic stratification as compared to TTE, which may have direct impact on the indication of implantable cardioverter–defibrillator implantation.
Novel Angiographic Classification of Each Vascular Lesion in Chronic Thromboembolic Pulmonary Hypertension Based on Selective Angiogram and Results of Balloon Pulmonary Angioplasty
Authors: Kawakami Takashi , Ogawa Aiko , Miyaji Katsumasa , Mizoguchi Hiroki , Shimokawahara Hiroto , Naito Takanori , Oka Takashi , Yunoki Kei , Munemasa Mitsuru , Matsubara Hiromi 
Published: October 2016

Background—
Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions.

Methods and Results—
We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success rate was higher, and the complication rate was lower in ring-like stenosis and web lesions. The total occlusion lesions had the lowest success rate. Tortuous lesions were associated with a high complication rate and should be treated only by operators with extensive experience with BPA.

Conclusions—
We modified the previous angiographic classification and established a new classification for each vascular lesion. We clarified that the outcome and complication rate of the BPA are highly dependent on the lesion characteristics.
Development and Validation of a Scoring System for Predicting Periprocedural Complications During Percutaneous Coronary Interventions of Chronic Total Occlusions: The Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO) Complications Score
Authors: Danek Barbara Anna , Karatasakis Aris , Karmpaliotis Dimitri , Alaswad Khaldoon , Yeh Robert W. , Jaffer Farouc A. , Patel Mitul P. , Mahmud Ehtisham , Lombardi William L. , Wyman Michael R. , Grantham J. Aaron , Doing Anthony , Kandzari David E. , Lembo Nicholas J. , Garcia Santiago , Toma Catalin , Moses Jeffrey W. , Kirtane Ajay J. , Parikh Manish A. , Ali Ziad A. , Karacsonyi Judit , Rangan Bavana V. , Thompson Craig A. , Banerjee Subhash , Brilakis Emmanouil S. 
Published: October 2016

Background

High success rates are achievable for chronic total occlusion (
CTO
) percutaneous coronary intervention (
PCI
) using the hybrid approach, but periprocedural complications remain of concern. Although scores estimating success and efficiency in
CTO PCI
have been developed, there is currently no available score for estimation of the risk for periprocedural complications. We sought to develop a scoring tool for prediction of periprocedural complications during
CTO PCI
.

Methods and Results

We analyzed data from 1569
CTO PCI
s in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (
PROGRESS CTO
) using a derivation and validation sampling ratio of 2:1. Variables independently associated with periprocedural complications in multivariable analysis in the derivation set were assigned points based on their respective odds ratios. Forty‐four (2.8%) patients experienced complications. Three factors were independent predictors of complications and were included in the score: patient age >65 years, +3 points (odds ratio,
OR
=4.85,
CI
1.82‐16.77); lesion length ≥23 mm, +2 points (
OR
=3.22,
CI
1.08‐13.89); and use of the retrograde approach +1 point (
OR
=2.41,
CI
1.04‐6.05). The resulting score showed good calibration and discriminatory capacity in the derivation (Hosmer‐Lemeshow χ
2
6.271,
P
=0.281, receiver‐operating characteristic [
ROC
] area=0.758) and validation (Hosmer‐Lemeshow χ
2
4.551,
P
=0.473,
ROC
area=0.793) sets. Score values of 0 to 2, 3 to 4, and ≥5 were defined as low, intermediate, and high risk of complications (derivation cohort 0.4%, 1.8%, 6.5%,
P
<0.001; validation cohort 0.0%, 2.5%, 6.8%,
P
<0.001).

Conclusions

The
PROGRESS CTO
complication score is a useful tool for prediction of periprocedural complications in
CTO PCI
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02061436.
Atherosclerotic Plaques in the Aortic Arch and Subclinical Cerebrovascular Disease
Authors: Tugcu Aylin , Jin Zhezhen , Homma Shunichi , Elkind Mitchell S.V. , Rundek Tatjana , Yoshita Mitsuhiro , DeCarli Charles , Nakanishi Koki , Shames Sofia , Wright Clinton B. , Sacco Ralph L. , Di Tullio Marco R. 
Published: October 2016

Background and Purpose—
Aortic arch plaque (AAP) is a risk factor for ischemic stroke, but its association with subclinical cerebrovascular disease is not established. We investigated the association between AAP and subclinical cerebrovascular disease in an elderly stroke-free community-based cohort.

Methods—
The CABL study (Cardiovascular Abnormalities and Brain Lesions) was designed to investigate cardiovascular predictors of silent cerebrovascular disease in the elderly. AAPs were assessed by suprasternal transthoracic echocardiography in 954 participants. Silent brain infarcts and white matter hyperintensity volume (WMHV) were assessed by brain magnetic resonance imaging. The association of AAP thickness with silent brain infarcts and WMHV was evaluated by logistic regression analysis.

Results—

Mean age was 71.6±9.3 years; 63% were women. AAP was present in 658 (69%) subjects. Silent brain infarcts were detected in 138 participants (14.5%). In multivariate analysis adjusted for potential confounders, AAP thickness and large AAP (≥4 mm in thickness) were significantly associated with the upper quartile of WMHV (WMHV-Q4; odds ratio =1.17; 95% confidence interval, 1.04–1.32;
P
=0.009 and odds ratio =1.79; 95% confidence interval, 1.40–3.09;
P
=0.036, respectively), but not with silent brain infarcts (odds ratio =1.08; 95% confidence interval, 0.94–1.23;
P
=0.265 and odds ratio =1.46; 95% confidence interval, 0.77–2.77;
P
=0.251, respectively).

Conclusions—
Aortic arch atherosclerosis was associated with WMHV in a stroke-free community-based elderly cohort. This association was stronger in subjects with large plaques and independent of cardiovascular risk factors. Aortic arch assessment by transthoracic echocardiography may help identify subjects at higher risk of subclinical cerebrovascular disease, who may benefit from aggressive stroke risk factors treatment.
The Effect of Soldier Marching, Rucksack Load, and Heart Rate on Marksmanship
Authors: Tenan Matthew S. , LaFiandra Michael E. , Ortega Samson V. 
Published: October 2016

Objective: The purpose was to determine if Soldier rucksack load, marching distance, and average heart rate (HR) during shooting affect the probability of hitting the target. Background: Infantry Soldiers routinely carry heavy rucksack loads and are expected to engage enemy targets should a threat arise. Method: Twelve male Soldiers performed two 11.8 km marches in forested terrain at 4.3 km/hour on separate days (randomized, counterbalanced design). The Rifleman load consisted of protective armor (26.1 kg); the Rucksack load included the Rifleman load plus a weighted rucksack (48.5 kg). Soldiers performed a live-fire shooting task (48 targets) prior to the march, in the middle of the march, and at the end of the march. HR was collected during the shooting task. Data were assessed with multilevel logistic regression controlling for the multiple observations on each subject and shooting target distance. Predicted probabilities for hitting the target were calculated. Results: There was a three-way interaction effect between rucksack load, average HR, and march ( p = .02). Graphical assessment of predicted probabilities indicated that regardless of load, marching increases shooting performance. Increases in shooting HR after marching result in lower probability of hitting the target, and rucksack load has inconsistent effects on marksmanship. Conclusion: Early evidence suggests that rucksack load and marching may not uniformly decrease marksmanship but that an inverted-U phenomenon may govern changes in marksmanship. Application: The effects of load and marching on marksmanship are not linear; the abilities of Soldiers should be continuously monitored to understand their capabilities in a given scenario.
Extracorporeal Shock Wave Therapy Accelerates Regeneration After Acute Skeletal Muscle Injury
Authors: Zissler Angela , Steinbacher Peter , Zimmermann Reinhold , Pittner Stefan , Stoiber Walter , Bathke Arne C. , Sänger Alexandra M. 
Published: October 2016

Background: Muscle injuries are among the most common sports-related lesions in athletes; however, optimal treatment remains obscure. Extracorporeal shock wave therapy (ESWT) may be a promising approach in this context, because it has gained increasing importance in tissue regeneration in various medical fields. Hypothesis: ESWT stimulates and accelerates regenerative processes of acute muscle injuries. Study Design: Controlled laboratory study. Methods: Adult Sprague-Dawley rats were divided into 4 experimental groups (2 ESWT+ groups and 2 ESWT– groups) as well as an uninjured control group (n ≥ 6 in each group). An acute cardiotoxin-induced injury was set into the quadriceps femoris muscle of rats in the experimental groups. A single ESWT session was administered to injured muscles of the ESWT+ groups 1 day after injury, whereas ESWT– groups received no further treatment. At 4 and 7 days after injury, 1 each of the ESWT+ and ESWT– groups was euthanized. Regenerating lesions were excised and analyzed by histomorphometry and immunohistochemistry to assess fiber size, myonuclear content, and recruitment of satellite cells. Results: The size and myonuclear content of regenerating fibers in ESWT+ muscle was significantly increased compared with ESWT– muscle fibers at both 4 and 7 days after injury. Similarly, at both time points, ESWT+ muscles exhibited significantly higher contents of pax7-positive satellite cells, mitotically active H3P+ cells, and, of cells expressing the myogenic regulatory factors, myoD and myogenin, indicating enhanced proliferation and differentiation rates of satellite cells after ESWT. Mitotic activity at 4 days after injury was doubled in ESWT+ compared with ESWT– muscles. Conclusion: ESWT stimulates regeneration of skeletal muscle tissue and accelerates repair processes. Clinical Relevance: We provide evidence for accelerated regeneration of damaged skeletal muscle after ESWT. Although further studies are necessary, our findings support the view that ESWT is an effective method to improve muscle healing, with special relevance to sports injuries.
Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis
Authors: Chakraborty Rikhia , Burke Thomas M. , Hampton Oliver A. , Zinn Daniel J. , Lim Karen Phaik Har , Abhyankar Harshal , Scull Brooks , Kumar Vijetha , Kakkar Nipun , Wheeler David A. , Roy Angshumoy , Poulikakos Poulikos I. , Merad Miriam , McClain Kenneth L. , Parsons D. Williams , Allen Carl E. 
Published: October 2016

Key Points
A BRAF gene fusion and small in-frame BRAF deletions were found in a subset of LCH lesions lacking BRAF-V600E or MAP2K1 mutations. In LCH model systems, responses to MAPK pathway inhibitors depend on the specific genetic alteration that drives ERK activation.
Plausible mass-spring system using parallel computing on mobile devices
Authors: Hong Min , Jeon Jae-Hong , Yum Hyo-Sub , Lee Seung-Hyun 
Published: October 2016

AbstractRecently the hardware performance of mobile devices have been extremely increased and advanced mobile devices provide multi-cores and high clock speed. In addition, mobile devices have advantages in mobility and portability compared with PC and Console, so many games and simulation programs have been developed under mobile environments. Physically-based simulation is a one of the key issues for deformable object modeling which is widely used to represent the realistic expression of 3D soft objects with tetrahedrons for game and 3D simulation. However, it requires high computation power to plausibly and realistically represent the physical behaviors and interactions of deformable objects. In this paper, we implemented parallel cloth and mass-spring simulation using graphics processing unit (GPU) with OpenCL and multi-threaded central processing unit (CPU) on a mobile device. We applied CPU and GPU parallel computing technique into spring force computation and integration methods such as Euler, Midpoint, 4th-order Runge-Kutta to optimize the computational burden of dynamic simulation. The integration methods compute the next step of positions and velocities in each node. In this paper, we tested the performance analysis for the spring force calculation and integration method process using CPU only, multi-threaded CPU, and GPU on mobile device respectively. Our experimental results concluded that the calculation using proposed multi-threaded CPU and GPU multi-threaded CPU are much faster than using just the CPU only.
Taguchi-Grey relation analysis for assessing the optimal set of control factors of thermal barrier coatings for high-temperature applications
Authors: Yunus Mohammed , Alsoufi Mohammad S. , Munshi Shadi M. 
Published: October 2016

Abstract
Background
In an aerospace industry, the efficient use of thermally sprayed coatings for high-temperature applications is achieved by improving the thermal characteristics (TC) such as thermal drop/barrier (TD) and thermal fatigue cycles (TFC). The characterization of ceramic coatings demands a better understanding of TC and their performance.

Methods
In this paper, an attempt has been made to use hybrid Taguchi design method based grey relation analysis (GRA) for optimizing the control factors such as the thickness of coating, type of coating, bond coating and exposed temperature. The necessary experiments were carried out using Taguchi L16 factorial design of experiments for analysis based on the larger the better signal-to-noise (S/N) ratio. The multi-response/output optimization and grading of control factors were successfully carried out by GRA.

Results
The significance of each factor as regards TD and TFC were investigated. The ANOVA results showed that most important parameters at 95 % confidence level and were validated with a confirmation test using optimum process factors. It shows an improvement in the TC of thermal barrier coatings.

Conclusions
This work revealed that the hybrid GRA with Taguchi technique had improved the durability and efficient usage of TBC for high-temperature applications.
MIxS-HCR: a MIxS extension defining a minimal information standard for sequence data from environments pertaining to hydrocarbon resources
Authors: Tsesmetzis Nicolas , Yilmaz Pelin , Marks Peter C. , Kyrpides Nikos C. , Head Ian M. , Lomans Bart P. 
Published: October 2016

AbstractHere we introduce a MIxS extension to facilitate the recording and cataloguing of metadata from samples related to hydrocarbon resources. The proposed MIxS-HCR package incorporates the core features of the MIxS standard for marker gene (MIMARKS) and metagenomic (MIMS) sequences along with a hydrocarbon resources customized environmental package. Adoption of the MIxS-HCR standard will enable the comparison and better contextualization of investigations related to hydrocarbon rich environments. The insights from such standardized way of reporting could be highly beneficial for the successful development and optimization of hydrocarbon recovery processes and management of microbiological issues in petroleum production systems.
Current status of kilovoltage (kV) radiotherapy in the UK: installed equipment, clinical workload, physics quality control and radiation dosimetry
Authors: Palmer Antony L , Pearson Michael , Whittard Paul , McHugh Katie E , Eaton David J 
Published: October 2016

Objective:
To assess the status and practice of kilovoltage (kV) radiotherapy in the UK.

Methods:
96% of the radiotherapy centres in the UK responded to a comprehensive survey. An analysis of the installed equipment base, patient numbers, clinical treatment sites, quality control (QC) testing and radiation dosimetry processes were undertaken.

Results:
73% of UK centres have at least one kV treatment unit, with 58 units installed across the UK. Although 35% of units are over 10 years old, 39% units have been installed in the last 5 years. Approximately 6000 patients are treated with kV units in the UK each year, the most common site (44%) being basal cell carcinoma. A benchmark of QC practice in the UK is presented, against which individual centres can compare their procedures, frequency of testing and acceptable tolerance values. We propose the use of internal “notification” and “suspension” levels for analysis. All surveyed centres were using recommended Codes of Practice for kV dosimetry in the UK; approximately the same number using in-air and in-water methodologies for medium energy, with two-thirds of all centres citing “clinical relevance” as the reason for choice of code. 64% of centres had hosted an external dosimetry audit within the last 3 years, with only one centre never being independently audited. The majority of centres use locally measured applicator factors and published backscatter factors for treatments. Monitor unit calculations are performed using software in only 36% of centres.

Conclusion:
A comprehensive review of current kV practice in the UK is presented.

Advances in knowledge:
Data and discussion on contemporary kV radiotherapy in the UK, with a particular focus on physics aspects.