bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67
Authors: Jovanović Bojana , Mayer Ingrid A. , Mayer Erica L. , Abramson Vandana G. , Bardia Aditya , Sanders Melinda E. , Kuba M. Gabriela , Estrada Monica V. , Beeler J. Scott , Shaver Timothy M. , Johnson Kimberly C. , Sanchez Violeta , Rosenbluth Jennifer M. , Dillon Patrick M. , Forero-Torres Andres , Chang Jenny C. , Meszoely Ingrid M. , Grau Ana M. , Lehmann Brian D. , Shyr Yu , Sheng Quanhu , Chen Sheau-Chiann , Arteaga Carlos L. , Pietenpol Jennifer A. 
Published: March 2017

AbstractPurpose: Because of inherent disease heterogeneity, targeted therapies have eluded triple-negative breast cancer (TNBC), and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine whether the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic antitumor effects in TNBC.Methods: Patients with stage II/III TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery. Tumor specimens were obtained at baseline, cycle 1, and surgery. Primary endpoint was pathologic complete response (pCR); secondary endpoints included clinical responses, breast conservation rate, safety, and discovery of molecular features associated with outcome.Results: Between 2009 and 2013, 145 patients were accrued; 36% of patients in the everolimus arm and 49% of patients in the placebo arm achieved pCR; in each arm, 50% of patients achieved complete responses by imaging. Higher rates of neutropenia, mucositis, and transaminase elevation were seen with everolimus. Clinical response to therapy and long-term outcome correlated with increased frequency of DNA damage response (DDR) gene mutations, Basal-like1 and Mesenchymal TNBC-subtypes, AR-negative status, and high Ki67, but not with tumor-infiltrating lymphocytes.Conclusions: The paclitaxel/cisplatin combination was well tolerated and active, but addition of everolimus was associated with more adverse events without improvement in pCR or clinical response. However, discoveries made from correlative studies could lead to predictive TNBC biomarkers that may impact clinical decision-making and provide new avenues for mechanistic exploration that could lead to clinical utility. Clin Cancer Res; 23(15); 4035–45. ©2017 AACR.
Focal Adhesion Kinase as a Potential Target in AML and MDS
Authors: Carter Bing Z. , Mak Po Yee , Wang Xiangmeng , Yang Hui , Garcia-Manero Guillermo , Mak Duncan H. , Mu Hong , Ruvolo Vivian R. , Qiu Yihua , Coombes Kevin , Zhang Nianxiang , Ragon Brittany , Weaver David T. , Pachter Jonathan A. , Kornblau Steven , Andreeff Michael 
Published: March 2017

Abstract
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 × 10−4) and relapse (P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3-ITD (P = 0.0024) or RAS (P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34+ (P = 5.42 × 10−20) and CD34+CD38− MDS (P = 7.62 × 10−9) cells compared with normal CD34+ cells. MDS patients with higher FAK in CD34+ cells tended to have better overall survival (P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia–stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133–44. ©2017 AACR.
Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index
Authors: Iyengar Neil M. , Brown Kristy A. , Zhou Xi Kathy , Gucalp Ayca , Subbaramaiah Kotha , Giri Dilip D. , Zahid Heba , Bhardwaj Priya , Wendel Nils K. , Falcone Domenick J. , Wang Hanhan , Williams Samantha , Pollak Michael , Morrow Monica , Hudis Clifford A. , Dannenberg Andrew J. 
Published: March 2017

Abstract
Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here, we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (&lt;25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are composed of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2. The primary objective was to determine whether breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 kg/m2 (range, 18.4–24.9 kg/m2) in women with breast WAT inflammation versus 21.8 kg/m2 (range, 17.3–24.6 kg/m2) in those without inflammation (P = 0.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P &lt; 0.05). Breast WAT inflammation correlated with larger adipocytes (P = 0.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P ≤ 0.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer. Cancer Prev Res; 10(4); 235–43. ©2017 AACR.
See related article by Berger, p. 223–25.
Obesity Increases Risk‐Adjusted Morbidity, Mortality, and Cost Following Cardiac Surgery
Authors: Ghanta Ravi K. , LaPar Damien J. , Zhang Qianzi , Devarkonda Vishal , Isbell James M. , Yarboro Leora T. , Kern John A. , Kron Irving L. , Speir Alan M. , Fonner Clifford E. , Ailawadi Gorav 
Published: March 2017

Background

Despite the epidemic rise in obesity, few studies have evaluated the effect of obesity on cost following cardiac surgery. We hypothesized that increasing body mass index (
BMI
) is associated with worse risk‐adjusted outcomes and higher cost.

Methods and Results

Medical records for 13 637 consecutive patients who underwent coronary artery bypass grafting (9702), aortic (1535) or mitral (837) valve surgery, and combined valve–coronary artery bypass grafting (1663) procedures were extracted from a regional Society of Thoracic Surgeons certified database. Patients were stratified by
BMI
: normal to overweight (
BMI
18.5–30), obese (
BMI
30–40), and morbidly obese (
BMI
>40). Differences in outcomes and cost were compared between
BMI
strata and also modeled as a continuous function of
BMI
with adjustment for preoperative risk using Society of Thoracic Surgeons predictive risk indices. Morbidly obese patients incurred nearly 60% greater observed mortality than normal weight patients. Moreover, morbidly obese patients had greater than 2‐fold increase in renal failure and 6.5‐fold increase in deep sternal wound infection. After risk adjustment, a significant association was found between
BMI
and mortality (
P
<0.001) and major morbidity (
P
<0.001). The risk‐adjusted odds ratio for mortality for morbidly obese patients was 1.57 (
P
=0.02) compared to normal patients. Importantly, risk‐adjusted total hospital cost increased with
BMI
, with 17.2% higher costs in morbidly obese patients.

Conclusions

Higher
BMI
is associated with increased mortality, major morbidity, and cost for hospital care. As such,
BMI
should be more strongly considered in risk assessment and resource allocation.
Positive and Negative Eddy Feedbacks Acting on Midlatitude Jet Variability in a Three-Level Quasigeostrophic Model
Authors: Robert Loïc , Rivière Gwendal , Codron Francis 
Published: March 2017

Abstract
The variability of midlatitude jets is investigated in a long-term integration of a dry three-level quasigeostrophic model on the sphere. As for most observed jets, the leading EOF of the zonal-mean wind corresponds to latitudinal shifts of the jet, and the second EOF to pulses of the jet speed. The first principal component (PC1) is also more persistent than the second one (PC2); this longer persistence arises from different eddy feedbacks both in the short term (i.e., within a few days following the peak of the PCs) and in the long term. The short-term eddy feedbacks come from two distinct mechanisms. First, a planetary waveguide effect acts as a negative feedback on both PCs. The positive phases of PC1 and PC2, which correspond to poleward-shifted and accelerated jets, respectively, are first driven then canceled by planetary waves reflecting on the equatorward flank of the jet. A similar process occurs for the negative phases when planetary waves reflect on the poleward flank of the jet. Second, synoptic waves also exert a short-term negative feedback on PC2: when the jet accelerates, the enhanced meridional wind shear increases the barotropic sink of eddy energy and depletes it very rapidly, therefore preventing synoptic eddies from maintaining the accelerated jet. Finally, at lags longer than their typical time scale, synoptic eddies drive a positive feedback on PC1 only. This feedback can be explained by a baroclinic mechanism in which the jet shift modifies the baroclinicity, causing, first, eddy heat flux anomalies and, then, momentum convergence anomalies. This feedback is absent for PC2, despite some changes in the baroclinicity.
The family economic status and outcome of people with schizophrenia in Xinjin, Chengdu, China: 14-year follow-up study
Authors: Ran Mao-Sheng , Yang Lawrence H , Liu Yu-Jun , Huang Debbie , Mao Wen-Jun , Lin Fu-Rong , Li Jie , Chan Cecilia Lai-Wan 
Published: March 2017

Background: Little is known about whether family economic status might influence the long-term (e.g. over 10 years) outcome of persons with schizophrenia in the community. Aim: To examine the differences in outcome at 14-year follow-up of persons with schizophrenia from high versus low family economic status backgrounds in a Chinese rural area. Method: A prospective 14-year follow-up study was conducted in six townships in Xinjin County, Chengdu, China. All participants with schizophrenia ( n = 510) were identified in an epidemiological investigation of 123,572 people aged 15 years and older and followed up from 1994 to 2008. Results: Individuals from low family economic status (<mean) in 1994 had significantly higher rate of homelessness (9.9%) and lower rate of survival (63.8%) in 2008 than those from high family economic status (⩾mean; 3.2% and 76.6%, respectively). Individuals from low family economic status had significantly lower rates of marriage and complete remission, higher mean scores on Positive and Negative Syndrome Scale (PANSS) and lower mean score on Global Assessment of Functioning (GAF) than those from high family economic status in 2008. The predictors of low family economic status of individuals in 2008 encompassed the baseline low family economic status, poor families’ attitude toward the patient, younger age, older age of first onset and longer duration of illness. Conclusion: Low family economic status is a predictive factor of poor long-term outcome of persons with schizophrenia in the rural community. Individuals’ family economic status should be considered in making mental health policy and providing community-based mental health services.
Denosumab Improves Bone Mineral Density in Patients With Intestinal Failure Receiving Home Parenteral Nutrition: Results From a Randomized, Controlled Clinical Trial
Authors: Szczepanek Kinga , Pedziwiatr Michal , Klek Stanisław 
Published: March 2017

AbstractAim: Low bone mineral density (BMD) is commonly reported in patients receiving home parenteral nutrition (HPN). Oral and intravenous calcium, vitamin D, and bisphosphonates have been used to treat BMD but with low efficiency due to their limited absorption and patient compliance. Denosumab is a new drug that helps prevent osteoclast development and activation and led to decreased bone resorption in some studies. The aim of this study was to assess its value in HPN patients. Methods: Between November 2011 and March 2013, 49 patients receiving HPN (29 women, 20 men, mean age 55.3 years) who met the eligibility criteria were randomly assigned to a denosumab or control group. Regional dual‐energy x‐ray absorptiometry of the spine and hip was performed before therapy and after 12 months. BMD, T score, and z score were assessed. Results: Fifteen patients received 2 doses of therapy and were fully reassessed after 1 year. At baseline and after 12 months, the absorptiometry revealed T scores of −3.439 standard deviations (SD) vs −2.33 SD at lumbar segment 2 (L2) and −2.957 SD vs −2.067 SD at lumbar segment 3 (L3), z scores of −2.24 SD vs −1.36 SD at L2 and −1.995 vs −1.067 SD at L3, and BMD of 0.801 vs 0.946 at L2 and 0.857 vs 0.979 at L3, respectively. Two serious outcomes were reported, without any correlation to the intervention. Two patients were weaned off HPN and hence discontinued. One patient experienced sciatica, resulting in discontinuation of the intervention. Conclusions: This study showed that denosumab may be a valuable treatment option for improving BMD in HPN patients.
Rebalancing the Board's Agenda
Authors: Nordberg Donald 
Published: March 2017

Since 2002, the activities of corporate boards have been dominated by the governance agenda. In Europe – to an even greater degree than the United States – governance codes have proliferated. This paper examines the resulting imbalance, where compliance with codes of conduct threatens to overwhelm the board's primary responsibility, i.e. the creation of wealth. We consider a model of board processes that starts with four key roles: setting direction, marshalling resources, controlling and reporting, and evaluating and enhancing for the next cycle. “We must urgently bring back some pragmatism to corporate governance … And if we want governance schemes that actually work in a real business environment, they must be based on principles, not detailed rules that try to pre-empt all the eventualities a lawyer can think of.” Peter Brabeck-Letmathe, CEO, Nestlé SA. The governance agenda has rightly drawn attention to the work of board committees and the question of the independence of mind directors need to show. But it may have diverted focus from three questions that ought to figure more prominently in the board's work: • How should the board apportion its work between compliance, risk assessment and setting strategic direction? • How do directors become determine when to focus on risk-mitigation and when to encourage strategic risk-taking? • In face of greater personal accountability for governance compliance, where do they draw the line between their role overseeing management and interfering with management's responsibilities?
Diversity of Welfare Systems in the EU: A Challenge to Policy Coordination
Authors: Biffl Gudrun 
Published: March 2017

As the EU economies and societies become increasingly integrated, and as labour market behaviour patterns converge across borders, the EU is striving to develop a substantially common social identity. To this end, it is seeking to promote the development of a sustainable institutional framework that facilitates flexibility and structural change in the economy and the labour market, and, at the same time, to provide a meaningful social safety net (‘flexicurity’). However, while there are such great differences in social organisation among EU countries, it would be unrealistic to try to establish a common social protection model. The more immediate goals for the EU should be to identify a mechanism for ensuring social protection, the developments that jeopardise the continuation of universal coverage for all members of society, the factors that are responsible for the exclusion of certain groups of people and how this is affected by different models of social organisation and, last but not least, the gaps are in the statistical data that prevent a proper evaluation of economic well-being under different welfare models. These are the questions that are addressed in this paper. The argument advanced in this paper is that the well-being of every society depends upon the interaction of the market, the household/family and the state. The exclusion of the household sector from the conventional statistical framework – and its exclusion from orthodox economic theory – ignores the fact that the various models of social organisation give different relative weights to – and impose different roles on – the three pillars of social organisation. A different set of taxes, transfer payments and public services in the various welfare models that are found in the EU leads to a divergence of incentives to the private sector and/or the household to provide social services. This results in a different degree of integration of the working age population into the labour force, the quality of work and the price and quality of social protection. Models that allow for the targeting of individual needs are best able to cope with the current trends of increasing flexibility of work and family relationships and the concomitant challenge of universal social protection.
Citizen science for pedestrian cartography: collection and moderation of walkable routes in cities through mobile gamification
Authors: Kapenekakis Ippokratis , Chorianopoulos Konstantinos 
Published: March 2017

AbstractDigital geographical maps can be regarded as a user interface for understanding and navigating the city. Nevertheless, contemporary digital maps over-emphasize the needs of motor vehicles. Pedestrian routes have only been considered as an add-on option in existing digital maps and the respective data collection has not been performed in the field. In this article, we present a mobile application that employs gamification as a means to engage users to collect pragmatic data about walkable routes, which are then processed with the goal of creating a new kind of pedestrian-friendly cartography. Besides the technical infrastructure for collecting and filtering the route traces, the main challenge in user-generated walkable routes is the identification of malicious data, which should be rejected, as well as the rewarding of constructive behavior through peer-review. For this purpose, the mobile application employs a point system in order to identify and discourage the submission of bad routes. A longitudinal (2-months) field study of the mobile application confirmed that gamification facilitates effective data collection for producing pedestrian cartography even with few users and demonstrated that gamification infuses a shared responsibly about the quality of data collection. The visualization of the pedestrian-generated data on a map required a partially manual process, thus, further research should explore the gamification of the data visualization part, too.
Automatic early arrival traveltime tomography and its applications
Authors: Peng Chengbin (Chuck) , Tang Jun 
Published: March 2017

We have developed a method of macrovelocity inversion that does not require explicit picking of either common-image point gathers or first breaks. The method uses head waves, diving waves, and wide-angle reflections in seismic data (collectively early arrival energies) for accurate estimation of velocity and anisotropy parameters. In this method, seismic data are first decomposed into Gaussian packets. Packets associated with early arrival energies are selected and used as input to a tomography solver. The outputs of the solver are velocity and Thomsen’s anisotropy parameters, or any of their combinations. Using information contained in the packets, we can correctly model the early arrival energies (first breaks and/or other refractions). The workflow is fully automatic and can be used in a batch processing environment with minimum human intervention. We have tested the method on synthetic and field data sets. In one synthetic test, we were able to reduce traveltime residuals of diving waves from 400 to 5 ms and recover anisotropic model parameters that are sensitive to early arrival traveltimes. In another synthetic test, we were able to recover a large shallow low-velocity anomaly with a very simple starting velocity model. The first field data set was for a shallow marine seismic data project. We were able to obtain a better shallow velocity model using our method than when using a legacy approach. In the second field data test, we applied our method on a deepwater data set from a dual-coil acquisition, with full-azimuth and long-offset coverage. Our method can correctly model early arrival energies recorded at long offsets and use them in the iterative inversion such that better estimation of velocities and anisotropy parameters in shallow sediments can be achieved. We have tested different starting models for the inversion. We are able to get very similar results, suggesting that our method is not sensitive to the accuracy of a starting model.