bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis
Authors: Arora Shaily , Balasubramaniam Sanjeeve , Zhang Wei , Zhang Lijun , Sridhara Rajeshwari , Spillman Dianne , Mathai Jaigi P. , Scott Bradley , Golding Sarah J. , Coory Michael , Pazdur Richard , Beaver Julia A. 
Published: April 2020

AbstractOn September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%–48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit–risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.
The Science Underlying COVID-19
Authors: Liu Peter P. , Blet Alice , Smyth David , Li Hongliang 
Published: April 2020

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission.
The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients.
Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death.
In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death.
Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.
Out‐of‐Hospital Cardiac Arrests and Wildfire‐Related Particulate Matter During 2015–2017 California Wildfires
Authors: Jones Caitlin G. , Rappold Ana G. , Vargo Jason , Cascio Wayne E. , Kharrazi Martin , McNally Bryan , Hoshiko Sumi ,   with the CARES Surveillance Group
Published: April 2020

Background
The natural cycle of large‐scale wildfires is accelerating, increasingly exposing both rural and populous urban areas to wildfire emissions. While respiratory health effects associated with wildfire smoke are well established, cardiovascular effects have been less clear.

Methods and Results
We examined the association between out‐of‐hospital cardiac arrest and wildfire smoke density (light, medium, heavy smoke) from the National Oceanic Atmospheric Association's Hazard Mapping System. Out‐of‐hospital cardiac arrest data were provided by the Cardiac Arrest Registry to Enhance Survival for 14 California counties, 2015–2017 (N=5336). We applied conditional logistic regression in a case‐crossover design using control days from 1, 2, 3, and 4 weeks before case date, at lag days 0 to 3. We stratified by pathogenesis, sex, age (19–34, 35–64, and ≥65 years), and socioeconomic status (census tract percent below poverty). Out‐of‐hospital cardiac arrest risk increased in association with heavy smoke across multiple lag days, strongest on lag day 2 (odds ratio, 1.70; 95% CI, 1.18–2.13). Risk in the lower socioeconomic status strata was elevated on medium and heavy days, although not statistically significant. Higher socioeconomic status strata had elevated odds ratios with heavy smoke but null results with light and medium smoke. Both sexes and age groups 35 years and older were impacted on days with heavy smoke.

Conclusions
Out‐of‐hospital cardiac arrests increased with wildfire smoke exposure, and lower socioeconomic status appeared to increase the risk. The future trajectory of wildfire, along with increasing vulnerability of the aging population, underscores the importance of formulating public health and clinical strategies to protect those most vulnerable.
Contemporary China and the “Harmonious” World Order in the Age of Globalization
Authors: Coco Orazio 
Published: April 2020

Abstract
This paper examines the Chinese political vision of the world order and how the West has, so far, reacted to the presence of a new rising power in the global system. It takes inspiration from the current complex international scenario of confrontation between China and the West. The concept of socialist “harmonious” world order is not a political creative idea, but the long-term vision proposed by China since the beginning of this century. It has become topic of political interest, attracting the attention of the Western world, only in the last decade and in connection with the theoretical debate inspired by the power transition theory. The idea of a hegemonic transition and the making of a new international order, as alternative to the liberal democratic model, is gaining consistency with the economic development and the growing political influence of China, but also as consequence of the retreat of democracy worldwide.
Mapping on Transnational Crime Routes in the New Silk Road: a Case Study of the Greater Mekong Sub-region
Authors: Luong Hai Thanh 
Published: April 2020

Abstract
The Greater Mekong Sub-region (GMS), including five Southeast Asian countries and China, has experienced a significant increase in the cultivation of opium, trafficking of heroin and methamphetamine, and consumption of these illicit drugs. In recent years, the GMS has been expanded considerably as supply, destination, and transit route for illegal drug trade’s networks to and through, particularly when China officially applied ‘Belt and Road’ strategy. This paper reviews historical aspects and current trends in drug production and trafficking in the GMS, with special emphasis on Mekong River areas where China is ‘located’ as the heart of the transition. Some evidence consistent with the ‘supply, destination, and transit route’ arguments is found through locating and mapping drug trafficking networks to connect with China. Finally, this paper calls for some initial recommendations to improve the process of bilateral and multilateral cooperation in the GMS within the scope of Belt and Road Initiative.
A Review of the Academic Debate about United Nations Security Council Reform
Authors: Winther Bjarke Zinck 
Published: April 2020

Abstract
This article outlines and discusses the research on UNSC reform. The interdisciplinary field of UNSC reform research can be placed into two broad categories and four sub categories, each indicating the degree to which scholars believe in the benefits of either structural or working methods reform. These include topics such as legitimacy and efficiency and the question of (un)equal representation. The role of The Global South will feature heavily in analyses of how best to reform the UNSC, and of which actors or structures mainly prevent a reform from materialising. There has been a significant gap in research focusing on how the factors that feature as instruments of opposition, e.g. the presented benefits and detriments of the different approaches to reform, can potentially be converged to rethink the direction of the research.
Detectable Anthropogenic Influence on Changes in Summer Precipitation in China
Authors: Lu Chunhui , Lott Fraser C. , Sun Ying , Stott Peter A. , Christidis Nikolaos 
Published: April 2020

AbstractIn China, summer precipitation contributes a major part of the total precipitation amount in a year and has major impacts on society and human life. Whether any changes in summer precipitation are affected by external forcing on the climate system is an important issue. In this study, an optimal fingerprinting method was used to compare the observed changes of total, heavy, moderate, and light precipitation in summer derived from newly homogenized observation data with the simulations from multiple climate models participating in phase 5 of the Coupled Model Intercomparison Project (CMIP5). The results demonstrate that the anthropogenic forcing signal can be detected and separated from the natural forcing signal in the observed increase of seasonal accumulated precipitation amount for heavy precipitation in summer in China and eastern China (EC). The simulated changes in heavy precipitation are generally consistent with observed change in China but are underestimated in EC. When the changes in precipitation of different intensities are considered simultaneously, the human influence on simultaneous changes in moderate and light precipitation can be detected in China and EC in summer. Changes attributable to anthropogenic forcing explain most of the observed regional changes for all categories of summer precipitation, and natural forcing contributes little. In the future, with increasing anthropogenic influence, the attribution-constrained projection suggests that heavy precipitation in summer will increase more than that from the model raw outputs. Society may therefore face a higher risk of heavy precipitation in the future.
The Southeastern Tropical Atlantic SST Bias Investigated with a Coupled Atmosphere–Ocean Single-Column Model at a PIRATA Mooring Site
Authors: Deppenmeier Anna-Lena , Haarsma Rein J. , van Heerwaarden Chiel , Hazeleger Wilco 
Published: April 2020

AbstractWarm sea surface temperature (SST) biases in the tropical Atlantic Ocean form a longstanding problem in coupled general circulation models (CGCMs). Considerable efforts to understand the origins of these biases and alleviate them have been undertaken, but state-of-the-art CGCMs still suffer from biases that are very similar to those of the generation of models before. In this study, we use a powerful combination of in situ moored buoy observations and a new coupled ocean–atmosphere single-column model (SCM) with parameterization that is identical to that of a three-dimensional CGCM to investigate the SST bias. We place the SCM at the location of a Prediction and Research Moored Array in the Tropical Atlantic (PIRATA) mooring in the southeastern tropical Atlantic, where large SST biases occur in CGCMs. The SCM version of the EC-Earth state-of-the-art coupled GCM performs well for the first five days of the simulation. Then, it develops an SST bias that is very similar to that of its three-dimensional counterpart. Through a series of sensitivity experiments we demonstrate that the SST bias can be reduced by 70%. We achieve this result by enhancing the turbulent vertical ocean mixing efficiency in the ocean parameterization scheme. The underrepresentation of vertical mixing in three-dimensional CGCMs is a candidate for causing the warm SST bias. We further show that surface shortwave radiation does not cause the SST bias at the location of the PIRATA mooring. Rather, a warm atmospheric near-surface temperature bias and a wet moisture bias contribute to it. Strongly nudging the atmosphere to profiles from reanalysis data reduces the SST bias by 40%.
Validation of a G-Band Differential Absorption Cloud Radar for Humidity Remote Sensing
Authors: Roy Richard J. , Lebsock Matthew , Millán Luis , Cooper Ken B. 
Published: April 2020

AbstractDifferential absorption radar (DAR) offers an active remote sensing solution to the problem of measuring humidity profiles with high vertical and horizontal resolution in hydrometeor layers. The Vapor In-Cloud Profiling Radar (VIPR) is a frequency-modulated continuous-wave (FMCW) G-band DAR tunable from 167 to 174.8 GHz being developed at the Jet Propulsion Laboratory (JPL). Here we describe ground-based measurements from VIPR performed at the Department of Energy’s Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site for humidity product validation. Two distinct measurement capabilities are investigated: 1) humidity profiles inside of cloudy volumes with 180 m vertical resolution, and 2) integrated water vapor (IWV) between the surface and cloud base. High radar sensitivity permits detection of upper-tropospheric clouds and retrieval of humidity profiles above 10 km in height. We develop an improved humidity retrieval algorithm based on a regularized least squares method that includes detailed accounting of measurement covariances and systematic error sources. This regularization mitigates high-spatial-frequency humidity biases that arise from frequency-dependent hydrometeor scattering, which is an important limitation for DAR systems. Through comparisons with over 20 coincident radiosondes, we find close agreement between in situ and remotely sensed humidity profiles, with a correlation coefficient of r = 0.96, root-mean-square error (RMSE) of 0.8 g m−3, and median retrieval precision of 0.5 g m−3. Using a merged radiosonde and Raman lidar product for surface-to-cloud-base IWV, we demonstrate precise column sounding capabilities with r = 1.00, RMSE of 1.2 mm, and median retrieval precision of 0.25 mm.
A Rapid Forecasting and Mapping System of Storm Surge and Coastal Flooding
Authors: Yang Kun , Paramygin Vladimir A. , Sheng Y. Peter 
Published: April 2020

AbstractA prototype of an efficient and accurate rapid forecasting and mapping system (RFMS) of storm surge is presented. Given a storm advisory from the National Hurricane Center, the RFMS can generate a coastal inundation map on a high-resolution grid in 1 min (reference system Intel Core i7–3770K). The foundation of the RFMS is a storm surge database consisting of high-resolution simulations of 490 optimal storms generated by a robust storm surge modeling system, Curvilinear-Grid Hydrodynamics in 3D (CH3D-SSMS). The RFMS uses an efficient quick kriging interpolation scheme to interpolate the surge response from the storm surge database, which considers tens of thousands of combinations of five landfall parameters of storms: central pressure deficit, radius to maximum wind, forward speed, heading direction, and landfall location. The RFMS is applied to southwest Florida using data from Hurricane Charley in 2004 and Hurricane Irma in 2017, and to the Florida Panhandle using data from Hurricane Michael in 2018 and validated with observed high water mark data. The RFMS results agree well with observation and direct simulation of the high-resolution CH3D-SSMS. The RFMS can be used for real-time forecasting during a hurricane or “what-if” scenarios for mitigation planning and preparedness training, or to produce a probabilistic flood map. The RFMS can provide more accurate surge prediction with uncertainties if NHC can provide more accurate storm forecasts in the future. By incorporating storms for future climate and sea level rise, the RFMS could be used to generate future flood maps for coastal resilience and adaptation planning.
Evaluation of the anti-angiogenic effect of bevacizumab on rat C6 glioma by spectral computed tomography
Authors: Han Lei , Huang Xiaoyu , Liu Xianwang , Deng Yajun , Ke Xiaoai , Zhou Qing , Zhou Junlin 
Published: April 2020

Background Anti-angiogenic drugs have become a research hotspot in recent years. However, dynamically observing their therapeutic effect at different time points during treatment is a clinical problem. Purpose To explore the feasibility of the quantitative parameters of spectral computed tomography (CT) in evaluating the anti-angiogenic effect of bevacizumab on rat C6 glioma. Material and Methods Twenty-six male Sprague-Dawley rats were used to establish the C6 glioma model. The rats were randomly divided into the experimental group (n = 13) and control group (n = 13). The experimental group was intraperitoneally injected with 0.2 µL/g bevacizumab every day, whereas the control group was injected with the same dose of normal saline every day for one week. Spectral CT scanning was performed on the 4th and 8th days after treatment; meanwhile, the brain tissues were collected by heart perfusion for H&E staining, and VEGF and HIF-1α immunohistochemical staining. Results On the 4th and 8th days, significant differences in the 70-keV single-energy CT value, slope of the energy spectrum curve, and iodine concentration were found between the experimental group and the control group. Correlation analysis between immunohistochemistry and quantitative parameters of spectral CT showed that the single energy CT value of 70 keV, slope of the energy spectrum curve, and concentration of iodine were positively correlated with VEGF and HIF-1α at different time points in the experimental group and the control group. Conclusion Spectral CT multi-parameter imaging can be employed as a new method to evaluate the anti-angiogenic effect of bevacizumab on rat C6 glioma.
Lower Limb Kinetic Asymmetries in Professional Soccer Players With and Without Anterior Cruciate Ligament Reconstruction: Nine Months Is Not Enough Time to Restore “Functional” Symmetry or Return to Performance
Authors: Read Paul J. , Michael Auliffe Sean , Wilson Mathew G. , Graham-Smith Philip 
Published: April 2020

Background: Residual between-limb deficits are a possible contributing factor to poor outcomes in athletic populations after anterior cruciate ligament reconstruction (ACLR). Comprehensive appraisals of movement strategies utilized by athletes at key clinical milestones during rehabilitation are warranted. Purpose: To examine kinetic parameters recorded during a countermovement jump with a force platform in healthy professional soccer players and to compare their performance with those who had undergone ACLR at different stages of their rehabilitation. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 370 male professional soccer players attended a physical screening assessment where they performed at counter jump movement protocol on dual force plates and were divided into 4 groups: group 1 (<6 months post-ACLR), group 2 (6-9 months post-ACLR), group 3 (>9 months post-ACLR), and group 4 (healthy matched controls). Results: Players in the later phases of rehabilitation increased their jump performance; however, values were significantly lower than those of healthy matched controls ( P > .05). Significant between-limb differences were present for both eccentric- and concentric-phase variables ( P < .05), with effect sizes ranging from moderate to very large ( d = 0.42-1.35). Asymmetries were lower in players who were further away from surgery; however, between-limb differences remained significantly greater in players >9 months after ACLR versus matched controls—specifically, for concentric impulse, concentric peak force, eccentric deceleration impulse, and eccentric deceleration rate of force development asymmetry ( P < .05). Logistic regression identified concentric impulse asymmetry as being most strongly associated with a history of ACLR when group prediction analysis was performed (ACLR group 1, 2, or 3 vs matched controls), with odds ratios ranging from 1.50 to 1.91. Conclusion: Between-limb deficits in key eccentric and concentric loading parameters remain >9 months after ACLR, indicating a compensatory offloading strategy to protect the involved limb during an athletic performance task. Concentric impulse asymmetry could be considered an important variable to monitor during rehabilitation.
Education Strategies Supporting Internationally Educated Registered Nurse Students With English as a Second Language in Canada
Authors: Hopkins Nicole M. , Stephens Jennifer M. L. 
Published: April 2020

Introduction The purpose of this literature synthesis is to highlight some of the challenges faced by internationally educated nurses with English as a second language when integrating into the Canadian health-care environment and to suggest educational strategies that work to support these diverse learners to acculturate and fill gaps. Methodology: A search of Google Scholar, PubMed, CINAHL, MEDLINE, and ProQuest Nursing and Allied Health databases, as well as reference lists, conference presentations, and gray literature produced pertinent research studies and commentary published between 2008 and 2018. Results Common themes in the literature include challenges relating to communication, cultural competence, and critical thinking. Discussion Some strategies that should be included in bridging education programs to address these challenges are evolving case studies, simulation and role-play, and practice performing multiple-choice tests. Research is needed examining the effectiveness of experiential techniques in preparing internationally educated nurses for nursing in the Canadian context.