Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and pharmacodynamics of sunitinib for the treatment of advanced pancreatic neuroendocrine tumors

Introduction: Despite being the second most common malignancy of the pancreas, pancreatic neuroendocrine tumors (PNET) have long been understudied due to their low incidence and heterogeneous clinical presentation. Emerging data from a Phase III trial demonstrates improved progression-free survival of patients with advanced PNET on treatment with sunitinib. Areas covered: This article reviews the role of sunitinib, a multitargeted tyrosine kinase inhibitor with potent antiangiogenic and antitumor effects, in the clinical management of PNET. Furthermore, the authors also discuss the pharmacokinetics and pharmacodynamics as well as other clinically relevant aspects regarding sunitinib. Expert opinion: A recent Phase III clinical trial of sunitinib demonstrated significant improvement of progression-free survival in patients with advanced or metastatic well-differentiated PNET that led to its approval in several countries, including Europe and United States. This marks a significant step forward in the clinical management of this disease and spurs hopes to further improve overall survival in this once difficult-to-treat set of patients in the coming years. Fields of future interest will include evaluation of combinatorial regimens, including conventional cytotoxic agents as well as additional targeted drugs in order to overcome resistance to sunitinib.
Refractory Anemia and the Myelodysplastic Syndromes

Refractory anemia is a component of each of the myelodysplastic syndromes (MDSs). MDSs are acquired pluripotent stem cell disorders leading to one or more peripheral blood cytopenias with dysplasia in the peripheral blood and bone marrow. MDS and aplastic anemia are sometimes grouped as bone marrow failure disorders because patients present with similar peripheral blood pictures. The bone marrow in MDS is generally hypercellular, due to ineffective hematopoiesis, in contrast to the hypocellular bone marrow of aplastic anemia. MDS is more common in the elderly, differing from aplastic anemia that affects all ages. The characteristics of each of the subgroups of the MDS using the World Health Organization (WHO) classification are described. Cytogenetic analysis provides a useful part of disease diagnosis in this new classification system. There is no successful treatment for MDS other than hematopoietic stem cell transplantation which is usually recommended for patients under age 50. A prognostic scoring system has been developed to help predict the severity of disease and guide treatment. Approximately 10% to 40% of MDS cases terminate in acute leukemia. Current treatment consists mostly of supportive measures; however several new therapies are being explored. Refractory anemia (RA) is part of the group of disorders known as the myelodysplastic syndromes (MDSs). MDSs are neoplastic clonal stem cell disorders characterized by one or more cytopenias in the peripheral blood and dysplasia in both peripheral blood and bone marrow. The bone marrow is typically hypercellular and the cytopenias are a result of ineffective hematopoiesis. About one third… ABBREVIATIONS: AA = aplastic anemia; AML = acute myelogenous leukemia; CMML = chronic myelomonocytic leukemia; FAB = French-American-British; MDS = myelodysplastic syndrome; RA = refractory anemia.
Role of Social Network Services (SNS) Sales Promotions in Generating Brand Loyalty for Chain Steakhouses

ABSTRACT This research aimed to explore the impact of social network services (SNS) sales promotions on the brand loyalty generation process by considering the role of brand attitude, awareness, service quality, experience, trust, and attachment in the chain steakhouse industry. A field survey was conducted to collect data in a metropolitan city of South Korea. According to our structural equation modeling results, SNS sales promotions significantly increased loyalty and its antecedents, and brand attachment had the greatest influence on brand loyalty. The mediating impact of study variables was also identified. The proposed model had a satisfactory level of prediction power for loyalty. Overall, our findings provided important insights into how steakhouse practitioners can deal with SNS as essential promotional tools and provided valuable insights into why using SNS sales promotions is critical in the fast-changing chain restaurant industry.
Corporate Tax Aggressiveness and Insider Trading

Recent studies argue that aggressive forms of tax avoidance can be used to facilitate managerial rent extraction from shareholders (e.g., Desai 2004; Desai and Dharmapala 2006; Desai et al. 2007). Despite this agency view of tax avoidance receiving increasing attention in the literature, there is limited empirical evidence that managers actually extract rents generated from tax avoidance activities. In this paper, we examine the association between corporate tax aggressiveness and managerial rent extraction in the form of insider trading profitability. We document that, on average, insider purchase profitability, but not sale profitability, is significantly higher in more tax aggressive firms. The positive association between tax aggressiveness and insider purchase profitability is attenuated for firms with more effective monitoring and for firms with better information environments. Finally, we find that tax aggressiveness is significantly associated with greater insider sale volume in the fiscal year prior to a stock price crash. Our study contributes to the literature by providing empirical evidence that managers do, in fact, extract insider trading rents through corporate tax aggressiveness (Armstrong et al. 2015) and the findings are particularly important in light of the number of studies relying on the agency view of tax avoidance to develop arguments or to draw inferences.
Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content

Consecutive cleavages of amyloid precursor protein (APP) generate APP intracellular domain (AICD). Its cellular function is still unclear. In this study, we investigated the functional role of AICD in cellular Ca2+ homeostasis. We could confirm previous observations that endoplasmic reticulum Ca2+ stores contain less calcium in cells with reduced APP γ‐secretase cleavage products, increased AICD degradation, reduced AICD expression or in cells lacking APP. In addition, we observed an enhanced resting cytosolic calcium concentration under conditions where AICD is decreased or missing. In view of the reciprocal effects of Ca2+ on mitochondria and of mitochondria on Ca2+ homeostasis, we analysed further the cellular ATP content and the mitochondrial membrane potential. We observed a reduced ATP content and a mitochondrial hyperpolarisation in cells with reduced amounts of AICD. Blockade of mitochondrial oxidative phosphorylation chain in control cells lead to similar alterations as in cells lacking AICD. On the other hand, substrates of Complex II rescued the alteration in Ca2+ homeostasis in cells lacking AICD. Based on these observations, our findings indicate that alterations observed in endoplasmic reticulum Ca2+ storage in cells with reduced amounts of AICD are reciprocally linked to mitochondrial bioenergetic function.
Designing the Cash and Counseling Demonstration and Evaluation.

OBJECTIVE The Cash and Counseling Demonstration and Evaluation (CCDE) was designed as an experiment in shifting the paradigm in home and community-based long-term care from a professional/bureaucratic model of service delivery to one emphasizing consumer choice and control. The experimental intervention was an individualized budget offered in lieu of traditional Medicaid-covered services, such as agency-delivered aide services or a plan of care developed and coordinated by a professional case-manager, which typically involves authorization for several different providers to deliver a range of services. Within the spending limits established by their budgets, program participants were largely free to choose the types and amounts of paid services and supports they judged best able to meet their disability-related personal assistance needs. STUDY POPULATION Medicaid beneficiaries in selected states who volunteered to participate. In all of the participating state Medicaid programs, beneficiaries eligible to participate included elders and younger adults with chronic disabilities and, in one state, adults and children with mental retardation/developmental disabilities could also participate. Minor children and adults with cognitive impairment could participate via representatives (family or friends who agreed to assist them in managing their services or to act as their surrogate decision-makers). DATA SOURCES Members of the CCDE management team describe the rationale for and implications of key design decisions. STUDY DESIGN Key design decisions included the choice of research methodology (random assignment of CCDE participants in each state to treatment and control groups), selection of the state sites (AR, FL, NJ, NY), and the need for the CCDE to comply with federal waiver requirements for Medicaid research and demonstration projects. Principle Findings. The CCDE design was successfully implemented in three of the four state Medicaid programs selected for participation. CONCLUSIONS The successful implementation of the CCDE (results from the evaluation are reported elsewhere) led to replication efforts in other states. The CCDE also inspired changes in Medicaid law and policy, including the 2002 "Independence Plus" Initiative by the Centers for Medicare and Medicaid and sections of the Deficit Reduction Act of 2005 intended to promote consumer-direction in Medicaid.
Dopamine‐induced changes in renal blood flow in normals and in patients with renal dysfunction

Background: Despite their controversial effect, “renal” doses of dopamine (3–5 μg · kg−1 · min−1) are often used in intensive care units to preserve renal function and to improve final outcome. Aim: To assess the effects of different doses of dopamine on renal blood flow in patients with normal renal function and in patients with renal dysfunction. Methods and Results: In 17 patients with normal renal function and in 12 patients with moderate renal dysfunction, mean arterial pressure (MAP), heart rate (HR), and average peak renal flow velocities (FlowWire APV) were continuously recorded at baseline and during IV administration of increasing dopamine doses (3, 5, 10, 20, and 30 μg · kg−1 · min−1). MAP and HR did not change during infusion of 3–5 μg · kg−1 · min−1 but increased to the same extent in both groups during infusion of >10 μg · kg−1 · min−1. Baseline APV was similar in both groups. Infusion of 3–5 μg · kg−1 · min−1 induced a significant change in APV only in patients with normal renal function. In patients with renal dysfunction, APV increased only during infusion of >10 μg · kg−1 · min−1 in parallel with MAP and HR. Conclusion: “Renal” doses of dopamine increase renal blood flow in normals but not in patients with moderate renal dysfunction. © 2008 Wiley‐Liss, Inc.
Co-Creation of Social Entrepreneurial Opportunities with Refugees

Abstract This explorative study examines how local and refugee entrepreneurs team up on social entrepreneurial initiatives and combine their strengths and resources to construct, evaluate and pursue new opportunities. We interviewed social venture teams including both groups in a social entrepreneurship accelerator in Germany. The findings suggest that such mixed social venture teams can overcome the liabilities of the foreignness of entrepreneurial refugee individuals while gaining legitimacy in both host societies and the refugee community.
Diversity and phylogeny of plant growth‐promoting bacilli from moderately acidic soil

The molecular diversity of aerobic endospore‐forming bacteria, typically Bacillus and its derived genera, has been investigated in various environments. However, there have been few investigations concerning Bacillus in acidic soils. In this study, the genotypic diversity and phylogenetic relationships among plant growth‐promoting (PGP) bacilli isolated from the rice rhizosphere growing in acidic soils of Kerala (pH varying from 6.3 to 6.8) were investigated. For assessing their biocontrol potential and PGP attributes, 115 isolates were randomly selected and 49 isolates that were positive for multiple traits were selected. Metabolic characterization of representative strains, using the Biolog GP2 (Gram Positive) MicroPlateTM, revealed a large versatility with respect to carbohydrate utilization. Amplified ribosomal DNA restriction analysis revealed 13 clusters at 65% similarity level, which consisted of 1–21 strains. 16S rDNA partial sequencing assigned all the isolates, except for one, to the Bacillus genus, with close relatedness to Bacillus humi, B. megaterium, B. drentensis, B. pocheonensis, B. aestuarii, B. arbutinivorans, B. niacini, and Brevibacterium casei. The Bacillus species with different metabolic capabilities, PGP abilities, and genetic diversity found in this study are likely to have ecological relevance. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Grid Based Target Motion Analysis

To achieve substantial tactical advantage over future submarine threats the combat management system has to quickly plot and maintain the trajectory of the moving targets for early response. Within this objective, the focus is to develop optimal end to end processing approaches that produce significant gain in establishing faster submarine reliable trajectory and motion. The method, based upon grid filtering, described in this article will contribute to this aim as a key component. The paper is organized as follows: first, the particular context of angle only tracking is recalled. Second, the theoretical framework is briefly introduced and we describe our approach. Then, using a typical testing scenario, we compare the target kinematics features obtained by our approach versus the well known least square solution widely used in this context and the more recent unscented Kalman filter. Finally we will see how the grid filter allows for a supplementary time reduction in the convergence of the estimated trajectory.
Survival After Surgical Treatment of Lung Cancer Arising in the Population Exposed to Illegal Dumping of Toxic Waste in the Land of Fires ('Terra dei Fuochi') of Southern Italy.

AIM Terra dei Fuochi (TdF), the so-called 'Land of Fires' in Southern Italy, is an agricultural territory characterized by illegal dumping of toxic waste known to occur since the 1980s. It is unknown whether prognosis of patients developing cancer and living in that area may differ compared to those living in areas not exposed to this specific type of pollution. We retrospectively analyzed the 5-year survival rates of patients originating from the TdF diagnosed with lung cancer compared to patients from other areas. MATERIALS AND METHODS Patients consecutively operated on for non-small cell lung cancer (NSCLC) between November 2004 and April 2013 at the Division of Thoracic Surgery of the National Cancer Institute of Naples were eligible. The study outcome was overall survival (OS). In addition, the TdF and non-TdF groups were compared through propensity score matching (PSM). RESULTS Overall, 439 patients with resectable NSCLC were operated on, 123 (28%) from the TdF and 316 (72%) from other referral centers of our catchment area. There were 301 males and 138 females; the median age of the entire surgical population was 65 years (range=25-83) years. Apart from a different prevalence of hypertension and underweight patients, preoperative factors were evenly distributed between the two groups. At univariate analysis, OS was not different between the TdF and non TdF group (median 72 and 68 months, respectively; p=0.75 log-rank test). Multivariable analysis confirmed that living in the TdF area had no prognostic impact (hazard ratio=1.05; 95% confidence interval=0.70-1.57; p=0.78) on OS. PSM confirmed no statistically significant difference of OS (hazard ratio=1.01, 95% confidence interval=0.67-1.52; p=0.93). CONCLUSION Following surgery for lung cancer, TdF and non-TdF surgical candidates had similar long-term survival. Originating from the TdF does not seem to be associated with worse outcomes after surgical treatment of patients with lung cancer.
Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea

Rationale: Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes (“traits”) if a clinically applicable approach were available. Objectives: Here we aimed to provide a means to quantify two key contributors to OSA—pharyngeal collapsibility and compensatory muscle responsiveness—that is applicable to diagnostic polysomnography. Methods: Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g., during spontaneous cyclic events) should reveal a patient's phenotypic traits without specialized intervention. We demonstrate this concept in patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using “gold standard” ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). Measurements and Main Results: Polysomnography‐derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P < 0.0001; and R = 0.64, P < 0.001; respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy, 69‐86% vs. ventilatory drive measures; P < 0.05). Traits were near‐identical using nasal pressure versus pneumotach (N = 11, R ≥ 0.98, both traits; P < 0.001). Conclusions: Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.
Collaborative in-network caching for multi-path routing

This paper proposes a collaborative in-network caching method for multi-path routing. In-network caching allows routers in networks to store contents in their caches and users can download the contents from the routers in addition to content servers. In such a situation, the proposed method introduces a joint optimization problem of in-network caching and multi-path routing, which is formulated as linear programming. The in-network caching problem decides location of contents and the multi-path routing problem decides multiple routing paths to download the contents. Through numerical experiments, we show that the proposed method efficiently reduces the loads of congested links.
EMC pre-design research based on system engineering approach

Nowadays electronic, electrical equipments are more and more intensive, which means that the quantitative analysis of a system has became increasingly complex, and it makes the introduction of systems engineering approach for qualitative analysis to be a trend in the field of electromagnetic compatibility. The main systems engineering approach in the field of electromagnetic compatibility is the analytic hierarchy process (AHP) and its various derivative algorithms. It is only applied to electromagnetic compatibility assessment of the EMC basic design, but little reference value for EMC pre-design. For electromagnetic compatibility characteristics of the study, we use the combination of `decision making trial and evaluation laboratory' and `interpretation of the structure model' to analyse the problem of electromagnetic compatibility. A new systems engineering approach applicable to electromagnetic compatibility pre-design, EMCSAM, is proposed. An example is presented to prove the feasibility and efficiency of the new method.
Statistical properties of hybrid estimators proposed for GEDI—NASA’s global ecosystem dynamics investigation

NASA’s Global Ecosystem Dynamics Investigation (GEDI) mission will collect waveform lidar data at a dense sample of ∼25 m footprints along ground tracks paralleling the orbit of the International Space Station (ISS). GEDI’s primary science deliverable will be a 1 km grid of estimated mean aboveground biomass density (Mg ha−1), covering the latitudes overflown by ISS (51.6 °S to 51.6 °N). One option for using the sample of waveforms contained within an individual grid cell to produce an estimate for that cell is hybrid inference, which explicitly incorporates both sampling design and model parameter covariance into estimates of variance around the population mean. We explored statistical properties of hybrid estimators applied in the context of GEDI, using simulations calibrated with lidar and field data from six diverse sites across the United States. We found hybrid estimators of mean biomass to be unbiased and the corresponding estimators of variance appeared to be asymptotically unbiased, with under-estimation of variance by approximately 20% when data from only two clusters (footprint tracks) were available. In our study areas, sampling error contributed more to overall estimates of variance than variability due to the model, and it was the design-based component of the variance that was the source of the variance estimator bias at small sample sizes. These results highlight the importance of maximizing GEDI’s sample size in making precise biomass estimates. Given a set of assumptions discussed here, hybrid inference provides a viable framework for estimating biomass at the scale of a 1 km grid cell while formally accounting for both variability due to the model and sampling error.
Association of HLA‐DP/DQ, STAT4 and IL‐28B variants with HBV viral clearance in Tibetans and Uygurs in China

Several genome‐wide association studies have revealed that HLA‐DP/DQ, STAT4 and IL‐28B associated with liver diseases. But because of population heterogeneity, different races would have different causative polymorphisms. Therefore, in this study, we included Chinese Tibetans and Uygurs to examine the roles of these genes on HBV natural clearance.