bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between years in the trade and the development of radiographic knee osteoarthritis and MRI-detected meniscal tears and bursitis in floor layers. A cross-sectional study of a historical cohort
Authors: Jensen Lilli Kirkeskov , Rytter Søren , Marott Jacob Louis , Bonde Jens Peter 
Published: May 2012

ObjectivesAn increased risk of developing knee disorders including radiographic knee osteoarthritis (OA) have been shown among workers with kneeling working demands. There may also be a dose-related association between duration of employment in occupations with kneeling work and development of radiographic knee OA and magnetic resonance imaging (MRI)-detected meniscal tears and bursitis.DesignA cross-sectional study of a historical cohort.SettingMembers of the trade unions for floor layers and graphic designers in Denmark.Participants92 male floor layers and 49 graphic designers aged 36–70 years were randomly selected among participants from a clinical and radiographic study of 156 floor layers and 152 graphic designers.Outcome measuresRadiographic tibiofemoral (TF) and patellofemoral (PF) knee-OA and MRI-detected meniscal tears and bursitis. Results were adjusted for age, earlier knee traumas, sports activities and body mass index in logistic regression models. Association between TF OA and years in the floor-laying trade was graphically examined by a restricted cubic spline with four knots.ResultsIncrease in number of years with exposure to kneeling work is associated with radiographic TF knee OA with ORs 0.7, 95% CI 0.07 to 4.42; OR 1.89, 95% CI 0.29 to 12.3; OR 4.82, 95% CI 1.38 to 17 for <20 years, 20–30 years and >30 years of kneeling work, respectively. MRI-verified medial meniscal tears was increased among subjects with kneeling work with OR 1.96, 95% CI 0.79 to 4.88 to OR 4.73, 95% CI 1.16 to 19.4 but was not associated with duration of employment. Periarticular bursitis was increased in subjects with <20 years of kneeling working activity. Lateral meniscal tears and PF knee OA were not associated with duration of kneeling working activity or with kneeling work in general.ConclusionsThe findings suggest a dose–response relationship for radiographic TF knee OA in floor layers with a significant amount of kneeling work and an increase of MRI-verified medial meniscal tears among workers with kneeling work.
Do statins improve outcomes in patients with asthma on inhaled corticosteroid therapy? A retrospective cohort analysis
Authors: Lokhandwala Tasneem , West-Strum Donna , Banahan Benjamin F , Bentley John P , Yang Yi 
Published: May 2012

ObjectivesAnimal studies and clinical trials have examined the potential benefits of statins in asthma management with contradictory results. The objective of this study was to determine if asthma patients on concurrent statins are less likely to have asthma-related hospitalisations.DesignA retrospective cohort study using Mississippi Medicaid data for 2002–2004.ParticipantsAsthma patients ≥18 years were identified using the ICD9 code 493.xx from 1 July 2002 through 31 December 2003. The index date for an exposed subject was any date within the identification period, 180 days prior to which the subject had at least one inhaled corticosteroid prescription and at least an 80% adherence rate to statins. Asthma patients on inhaled corticosteroids, but not on statins, were selected as the unexposed population. The two groups were matched and followed for 1 year beginning the index date.Main outcomes measuresPatient outcomes in terms of hospitalisations and ER visits were compared using conditional logistic regression.ResultsAfter matching, there were 479 exposed subjects and 958 corresponding unexposed subjects. The odds of asthma-related hospitalisation and/or emergency room (ER) visits for asthma patients on concurrent statins were almost half the odds for patients not on statins (OR=0.55; 95% CI (0.37 to 0.84); p=0.0059). Similarly, the odds of asthma-related ER visits were significantly lower for patients on statins (OR=0.48; 95% CI (0.28 to 0.82); p=0.0069).ConclusionThe findings suggest beneficial effects of statins in asthma management. Further prospective investigations are required to provide more conclusive evidence.
A Measurement Framework for Evaluating Emulators for Digital Preservation
Authors: Guttenbrunner Mark , Rauber Andreas 
Published: May 2012

Accessible emulation is often the method of choice for maintaining digital objects, specifically complex ones such as applications, business processes, or electronic art. However, validating the emulator’s ability to faithfully reproduce the original behavior of digital objects is complicated.
This article presents an evaluation framework and a set of tests that allow assessment of the degree to which system emulation preserves original characteristics and thus significant properties of digital artifacts. The original system, hardware, and software properties are described. Identical environment is then recreated via emulation. Automated user input is used to eliminate potential confounders. The properties of a rendered form of the object are then extracted automatically or manually either in a target state, a series of states, or as a continuous stream. The concepts described in this article enable preservation planners to evaluate how emulation affects the behavior of digital objects compared to their behavior in the original environment. We also review how these principles can and should be applied to the evaluation of migration and other preservation strategies as a general principle of evaluating the invocation and faithful rendering of digital objects and systems. The article concludes with design requirements for emulators developed for digital preservation tasks.
MARCKS Regulates Growth and Radiation Sensitivity and Is a Novel Prognostic Factor for Glioma
Authors: Jarboe John S. , Anderson Joshua C. , Duarte Christine W. , Mehta Tapan , Nowsheen Somaira , Hicks Patricia H. , Whitley Alexander C. , Rohrbach Timothy D. , McCubrey Raymond O. , Chiu Sherard , Burleson Tamara M. , Bonner James A. , Gillespie G. Yancey , Yang Eddy S. , Willey Christopher D. 
Published: May 2012

AbstractPurpose: This study assessed whether myristoylated alanine-rich C-kinase substrate (MARCKS) can regulate glioblastoma multiforme (GBM) growth, radiation sensitivity, and clinical outcome.Experimental Design: MARCKS protein levels were analyzed in five GBM explant cell lines and eight patient-derived xenograft tumors by immunoblot, and these levels were correlated to proliferation rates and intracranial growth rates, respectively. Manipulation of MARCKS protein levels was assessed by lentiviral-mediated short hairpin RNA knockdown in the U251 cell line and MARCKS overexpression in the U87 cell line. The effect of manipulation of MARCKS on proliferation, radiation sensitivity, and senescence was assessed. MARCKS gene expression was correlated with survival outcomes in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) Database and The Cancer Genome Atlas (TCGA).Results: MARCKS protein expression was inversely correlated with GBM proliferation and intracranial xenograft growth rates. Genetic silencing of MARCKS promoted GBM proliferation and radiation resistance, whereas MARCKS overexpression greatly reduced GBM growth potential and induced senescence. We found MARCKS gene expression to be directly correlated with survival in both the REMBRANDT and TCGA databases. Specifically, patients with high MARCKS expressing tumors of the proneural molecular subtype had significantly increased survival rates. This effect was most pronounced in tumors with unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoters, a traditionally poor prognostic factor.Conclusions: MARCKS levels impact GBM growth and radiation sensitivity. High MARCKS expressing GBM tumors are associated with improved survival, particularly with unmethylated MGMT promoters. These findings suggest the use of MARCKS as a novel target and biomarker for prognosis in the proneural subtype of GBM. Clin Cancer Res; 18(11); 3030–41. ©2012 AACR.
Yes-Associated Protein 1 Is Activated and Functions as an Oncogene in Meningiomas
Authors: Baia Gilson S. , Caballero Otavia L. , Orr Brent A. , Lal Anita , Ho Janelle S. Y. , Cowdrey Cynthia , Tihan Tarik , Mawrin Christian , Riggins Gregory J. 
Published: May 2012

Abstract
The Hippo signaling pathway is functionally conserved in Drosophila melanogaster and mammals, and its proposed function is to control tissue homeostasis by regulating cell proliferation and apoptosis. The core components are composed of a kinase cascade that culminates with the phosphorylation and inhibition of Yes-associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm. In the absence of Hippo signaling, YAP1 translocates to the nucleus, associates with co-activators TEAD1-4, and functions as a transcriptional factor promoting the expression of key target genes. Components of the Hippo pathway are mutated in human cancers, and deregulation of this pathway plays a role in tumorigenesis. Loss of the NF2 tumor suppressor gene is the most common genetic alteration in meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo pathway. Here, we show that primary meningioma tumors have high nuclear expression of YAP1. In meningioma cells, Merlin expression is associated with phosphorylation of YAP1. Using an siRNA transient knockdown of YAP1 in NF2-mutant meningioma cells, we show that suppression of YAP1 impaired cell proliferation and migration. Conversely, YAP1 overexpression led to a strong augment of cell proliferation and anchorage-independent growth and restriction of cisplatin-induced apoptosis. In addition, expression of YAP1 in nontransformed arachnoidal cells led to the development of tumors in nude mice. Together, these findings suggest that in meningiomas, deregulation of the Hippo pathway is largely observed in primary tumors and that YAP1 functions as an oncogene promoting meningioma tumorigenesis. Mol Cancer Res; 10(7); 904–13. ©2012 AACR.
Key Principles and Clinical Applications of “Next-Generation” DNA Sequencing
Authors: Rizzo Jason M. , Buck Michael J. 
Published: May 2012

Abstract
Demand for fast, inexpensive, and accurate DNA sequencing data has led to the birth and dominance of a new generation of sequencing technologies. So-called “next-generation” sequencing technologies enable rapid generation of data by sequencing massive amounts of DNA in parallel using diverse methodologies which overcome the limitations of Sanger sequencing methods used to sequence the first human genome. Despite opening new frontiers of genomics research, the fundamental shift away from the Sanger sequencing that next-generation technologies has created has also left many unaware of the capabilities and applications of these new technologies, especially those in the clinical realm. Moreover, the brisk evolution of sequencing technologies has flooded the market with commercially available sequencing platforms, whose unique chemistries and diverse applications stand as another obstacle restricting the potential of next-generation sequencing. This review serves to provide a primer on next-generation sequencing technologies for clinical researchers and physician scientists. We provide an overview of the capabilities and clinical applications of DNA sequencing technologies to raise awareness among researchers about the power of these novel genomic tools. In addition, we discuss that key sequencing principles provide a comparison between existing and near-term technologies and outline key advantages and disadvantages between different sequencing platforms to help researchers choose an appropriate platform for their research interests. Cancer Prev Res; 5(7); 887–900. ©2012 AACR.
Hippocampal–Prefrontal Engagement and Dynamic Causal Interactions in the Maturation of Children's Fact Retrieval
Authors: Cho Soohyun , Metcalfe Arron W. S. , Young Christina B. , Ryali Srikanth , Geary David C. , Menon Vinod 
Published: May 2012

Abstract
Children's gains in problem-solving skills during the elementary school years are characterized by shifts in the mix of problem-solving approaches, with inefficient procedural strategies being gradually replaced with direct retrieval of domain-relevant facts. We used a well-established procedure for strategy assessment during arithmetic problem solving to investigate the neural basis of this critical transition. We indexed behavioral strategy use by focusing on the retrieval frequency and examined changes in brain activity and connectivity associated with retrieval fluency during arithmetic problem solving in second- and third-grade (7- to 9-year-old) children. Children with higher retrieval fluency showed elevated signal in the right hippocampus, parahippocampal gyrus (PHG), lingual gyrus (LG), fusiform gyrus (FG), left ventrolateral PFC (VLPFC), bilateral dorsolateral PFC (DLPFC), and posterior angular gyrus. Critically, these effects were not confounded by individual differences in problem-solving speed or accuracy. Psychophysiological interaction analysis revealed significant effective connectivity of the right hippocampus with bilateral VLPFC and DLPFC during arithmetic problem solving. Dynamic causal modeling analysis revealed strong bidirectional interactions between the hippocampus and the left VLPFC and DLPFC. Furthermore, causal influences from the left VLPFC to the hippocampus served as the main top–down component, whereas causal influences from the hippocampus to the left DLPFC served as the main bottom–up component of this retrieval network. Our study highlights the contribution of hippocampal–prefrontal circuits to the early development of retrieval fluency in arithmetic problem solving and provides a novel framework for studying dynamic developmental processes that accompany children's development of problem-solving skills.
The Influence of Topography and Ambient Stability on the Characteristics of Cold-Air Pools: A Numerical Investigation
Authors: Katurji Marwan , Zhong Shiyuan 
Published: May 2012

AbstractA high-resolution numerical investigation of a cold-air pooling process (under quiescent conditions) is carried out that systematically highlights the relations between the characteristics of the cold-air pools (e.g., slope winds, vertical temperature and wind structure, and cooling rate) and the characteristics of the topography (e.g., basin size and slope angle) under different ambient stabilities. The Advanced Regional Prediction System model is used to simulate 40 different scenarios at 100-m (10 m) horizontal (vertical) resolution. Results are within the range of similar observed phenomena. The main physical process governing the cooling process near the basin floor (<200 m in height) was found to be longwave radiative flux divergence, whereas vertical advection of temperature dominated the cooling process for the upper-basin areas. The maximum downslope wind speed is linearly correlated with both basin size and slope angle, with stronger wind corresponding to larger basin and lower slope angle. As the basin size increases, the influence of slope angle on maximum downslope wind decreases and the maximum is located farther down the slope. These relationships do not appear to be sensitive to stability, but weaker stability produces more cooling in the basin atmosphere by allowing stronger rising motion and adiabatic cooling. Insight gained from this study helps to improve the understanding of the cold-air pooling process within the investigated settings.
Soil Moisture–Precipitation Feedback Processes in the Indian Summer Monsoon Season
Authors: Asharaf Shakeel , Dobler Andreas , Ahrens Bodo 
Published: May 2012

Abstract
Soil moisture can influence precipitation through a feedback loop with land surface evapotranspiration. A series of numerical simulations, including soil moisture sensitivity experiments, have been performed for the Indian summer monsoon season (ISM). The simulations were carried out with the nonhydrostatic regional climate model Consortium for Small-Scale Modeling (COSMO) in climate mode (COSMO-CLM), driven by lateral boundary conditions derived from the ECMWF Interim reanalysis (ERA-Interim). Positive as well as negative feedback processes through local and remote effects are shown to be important. The regional moisture budget studies have exposed that changes in precipitable water and changes in precipitation efficiency vary in importance, in time, and in space in the simulations for India. Overall, the results show that the premonsoonal soil moisture has a significant influence on the monsoonal precipitation, and thus confirmed that modeling of soil moisture is essential for reliable simulation and forecasting of the ISM.
Ensemble-Based Data Assimilation for Estimation of River Depths
Authors: Wilson Greg , Özkan-Haller H. Tuba 
Published: May 2012

Abstract
A method is presented for estimating bathymetry in a river, based on observations of depth-averaged velocity during steady flow. The estimator minimizes a cost function that combines known information in the form of a prior estimate and measured data (including measurement noise). State augmentation is used to relate the measured variable (velocity) to the unknown parameter (bathymetry). Specifically, the unknown consists of deviations in depth about a known along-channel mean. Verification of the method is performed using a simple 1D channel geometry as well as for two real-world reaches. In all cases, the verification is based on nominal river depths of 3–10 m, channel widths of 50–100 m, and Froude numbers much less than one. Further tests are performed to assess the usefulness of various observation types and sampling schemes for this type of estimation.
Assimilation of Radar Radial Velocity Data with the WRF Hybrid Ensemble–3DVAR System for the Prediction of Hurricane Ike (2008)
Authors: Li Yongzuo , Wang Xuguang , Xue Ming 
Published: May 2012

Abstract
An enhanced version of the hybrid ensemble–three-dimensional variational data assimilation (3DVAR) system for the Weather Research and Forecasting Model (WRF) is applied to the assimilation of radial velocity (Vr) data from two coastal Weather Surveillance Radar-1988 Doppler (WSR-88D) radars for the prediction of Hurricane Ike (2008) before and during its landfall. In this hybrid system, flow-dependent ensemble covariance is incorporated into the variational cost function using the extended control variable method. The analysis ensemble is generated by updating each forecast ensemble member with perturbed radar observations using the hybrid scheme itself. The Vr data are assimilated every 30 min for 3 h immediately after Ike entered the coverage of the two coastal radars.
The hybrid method produces positive temperature increments indicating a warming of the inner core throughout the depth of the hurricane. In contrast, the 3DVAR produces much weaker and smoother increments with negative values at the vortex center at lower levels. Wind forecasts from the hybrid analyses fit the observed radial velocity better than that from 3DVAR, and the 3-h accumulated precipitation forecasts from the hybrid are also more skillful. The track forecast is slightly improved by the hybrid method and slightly degraded by the 3DVAR compared to the forecast from the Global Forecast System (GFS) analysis. All experiments assimilating the radar data show much improved intensity analyses and forecasts compared to the experiment without assimilating radar data. The better forecast of the hybrid indicates that the hybrid method produces dynamically more consistent state estimations. Little benefit of including the tuned static component of background error covariance in the hybrid is found.
An Analysis of Vortices Embedded within a Quasi-Linear Convective System Using X-Band Polarimetric Radar
Authors: Mahale Vivek N. , Brotzge Jerald A. , Bluestein Howard B. 
Published: May 2012

Abstract
On 2 April 2010, a developing quasi-linear convective system (QLCS) moved rapidly northeastward through central Oklahoma spawning at least three intense, mesoscale vortices. At least two of these vortices caused damage rated as category 0 to 1 on the enhanced Fujita scale (EF0–EF1) in and near the town of Rush Springs. Two radar networks—the National Weather Service Weather Surveillance Radar-1988 Doppler network (WSR-88D) and the Engineering Research Center for Collaborative Adaptive Sensing of the Atmosphere (CASA) radar network—collected high spatial and temporal resolution data of the event. This study is an in-depth polarimetric analysis of mesovortices within a QLCS. In this case study, the storm development and evolution of the QLCS mesovortices are examined. Significant findings include the following: 1) The damage in Rush Springs was caused by a combination of the fast translation speed and the embedded circulations associated with QLCS vortices. The vortices’ relative winds nearly negated the storm motion to the left of the vortex, but doubled the ground-relative wind to the right of the vortex. 2) A significant differential reflectivity (ZDR) arc developed along the forward flank of the first vortex. The ZDR arc propagated northeastward along the QLCS with the development of each new vortex. 3) A minimum in the copolar correlation coefficient (ρhv) in the center of the strongest vortex was observed, indicating the likely existence of a polarimetric tornado debris signature (TDS). A secondary ρhv minimum also was found just to the right of the vortex center, possibly associated with lofted debris from straight-line winds.
CCR1 blockade reduces tumor burden and osteolysis in vivo in a mouse model of myeloma bone disease
Authors: Dairaghi Daniel J. , Oyajobi Babatunde O. , Gupta Anjana , McCluskey Brandon , Miao Shichang , Powers Jay P. , Seitz Lisa C. , Wang Yu , Zeng Yibin , Zhang Penglie , Schall Thomas J. , Jaen Juan C. 
Published: May 2012

Abstract
The chemokine CCL3/MIP-1α is a risk factor in the outcome of multiple myeloma (MM), particularly in the development of osteolytic bone disease. This chemokine, highly overexpressed by MM cells, can signal mainly through 2 receptors, CCR1 and CCR5, only 1 of which (CCR1) is responsive to CCL3 in human and mouse osteoclast precursors. CCR1 activation leads to the formation of osteolytic lesions and facilitates tumor growth. Here we show that formation of mature osteoclasts is blocked by the highly potent and selective CCR1 antagonist CCX721, an analog of the clinical compound CCX354. We also show that doses of CCX721 selected to completely inhibit CCR1 produce a profound decrease in tumor burden and osteolytic damage in the murine 5TGM1 model of MM bone disease. Similar effects were observed when the antagonist was used prophylactically or therapeutically, with comparable efficacy to that of zoledronic acid. 5TGM1 cells were shown to express minimal levels of CCR1 while secreting high levels of CCL3, suggesting that the therapeutic effects of CCX721 result from CCR1 inhibition on non-MM cells, most likely osteoclasts and osteoclast precursors. These results provide a strong rationale for further development of CCR1 antagonists for the treatment of MM and associated osteolytic bone disease.