bluuebunny/crossref_metadata_2025_split huggingface dataset:
Football injuries during the 2014 FIFA World Cup
Authors: Junge Astrid , Dvořák Jiri 
Published: April 2015

BackgroundFIFA has surveyed match injuries in its tournaments since 1998.AimTo analyse the incidence and characteristics of match injuries incurred during the 2014 FIFA World Cup in comparison to previous FIFA World Cups.MethodsThe chief physicians of the participating teams reported all newly incurred injuries of their players after the match on a standardised report form. 124 (97%) forms were returned.ResultsA total of 104 injuries were reported, equivalent to an incidence of 1.68 injuries per match (95% CI 1.36 to 2.00). 64 (63.4%) injuries were caused by contact with another player. Thigh (26; 25%) and head (19; 18%) were the most frequently injured body parts. The most frequent diagnosis was thigh strain (n=18). Five concussions and three fractures to the head were reported. While most thigh strains (15/17; 88.2%) occurred without contact, almost all head injuries (18/19; 94.7%) were caused by contact. 0.97 injuries per match (95% CI 0.72 to 1.22) were expected to result in absence from training or match. Eight injuries were classified as severe. The incidence of match injuries in the 2014 FIFA World Cup was significantly lower than the average of the four preceding FIFA World Cups, both for all injuries (2.34; 95% CI 2.15 to 2.53) and time-loss injuries (1.51; 95% CI 1.37 to 1.65).ConclusionsThe overall incidence of injury during the FIFA World Cups decreased from 2002 to 2014 by 37%. A detailed analysis of the injury mechanism is recommended to further improve prevention strategies.
Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis
Authors: Wang Min , Cao Jun-Xia , Liu Yi-Shan , Xu Bei-Lei , Li Duo , Zhang Xiao-Yan , Li Jun-Li , Liu Jin-Long , Wang Hai-Bo , Wang Zheng-Xu 
Published: April 2015

ObjectivesOur meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of tumour vaccines for the treatment of advanced non-small cell lung cancer (NSCLC).DesignSystematic review and meta-analysis of randomised controlled trials (RCT).Data sourcesPubMed, the Cochrane Center Register of Controlled Trials, Science Direct and EMBASE were searched from January 1980 until January 2015.Eligibility criteria for selecting studiesRCT were included; the control arm had to receive either placebo or chemotherapy or no treatment.Main outcome measuresThe quality of the data from individual papers was assessed for overall survival (OS), clinical response rate and side effects.ResultsOverall, 11 RCT of advanced NSCLC with a total of 3986 patients were conducted for meta-analysis. The results showed that the vaccine arm significantly extended primary endpoint median overall survival compared with control group (p<0.00001) (HR 0.760; 95% CI 0.644 to 0.896; p=0.001). Three subgroup patients with tumour vaccine at 1-year, 2-year and 3-year survival rates also gained significant benefits compared with their corresponding control group (p=0.0004, 0.03 and 0.19, respectively). Besides, a significant improvement in median time to progression (TTP), median progression-free survival (PFS) and a trend of improvement in objective response rate were observed after tumour vaccine treatment (p=0.001, 0.005 and 0.05, respectively; median PFS HR 0.842; 95% CI 0.744 to 0.954; p=0.007). A few severe adverse effects occurred in the tumour vaccine group, but fewer side effects were observed in the vaccine group compared with the control group (p<0.00001).ConclusionsTaken together, NSCLC tumour vaccines markedly prolong median OS (p<0.00001), median TTP (p=0.001) and median PFS (p=0.005), improve clinical response rate (p=0.05) and lessen adverse side effects (p<0.00001). Our meta-analysis suggests tumour vaccines improve the efficacy of the treatment, and also provide superiority in treatment of patients with advanced NSCLC among a variety of immunotherapy strategies.
Inner conflict in patients receiving oral anticancer agents: a qualitative study
Authors: Yagasaki Kaori , Komatsu Hiroko , Takahashi Tsunehiro 
Published: April 2015

ObjectivesTo explore the experiences of patients receiving oral anticancer agents.DesignA qualitative study using semistructured interviews with a grounded theory approach.SettingA university hospital in Japan.Participants14 patients with gastric cancer who managed their cancer with oral anticancer agents.ResultsPatients with cancer experienced inner conflict between rational belief and emotional resistance to taking medication due to confrontation with cancer, doubt regarding efficacy and concerns over potential harm attached to use of the agent. Although they perceived themselves as being adherent to medication, they reported partial non-adherent behaviours. The patients reassessed their lives through the experience of inner conflict and, ultimately, they recognised their role in medication therapy.ConclusionsPatients with cancer experienced inner conflict, in which considerable emotional resistance to taking their medication affected their occasional non-adherent behaviours. In patient-centred care, it is imperative that healthcare providers understand patients’ inner conflict and inconsistency between their subjective view and behaviour to support patient adherence.
Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma
Authors: Janssen Ingo , Blanchet Elise M. , Adams Karen , Chen Clara C. , Millo Corina M. , Herscovitch Peter , Taieb David , Kebebew Electron , Lehnert Hendrik , Fojo Antonio T. , Pacak Karel 
Published: April 2015

Abstract
Purpose: Patients with succinate dehydrogenase subunit B(SDHB) mutation–related pheochromocytoma/paraganglioma (PHEO/PGL) are at a higher risk for metastatic disease than other hereditary PHEOs/PGLs. Current therapeutic approaches are limited, but the best outcomes are based on the early and proper detection of as many lesions as possible. Because PHEOs/PGLs overexpress somatostatin receptor 2 (SSTR2), the goal of our study was to assess the clinical utility of [68Ga]-DOTA(0)-Tyr(3)-octreotate ([68Ga]-DOTATATE) positron emission tomography/computed tomography (PET/CT) and to evaluate its diagnostic utility in comparison with the currently recommended functional imaging modalities [18F]-fluorodopamine ([18F]-FDA), [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA), [18F]-fluoro-2-deoxy-d-glucose ([18F]- FDG) PET/CT as well as CT/MRI.
Experimental Design: [68Ga]-DOTATATE PET/CT was prospectively performed in 17 patients with SDHB-related metastatic PHEOs/PGLs. All patients also underwent [18F]-FDG PET/CT and CT/MRI, with 16 of the 17 patients also receiving [18F]-FDOPA and [18F]-FDA PET/CT scans. Detection rates of metastatic lesions were compared between all these functional imaging studies. A composite synthesis of all used functional and anatomical imaging studies served as the imaging comparator.
Results: [68Ga]-DOTATATE PET/CT demonstrated a lesion-based detection rate of 98.6% [95% confidence interval (CI), 96.5%–99.5%], [18F]-FDG, [18F]-FDOPA, [18F]-FDA PET/CT, and CT/MRI showed detection rates of 85.8% (CI, 81.3%–89.4%; P &lt; 0.01), 61.4% (CI, 55.6%–66.9%; P &lt; 0.01), 51.9% (CI, 46.1%–57.7%; P &lt; 0.01), and 84.8% (CI, 80.0%–88.5%; P &lt; 0.01), respectively.
Conclusions: [68Ga]-DOTATATE PET/CT showed a significantly superior detection rate to all other functional and anatomical imaging modalities and may represent the preferred future imaging modality in the evaluation of SDHB-related metastatic PHEO/PGL. Clin Cancer Res; 21(17); 3888–95. ©2015 AACR.
See related commentary by Hofman and Hicks, p. 3815
The Novel ATP-Competitive MEK/Aurora Kinase Inhibitor BI-847325 Overcomes Acquired BRAF Inhibitor Resistance through Suppression of Mcl-1 and MEK Expression
Authors: Phadke Manali S. , Sini Patrizia , Smalley Keiran S.M. 
Published: April 2015

Abstract
Resistance to BRAF inhibitors is a major clinical problem. Here, we evaluate BI-847325, an ATP-competitive inhibitor of MEK and Aurora kinases, in treatment-naïve and drug-resistant BRAF-mutant melanoma models. BI-847325 potently inhibited growth and survival of melanoma cell lines that were both BRAF inhibitor naïve and resistant in 2D culture, 3D cell culture conditions, and in colony formation assays. Western blot studies showed BI-847325 to reduce expression of phospho-ERK and phospho-histone 3 in multiple models of vemurafenib resistance. Mechanistically, BI-847325 decreased the expression of MEK and Mcl-1 while increasing the expression of the proapoptotic protein BIM. Strong suppression of MEK expression was observed after 48 hours of treatment, with no recovery following &gt;72 hours of washout. siRNA-mediated knockdown of Mcl-1 enhanced the effects of BI-847325, whereas Mcl-1 overexpression reversed this in both 2D cell culture and 3D spheroid melanoma models. In vivo, once weekly BI-847325 (70 mg/kg) led to durable regression of BRAF-inhibitor naïve xenografts with no regrowth seen (&gt;65 days of treatment). In contrast, treatment with the vemurafenib analog PLX4720 was associated with tumor relapse at &gt;30 days. BI-847325 also suppressed the long-term growth of xenografts with acquired PLX4720 resistance. Analysis of tumor samples revealed BI-847325 to induce apoptosis associated with suppression of phospho-ERK, total MEK, phospho-Histone3, and Mcl-1 expression. Our studies indicate that BI-847325 is effective in overcoming BRAF inhibitor resistance and has long-term inhibitory effects upon BRAF-mutant melanoma in vivo, through a mechanism associated with the decreased expression of both MEK and Mcl-1. Mol Cancer Ther; 14(6); 1354–64. ©2015 AACR.
Treatment and Clinical Outcomes of Transcatheter Heart Valve Thrombosis
Authors: Latib Azeem , Naganuma Toru , Abdel-Wahab Mohamed , Danenberg Haim , Cota Linda , Barbanti Marco , Baumgartner Helmut , Finkelstein Ariel , Legrand Victor , de Lezo José Suárez , Kefer Joelle , Messika-Zeitoun David , Richardt Gert , Stabile Eugenio , Kaleschke Gerrit , Vahanian Alec , Laborde Jean-Claude , Leon Martin B. , Webb John G. , Panoulas Vasileios F. , Maisano Francesco , Alfieri Ottavio , Colombo Antonio 
Published: April 2015

Background—
Valve thrombosis has yet to be fully evaluated after transcatheter aortic valve implantation. This study aimed to report the prevalence, timing, and treatment of transcatheter heart valve (THV) thrombosis.

Methods and Results—
THV thrombosis was defined as follows (1) THV dysfunction secondary to thrombosis diagnosed based on response to anticoagulation therapy, imaging modality or histopathology findings, or (2) mobile mass detected on THV suspicious of thrombus, irrespective of dysfunction and in absence of infection. Between January 2008 and September 2013, 26 (0.61%) THV thromboses were reported out of 4266 patients undergoing transcatheter aortic valve implantation in 12 centers. Of the 26 cases detected, 20 were detected in the Edwards Sapien/Sapien XT cohort and 6 in the Medtronic CoreValve cohort. In patients diagnosed with THV thrombosis, the median time to THV thrombosis post–transcatheter aortic valve implantation was 181 days (interquartile range, 45–313). The most common clinical presentation was exertional dyspnea (n=17; 65%), whereas 8 (31%) patients had no worsening symptoms. Echocardiographic findings included a markedly elevated mean aortic valve pressure gradient (40.5±14.0 mm Hg), presence of thickened leaflets or thrombotic apposition of leaflets in 20 (77%) and a thrombotic mass on the leaflets in the remaining 6 (23%) patients. In 23 (88%) patients, anticoagulation resulted in a significant decrease of the aortic valve pressure gradient within 2 months.

Conclusions—
THV thrombosis is a rare phenomenon that was detected within the first 2 years after transcatheter aortic valve implantation and usually presented with dyspnea and increased gradients. Anticoagulation seems to have been effective and should be considered even in patients without visible thrombus on echocardiography.
Role of Moist Processes in the Tracks of Idealized Midlatitude Surface Cyclones
Authors: Coronel Benoît , Ricard Didier , Rivière Gwendal , Arbogast Philippe 
Published: April 2015

Abstract
The effects of moist processes on the tracks of midlatitude surface cyclones are studied by performing idealized mesoscale simulations. In each simulation, a finite-amplitude surface cyclone is initialized on the warm-air side of a zonal baroclinic jet. For some simulations, an upper-level cyclonic anomaly upstream of the surface cyclone is also added initially. Sensitivities to the upper-level perturbation and moist processes are analyzed by both performing a relative vorticity budget analysis and adopting a potential vorticity (PV) perspective.
Whatever the simulation, there is a systematic crossing of the zonal jet by the surface cyclone occurring after roughly 30 h. A PV inversion tool shows that it is the nonlinear advection of the surface cyclone by the upper-level PV dipole, which explains the cross-jet motion of the surface cyclone. The simulation with an initial upper-level cyclonic anomaly creates a stronger surface cyclone and a more intense upper-level PV dipole than the simulation without it. It results in faster northward and slower eastward motions of the surface cyclone.
A moist run including full microphysics has a more intense surface cyclone and induces a faster northeastward motion than the dry run. The faster eastward motion is due to the diabatically produced cyclonic circulation at low levels. The faster northward motion is explained by the stronger upper-level anticyclone due to released latent heat, together with the closer location of the surface cyclone to the upper-level anticyclone. Finally, a moist run with only condensation and evaporation exhibits less latent heat release and a slower northeastward motion of the surface cyclone than the full moist run.
A randomized clinical trial to determine effectiveness of driving simulator retraining on the driving performance of clients with neurological impairment
Authors: Mazer Barbara , Gélinas Isabelle , Duquette Josee , Vanier Marie , Rainville Constant , Chilingaryan Gevorg 
Published: April 2015

Introduction Following a neurological event, returning to driving is an important activity contributing to improved participation within the community. The purpose of this study was to examine the effectiveness of driving simulator retraining on driving in clients with neurological impairment and to examine factors associated with treatment effectiveness. Method Individuals with non-degenerative brain injury were randomized to either a simulator training or control group. The simulator group received individualized training (16 sessions) using a driving simulator. The control group did not receive intervention. A blind evaluator assessed participants on the DriveAble On-Road Driving Evaluation. Results There was no significant difference between groups in the proportion of individuals who passed the driving evaluation (Chi2 = 0.65; p = 0.42; CI = −0.41 to +0.17). However, participants with moderate impairment who received simulator training were more likely to pass the driving test compared with those in the control group (86% versus 17%; Chi2 = 6.2; p = 0.03; CI = −1.00 to −0.30). There were no differences in pass rate according to diagnosis, gender, or for those with severe impairments. Conclusion Results provide clinicians with preliminary information on the potential clinical usefulness of driving simulator training. While the findings do not support simulator retraining for the group as a whole, they suggest that clients with moderate impairment have the potential to benefit.
Long-term hazard of recurrence in HER2+ breast cancer patients untreated with anti-HER2 therapy
Authors: Strasser-Weippl Kathrin , Horick Nora , Smith Ian E , O’Shaughnessy Joyce , Ejlertsen Bent , Boyle Frances , Buzdar Aman U , Fumoleau Pierre , Gradishar William , Martin Miguel , Moy Beverly , Piccart-Gebhart Martine , Pritchard Kathleen I , Lindquist Deborah , Rappold Erica , Finkelstein Dianne M , Goss Paul E 
Published: April 2015

Abstract
Introduction
Worldwide, many patients with HER2+ (human epidermal growth factor receptor 2-positive) early breast cancer (BC) do not receive adjuvant trastuzumab. Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described.

Methods
Using data from 1,260 patients randomized to placebo in the adjuvant TEACH trial, we report 10-year annual hazards of recurrence in HER2+ patients not treated with anti-HER2 therapy.

Results
Disease-free survival (DFS) was 75% after 5 and 61% after 10 years, respectively. Patients with HER2+ hormone receptor-positive (HR+ (hormone receptor-positive); ER+ (estrogen receptor-positive) or PR+ (progesterone receptor-positive)) disease had a significantly better DFS than patients with HER2+ HR- (ER-/PR-) disease (hazard ratio 0.72, P = 0.02). This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2+ HR- compared to HER2+ HR+ patients, with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients (hazard ratio 0.59, P = 0.002 for years 1 to 5). The high early risk of recurrence of HER2+ HR- patients declined sharply over time, so that it was similar to that seen in HER2+ HR+ patients in years 6 to 10 (hazard ratio 0.97, P = 0.92 for years 6 to 10).

Conclusions
Our results show that outcomes in HER2+ patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression. The very high early risk of relapse seen in HER2+ HR- patients is particularly relevant in health care settings with limited access to adjuvant anti-HER2 treatment. The event rates shown for subpopulations of HER2+ BC patients suggest that in resource-constrained environments patients with HER2+ HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy.
Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin
Authors: Vandiver Amy R , Irizarry Rafael A , Hansen Kasper D , Garza Luis A , Runarsson Arni , Li Xin , Chien Anna L , Wang Timothy S , Leung Sherry G , Kang Sewon , Feinberg Andrew P 
Published: April 2015

Abstract
Background
Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans.

Results
We compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples.

Conclusions
These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.
Enhanced activation of dendritic cells by autologous apoptotic microvesicles in MRL/lpr mice
Authors: Dieker Jürgen , Hilbrands Luuk , Thielen Astrid , Dijkman Henry , Berden Jo H , van der Vlag Johan 
Published: April 2015

Abstract
Introduction
Systemic lupus erythematosus is associated with a persistent circulation of modified autoantigen-containing apoptotic debris that might be capable of breaking tolerance. We aimed to evaluate apoptotic microvesicles obtained from lupus or control mice for the presence of apoptosis-associated chromatin modifications and for their capacity to stimulate dendritic cells (DC) from lupus and control mice.

Method
Apoptotic microvesicles were in vitro generated from splenocytes, and ex vivo isolated from plasma of both MRL/lpr lupus mice and normal BALB/c mice. Microvesicles were analyzed using flow cytometry. Bone marrow-derived (BM)-DC cultured from MRL/lpr or BALB/c mice were incubated with microvesicles and CD40 expression and cytokine production were determined as measure of activation.

Results
Microvesicles derived from apoptotic splenocytes or plasma of MRL/lpr mice contained more modified chromatin compared to microvesicles of BALB/c mice, and showed enhanced activation of DC, either from MRL/lpr or BALB/c mice, and consecutively an enhanced DC-mediated activation of splenocytes. The content of apoptosis-modified chromatin in microvesicles of apoptotic splenocytes correlated with their potency to induce interleukin-6 (IL-6) production by DC. Microvesicle-activated MRL/lpr DC showed a significant higher production of IL-6 and tumor growth factor-β (TGF-β) compared to BALB/c DC, and were more potent in the activation of splenocytes.

Conclusion
Apoptotic microvesicles from MRL/lpr mice are more potent activators of DC, and DC from MRL/lpr mice appear relatively more sensitive to activation by apoptotic microvesicles. Our findings indicate that aberrations at the level of apoptotic microvesicles and possibly DC contribute to the autoimmune response against chromatin in MRL/lpr mice.