bluuebunny/crossref_metadata_2025_split huggingface dataset:
Access to innovation through the national early access program and clinical trials for patients with malignant melanoma
Authors: Christen Claire , Belgodère Laetitia , Guillot Bernard , Jumeau Céline , Lorence Annie , Kerouani‐Lafaye Ghania , Brunel Liora , Turcry Florence , Monard Adrien , Grudé Francoise , Guyader Gaëlle , Boudali Lotfi , Albin Nicolas 
Published: March 2021

BackgroundThe arrival of immunotherapies and targeted therapies challenged the authorities to make them available as soon as possible. France has effective tools, such as clinical trials (CTs) and a national early access program (temporary authorizations for use [ATUs] and temporary recommendations for use [RTUs]), allowing the use of innovative drugs, whether or not they have been authorized or used off‐label, for cases that have reached a therapeutic impasse.MethodsThe methodology involved real‐time data collection from ATUs, RTUs (between September 1, 2009 and September 1, 2019), and CT authorizations (from December 1, 2017 to September 1, 2019) that were filed and reviewed by the French National Agency for Medicines for metastatic melanoma (MM).ResultsIn total, 45 CTs were authorized for MM (51% early phase trials and 44% phase 2 and 3 trials), mainly for the metastatic line (86%) and with an industrial sponsor (73%). Immunotherapies and targeted therapies (63% and 24%, respectively) mostly were used in combination. Three RTUs were authorized for the adjuvant treatment of MM, whereas 13 drugs were available through nominal ATUs (nATUs), of which 5 were awarded a cohort ATU (cATU). This enabled the treatment of 6538 patients (28% through nATUs and 72% through cATUs). All of these drugs were granted marketing authorization and were included in the reimbursement list.ConclusionsThanks to CTs and the national early access program, patients in France have been able to benefit from innovative MM treatments.Lay Summary

Several tools allow the use of innovative drugs in France, even if they are not yet authorized or used off‐label.

From December 1, 2017 to September 1, 2019, 45 clinical trials have been authorized for metastatic melanoma, mostly using immunotherapy (63%) and targeted therapy (24%) at an early phase (51%).

Since 2010, the national early access program has treated 6538 patients, including 28% under nominative temporary authorizations for use and 72% under cohort temporary authorizations for use.

Fourteen drugs are available through nominative temporary authorizations for use, and 5 are available through cohort temporary authorizations for use, and all of these drugs were granted marketing authorization.
Posttraumatic stress disorder symptoms in patients with acute myeloid leukemia
Authors: Amonoo Hermioni L. , LeBlanc Thomas W. , Kavanaugh Alison R. , Webb Jason A. , Traeger Lara N. , Jagielo Annemarie D. , Vaughn Dagny M. , Elyze Madeleine , Longley Regina M. , Fathi Amir T. , Hobbs Gabriela S. , Brunner Andrew M. , O’Connor Nina R. , Luger Selina M. , Gustin Jillian L. , Bhatnagar Bhavana , Horick Nora K. , El‐Jawahri Areej 
Published: March 2021

BACKGROUNDPatients with acute myeloid leukemia (AML) receiving intensive chemotherapy face a life‐threatening illness, isolating hospitalization, and substantial physical and psychological symptoms. However, data are limited regarding risk factors of posttraumatic stress disorder (PTSD) symptoms in this population.METHODSThe authors conducted a secondary analysis of data from 160 patients with high‐risk AML who were enrolled in a supportive care trial. The PTSD Checklist‐Civilian Version was used to assess PTSD symptoms at 1 month after AML diagnosis. The Brief COPE and the Functional Assessment of Cancer Therapy‐Leukemia were to assess coping and quality of life (QOL), respectively. In addition, multivariate regression models were constructed to assess the relation between PTSD symptoms and baseline sociodemographic factors, coping, and QOL.RESULTSTwenty‐eight percent of patients reported PTSD symptoms, describing high rates of intrusion, avoidance, and hypervigiliance. Baseline sociodemographic factors significantly associated with PTSD symptoms were age (B = −0.26; P = .002), race (B = −8.78; P = .004), and postgraduate education (B = −6.30; P = .029). Higher baseline QOL (B = −0.37; P ≤ .001) and less decline in QOL during hospitalization (B = −0.05; P = .224) were associated with fewer PTSD symptoms. Approach‐oriented coping (B = −0.92; P = .001) was associated with fewer PTSD symptoms, whereas avoidant coping (B = 2.42; P ≤ .001) was associated with higher PTSD symptoms.CONCLUSIONSA substantial proportion of patients with AML report clinically significant PTSD symptoms 1 month after initiating intensive chemotherapy. Patients' baseline QOL, coping strategies, and extent of QOL decline during hospitalization emerge as important risk factors for PTSD, underscoring the need for supportive oncology interventions to reduce the risk of PTSD in this population.
Refined Description and Stability for Singular Solutions of the 2D Keller‐Segel System
Authors: Collot Charles , Ghoul Tej‐Eddine , Masmoudi Nader , Nguyen Van Tien 
Published: March 2021

We construct solutions to the two‐dimensional parabolic‐elliptic Keller‐Segel model for chemotaxis that blow up in finite time T. The solution is decomposed as the sum of a stationary state concentrated at scale λ and of a perturbation. We rely on a detailed spectral analysis for the linearised dynamics in the parabolic neighbourhood of the singularity performed by the authors in [10], providing a refined expansion of the perturbation. Our main result is the construction of a stable dynamics in the full nonradial setting for which the stationary state collapses with the universal law
where γ is the Euler constant. This improves on the earlier result by Raphael and Schweyer and gives a new robust approach to so‐called type II singularities for critical parabolic problems. A by‐product of the spectral analysis we developed is the existence of unstable blowup dynamics with speed
© 2021 Wiley Periodicals LLC.
Crystal Morphology Prediction of Olanzapine Forms III and IV
Authors: Lu Qianqian , Ali Imran , Wei Zhiyun , Li Jinjin 
Published: March 2021

AbstractIt is of great significance to explore and predict crystal growth behavior that can target the optimal growth conditions and obtain ideal properties. The ability to effectively treat schizophrenia and other psychoses has led to numerous studies of olanzapine (OZPN) polymorphs. There are four reported anhydrous forms of OZPN, but two of whose crystal morphologies (forms III and IV) are still unavailable in the laboratory. Based on the advanced spiral growth model, this study predicts the crystal morphologies of OZPN forms III and IV from vapor and different solvents (i.e., water, ethyl acetate, ethanol, cyclohexane, and dichloromethane), where the potential energies between dimeric growth units (stronger than specific energy cutoff) are considered as strong bond. It is demonstrated that the growth rate of form III increases with the increase of supersaturation from 1.01 to 1.07. Form III crystallizes from solvents with the block‐like shape, whereas form IV grows with the rectangular shape, that obviously differs from the flat‐square shapes of form I and form II. This mechanistic model is able to apply on various compounds, especially for the crystals with non‐centrosymmetric molecules to obtain important guidance for their experimental preparations.
Board structure, financial performance, corporate social responsibility performance, CSR committee, and CEO duality: Disentangling the connection in healthcare
Authors: Uyar Ali , Kuzey Cemil , Kilic Merve , Karaman Abdullah S. 
Published: March 2021

AbstractDespite the growing importance of responsible behavior in the healthcare sector, research on corporate social responsibility (CSR) in association with board structure is scarce. Hence, the objective of this study is twofold: (1) to test whether a board structure is associated with firm financial and CSR performance and (2) whether the CSR committee and CEO duality moderates this association in the healthcare sector. Examining the moderation of CSR committee is important to understand whether CSR committee strengthens or weakens the link between female directors and CSR performance. Moreover, CEO duality's moderation will highlight whether powerful CEOs are a barrier for female directors' monitoring role. The data for the study was derived from the Thomson Reuters Eikon database for the years between 2011–2018. Overall, the results suggest that while female directors contribute to firm performance, CEOs with dual roles and larger boards harm firm performance. Further, independent directors have a limited contribution to CSR performance whereas they have no contribution to financial performance. Moderation analysis shows that CSR committees and female directors are not the replacement of one another; they are both needed and beneficial to the corporate structure. Although CEOs with a dual role impair the performance of a firm, they do not exert considerable influence on the other directors. As one of the important functions of a board is monitoring, these findings assist healthcare firms to configure their boards to improve their monitoring functions. The results are therefore helpful in terms of alleviating agency costs and in appeasing stakeholders.
Uncovering the different scales in deer–forest interactions
Authors: Ramirez Juan Ignacio 
Published: March 2021

AbstractDeer are regarded to be a keystone species as they play a crucial role in the way an ecosystem functions. Most deer–forest interaction studies apply a single scale — process of analyzing ecological interactions by only taking into account one dependent variable — to understand how deer browsing behavior shapes different forest components, but they overlook the fact that forests respond to multiple scales simultaneously. This research evaluates the effect of browsing by wild deer on temperate and boreal forests at different scales by synthesizing seminal papers, specifically (a) what are the effects of deer population density in forest regeneration? (b) What are the effects of deer when forests present diverging spatial characteristics? (c) What are the effects on vegetation at different temporal scales? and (d) What are the hierarchical effects of deer when considering other trophic levels? Additionally, a framework based on modern technology is proposed to answer the multiscale research questions previously identified. When analyzing deer–forest interactions at different scales, the strongest relationships occur at the extremes. For example: when deer assemblage occurs in low or high density and is composed of a mix of small and large species. As forests on poor soils remain restrained in size, isolated and chronically browsed. When forests harbor incomplete trophic levels, the effects spill over to lower trophic levels. To better understand the complexities in deer–forest interactions, researchers should combine technology‐based instruments like fixed sensors and drones with field‐tested methods such observational studies and experiments to tackle multiscale research questions.
Degradation modeling of water environmental DNA: Experiments on multiple DNA sources in pond and seawater
Authors: Saito Tatsuya , Doi Hideyuki 
Published: March 2021

AbstractEnvironmental DNA (eDNA) analysis methods have been developed to detect organism distribution and abundance/biomass in various environments. eDNA degradation is critical for eDNA evaluation. However, the dynamics and mechanisms of eDNA degradation are largely unknown, especially when considering different eDNA sources, for example, cells and fragmental DNA. We experimentally evaluated the degradation rates of eDNA derived from multiple sources, including fragmental DNA (internal PCR control [IPC]), free cells (from Oncorhynchus kisutch), and resident species. We conducted the experiment with pond and seawater to evaluate the differences between freshwater and marine habitats. We quantified the eDNA copies of free cells, fragmental DNA, and resident species (Cyprinus carpio in the pond and Trachurus japonicus in the sea). We found that eDNA derived from both cells and fragmental DNA decreased exponentially in both the sea and pond samples. The degradation of eDNA from resident species showed similar behavior to the cell‐derived eDNA. We evaluated three degradation models with different assumptions and degradation steps and found that a simple exponential model was effective in most cases. Our findings on cell‐ and fragmental DNA‐derived eDNA provide fundamental information about the eDNA degradation process and can be applied to quantify eDNA behavior in natural environments.
Impact of activation energy and gyrotactic microorganisms on flow of Casson hybrid nanofluid over a rotating moving disk
Authors: Jyothi Anigere Marikempaiah , Naveen Kumar Rangaswamy , Punith Gowda Ramanahalli Jayadevamurthy , Veeranna Yarranna , Prasannakumara Ballajja Chandrappa 
Published: March 2021

AbstractMany models of various non‐Newtonian fluid flows for different geometries are available for analyzing the mass and heat transfer. Nevertheless, for researchers, it is challenging to choose the most suitable model for a specific geometry. Here, we have adopted a modified Buongiorno model to explore the impact of activation energy on the Casson hybrid nanofluid flow over an upward/downward‐moving rotating disk filled with the gyrotactic microorganisms. Moreover, the external magnetic field can establish the magnetic effect, which normalizes the features of heat, mass transfer, and fluid flow. Here, we used silver and copper as nanoparticles suspended in human blood as the carrier fluid. The modeled partial differential equations are converted to ordinary differential equations by opting suitable similarity variables. The numerical solutions of these reduced equations are attained by means of Runge–Kutta–Fehlberg fourth‐fifth‐order method by adopting a shooting scheme. An investigation of the attained outcomes reveals that the flow field is affected appreciably by the activation energy, bioconvection, and magnetic effect. Peclet and concentration difference numbers diminish the microorganism's profile. A rise in values of the Brownian motion parameter leads to an increase in the rate of heat transfer.
The Kings River Experimental Watersheds: Infrastructure and data
Authors: Wagenbrenner Joseph W. , Dralle David N. , Safeeq Mohammad , Hunsaker Carolyn T. 
Published: March 2021

AbstractThe Kings River Experimental Watersheds (KREW) were established in 2002 to expand our knowledge of catchment physical, chemical, and biological processes in Sierra Nevada headwater forests, and to better understand the impacts of prescribed burning and forest thinning on these processes. Two elevation strata (high and low) were selected for the KREW sites, with four independent catchments and one nested catchment within each stratum. Both high and low elevation study areas were instrumented for continuous measurements of meteorology, streamflow, and turbidity. Atmospheric and stream chemistry, suspended sediment concentration, and bedload sediment delivery were measured on a regular schedule. Soil chemical and physical properties and vegetation were systematically sampled before and after the initial thinning and prescribed burning treatments, which were implemented between 2012 and 2016. Post‐treatment data collection continues today as we explore opportunities for the second round of possible treatments. The critical research infrastructure and long‐term baseline data collection has been instrumental in building partnerships with downstream managers, end users, non‐governmental organizations, academic researchers, and national research programmes. Contributions to date include fundamental understanding of magnitude and variability of nutrient deposition; carbon, nutrient, and major ion dynamics in headwater streams; aquatic algae and macroinvertebrate populations; vegetation composition and structure; and streamflow responses to precipitation in the two elevation strata. Data from the experimental watersheds also support calibration and validation of diverse hydrologic models used for water resources planning.
Exposure assessment of PFAS-contaminated sites using avian eggs as a biomonitoring tool: A frame of reference and a case study in the Po River valley (Northern Italy)
Authors: Morganti Michelangelo , Polesello Stefano , Pascariello Simona , Ferrario Claudia , Rubolini Diego , Valsecchi Sara , Parolini Marco 
Published: March 2021

Abstract
For many years, eggs of diverse bird species have been used as monitoring tools in studies investigating perfluoroalkyl substances (PFAS) contamination, especially in marine and remote areas. Avian eggs are a suitable monitoring matrix because they are relatively easy to collect and their yolks store diverse maternally transferred PFAS. Moreover, the concentrations of PFAS detected in the eggs are a good proxy for maternal exposure and allow the assessment of the potential risk for birds. These features support the use of avian eggs as a key monitoring tool in exposure assessment of PFAS-contaminated sites. We first review the recent application of avian eggs in PFAS monitoring in environmental risk assessment schemes, highlighting strengths and limitations and suggesting which criteria should be considered when selecting a proper study species and structuring the sampling and analytical protocol. Eventually, we report findings from a field study realized in 2020 near a perfluoropolymer factory site in the upper Po plain (Northern Italy), revealing an unprecedented contamination level of PFOA and C6O4 in three species of wild passerines. In future, long-term monitoring of PFAS contamination using avian eggs should be maintained, to provide crucial information on the temporal trend of fluorochemical production and waste disposal, while facilitating early identification of emerging PFAS as well as the quantification of their biomagnification across the trophic web. Integr Environ Assess Manag 2021;17:733–745. © 2021 SETAC
KEY POINTS
Bird eggs are a valuable indicator of PFAS contamination in exposure assessment of contaminated sites, because the concentrations of PFAS detected in the eggs are a good proxy of maternal exposure and allow the assessment of the potential risk for birds. Results of PFAS levels in eggs of wild birds collected around a fluoropolymer industrial site (Northern Italy) revealed an unprecedented contamination level of PFOA and its recently introduced alternative, C6O4, in three species of wild passerines. Long-term monitoring of PFAS contamination using avian eggs provides crucial information on the temporal trend of contaminated sites, facilitating early identification of emerging PFAS as well as the quantification of their biomagnification across the trophic web.
Application of the original site point method in determining a baseline for two different types of sites in northern China
Authors: Fu Jinxiang , Wei Jianyu , Li Ting , Tang Yulan , Ren Yue , Guo Qixuan 
Published: March 2021

Abstract
Determining an ecological and environment damage baseline is the foundation of natural resource damage assessment. In complex damage assessment, the importance of a baseline is often underestimated or ignored. Existing baseline determination methods are insufficiently accurate and poorly available in practical application, which affect the damage assessment work. Based on the definition of baseline and the shortcomings of existing baseline-determination methods, this paper suggests the original site point (OSP) method as a determination principle. The baseline calculation area can be directly determined according to the site conditions in a sludge storage site with clear pollution distribution, and the OSP method has the advantage of determining the baseline rapidly. For a waste oil sludge storage site with unclear pollution distribution, the baseline calculation area should be determined according to preliminary and detailed sampling data. The calculation results of the two sites indicate that the baseline determined using the OSP method and the reference point (RP) method are similar, and the results of the environmental standard (ES) method are superior to those of the other two methods. The order of accuracy of baseline determination methods is the historical data (HD) method &gt; the OSP method &gt; the RP method &gt; the model calculation (MC) method &gt; the ES method. Through two application cases, this paper discusses the applicability of the OSP method and finally establishes the determination steps of the method. The OSP method has proven effective in determining the baseline, and the fast and accurate baseline determination method is more helpful for damage assessment. Integr Environ Assess Manag 2021;17:1263–1273. © 2021 SETAC
KEY POINTS
We propose a new method, the original site point method, in view of the shortcomings of existing baseline determination methods and definition of baseline. We use different methods to determine the baseline by taking two typical sites in Northern China as examples. We analyze the rapidity and accuracy of different methods to determine the baseline. The determination steps of the original site point method are obtained according to different site conditions, and the application prospect of the method is analyzed.
Preparation of multilayer electrospun nanofibrous scaffolds containing soluble eggshell membrane as potential dermal substitute
Authors: Amirsadeghi Armin , Khorram Mohammad , Hashemi Seyeddeh‐Sara 
Published: March 2021

AbstractElectrospinning of natural and synthetic polymers has shown to be a great candidate for the fabrication of tissue engineering scaffolds due to their similarity to the nanofibrous structure of natural extracellular matrix (ECM). Moreover, the addition of ECM‐like proteins could enhance the biocompatibility of these scaffolds. In this study, soluble eggshell protein (SEP) was first extracted and synthesized from the raw eggshell membrane. The characteristics and biocompatibility of the extracted SEP were evaluated using attenuated total reflectance‐Fourier transform infrared (ATR‐FTIR) analysis and 3‐(4,5‐ dimethylthiazol‐2‐yl‐2,5‐diphenyltetrazolium bromide) (MTT) assay. For scaffolds fabrication, a three‐layer nanofibrous composite structure was produced using the electrospinning technique. The outer layers composed of polyvinyl alcohol, chitosan, and extracted SEP while the middle layer composed of polyethylene oxide, gelatin, and zinc oxide nanoparticles (ZnO‐NPs). For each layer, the electrospinning parameters were adjusted to form bead‐free fibers. To improve fibers' stability against body fluids, the produced fibers were crosslinked using glutaraldehyde vapor. Several techniques such as scanning electron microscopy (SEM), energy dispersive X‐ray, ATR‐FTIR, swelling, tensile test, in vitro biodegradation, and MTT assay were implemented to evaluate the physical, chemical, and biological characterization of the fabricated fibers. The results showed that crosslinked fibers have adequate stability in water, suitable mechanical properties, and promising water uptake capacity. The MTT results also revealed that SEP and ZnO‐NPs could increase scaffolds biocompatibility. Moreover, SEM photographs of cultured fibroblasts cells on the scaffolds showed that cells were well attached on the scaffolds and preserve their natural spindle shapes. Altogether, our findings demonstrated that the produced three‐layer composite scaffolds are potential candidates for skin tissue engineering.