bluuebunny/crossref_metadata_2025_split huggingface dataset:
The accuracy of existing prehospital triage tools for injured children in England—an analysis using trauma registry data
Authors: Cheung Ronny , Ardolino Antonella , Lawrence Thomas , Bouamra Omar , Lecky Fiona , Berry Kathleen , Lyttle Mark D , Maconochie Ian K 
Published: June 2012

ObjectivesTo investigate the performance characteristics of prehospital paediatric triage tools for identifying seriously injured children in England.DesignEight prehospital paediatric triage tools were identified by literature review and by survey of the Lead Trauma Clinicians across English Strategic Health Authorities. Retrospective clinical registry data from the Trauma Audit and Research Network were used to determine the performance characteristics of each tool, using ‘gold standards’ for under- and over-triage of <5% and <25–50%, respectively, as benchmarks for performance.Participants701 patient records were included. Inclusion criteria were all injured patients aged <16 years admitted to a receiving unit direct from the scene of accident in the period 2007–2010, for whom all key discriminator fields were recorded in the Trauma Audit and Research Network database.Outcome measuresThe main outcome measure was how each tool functioned with regard to their under- and over-triaging features. Other performance characteristics, for example, predictive values and likelihood ratios were also calculated.ResultsTwo (of eight) triage tools demonstrated acceptable under-triage rates (3% and 4%) but had unacceptably high over-triage rates (83% and 72%). Two tools demonstrated acceptable over-triage rates (7% and 16%), but with unacceptably high under-triage rates (61% and 63%). Four tools had unacceptably high under- and over-triage rates.ConclusionsNone of the prehospital triage tools currently used or being developed in England meet recommended criteria for over- and under-triage rates. There is an urgent need for the development of triage tools to accurately risk-stratify injured children in the prehospital setting.
Distribution and determinants of risk of teenage motherhood in three British longitudinal studies: implications for targeted prevention interventions
Authors: Kneale Dylan , Fletcher Adam , Wiggins Richard , Bonell Chris 
Published: June 2012

PurposeIn order to consider the potential contribution of universal versus targeted prevention interventions, the authors examined what is the distribution of established risk variables for teenage motherhood? from where in these distributions do births arise? and how does this distribution/determination of risk vary between studies?MethodsSecondary data analysis of three British longitudinal studies.ResultsFor all cohorts and variables, the ‘risk’ category was the least frequent. Continuous risk factors were normally distributed. A high rate of teenage motherhood within a risk category often translated into low ‘contribution’ to the overall rate (eg, expectation to leave school at the minimum age among the 1989/1990-born cohort) and vice versa. Most young women had a low probability of teenage motherhood. For any targeting strategy, combining risk factors and a low threshold of predicted probability would be necessary to achieve adequate sensitivity. Assessing between-cohort applicability of findings, the authors find that the numbers of teenage parents is poorly estimated and estimates of the variability and direction of risk may also be inadequate.ConclusionsWith reference to a number of established risk factors, there is not a core of easily identifiable multiply disadvantaged girls who go on to constitute the majority of teenage mothers in these studies. While individual risk factors are unlikely to enable targeting, a composite may have some limited potential, albeit with a low threshold for ‘risk’ and with the caveat that evidence from one population may not inform good targeting in another. It is likely that universal approaches will have more impact.
Safety of full-dose intravenous recombinant tissue plasminogen activator followed by multimodal endovascular therapy for acute ischemic stroke
Authors: Nogueira Raul G , Yoo Albert J , Masrur Shihab , Batista Leonardo M , Hakimelahi Reza , Hirsch Joshua A , Schwamm Lee H 
Published: June 2012

Background and purposeThe optimal management of stroke patients who fail treatment with intravenous recombinant tissue plasminogen activator (rt-PA) remains unknown. A study was undertaken to establish whether treatment with a standard intravenous t-PA dose (0.9 mg/kg) followed by multimodal endovascular therapy would have a similar safety profile to reduced dose (0.6 mg/kg) bridging therapy.MethodsA retrospective analysis was performed of a prospectively collected database. All patients treated with full-dose t-PA and endovascular therapy were included. The primary safety endpoints included ECASS-III symptomatic intracranial hemorrhage (sICH) and ECASS parenchymal hematomas (PH). Secondary safety endpoints included severe systemic bleeding and 90-day mortality. Clinical efficacy endpoints included rates of recanalization (TICI 2–3), ambulation at hospital discharge and 90-day independent outcomes (mRS 0–2).Results106 consecutive patients (mean age 69±17 years; mean baseline NIH Stroke Scale 17.8±4.8; 55% women; occlusion sites: MCA-M1 60.4%; MCA-M2 6.6%; ICA-T 19.8%; tandem cervical ICA+MCA-M1 7.5%; basilar artery 5.7%) were identified over a 10-year period. The sICH rate was 8.5% and the PH-1, PH-2 and subarachnoid hemorrhage rates were 2.8%, 8.5% and 2.8%, respectively. There were two (1.9%) severe groin hematomas. The recanalization rate was 66%. At hospital discharge, 41.4% of the patients were ambulatory. The rate of independent functional outcomes at 90 days was 24%; however, this sample is biased since nearly all deaths were captured but detailed 90-day functional outcomes were missing in 27 patients. The 90-day death rate was 32.4%.ConclusionCombined treatment with full-dose intravenous rt-PA followed by multimodal endovascular therapy seems to be associated with similar rates of sICH to that of bridging therapy with reduced rt-PA dosage.
MAX and MYC: A Heritable Breakup
Authors: Cascón Alberto , Robledo Mercedes 
Published: June 2012

Abstract
The overexpression of MYC, which occurs in many tumors, dramatically disrupts the equilibrium between activation and repression of the oncogenic MYC/MYC-associated protein X (MAX)/MAX dimerization protein 1 (MXD1) network, favoring MYC–MAX complexes and thereby impairing differentiation and promoting cell growth. Although for some time it has appeared that MAX is necessary for both the activation and repression of the axis, recent evidence shows that MYC retains considerable biologic function in the absence of MAX. The presence of germline MAX mutations in patients with hereditary pheochromocytoma supports the predominant role of MAX as a negative regulator of the network and suggests that MYC deregulation plays a role in hereditary cancer predisposition. This finding also confirms the importance of impairment of the MYC/MAX/MXD1 axis in the development of aggressive neural tumors, because MYCN overexpression is an established genetic hallmark of malign neuroblastoma, and it is likely that MXI1 plays a relevant role in the development of medulloblastoma and glioblastoma. Finally, the likely malignant behavior of tumors with mutations in MAX points to MYC as a candidate therapeutic target in the treatment of metastatic pheochromocytoma. Cancer Res; 72(13); 3119–24. ©2012 AACR.
The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer
Authors: Jönsson Göran , Staaf Johan , Vallon-Christersson Johan , Ringnér Markus , Gruvberger-Saal Sofia K. , Saal Lao H. , Holm Karolina , Hegardt Cecilia , Arason Adalgeir , Fagerholm Rainer , Persson Camilla , Grabau Dorthe , Johnsson Ellinor , Lövgren Kristina , Magnusson Linda , Heikkilä Päivi , Agnarsson Bjarni A. , Johannsson Oskar T. , Malmström Per , Fernö Mårten , Olsson Håkan , Loman Niklas , Nevanlinna Heli , Barkardottir Rosa B. , Borg Åke 
Published: June 2012

Abstract
Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we used gene expression profiling to molecularly subtype 577 breast tumors, including 73 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated, and 48 non-BRCA1/2–mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter methylation but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter–methylated basal-like tumors, 13% of non-BRCA1–deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1 hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer but rarely in BRCA2 hereditary breast cancer and non-BRCA1–deficient sporadic breast cancers. Together, our findings show the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1 status. Cancer Res; 72(16); 4028–36. ©2012 AACR.
IGKV3 Proteins as Candidate “Off-the-Shelf” Vaccines for Kappa-Light Chain–Restricted B-Cell Non-Hodgkin Lymphomas
Authors: Martorelli Debora , Guidoboni Massimo , De Re Valli , Muraro Elena , Turrini Riccardo , Merlo Anna , Pasini Elisa , Caggiari Laura , Romagnoli Luca , Spina Michele , Mortarini Roberta , Gasparotto Daniela , Mazzucato Mario , Carbone Antonino , Rosato Antonio , Anichini Andrea , Dolcetti Riccardo 
Published: June 2012

AbstractPurpose: An increasing set of B-cell non-Hodgkin lymphomas (B-NHL) show a biased usage of IGKV3-20 and IGKV3-15 immunoglobulin genes, a feature that could be exploited for the development of ready-to-use, broadly applicable cancer vaccines.Experimental Design: The immunogenic properties of clonal IGKV3-20 and IGKV3-15 proteins were analyzed with particular focus on their ability to elicit cross-reactive responses against molecularly related IGKV proteins expressed by different B-cell lymphoproliferative disorders.Results: IGK+ lymphoma patients show humoral and T-cell responses to IGKV3-20 and IGKV3-15 proteins and IGKV3-specific cytotoxic T lymphocytes (CTL) can be easily induced ex vivo. IGKV3-20–specific CTLs cross-react against different IGKV3 proteins, an effect mediated by the presence of 21 shared, sometimes promiscuous, T-cell epitopes, presented by common HLA class I allele products, thus assuring a broad HLA coverage of IGKV3-based vaccines. Many natural epitope variants are carried by IGK light chains expressed by a broad spectrum of B-NHLs and we show that IGKV3-20–specific CTLs cross-react also against several of these variant epitopes. Both humoral and CTL-specific responses were induced by KLH-conjugated IGKV3-20 protein in HLA-A2-transgenic mice and coinjection of IGKV3-20–specific CTLs with IGKV3-20+ or IGKV3-15+ lymphoma cells into SCID mice totally prevented tumor growth, thus confirming the ability of these effectors to mediate efficient and cross-reactive cytotoxic responses also in vivo.Conclusions: These results provide the rationale to exploit IGKV3 proteins as “off-the-shelf” vaccines for a large fraction of lymphoma patients. Clin Cancer Res; 18(15); 4080–91. ©2012 AACR.
TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism
Authors: Ho Ming-Yi , Tang Shye-Jye , Chuang Mei-Jen , Cha Tai-Lung , Li Jing-Yao , Sun Guang-Huan , Sun Kuang-Hui 
Published: June 2012

AbstractTNF-α is a cytokine with antitumorigenic property. In contrast, low dose, chronic TNF-α production by tumor cells or stromal cells may promote tumor growth and metastasis. Serum levels of TNF-α are significantly elevated in renal cell carcinoma (RCC) patients. Here, we showed that TNF-α induced epithelial–mesenchymal transition (EMT) and promoted tumorigenicity of RCC by repressing E-cadherin, upregulating vimentin, activating MMP9, and invasion activities. In addition, TNF-α treatment inhibited glycogen synthase kinase 3β (GSK-3β) activity through serine-9 phosphorylation mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway in RCC cells. Inhibition of PI3K/AKT by LY294002 reactivated GSK-3β and suppressed the TNF-α–induced EMT of RCC cells. Inactivation of GSK-3β by LiCl significantly increased MMP9 activity and EMT of RCC cells. Activation of GSK-3β by transduction of constitutively active GSK-3β into RCC cells suppressed TNF-α–mediated anchorage-independent growth in soft agar and tumorigenicity in nude mice. Overexpression of a kinase-deficient GSK-3β, in contrast, potentiated EMT, anchorage-independent growth and drastically enhanced tumorigenicity in vivo. Most importantly, a 15-fold inactivation of GSK-3β activity, 3-fold decrease of E-cadherin, and 2-fold increase of vimentin were observed in human RCC tumor tissues. These results indicated that inactivation of GSK-3β plays a pivotal role in the TNF-α–mediated tumorigenesis of RCC. Mol Cancer Res; 10(8); 1109–19. ©2012 AACR.
Janus Kinase 3–Activating Mutations Identified in Natural Killer/T-cell Lymphoma
Authors: Koo Ghee Chong , Tan Soo Yong , Tang Tiffany , Poon Song Ling , Allen George E. , Tan Leonard , Chong Soo Ching , Ong Whee Sze , Tay Kevin , Tao Miriam , Quek Richard , Loong Susan , Yeoh Kheng-Wei , Yap Swee Peng , Lee Kuo Ann , Lim Lay Cheng , Tan Daryl , Goh Christopher , Cutcutache Ioana , Yu Willie , Young Ng Cedric Chuan , Rajasegaran Vikneswari , Heng Hong Lee , Gan Anna , Ong Choon Kiat , Rozen Steve , Tan Patrick , Teh Bin Tean , Lim Soon Thye 
Published: June 2012

AbstractThe molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic–activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs.Significance: Gene mutations causing NKTCL have not been fully identified. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Our findings have important implications for the management of patients with NKTCLs. Cancer Discov; 2(7); 591–7. ©2012 AACR.This article is highlighted in the In This Issue feature, p. 569.
Agonist-Induced Hypertrophy and Diastolic Dysfunction Are Associated With Selective Reduction in Glucose Oxidation
Authors: Mori Jun , Basu Ratnadeep , McLean Brent A. , Das Subhash K. , Zhang Liyan , Patel Vaibhav B. , Wagg Cory S. , Kassiri Zamaneh , Lopaschuk Gary D. , Oudit Gavin Y. 
Published: June 2012

Background—
Activation of the renin-angiotensin and sympathetic nervous systems may alter the cardiac energy substrate preference, thereby contributing to the progression of heart failure with normal ejection fraction. We assessed the qualitative and quantitative effects of angiotensin II (Ang II) and the α-adrenergic agonist, phenylephrine (PE), on cardiac energy metabolism in experimental models of hypertrophy and diastolic dysfunction and the role of the Ang II type 1 receptor.

Methods and Results—

Ang II (1.5 mg·kg
−1
·day
−1
) or PE (40 mg·kg
−1
·day
−1
) was administered to 9-week-old male C57/BL6 wild-type mice for 14 days via implanted microosmotic pumps. Echocardiography showed concentric hypertrophy and diastolic dysfunction, with preserved systolic function in Ang II- and PE-treated mice. Ang II induced marked reduction in cardiac glucose oxidation and lactate oxidation, with no change in glycolysis and fatty acid β-oxidation. Tricarboxylic acid acetyl coenzyme A production and ATP production were reduced in response to Ang II. Cardiac pyruvate dehydrogenase kinase 4 expression was upregulated by Ang II and PE, resulting in a reduction in the pyruvate dehydrogenase activity, the rate-limiting step for carbohydrate oxidation. Pyruvate dehydrogenase kinase 4 upregulation correlated with the activation of the cyclin/cyclin-dependent kinase-retinoblastoma protein-E2F pathway in response to Ang II. Ang II type 1 receptor blockade normalized the activation of the cyclin/cyclin-dependent kinase-retinoblastoma protein-E2F pathway and prevented the reduction in glucose oxidation but increased fatty acid oxidation.

Conclusions—
Ang II- and PE-induced hypertrophy and diastolic dysfunction is associated with reduced glucose oxidation because of the cyclin/cyclin-dependent kinase-retinoblastoma protein-E2F–induced upregulation of pyruvate dehydrogenase kinase 4, and targeting these pathways may provide novel therapy for heart failure with normal ejection fraction.
Normal Left Ventricular Myocardial Thickness for Middle-Aged and Older Subjects With Steady-State Free Precession Cardiac Magnetic Resonance
Authors: Kawel Nadine , Turkbey Evrim B. , Carr J. Jeffrey , Eng John , Gomes Antoinette S. , Hundley W. Gregory , Johnson Craig , Masri Sofia C. , Prince Martin R. , van der Geest Rob J. , Lima João A.C. , Bluemke David A. 
Published: June 2012

Background—
Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac magnetic resonance and to assess variation with image acquisition plane, demographics, and left ventricular function.

Methods and Results—

End-diastolic LVMT was measured on cardiac magnetic resonance steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9 mm and 6.3±1.1 mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men was 7/9 mm (long axis) and 7/8 mm (short axis). Mean LVMT was positively associated with weight (0.02 mm/kg;
P
=0.01) and body surface area (1.1 mm/m
2
;
P
<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower left ventricular end-diastolic volume (0.01 mm/mL;
P
<0.01), a lower left ventricular end-systolic volume (−0.01 mm/mL;
P
=0.01), and lower left ventricular stroke volume (−0.01 mm/mL;
P
<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.

Conclusions—
Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
How Dangerous Is Looking Away From the Road? Algorithms Predict Crash Risk From Glance Patterns in Naturalistic Driving
Authors: Liang Yulan , Lee John D. , Yekhshatyan Lora 
Published: June 2012

Objective: In this study, the authors used algorithms to estimate driver distraction and predict crash and near-crash risk on the basis of driver glance behavior using the data set of the 100-Car Naturalistic Driving Study. Background: Driver distraction has been a leading cause of motor vehicle crashes, but the relationship between distractions and crash risk lacks detailed quantification. Method: The authors compared 24 algorithms that varied according to how they incorporated three potential contributors to distraction—glance duration, glance history, and glance location—on how well the algorithms predicted crash risk. Results: Distraction estimated from driver eye-glance patterns was positively associated with crash risk. The algorithms incorporating ongoing off-road glance duration predicted crash risk better than did the algorithms incorporating glance history. Augmenting glance duration with other elements of glance behavior—1.5th power of duration and duration weighted by glance location—produced similar prediction performance as glance duration alone. Conclusions: The distraction level estimated by the algorithms that include current glance duration provides the most sensitive indicator of crash risk. Application: The results inform the design of algorithms to monitor driver state that support real-time distraction mitigation systems.
The Instituto Indigenista Peruano
Authors: Gonzales Osmar 
Published: June 2012

The creation of the Instituto Indigenista Peruano (Peruvian Indigenist Institute—IIP) in 1946 was the result of several decades of discussion regarding the role of indigenous people in the Peruvian nation-state. The debate led to at least two main stances: that the indigenous presence constituted an obstacle to the constitution of the Peruvian nationality and that the nation had indigenous foundations. The IIP took a middle path by proposing a gradual, state-led process of assimilation that focused on cultural and pedagogical factors. Its creation involved the defeat of radical proposals and the conversion of those intellectuals who at some point took revolutionary stances. La creación del Instituto Indigenista Peruano en 1946 fue el resultado de varias décadas de discusiones en torno al papel de los pueblos indígenas en el estado peruano. El debate conllevó a por lo menos dos posturas fundamentales: que le presencia indígena constituido un obstáculo a la constitución nacional del Perú y que la nación tenia fundaciones indígenas. El IIP tomó el camino intermedio, proponiendo un proceso gradual de asimilación que priorizaba factores culturales y pedagógicos. Su creación involucró la derrota de propuestas radicales y la conversión de esos intelectuales quienes habían tomado, en un momento dado, posturas revolucionarias.