bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-Src Activation Mediates Erlotinib Resistance in Head and Neck Cancer by Stimulating c-Met
Authors: Stabile Laura P. , He Guoqing , Lui Vivian Wai Yan , Thomas Sufi M. , Henry Cassandra , Gubish Christopher T. , Joyce Sonali , Quesnelle Kelly M. , Siegfried Jill M. , Grandis Jennifer R. 
Published: December 2012

Abstract
Purpose: Strategies to inhibit the EGF receptor (EGFR) using the tyrosine kinase inhibitor erlotinib have been associated with limited clinical efficacy in head and neck squamous cell carcinoma (HNSCC). Co-activation of alternative kinases may contribute to erlotinib resistance.
Experimental Design: We generated HNSCC cells expressing dominant-active c-Src (DA-Src) to determine the contribution of c-Src activation to erlotinib response.
Results: Expression of DA-Src conferred resistance to erlotinib in vitro and in vivo compared with vector-transfected control cells. Phospho-Met was strongly upregulated by DA-Src, and DA-Src cells did not produce hepatocyte growth factor (HGF). Knockdown of c-Met enhanced sensitivity to erlotinib in DA-Src cells in vitro, as did combining a c-Met or c-Src inhibitor with erlotinib. Inhibiting EGFR resulted in minimal reduction of phospho-Met in DA-Src cells, whereas complete phospho-Met inhibition was achieved by inhibiting c-Src. A c-Met inhibitor significantly sensitized DA-Src tumors to erlotinib in vivo, resulting in reduced Ki67 labeling and increased apoptosis. In parental cells, knockdown of endogenous c-Src enhanced sensitivity to erlotinib, whereas treatment with HGF to directly induce phospho-Met resulted in erlotinib resistance. The level of endogenous phospho-c-Src in HNSCC cell lines was also significantly correlated with erlotinib resistance.
Conclusions: Ligand-independent activation of c-Met contributes specifically to erlotinib resistance, not cetuximab resistance, in HNSCC with activated c-Src, where c-Met activation is more dependent on c-Src than on EGFR, providing an alternate survival pathway. Addition of a c-Met or c-Src inhibitor to erlotinib may increase efficacy of EGFR inhibition in patients with activated c-Src. Clin Cancer Res; 19(2); 380–92. ©2012 AACR.
Effect of Exercise on Markers of Inflammation in Breast Cancer Survivors: The Yale Exercise and Survivorship Study
Authors: Jones Sara B. , Thomas Gwendolyn A. , Hesselsweet Sara D. , Alvarez-Reeves Marty , Yu Herbert , Irwin Melinda L. 
Published: December 2012

AbstractPhysical activity is associated with improved breast cancer survival, but the underlying mechanisms, possibly including modification of the inflammatory state, are not well understood. We analyzed changes in interleukin (IL)-6, C-reactive protein (CRP), and TNF-α in a randomized controlled trial of exercise in postmenopausal breast cancer survivors. Seventy-five women, recruited through the Yale-New Haven Hospital Tumor Registry, were randomized to either a six-month aerobic exercise intervention or usual care. Correlations were calculated between baseline cytokines, adiposity, and physical activity measures. Generalized linear models were used to assess the effect of exercise on IL-6, CRP, and TNF-α. At baseline, IL-6 and CRP were positively correlated with body fat and body mass index (BMI) and were inversely correlated with daily pedometer steps (P &lt; 0.001). We found no significant effect of exercise on changes in inflammatory marker concentrations between women randomized to exercise versus usual care, though secondary analyses revealed a significant reduction in IL-6 among exercisers who reached 80% of the intervention goal compared with those who did not. Future studies should examine the effect of different types and doses of exercise and weight loss on inflammatory markers in large-scale trials of women diagnosed with breast cancer. Cancer Prev Res; 6(2); 109–18. ©2012 AACR.
Inositol Hexaphosphate Inhibits Tumor Growth, Vascularity, and Metabolism in TRAMP Mice: A Multiparametric Magnetic Resonance Study
Authors: Raina Komal , Ravichandran Kameswaran , Rajamanickam Subapriya , Huber Kendra M. , Serkova Natalie J. , Agarwal Rajesh 
Published: December 2012

Abstract
Herein, employing anatomical and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), we evaluated noninvasively, the in vivo, chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate tumor growth and progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Male TRAMP mice, beginning at 4 weeks of age, were fed with 1%, 2%, or 4% (w/v) IP6 in drinking water or only drinking water till 28 weeks of age and monitored using MRI over the course of study. Longitudinal assessment of prostate volumes by conventional MRI and tumor vascularity by gadolinium-based DCE-MRI showed a profound reduction in tumor size, partly due to antiangiogenic effects by IP6 treatment. As potential mechanisms of IP6 efficacy, decrease in the expression of glucose transporter GLUT-4 protein together with an increase in levels of phospho-AMP-activated kinase (AMPKTh172) were observed in prostate tissues of mice from IP6 fed-groups, suggesting that IP6 is interfering with the metabolic events occurring in TRAMP prostate. Investigative metabolomics study using quantitative high-resolution 1H-NMR on prostate tissue extracts showed that IP6 significantly decreased glucose metabolism and membrane phospholipid synthesis, in addition to causing an increase in myoinositol levels in the prostate. Together, these findings show that oral IP6 supplement blocks growth and angiogenesis of prostate cancer in the TRAMP model in conjunction with metabolic events involved in tumor sustenance. This results in energy deprivation within the tumor, suggesting a practical and translational potential of IP6 treatment in suppressing growth and progression of prostate cancer in humans. Cancer Prev Res; 6(1); 40–50; ©2012 AACR.
Quantification of Chronic Functional Mitral Regurgitation by Automated 3-Dimensional Peak and Integrated Proximal Isovelocity Surface Area and Stroke Volume Techniques Using Real-Time 3-Dimensional Volume Color Doppler Echocardiography
Authors: Thavendiranathan Paaladinesh , Liu Shizhen , Datta Saurabh , Rajagopalan Sanjay , Ryan Thomas , Igo Stephen R. , Jackson Matthew S. , Little Stephen H. , De Michelis Nathalie , Vannan Mani A. 
Published: December 2012

Background—
The aim of this study was to test the accuracy of an automated 3-dimensional (3D) proximal isovelocity surface area (PISA) (in vitro and patients) and stroke volume technique (patients) to assess mitral regurgitation (MR) severity using real-time volume color flow Doppler transthoracic echocardiography.

Methods and Results—

Using an in vitro model of MR, the effective regurgitant orifice area and regurgitant volume (RVol) were measured by the PISA technique using 2-dimensional (2D) and 3D (automated true 3D PISA) transthoracic echocardiography. The mean anatomic regurgitant orifice area (0.35±0.10 cm
2
) was underestimated to a greater degree by the 2D (0.12±0.05 cm
2
) than the 3D method (0.25±0.10 cm
2
;
P
<0.001 for both). Compared with the flowmeter (40±14 mL), the RVol by 2D PISA (20±19 mL) was underestimated (
P
<0.001), but the 3D peak (43±16 mL) and integrated PISA-based (38±14 mL) RVol were comparable (
P
>0.05 for both). In patients (n=30, functional MR), 3D effective regurgitant orifice area correlated well with cardiac magnetic resonance imaging RVol
r
=0.84 and regurgitant fraction
r
=0.80. Compared with cardiac magnetic resonance imaging RVol (33±22 mL), the integrated PISA RVol (34±26 mL;
P
=0.42) was not significantly different; however, the peak PISA RVol was higher (48±27 mL;
P
<0.001). In addition, RVol calculated as the difference in automated mitral and aortic stroke volumes by real-time 3D volume color flow Doppler echocardiography was not significantly different from cardiac magnetic resonance imaging (34±21 versus 33±22 mL;
P
=0.33).

Conclusions—
Automated real-time 3D volume color flow Doppler based 3D PISA is more accurate than the 2D PISA method to quantify MR. In patients with functional MR, the 3D RVol by integrated PISA is more accurate than a peak PISA technique. Automated 3D stroke volume measurement can also be used as an adjunctive method to quantify MR severity.
Observations of Thermally Driven Wind Jets at the Exit of Weber Canyon, Utah
Authors: Chrust Morgan F. , Whiteman C. David , Hoch Sebastian W. 
Published: December 2012

AbstractThermally driven valley-exit jets were investigated at Utah’s Weber Canyon, a main tributary of the Great Salt Lake basin. An intensive measurement campaign during July–September 2010 supplemented longer-term measurements to characterize the wind and temperature structure in the vicinity of the canyon exit. Exit jets at Weber Canyon are most frequent in late summer or early fall. Strong low-level-wind jets formed at the canyon exit on 75 of 90 nights (83%) during the measurement campaign, with the best-developed winds forming during synoptically undisturbed, clear-sky periods. Winds inside the canyon consisted of a weak down-valley flow layer that occupied most of the 1000-m depth of the canyon. The flow was observed to descend, thin, and accelerate at the valley exit, producing winds that were typically 2.5 times as strong but much more shallow than those inside the canyon. Maximum nighttime jet-axis wind speeds of 15–20 m s−1 are typically found about 80–120 m above the ground at the canyon exit on clear undisturbed nights in the late summer and fall. The jets form 1–3 h after sunset, approach a near-steady state during the late night, and continue until 5–6 h after sunrise, although slowly losing speed after sunrise. The jet is a local modification at the canyon exit of the thermally driven down-valley flow. Its continuation after sunrise is thought to be caused by the nighttime buildup and persistence of a cold-air pool in the Morgan Basin at the east end of the canyon. The potential for utilizing the exit jet for wind power generation is discussed.
Can a Decadal Forecasting System Predict Temperature Extreme Indices?*
Authors: Hanlon Helen M. , Hegerl Gabriele C. , Tett Simon F. B. , Smith Doug M. 
Published: December 2012

Abstract
Daily maximum and minimum summer temperatures have increased throughout the majority of Europe over the past few decades, along with the frequency and intensity of heat waves. It is essential to learn whether this rise is expected to continue in the future for adaptation purposes. A study of predictability of European temperature indices with the Met Office Hadley Centre Decadal Prediction System (DePreSys) has revealed significant skill in predictions of 5- and 10-yr average indices of the summer mean and maximum 5-day average temperatures based on daily maximum and minimum temperatures for a large area of Europe, particularly in the Mediterranean. In contrast, the decadal forecasts of winter mean/minimum 5-day average temperature indices show poorer skill than the summer indices. Significant skill is shown for the United Kingdom in some cases but less than for the European/Mediterranean regions.
Comparison of two parallel ensembles, one initialized with observations and one without initialization, has shown that the skill largely originates from external forcing. However, there were a few cases with hints of additional skill in forecasts of decadal mean indices due to the initialization.
Model realizations of extreme indices can have large biases compared to observations that are different from those of the mean climate indices. Several methods were tested for correcting biases, as well as for testing the significance and quantifying uncertainty of the results to rule out cases of spurious skill. Bias correction of each index individually is required as biases vary across different extremes.
Spatial Patterns of Precipitation Change in CMIP5: Why the Rich Do Not Get Richer in the Tropics
Authors: Chadwick Robin , Boutle Ian , Martin Gill 
Published: December 2012

Abstract
Changes in the patterns of tropical precipitation (P) and circulation are analyzed in Coupled Model Intercomparison Project phase 5 (CMIP5) GCMs under the representative concentration pathway 8.5 (RCP8.5) scenario. A robust weakening of the tropical circulation is seen across models, associated with a divergence feedback that acts to reduce convection most in areas of largest climatological ascent. This is in contrast to the convergence feedback seen in interannual variability of tropical precipitation patterns. The residual pattern of convective mass-flux change is associated with shifts in convergence zones due to mechanisms such as SST gradient change, and this is often locally larger than the weakening due to the divergence feedback.
A simple framework is constructed to separate precipitation change into components based on different mechanisms and to relate it directly to circulation change. While the tropical mean increase in precipitation is due to the residual between the positive thermodynamic change due to increased specific humidity and the decreased convective mass flux due to the weakening of the circulation, the spatial patterns of these two components largely cancel each other out. The rich-get-richer mechanism of greatest precipitation increases in ascent regions is almost negated by this cancellation, explaining why the spatial correlation between climatological P and the climate change anomaly ΔP is only 0.2 over the tropics for the CMIP5 multimodel mean. This leaves the spatial pattern of precipitation change to be dominated by the component associated with shifts in convergence zones, both in the multimodel mean and intermodel uncertainty, with the component due to relative humidity change also becoming important over land.
Adjusting the Wind Stress Drag Coefficient in Storm Surge Forecasting Using an Adjoint Technique
Authors: Peng Shiqiu , Li Yineng , Xie Lian 
Published: December 2012

Abstract
A three-dimensional ocean model and its adjoint model are used to adjust the drag coefficient in the calculation of wind stress for storm surge forecasting. A number of identical twin experiments (ITEs) with different error sources imposed are designed and performed. The results indicate that when the errors come from the wind speed, the drag coefficient is adjusted to an “optimal value” to compensate for the wind errors, resulting in significant improvements of the specific storm surge forecasting. In practice, the “true” drag coefficient is unknown and the wind field, which is usually calculated by an empirical parameter model or a numerical weather prediction model, may contain large errors. In addition, forecasting errors may also come from imperfect model physics and numerics, such as insufficient resolution and inaccurate physical parameterizations. The results demonstrate that storm surge forecasting errors can be reduced through data assimilation by adjusting the drag coefficient regardless of the error sources. Therefore, although data assimilation may not fix model imperfection, it is effective in improving storm surge forecasting by adjusting the wind stress drag coefficient using the adjoint technique.
A Review of Human Factors Challenges of Complex Adaptive Systems
Authors: Karwowski Waldemar 
Published: December 2012

Objective: In this paper, the author explores a need for a greater understanding of the true nature of human–system interactions from the perspective of the theory of complex adaptive systems, including the essence of complexity, emergent properties of system behavior, nonlinear systems dynamics, and deterministic chaos. Background: Human performance, more often than not, constitutes complex adaptive phenomena with emergent properties that exhibit nonlinear dynamical (chaotic) behaviors. Methods: The complexity challenges in the design and management of contemporary work systems, including service systems, are explored. Examples of selected applications of the concepts of nonlinear dynamics to the study of human physical performance are provided. Results: Understanding and applications of the concepts of theory of complex adaptive and dynamical systems should significantly improve the effectiveness of human-centered design efforts of a large system of systems. Conclusion: Performance of many contemporary work systems and environments may be sensitive to the initial conditions and may exhibit dynamic nonlinear properties and chaotic system behaviors. Human-centered design of emergent human–system interactions requires application of the theories of nonlinear dynamics and complex adaptive system. Application: The success of future human–systems integration efforts requires the fusion of paradigms, knowledge, design principles, and methodologies of human factors and ergonomics with those of the science of complex adaptive systems as well as modern systems engineering.
Cluster headache is associated with an increased risk of depression: A nationwide population-based cohort study
Authors: Liang Jen-Feng , Chen Yung-Tai , Fuh Jong-Ling , Li Szu-Yuan , Liu Chia-Jen , Chen Tzeng-Ji , Tang Chao-Hsiun , Wang Shuu-Jiun 
Published: December 2012

Objective To investigate whether cluster headache (CH) was a risk factor for depression in a nationwide population-based follow-up study. Background There are few studies about the relationship between CH and depression, and prior research has been limited by cross-sectional studies or small sample sizes. Methods We identified 673 CH patients from the Taiwan National Health Insurance database between 2005 and 2009. The two comparison cohorts included age-, sex- and Charlson’s score-matched migraine patients ( n = 2692) and controls (patients free from migraine or CH, n = 2692). The cumulative incidence of depression was compared among these three cohorts until the end of 2009. We also calculated predictors of depression in the CH cohort. Results After the median 2.5-year follow-up duration, the CH cohort had a greater risk for developing depression compared to the control cohort (adjusted hazard ratio; aHR = 5.6, 95% CI 3.0–10.6, p < 0.001) but not the migraine cohort (aHR = 1.1, 95% CI 0.7–1.7, p = 0.77). Of the CH patients, the number of cluster bout periods per year was a risk factor for depression (aHR = 3.8, 95% CI 2.6–5.4, p < 0.001). Conclusion Our results showed that CH is associated with an increased risk for depression. The strength of this association is similar to that of migraine.
Factors Associated With Inappropriate Chemical Prophylaxis of Thromboembolism in Surgical Patients
Authors: Khorgami Zhamak , Mofid Roza , Soroush Ahmadreza , Aminian Ali , Araghi Negin Hosseini , Hanafi Somayeh 
Published: December 2012

Introduction: Despite various guidelines for venous thromboembolism (VTE) prevention, malpractice in prescribing thromboprophylaxis is common. In this study, factors associated with prescribing or not prescribing appropriate chemical thromboprophylaxis were assessed. Materials and methods: We enrolled high-risk patients for VTE (based on Caprini score) in the general surgery ward. They were divided into 2 groups based on receiving appropriate prophylaxis or not. Factors associated with prescribing thromboprophylaxis were analyzed. Results: A total of 613 patients were enrolled in this study. Head and neck operations ( P < .0001), minor surgeries ( P = .001), mastectomy ( P = .012), and medical treatment ( P = 0.034) were the factors associated with not prescribing thromboprophylaxis. In contrast, age ( P < .0001), laparoscopic surgeries ( P = .011), surgery duration (< .0001), oral contraceptive pill consumption ( P = .005), and complete bed rest ( P = .002) were protective factors. Conclusion: Minor surgeries, head and neck operations, mastectomy, and medical treatment are associated with overlooking anticoagulant administration. It is recommended to consider aforementioned pitfalls in routine practice and education.
The Needs of Patients With Early Onset Dementia
Authors: Armari Elizabeth , Jarmolowicz Anna , Panegyres Peter K. 
Published: December 2012

Aim: The burden of early-onset dementia (EOD) is often overshadowed by an ageing population. Methods: A questionnaire comprising 12 items was completed by 18 patients with EOD (15 with Alzheimer’s disease [AD] and 3 with frontotemporal dementia) and 39 caregivers (20 spouses, 8 children, 7 siblings, 2 carers, and 2 health professionals). The onset of patients’ symptoms was prior to the age of 65 years. Caregivers had to be supporting someone who matched these criteria. Results: Early recognition and referral was perceived as the principle area of improvement by both patients (94.4%) and carers (69.2%; P < .0002). Patients evaluated “diagnosis” as the area of most need (88.9%) compared with caregivers who rated “treatment” (69.2%) as their principle concern. Conclusion: The perceived concerns of patients with EOD differ from that of the caregivers. Continued consumer involvement is essential in ensuring a tailored approach to young people with dementia.
BCR-ABL1 compound mutations in tyrosine kinase inhibitor–resistant CML: frequency and clonal relationships
Authors: Khorashad Jamshid S. , Kelley Todd W. , Szankasi Philippe , Mason Clinton C. , Soverini Simona , Adrian Lauren T. , Eide Christopher A. , Zabriskie Matthew S. , Lange Thoralf , Estrada Johanna C. , Pomicter Anthony D. , Eiring Anna M. , Kraft Ira L. , Anderson David J. , Gu Zhimin , Alikian Mary , Reid Alistair G. , Foroni Letizia , Marin David , Druker Brian J. , O'Hare Thomas , Deininger Michael W. 
Published: December 2012

Abstract
BCR-ABL1 compound mutations can confer high-level resistance to imatinib and other ABL1 tyrosine kinase inhibitors (TKIs). The third-generation ABL1 TKI ponatinib is effective against BCR-ABL1 point mutants individually, but remains vulnerable to certain BCR-ABL1 compound mutants. To determine the frequency of compound mutations among chronic myeloid leukemia patients on ABL1 TKI therapy, in the present study, we examined a collection of patient samples (N = 47) with clear evidence of 2 BCR-ABL1 kinase domain mutations by direct sequencing. Using a cloning and sequencing method, we found that 70% (33/47) of double mutations detected by direct sequencing were compound mutations. Sequential, branching, and parallel routes to compound mutations were common. In addition, our approach revealed individual and compound mutations not detectable by direct sequencing. The frequency of clones harboring compound mutations with more than 2 missense mutations was low (10%), whereas the likelihood of silent mutations increased disproportionately with the total number of mutations per clone, suggesting a limited tolerance for BCR-ABL1 kinase domain missense mutations. We conclude that compound mutations are common in patients with sequencing evidence for 2 BCR-ABL1 mutations and frequently reflect a highly complex clonal network, the evolution of which may be limited by the negative impact of missense mutations on kinase function.
Coupled common fixed point results involving a "Equation missing" -contractive condition for mixed g-monotone operators in partially ordered metric spaces
Authors: Jain Manish , Tas Kenan , Kumar Sanjay , Gupta Neetu 
Published: December 2012

Abstract
In the setting of partially ordered metric spaces, using the notion of compatible mappings, we establish the existence and uniqueness of coupled common fixed points involving a

(
φ
,
ψ
)

-contractive condition for mixed g-monotone operators. Our results extend and generalize the well-known results of Berinde (Nonlinear Anal. TMA 74:7347-7355, 2011; Nonlinear Anal. TMA 75:3218-3228, 2012) and weaken the contractive conditions involved in the results of Alotaibi et al. (Fixed Point Theory Appl. 2011:44, 2011), Bhaskar et al. (Nonlinear Anal. TMA 65:1379-1393, 2006), and Luong et al. (Nonlinear Anal. TMA 74:983-992, 2011). The effectiveness of the presented work is validated with the help of suitable examples.

MSC:54H10, 54H25.