bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of traumatic shoulder injury in elite rugby players
Authors: Crichton James , Jones Doug R , Funk Lennard 
Published: April 2012

BackgroundShoulder injuries in rugby players are common, but the mechanisms of injury are less well understood. This study aims to elucidate common mechanisms of injury and identify the patterns of injury they produce.Materials and methodsTwenty-four elite rugby players, referred to the senior author for diagnosis and management of shoulder injuries, were selected. Videos of the injuries were independently reviewed by rugby-medical experts to describe the mechanisms of injury. The mechanisms reported were collated and analysed to determine the level of agreement between reviewers and conclude an overall description of injury mechanisms.ResultsThe authors identified three mechanisms of shoulder injury from the video analysis. These are the ‘Try-Scorer’, characterised by hyperflexion of the outstretched arm such as when scoring a try; the ‘Tackler’, extension of the abducted arm behind the player while tackling; and the ‘Direct Impact’, a direct blow to the arm or shoulder when held by the side in neutral or slight adduction. The Try Scorer and Tackler mechanisms both involve a levering force on the glenohumeral joint (GHJ). These mechanisms predominantly cause GHJ dislocation, with Bankart, reverse Bankart and superior labrum anterior–posterior tears. The Try-Scorer Mechanism also caused the majority (83%) of rotator cuff tears. The Direct Hit mechanism resulted in GHJ dislocation and labral injury in 37.5% of players and was most likely to cause acromioclavicular joint dislocation and scapula fractures, injuries that were not seen with the other mechanisms.ConclusionGreater understanding of the mechanisms involved in rugby shoulder injury is useful in understanding the pathological injuries, guiding treatment and rehabilitation and aiding the development of injury-prevention methods.
Where do young men want to access STI screening? A stratified random probability sample survey of young men in Great Britain
Authors: Saunders John M , Mercer Catherine H , Sutcliffe Lorna J , Hart Graham J , Cassell Jackie , Estcourt Claudia S 
Published: April 2012

ObjectivesRates of sexually transmitted infections (STIs) in UK young people remain high in men and women. However, the National Chlamydia Screening Programme has had limited success in reaching men. The authors explored the acceptability of various medical, recreational and sports venues as settings to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport.MethodsA stratified random probability survey of 411 (weighted n=632) men in Great Britain aged 18–35 years using computer-assisted personal and self-interviews.ResultsYoung men engaged well with healthcare with 93.5% registered with, and 75.3% having seen, a general practitioner in the last year. 28.7% and 19.8% had previously screened for STIs and HIV, respectively. Willingness to access self-collected tests for STIs (85.1%) and HIV (86.9%) was high. The most acceptable pick-up points for testing kits were general practice 79.9%, GUM 66.8% and pharmacy 65.4%. There was a low acceptability of sport venues as pick-up points in men as a whole (11.7%), but this was greater among those who participated in sport (53.9%).ConclusionsHealthcare settings were the most acceptable places for accessing STI and HIV self-testing kits. Although young men frequently access general practice, currently little STI screening occurs in this setting. There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice. While non-clinical settings are acceptable to a minority of men, more research is needed to understand how these venues could be used most effectively.
MEK1/2 Inhibition Elicits Regression of Autochthonous Lung Tumors Induced by KRASG12D or BRAFV600E
Authors: Trejo Christy L. , Juan Joseph , Vicent Silvestre , Sweet-Cordero Alejandro , McMahon Martin 
Published: April 2012

Abstract
Genetically engineered mouse (GEM) models of lung tumorigenesis allow careful evaluation of lung tumor initiation, progression, and response to therapy. Using GEM models of oncogene-induced lung cancer, we show the striking similarity of the earliest stages of tumorigenesis induced by KRASG12D or BRAFV600E. Cre-mediated expression of KRASG12D or BRAFV600E in the lung epithelium of adult mice initially elicited benign lung tumors comprising cuboidal epithelial cells expressing markers of alveolar pneumocytes. Strikingly, in a head-to-head comparison, oncogenic BRAFV600E elicited many more such benign tumors and did so more rapidly than KRASG12D. However, despite differences in the efficiency of benign tumor induction, only mice with lung epithelium expression of KRASG12D developed malignant non–small cell lung adenocarcinomas. Pharmacologic inhibition of mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK)1/2 combined with in vivo imaging showed that initiation and maintenance of both BRAFV600E- or KRASG12D-induced lung tumors was dependent on MEK→ERK signaling. Although the tumors dramatically regressed in response to MEK1/2 inhibition, they regrew following cessation of drug treatment. Together, our findings show that RAF→MEK→ERK signaling is both necessary and sufficient for KRASG12D-induced benign lung tumorigenesis in GEM models. The data also emphasize the ability of KRASG12D to promote malignant lung cancer progression compared with oncogenic BRAFV600E. Cancer Res; 72(12); 3048–59. ©2012 AACR.
Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples
Authors: Bertilsson Helena , Tessem May-Britt , Flatberg Arnar , Viset Trond , Gribbestad Ingrid , Angelsen Anders , Halgunset Jostein 
Published: April 2012

Abstract
Purpose: Low concentrations of citrate and high concentrations of choline-containing compounds (ChoCC) are metabolic characteristics observed by magnetic resonance spectroscopy of prostate cancer tissue. The objective was to investigate the gene expression changes underlying these metabolic aberrations to find regulatory genes with potential for targeted therapies.
Experimental design: Fresh frozen samples (n = 133) from 41 patients undergoing radical prostatectomy were included. Histopathologic evaluation was carried out for each sample before a metabolic profile was obtained with high-resolution magic angle spinning (HR-MAS) spectroscopy. Following the HR-MAS, RNA was extracted from the same sample and quality controlled before carrying out microarray gene expression profiling. A partial least square statistical model was used to integrate the data sets to identify genes whose expression show significant covariance with citrate and ChoCC levels.
Results: Samples were classified as benign, n = 35; cancer of low grade (Gleason score 6), n = 24; intermediate grade (Gleason score 7), n = 41; or high grade (Gleason score ≥8), n = 33. RNA quality was high with a mean RNA Integrity Number score of 9.1 (SD 1.2). Gene products predicting significantly a reduced citrate level were acetyl citrate lyase (ACLY, P = 0.003) and m-aconitase (ACON, P &lt; 0.001). The two genes whose expression most closely accompanied the increase in ChoCC were those of phospholipase A2 group VII (PLA2G7, P &lt; 0.001) and choline kinase α (CHKA, P = 0.002).
Conclusions: By integrating histologic, transcriptomic, and metabolic data, our study has contributed to an expanded understanding of the mechanisms underlying aberrant citrate and ChoCC levels in prostate cancer. Clin Cancer Res; 18(12); 3261–9. ©2012 AACR.
Safety and Pharmacokinetics of Ganitumab (AMG 479) Combined with Sorafenib, Panitumumab, Erlotinib, or Gemcitabine in Patients with Advanced Solid Tumors
Authors: Rosen Lee S. , Puzanov Igor , Friberg Gregory , Chan Emily , Hwang Yuying C. , Deng Hongjie , Gilbert Jill , Mahalingam Devalingam , McCaffery Ian , Michael Shaunita A. , Mita Alain C. , Mita Monica M. , Mulay Marilyn , Shubhakar Poornima , Zhu Min , Sarantopoulos John 
Published: April 2012

Abstract
Purpose: This phase 1b dose-escalation study assessed safety, tolerability, and pharmacokinetics of ganitumab, a fully human monoclonal antibody against the insulin-like growth factor 1 (IGF1) receptor, combined with targeted agents or cytotoxic chemotherapy in patients with advanced solid tumors.
Experimental Design: Patients with treatment-refractory advanced solid tumors were sequentially enrolled at 2 ganitumab dose levels (6 or 12 mg/kg i.v. every 2 weeks) combined with either sorafenib 400 mg twice daily, panitumumab 6 mg/kg every 2 weeks, erlotinib 150 mg once daily, or gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of each 4-week cycle. The primary end points were safety and pharmacokinetics of ganitumab.
Results: Ganitumab up to 12 mg/kg appeared well tolerated combined with sorafenib, panitumumab, erlotinib, or gemcitabine. Treatment-emergent adverse events were generally mild and included fatigue, nausea, vomiting, and chills. Three patients had dose-limiting toxicities: grade 3 hyperglycemia (ganitumab 6 mg/kg and panitumumab), grade 4 neutropenia (ganitumab 6 mg/kg and gemcitabine), and grade 4 thrombocytopenia (ganitumab 12 mg/kg and erlotinib). Ganitumab-binding and panitumumab-binding antibodies were detected in 5 and 2 patients, respectively; neutralizing antibodies were not detected. The pharmacokinetics of ganitumab and each cotherapy did not appear affected by coadministration. Circulating total IGF1 and IGF binding protein 3 increased from baseline following treatment. Four patients (9%) had partial responses.
Conclusions: Ganitumab up to 12 mg/kg was well tolerated, without adverse effects on pharmacokinetics in combination with either sorafenib, panitumumab, erlotinib, or gemcitabine. Ganitumab is currently under investigation in combination with some of these and other agents. Clin Cancer Res; 18(12); 3414–27. ©2012 AACR.
Carotid Intima‐Media Thickness Progression in HIV‐Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation
Authors: Hsue Priscilla Y. , Scherzer Rebecca , Hunt Peter W. , Schnell Amanda , Bolger Ann F. , Kalapus S.C. , Maka Kristinalisa , Martin Jeffrey N. , Ganz Peter , Deeks Steven G. 
Published: April 2012

Background
Shear stress gradients and inflammation have been causally associated with atherosclerosis development in carotid bifurcation regions. The mechanism underlying higher levels of carotid intima‐media thickness observed among HIV‐infected individuals remains unknown.

Methods and Results

We measured carotid intima‐media thickness progression and development of plaque in the common carotid, bifurcation region, and internal carotid artery in 300 HIV‐infected persons and 47 controls. The median duration of follow‐up was 2.4 years. When all segments were included, the rate of intima‐media thickness progression was greater in HIV‐infected subjects compared with controls after adjustment for traditional risk factors (0.055 vs. 0.024 mm/year,
P
=0.016). Rate of progression was also greater in the bifurcation region (0.067 vs. 0.025 mm/year,
P
=0.042) whereas differences were smaller in the common and internal regions. HIV‐infected individuals had a greater incidence of plaque compared with controls in the internal (23% vs. 6.4%,
P
=0.0037) and bifurcation regions (34% vs. 17%,
P
=0.014). Among HIV‐infected individuals, the rate of progression in the bifurcation region was more rapid compared with the common carotid, internal, or mean intima‐media thickness; in contrast, progression rates among controls were similar at all sites. Baseline hsCRP was elevated in HIV‐infected persons and was a predictor of progression in the bifurcation region.

Conclusions

Atherosclerosis progresses preferentially in the carotid bifurcation region in HIV‐infected individuals. hsCRP, a marker of inflammation, is elevated in HIV and is associated with progression in the bifurcation region. These data are consistent with a model in which the interplay between hemodynamic shear stresses and HIV‐associated inflammation contribute to accelerated atherosclerosis.

(
J Am Heart Assoc
. 2012;1:jah3‐e000422 doi

:
10.1161/JAHA.111.000422
.)

Clinical Trial Registration

URL:
http://clinicaltrials.gov
. Unique identifier: NCT01519141
The Role of Norepinephrine and Estradiol in the Pathogenesis of Cardiac Wall Motion Abnormality Associated With Subarachnoid Hemorrhage
Authors: Sugimoto Keiko , Inamasu Joji , Hirose Yuichi , Kato Yoko , Ito Keisuke , Iwase Masatsugu , Sugimoto Kunihiko , Watanabe Eiichi , Takahashi Ayako , Ozaki Yukio 
Published: April 2012

Background and Purpose—
The majority of patients with ventricular wall motion abnormality (WMA) associated with subarachnoid hemorrhage (SAH) are postmenopausal women. In addition to elevated catecholamine, the role of estrogen in the pathogenesis of WMA has recently been implicated. The objective of this study is to clarify the interrelation among catecholamine, estrogen, and WMA in patients with SAH.

Methods—
A retrospective analysis was performed on the medical records of 77 patients with SAH (23 men, 54 women) whose plasma levels of epinephrine, norepinephrine, and estradiol had been measured and echocardiograms had been obtained within 48 hours of SAH onset.

Results—

Twenty-four patients (31%) were found to sustain WMA on admission. Multivariate regression analysis revealed that decreased estradiol (
P
=0.018; OR, 0.902) and elevated norepinephrine levels (
P
=0.027; OR, 1.002) were associated with WMA. After quadrichotomization of 77 patients based on sex/WMA, plasma norepinephrine levels were markedly elevated in men with WMA, whereas estradiol levels were markedly decreased in women with WMA. Plasma norepinephrine and estradiol levels were not correlated. Fifty-four female patients with SAH were further quadrichotomized based on norepinephrine/estradiol levels with a threshold value of 1375 pg/mL for norepinephrine and 11 pg/mL for estradiol. The incidence of WMA in the high-norepinephrine/low-estradiol group was significantly higher than the low-norepinephrine/high-estradiol group.

Conclusions—
To our knowledge, this is the first study to evaluate the interrelation among catecholamine, estrogen, and SAH-induced WMA. Lack of estradiol in postmenopausal women may predispose them to develop WMA after poor-grade SAH. However, the precise role of multiple sex hormones in SAH-induced WMA should be evaluated in future prospective studies.
The Spectrum of Convectively Coupled Kelvin Waves and the Madden–Julian Oscillation in Regions of Low-Level Easterly and Westerly Background Flow
Authors: Roundy Paul E. 
Published: April 2012

Abstract
The zonal wavenumber–frequency power spectrum of outgoing longwave radiation in the global tropics suggests that power in convectively coupled Kelvin waves and the Madden–Julian oscillation (MJO) is organized into two distinct spectral peaks with a minimum in power in between. This work demonstrates that integration of wavelet power in the wavenumber–frequency domain over geographical regions of moderate trade winds yields a similar pronounced spectral gap between these peaks. In contrast, integration over regions of background low-level westerly wind yields a continuum of power with no gap between the MJO and Kelvin bands. Results further show that signals in tropical convection are redder in frequency in these low-level westerly wind zones, confirming that Kelvin waves tend to propagate more slowly eastward over the warm pool than other parts of the world. Results are consistent with the perspective that portions of disturbances labeled as Kelvin waves and the MJO that are proximate to Kelvin wave dispersion curves exist as a continuum over warm pool regions.
Physical Response of the Tropical–Subtropical North Atlantic Ocean to Decadal–Multidecadal Forcing by African Dust
Authors: Evan Amato T. , Foltz Gregory R. , Zhang Dongxiao 
Published: April 2012

Abstract
Dust storms are a persistent feature of the tropical North Atlantic and vary over a wide range of temporal scales. While it is well known that mineral aerosols alter the local radiative fluxes, far less is understood about the oceanic response to such forced changes to the radiative budget, particularly on long time scales. This study uses an observation-based climatology of dust surface forcing and an ocean general circulation model to examine the influence of anomalous atmospheric dust cover over the tropical North Atlantic on upper ocean temperature and circulation during 1955–2008. It is found that surface temperature anomalies from the model experiments are forced primarily by local radiation-induced changes to the surface heat budget. The subsurface temperature anomalies are additionally influenced by upper ocean circulation anomalies, which are the response to dust-forced steric changes in dynamic height. The results herein suggest that on decadal time scales dust-forced variability of ocean surface and subsurface temperatures are of a magnitude comparable to observed variability. On longer time scales dust-forced sea surface temperature anomalies vary in phase with the Atlantic multidecadal oscillation, implying that tropical North Atlantic multidecadal variability is related to changes in dust emissions from West Africa.
Restratification of the Upper Ocean after the Passage of a Tropical Cyclone: A Numerical Study
Authors: Mei Wei , Pasquero Claudia 
Published: April 2012

Abstract
The role of baroclinic instability in the restratification of the upper ocean after the passage of a tropical cyclone (TC) is determined by means of numerical simulations. Using a regional ocean model, the Regional Ocean Modeling System (ROMS), a high-resolution three-dimensional simulation that includes the process of baroclinic instability and is initialized with moderate-amplitude eddy structures reproduces the satellite-observed decay rate of the TC-induced sea surface temperature (SST) anomaly and is also in qualitative agreement with published observations after the passage of Hurricane Fabian in 2003 that showed decaying cold and warm anomalies located in the climatological mixed layer (CML) and upper thermocline, respectively. The model ocean is restratified after approximately one month with a net heat gain in the water column due to anomalous air–sea heat fluxes. The model shows, however, that vertical heat fluxes associated with baroclinic instability dominate over air–sea heat fluxes in restoring the CML heat content during the first month. A comparison with two-dimensional simulations that exclude baroclinic adjustment further highlights the importance of baroclinic instability: it can not only input a considerable amount of heat into the CML, but also establish strong stratification there, inhibiting the downward penetration of heat contributed by diabatic heating at the surface; both effects hasten the recovery of the SST.
Additional experiments were performed to examine the sensitivity of the model results to changes in Newtonian cooling rate, changes in the magnitude of the eddy structures used to initialize the simulation, and changes in poststorm wind strength; the results indicate that, although some of them may have a significant effect on the recovery time of the SST, their influence on the contribution of baroclinic instability to the recovery of the CML heat content is modest. However, the contribution of baroclinic instability exhibits pronounced positive dependence on the depth of the mixing layer relative to the CML depth and the relative size of the area with unperturbed water. Its dependence on the shape of the spatial variation of the mixing depth is relatively weak but in a more complicated manner. These dependencies are consistent with those predicted by a simple front adjustment model, whereas the latter also suggest that the contribution of baroclinic instability is independent of the prestorm stratification below the CML.
Overall, the idealized simulations in this study suggest that, for a typical situation in the real ocean, baroclinic instability can account for approximately 50% of the full recovery of the CML heat content, whereas under specific conditions the contribution can be significantly smaller. Those estimates provide a limit to the maximum net warming of the water column after the initial mixing event and thus have important implications regarding estimating the long-term effect of TCs on the upper-ocean heat budget.
Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets
Authors: Travert Marion , Huang Yenlin , de Leval Laurence , Martin-Garcia Nadine , Delfau-Larue Marie-Helene , Berger Françoise , Bosq Jacques , Brière Josette , Soulier Jean , MacIntyre Elizabeth , Marafioti Teresa , de Reyniès Aurélien , Gaulard Philippe 
Published: April 2012

Abstract
The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell–associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.
Bacteria in sputum of stable severe asthma and increased airway wall thickness
Authors: Zhang Qingling , Illing Rowland , Hui Christopher K , Downey Kate , Carr Denis , Stearn Martin , Alshafi Khalid , Menzies-Gow Andrew , Zhong Nanshan , Fan Chung Kian 
Published: April 2012

Abstract

Background
Patients with chronic asthma have thicker intrapulmonary airways measured on high resolution computed tomography (HRCT). We determined whether the presence of lower airway bacteria was associated with increased airway wall thickness.

Methods
In 56 patients with stable severe asthma, sputum specimens obtained either spontaneously or after induction with hypertonic saline were cultured for bacteria and thoracic HRCT scans obtained. Wall thickness (WT) and area (WA) expressed as a ratio of airway diameter (D) and total area, respectively, were measured at five levels.

Results
Positive bacterial cultures were obtained in 29 patients, with H. influenzae, P. aeruginosa and S. aureus being the commonest strains. Logistic regression analysis showed that this was associated with the duration of asthma and the exacerbations during the past year. In airways > 2 mm, there was no significant difference in WA (67.5 ± 5.4 vs 66.4 ± 5.4) and WT/D (21.6 ± 2.7 vs 21.3 ± 2.4) between the culture negative versus positive groups. Similarly, in airways (≤ 2 mm), there were no significant differences in these parameters. The ratio of √wall area to Pi was negatively correlated with FEV1% predicted (p < 0.05).

Conclusions
Bacterial colonization of the lower airways is common in patients with chronic severe asthma and is linked to the duration of asthma and having had exacerbations in the past year, but not with an increase in airway wall thickness.