bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingosine Kinase-1 Protects Multiple Myeloma from Apoptosis Driven by Cancer-Specific Inhibition of RTKs
Authors: Tsukamoto Shuntaro , Huang Yuhui , Kumazoe Motofumi , Lesnick Connie , Yamada Shuhei , Ueda Naoki , Suzuki Takashi , Yamashita Shuya , Kim Yoon Hee , Fujimura Yoshinori , Miura Daisuke , Kay Neil E. , Shanafelt Tait D. , Tachibana Hirofumi 
Published: August 2015

AbstractActivation of acid sphingomyelinase (ASM) leads to ceramide accumulation and induces apoptotic cell death in cancer cells. In the present study, we demonstrate that the activation of ASM by targeting cancer-overexpressed 67-kDa laminin receptors (67LR) induces lipid raft disruption and inhibits receptor tyrosine kinase (RTK) activation in multiple myeloma cells. Sphingosine kinase 1 (SphK1), a negative regulator of ceramide accumulation with antiapoptotic effects, was markedly elevated in multiple myeloma cells. The silencing of SphK1 potentiated the apoptotic effects of the green tea polyphenol epigallocatechin-3-O-gallate (EGCG), an activator of ASM through 67LR. Furthermore, the SphK1 inhibitor safingol synergistically sensitized EGCG-induced proapoptotic cell death and tumor suppression in multiple myeloma cells by promoting the prevention of RTK phosphorylation and activation of death-associated protein kinase 1 (DAPK1). We propose that targeting 67LR/ASM and SphK1 may represent a novel therapeutic strategy against multiple myeloma. Mol Cancer Ther; 14(10); 2303–12. ©2015 AACR.
Intrinsic Resistance to Cixutumumab Is Conferred by Distinct Isoforms of the Insulin Receptor
Authors: Forest Amelie , Amatulli Michael , Ludwig Dale L. , Damoci Christopher B. , Wang Ying , Burns Colleen A. , Donoho Gregory P. , Zanella Nina , Fiebig Heinz H. , Prewett Marie C. , Surguladze David , DeLigio James T. , Houghton Peter J. , Smith Malcolm A. , Novosiadly Ruslan 
Published: August 2015

Abstract
Despite a recent shift away from anti–insulin-like growth factor I receptor (IGF-IR) therapy, this target has been identified as a key player in the resistance mechanisms to various conventional and targeted agents, emphasizing its value as a therapy, provided that it is used in the right patient population. Molecular markers predictive of antitumor activity of IGF-IR inhibitors remain largely unidentified. The aim of this study is to evaluate the impact of insulin receptor (IR) isoforms on the antitumor efficacy of cixutumumab, a humanized mAb against IGF-IR, and to correlate their expression with therapeutic outcome. The data demonstrate that expression of total IR rather than individual IR isoforms inversely correlates with single-agent cixutumumab efficacy in pediatric solid tumor models in vivo. Total IR, IR-A, and IR-B expression adversely affects the outcome of cixutumumab in combination with chemotherapy in patient-derived xenograft models of lung adenocarcinoma. IR-A overexpression in tumor cells confers complete resistance to cixutumumab in vitro and in vivo, whereas IR-B results in a partial resistance. Resistance in IR-B–overexpressing cells is fully reversed by anti–IGF-II antibodies, suggesting that IGF-II is a driver of cixutumumab resistance in this setting. The present study links IR isoforms, IGF-II, and cixutumumab efficacy mechanistically and identifies total IR as a biomarker predictive of intrinsic resistance to anti–IGF-IR antibody.
Implications: This study identifies total IR as a biomarker predictive of primary resistance to IGF-IR antibodies and provides a rationale for new clinical trials enriched for patients whose tumors display low IR expression. Mol Cancer Res; 13(12); 1615–26. ©2015 AACR.
Effects of Cooperative Learning on Students’ Academic Achievement
Authors: Gull Fariha , Shehzad Shumaila 
Published: August 2015

Multiple teaching methods are used by teachers in order to improve learning of students. The most popular is lecture method, while very effective is cooperative learning method. Later teaching method had been preferred for teaching science and languages as cited by previous research studies. However, in the subjects of social sciences and humanities, its importance cannot be ignored. Following study is an effort to determine effect of cooperative learning method on students’ achievement in subject of Education. Qusi experimental design, with pre and post test of control and experimental group was used to achieve target of the study. Sample of the study consisted of 63 female students enrolled in grade 12 of a public college. An achievement test was used as a pre-test, the students were than divided in experimental and control groups. Multiple cooperative learning activities were performed with experimental group by using three common methods of cooperative learning i.e., STAD, TGT and Jigsaw II. The control group was taught by lecture method only. After 8 weeks a post test was administered on both experimental and control group in order to identify difference in achievement. The independent sample t-test was used to measure the mean scores difference between achievement scores of control and treatment groups on pretest. The results showed that there was no significant difference between the two groups (p=.825) leading to assumption that both groups were on equal level of achievement before intervention. Same test was applied to find out difference between two groups before and after intervention. The results showed that there was a significant difference in scores of control and experimental group in post-test. In addition to this paired sample t-test was conducted to compare the effect of intervention on achievement scores of experimental group. The results showed that there was significant difference between scores of experimental group before and after intervention (p=.000). It can be concluded from results that cooperative learning activities had a positive effect on academic achievement of students enrolled in the subject of Education. This study is a contribution in knowledge body of teaching methods for social sciences. This had clarified that cooperative learning activities are equally helpful for the subject that was considered truly a lecture subject. The teachers can use this teaching method in their classes.
Cross-National Key Performance Measures of the Quality of Acute Stroke Care in Western Europe
Authors: Norrving Bo , Bray Benjamin D. , Asplund Kjell , Heuschmann Peter , Langhorne Peter , Rudd Anthony G. , Wagner Markus , Wiedmann Silke , Wolfe Charles D.A. 
Published: August 2015

Background and Purpose—
There are no agreed measures of stroke care quality that enable the standardized comparison of stroke care between countries. We aimed to develop a set of measures of quality of acute stroke care involving stroke quality registers in Western Europe.

Methods—
A multinational working group identified 6 regional or national stroke quality registers in Europe and reviewed their data sets, performance measures, and the method by which these had been developed. Measures used in the registers were presented for discussion to a consensus group of representatives from the quality registers identified, as well as other stroke experts, and the final set of common performance measures was agreed through majority consensus.

Results—
Thirty final performance measures were agreed by the European consensus group, encompassing the domains of coordination of care (stroke unit–based care), diagnosis (brain imaging, vascular imaging, cardiac arrhythmia detection, and therapy assessment), preservation of neural tissue (thrombolytic therapy and door-to-needle time), prevention of complications (dysphagia screening), initiation of secondary prevention (antiplatelet, anticoagulation, lipid lowering, blood pressure lowering, carotid surgery, time from vascular imaging to carotid surgery, and smoking cessation), survival (90-day poststroke mortality), and functional outcomes (90-day modified Rankin Scale).

Conclusions—
On the basis of experience of quality registers in Europe, we have proposed a common set of performance measures that will facilitate the international comparison of acute stroke care quality.
Intracerebral Hematoma Contributes to Hydrocephalus After Intraventricular Hemorrhage via Aggravating Iron Accumulation
Authors: Chen Qianwei , Tang Jun , Tan Liang , Guo Jing , Tao Yihao , Li Lin , Chen Yujie , Liu Xin , Zhang John H. , Chen Zhi , Feng Hua 
Published: August 2015

Background and Purpose—
The intraventricular hemorrhage (IVH) secondary to intracerebral hemorrhage (ICH) was reported to be relevant to a higher incidence of hydrocephalus, which would result in poorer outcomes for patients with ICH. However, the mechanisms responsible for this relationship remain poorly characterized. Thus, this study was designed to further explore the development and progression of hydrocephalus after secondary IVH.

Methods—
Autologous blood injection model was induced to mimic ICH with ventricular extension (ICH/IVH) or primary IVH in Sprague-Dawley rats. Magnetic resonance imaging, Morris water maze, brain water content, Evans blue extravasation, immunohistochemistry staining, Western blot, iron determination, and electron microscopy were used in these rats. Then, deferoxamine treatment was used to clarify the involvement of iron in the development of hydrocephalus.

Results—
Despite the injection of equivalent blood volumes, ICH/IVH resulted in more significant ventricular dilation, ependymal cilia damage, and iron overload, as well as more severe early brain injury and neurological deficits compared with IVH alone. Systemic deferoxamine treatment more effectively reduced ventricular enlargement in ICH/IVH compared with primary IVH.

Conclusions—
Our results show that ICH/IVH caused more significant chronic hydrocephalus and iron accumulation than primary IVH alone. Intracerebral hematoma plays a vital role in persistent iron overload and aggravated hydrocephalus after ICH/IVH.
Cross–Time Scale Interactions and Rainfall Extreme Events in Southeastern South America for the Austral Summer. Part I: Potential Predictors
Authors: Muñoz Á. G. , Goddard L. , Robertson A. W. , Kushnir Y. , Baethgen W. 
Published: August 2015

Abstract
The physical mechanisms and predictability associated with extreme daily rainfall in southeastern South America (SESA) are investigated for the December–February season in a two-part study. Through a k-mean analysis, this first paper identifies a robust set of daily circulation regimes that are used to link the frequency of rainfall extreme events with large-scale potential predictors at subseasonal-to-seasonal scales. This represents a basic set of daily circulation regimes related to the continental and oceanic phases of the South Atlantic convergence zone (SACZ) and wave train patterns superimposed on the Southern Hemisphere polar jet. Some of these recurrent synoptic circulation types are conducive to extreme rainfall events in the region through synoptic control of different mesoscale physical features and, at the same time, are influenced by climate phenomena that could be used as sources of potential predictability. Extremely high rainfall (as measured by the 95th and 99th percentiles) is associated with two of these weather types (WTs), which are characterized by moisture advection intrusions from lower latitudes and the Pacific Ocean; another three WTs, characterized by above-normal moisture advection toward lower latitudes or the Andes, are associated with dry days (days with no rain). The analysis permits the identification of several subseasonal-to-seasonal scale potential predictors that modulate the occurrence of circulation regimes conducive to extreme rainfall events in SESA. It is conjectured that a cross–time scale interaction between the different climate drivers improves the predictive skill of extreme precipitation in the region.
The Relationship between Contiguous El Niño and La Niña Revealed by Self-Organizing Maps
Authors: Li Xin , Li Chongyin , Ling Jian , Tan Yanke 
Published: August 2015

Abstract
This study introduces a new methodology for identifying El Niño and La Niña events. Sea surface temperature (SST) anomaly patterns for El Niño and La Niña onset, peak, and end phases are classified by self-organizing maps (SOM) analysis. Both onset and end phases for El Niño and La Niña exhibit eastern Pacific (EP) and central Pacific (CP) types. The SST anomaly patterns in peak phase can be classified into EP, EP-like, and CP types for El Niño, and EP, mixed (MIX), and CP types for La Niña.
The general type of each El Niño or La Niña event is then defined according to the SST type for each of the three phases. There is no robust connection between the general types of the contiguous El Niño and La Niña except that the MIX La Niña rarely induces a subsequent CP El Niño. However, there are strong relationships between the end-phase type of El Niño and the onset-phase type of the subsequent La Niña. The EP-end-type El Niño favors transition to the CP-onset-type La Niña, while the CP-end-type El Niño favors transition to the EP-onset-type La Niña. On the other hand, the CP-end-type La Niña favors transition to EP-onset-type El Niño. Furthermore, an El Niño that occurs after the decay of La Niña favors initiating as an EP-onset type. These relationships are driven by different atmosphere–ocean dynamics, such as coupled air–sea feedback, thermocline feedback, slow SST mode, and Bjerknes feedbacks.
Spatiotemporal Long-Range Persistence in Earth’s Temperature Field: Analysis of Stochastic–Diffusive Energy Balance Models
Authors: Rypdal Kristoffer , Rypdal Martin , Fredriksen Hege-Beate 
Published: August 2015

Abstract
A two-dimensional stochastic–diffusive energy balance model (EBM) formulated on a sphere by G. R. North et al. is explored and generalized. Instantaneous and frequency-dependent spatial autocorrelation functions and local temporal power spectral densities are computed for local sites and for spatially averaged surface temperature signals up to the global scale. On time scales up to the relaxation time scale given by the effective heat capacities of the ocean mixed layer and land surface, respectively, scaling features are obtained that are reminiscent of what can be derived from the observed temperature field. On longer time scales, however, the EBM predicts a transition to a white-noise scaling, which is not reflected in the observed records. A fractional generalization, which can be considered as a spatial generalization of the zero-dimensional, long-memory EBM of M. Rypdal and K. Rypdal, is proposed and explored. It is demonstrated that this generalized model describes qualitatively the main correlation characteristics of the temperature field reported in the literature and those derived herein from 500-yr-long control simulations of the NorESM Earth system model. A further generalization of the model, to include long-term persistence in the stochastic forcing, is also discussed.
Semidiurnal Baroclinic Tides on the Central Oregon Inner Shelf
Authors: Suanda Sutara H. , Barth John A. 
Published: August 2015

AbstractSemidiurnal velocity and density oscillations are examined over the mid- and inner continental shelf near Heceta Bank on the Oregon coast. Measurements from two long-term observation networks with sites on and off the submarine bank reveal that both baroclinic velocities and displacements are dominated by the first mode, with larger velocities on the midshelf and northern parts of the bank. Midshelf sites have current ellipses that are near the theoretical value for single, progressive internal tidal waves compared to more linearly polarized currents over the inner shelf. Baroclinic current variability is not correlated to the spring–neap cycle and is uncorrelated between mooring locations. An idealized model of two internal waves propagating from different directions reproduces some of the observed variability in semidiurnal ellipse parameters. At times, the phasing between moorings along a cross-shelf transect are consistent with onshelf wave propagation, a characteristic also present in the output of a three-dimensional regional circulation model. Regional wind-driven upwelling/downwelling influences stratification at all shelf moorings. At locations north of the bank, stronger baroclinic velocities were found during periods of higher background stratification.
Configuration of the Shoulder Complex During the Arm-Cocking Phase in Baseball Pitching
Authors: Konda Shoji , Yanai Toshimasa , Sakurai Shinji 
Published: August 2015

Background: The role of the scapula during high-velocity baseball pitching has been described without 3-dimensional kinematic data. It has been speculated that the scapula functions to align the humerus with the spine of the scapula on both the transverse and scapular planes at the end of the arm-cocking phase. Hypothesis: Two hypotheses were formulated: (1) the scapulothoracic protraction angle correlates with the humerothoracic horizontal adduction angle among participants, and (2) the scapulohumeral rhythm of the humerothoracic elevation is not the same as the normal ratio (2:1) observed widely in controlled abductions. Study Design: Descriptive laboratory study. Methods: A total of 20 Japanese professional baseball pitchers were asked to pitch 3 fastballs as they would normally during pitching practice. The 3-dimensional kinematic data of the thorax, scapulae, humeri, and pelvis were recorded using an electromagnetic tracking device operating at 240 Hz. Humerothoracic, scapulothoracic, and glenohumeral joint configurations were determined at the instant of stride-foot contact (SFC) and the end of the arm-cocking phase (MER). Results: The mean (±SD) glenohumeral horizontal adduction (–6° ± 7°) and elevation (85° ± 10°) angles at the MER indicated that the humerus was positioned almost parallel to the spine of the scapula. The mean scapulothoracic protraction angle (15° ± 10°) was significantly correlated with the humerothoracic horizontal adduction angle (10° ± 11°) at the MER ( r = 0.76, P < .001) but not at the SFC ( r = 0.13, P = .58). The scapulohumeral rhythm (4.2 [±1.9]:1) expressed as the ratio of the glenohumeral elevation angle to the scapulothoracic upward rotation angle at the MER was significantly greater than the normal ratio (2:1) ( P < .01). Conclusion: The results supported the hypotheses, providing evidence to corroborate the widely accepted concept that the scapula functions to align the humerus with the spine of the scapula so as to limit the glenohumeral joint configuration within the “safe zone” at the MER. Clinical Relevance: Disruption of coordination, such as abnormal patterns including “SICK” scapula (scapular malposition, inferior medial border prominence, coracoid pain, and dyskinesis) and scapular dyskinesis, may result in an abnormal configuration of the glenohumeral joint at the MER.
Introducing the fit-criteria assessment plot – A visualisation tool to assist class enumeration in group-based trajectory modelling
Authors: Klijn Sven L , Weijenberg Matty P , Lemmens Paul , van den Brandt Piet A , Lima Passos Valéria 
Published: August 2015

Background and objective Group-based trajectory modelling is a model-based clustering technique applied for the identification of latent patterns of temporal changes. Despite its manifold applications in clinical and health sciences, potential problems of the model selection procedure are often overlooked. The choice of the number of latent trajectories (class-enumeration), for instance, is to a large degree based on statistical criteria that are not fail-safe. Moreover, the process as a whole is not transparent. To facilitate class enumeration, we introduce a graphical summary display of several fit and model adequacy criteria, the fit-criteria assessment plot. Methods An R-code that accepts universal data input is presented. The programme condenses relevant group-based trajectory modelling output information of model fit indices in automated graphical displays. Examples based on real and simulated data are provided to illustrate, assess and validate fit-criteria assessment plot’s utility. Results Fit-criteria assessment plot provides an overview of fit criteria on a single page, placing users in an informed position to make a decision. Fit-criteria assessment plot does not automatically select the most appropriate model but eases the model assessment procedure. Conclusions Fit-criteria assessment plot is an exploratory, visualisation tool that can be employed to assist decisions in the initial and decisive phase of group-based trajectory modelling analysis. Considering group-based trajectory modelling’s widespread resonance in medical and epidemiological sciences, a more comprehensive, easily interpretable and transparent display of the iterative process of class enumeration may foster group-based trajectory modelling’s adequate use.
Alcohol service provision for older people in an area experiencing high alcohol use and health inequalities
Authors: McCabe Karen E , Ling Jonathan , Wilson Graeme B , Crosland Ann , Kaner Eileen FS , Haighton Catherine A 
Published: August 2015

Background: UK society is ageing. Older people who drink alcohol, drink more than those from previous generations, drink more frequently than other age groups and are more likely to drink at home and alone. Alcohol problems in later life however are often under-detected and under-reported meaning older people experiencing alcohol problems have high levels of unmet need. Methods: This study sought to identify existing services within South of Tyne, North East England to capture the extent of service provision for older drinkers and identify any gaps. The Age UK definition of ‘older people’ (aged 50 and over) was used. Services were contacted by telephone, managers or their deputy took part in semi-structured interviews. Findings: Forty six service providers were identified. Only one provided a specific intervention for older drinkers. Others typically provided services for age 18+. Among providers, there was no definitive definition of an older person. Data collection procedures within many organisations did not enable them to confirm whether older people were accessing services. Where alcohol was used alongside other drugs, alcohol use could remain unrecorded. Conclusion: To enable alcohol services to meet the needs of older people, greater understanding is needed of the patterns of drinking in later life, the experiences of older people, the scale and scope of the issue and guidance as to the most appropriate action to take. An awareness of the issues related to alcohol use in later life also needs to be integrated into commissioning of other services that impact upon older people.
Options for managing raised intracranial pressure
Authors: Tan Tong Khee , Cheng Ming Hua , Sim Eileen Yilin 
Published: August 2015

This article reviews the current monitoring and management options for raised intracranial pressure (ICP), primarily in traumatic head injuries, in line with current literature and guidelines. The use of ICP monitoring is useful in managing, predicting outcomes, following the progression and guiding interventions of neurological disease states. Patients with raised ICP should be monitored closely in a neurocritical care setting where appropriate interventions can be instituted based on available monitoring parameters. Various first- and second-tier methods should be considered, with the primary goal to decrease secondary insult to brain tissue for best outcomes.
Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia
Authors: Karol Seth E. , Yang Wenjian , Van Driest Sara L. , Chang Tamara Y. , Kaste Sue , Bowton Erica , Basford Melissa , Bastarache Lisa , Roden Dan M. , Denny Joshua C. , Larsen Eric , Winick Naomi , Carroll William L. , Cheng Cheng , Pei Deqing , Fernandez Christian A. , Liu Chengcheng , Smith Colton , Loh Mignon L. , Raetz Elizabeth A. , Hunger Stephen P. , Scheet Paul , Jeha Sima , Pui Ching-Hon , Evans William E. , Devidas Meenakshi , Mattano Leonard A. , Relling Mary V. 
Published: August 2015

Key PointsComprehensive study of glucocorticoid-induced osteonecrosis identifies glutamate receptor gene variants as risk factors.