bluuebunny/crossref_metadata_2025 huggingface dataset:
Carpathian Basin climate according to Köppen and a clothing resistance scheme
Authors: Ács Ferenc , Zsákai Annamária , Kristóf Erzsébet , Szabó Amanda Imola , Breuer Hajnalka
Published: April 2020

The Carpathian Basin climate in the time period 1971–2000 is analyzed in terms of the results obtained by the Köppen method and a clothing resistance scheme. A clothing resistance scheme is based on human body energy balance considerations taking into account human interperson variations as simply as possible. Interperson variations are considered by estimating human body somatotypes using the Heath-Carter somatotype classification method. Non-sweating, walking humans in outdoor conditions are treated. Environmental and human data are taken from the CarpatClim dataset and a Hungarian human dataset, respectively. Though the biophysical bases of the methods are completely different, the spatial structure of thermal climates expressed in terms of Köppen climate types and the clothing resistance parameter rcl are basically similar. A clothing resistance scheme creates more information than the Köppen method not only in mountain, plateau areas but also in lowlands. It is shown that more human thermal climate categories can refer to one Köppen climate formula irrespective of which Köppen formulae are considered. The magnitude and area heterogeneity of rcl is strongly sensitive to human somatotype changes. A clothing resistance scheme cannot be used in classroom applications; it needs to be drastically simplified while maintaining its sensitivity to somatotype changes in order to be competitive with the Köppen method.
Brittle anisotropic fracture propagation in quartz sandstone: insights from phase-field simulations
Authors: Prajapati Nishant , Herrmann Christoph , Späth Michael , Schneider Daniel , Selzer Michael , Nestler Britta
Published: April 2020

We developed a generalized multiphase-field modeling framework for addressing the problem of brittle fracture propagation in quartz sandstones at microscopic length scale. Within this numerical approach, the grain boundaries and crack surfaces are modeled as diffuse interfaces. The two novel aspects of the model are the formulations of (I) anisotropic crack resistance in order to account for preferential cleavage planes within each randomly oriented quartz grain and (II) reduced interfacial crack resistance for incorporating lower fracture toughness along the grain boundaries that might result in intergranular crack propagation. The presented model is capable of simulating the competition between inter- and transgranular modes of fracturing based on the nature of grain boundaries, while exhibiting preferred fracturing directions within each grain. In the full parameter space, the model can serve as a powerful tool to investigate the complicated fracturing processes in heterogeneous polycrystalline rocks comprising of grains of distinct elastic properties, cleavage planes, and grain boundary attributes. We demonstrate the performance of the model through the representative numerical examples.
Atomism and Fundamentality
Authors: Schnieder Benjamin
Published: April 2020

The paper focusses on two claims about metaphysical structure: Atomism and Fundamentalism. The first of these claims says that there are mereological atoms, i.e. minimal elements in the mereological structure of reality. The second says that there are fundamental truths, i.e. minimal elements in the grounding structure of reality. A philosopher who defended both of these claims was Bernard Bolzano; the present paper is an exploration of his views on the matter.
The Power of Shared Embodiment: Renegotiating Non/belonging and In/exclusion in an Ephemeral Community of Care
Authors: von Poser Anita , Willamowski Edda
Published: April 2020

In this article, we explore the power of shared embodiment for the constitution of an affective community. More specifically, we examine how people afflicted by long-term, arduous experiences of war, migration, and discrimination sensually articulate and, at least temporarily, renegotiate feelings of non/belonging, care, and in/exclusion. Methodologically, we draw on emplaced ethnography and systematic phenomenological go-alongs with a group of elderly migrants, born and raised in different parts of Vietnam, who had arrived in Germany within different legal–political frameworks and who, during the time of our psychological–anthropological research, frequented the same psychotherapeutic clinic. We apply the notion of “affective communities” (Zink in Affective Societies: Key Concepts. Routledge, New York, 2019) to grasp how the group experienced a sensual place of mutual belonging outside the clinic when moving through different public spaces in Berlin as part of their therapy. Particular attention is paid to the participants’ embodied and emplaced memories that were reactivated during these excursions. Shared sensations and spatiality, we argue, made them feel they belonged to an ephemeral community of care that was otherwise hardly imaginable due to their distinct individual biographies, contrasting political attitudes, and ties to different social collectives. In analyzing this affective community, we highlight how significant spatio-sensorial modes of temporal solidification can be in eliciting embodied knowledge that positively contributes to therapeutic processes.
Journal research data sharing policies: a study of highly-cited journals in neuroscience, physics, and operations research
Authors: Rousi Antti M. , Laakso Mikael
Published: April 2020

The practices for if and how scholarly journals instruct research data for published research to be shared is an area where a lot of changes have been happening as science policy moves towards facilitating open science, and subject-specific repositories and practices are established. This study provides an analysis of the research data sharing policies of highly-cited journals in the fields of neuroscience, physics, and operations research as of May 2019. For these 120 journals, 40 journals per subject category, a unified policy coding framework was developed to capture the most central elements of each policy, i.e. what, when, and where research data is instructed to be shared. The results affirm that considerable differences between research fields remain when it comes to policy existence, strength, and specificity. The findings revealed that one of the most important factors influencing the dimensions of what, where and when of research data policies was whether the journal’s scope included specific data types related to life sciences which have established methods of sharing through community-endorsed public repositories. The findings surface the future research potential of approaching policy analysis on the publisher-level as well as on the journal-level. The collected data and coding framework is provided as open data to facilitate future research and journal policy monitoring.
Cross-disciplinary collaboration versus coexistence in LIS serials: analysis of authorship affiliations in four European countries
Authors: Urbano Cristóbal , Ardanuy Jordi
Published: April 2020

The interdisciplinary nature of library and information science (LIS) research has been highlighted for some time now. The term “interdisciplinary” is used primarily in the LIS literature as a general concept with different meanings that refer either to the coexistence of researchers from different scientific fields or to cross-disciplinary collaboration expressed in the form of coauthorship. This study analyses the disciplinary profile of LIS researchers with a view to ascertaining the actual level of cross-disciplinary collaboration and identifying all fields involved. Because of the complexity of identifying accurate affiliations at knowledge area level, the study was limited to authors from France, Germany, Spain and the UK. This analysis of authorship affiliation was performed based on research published in LIS serial titles indexed in Scopus during the 2010–2017 period. A rigorous and laborious process of identifying author affiliations was carried out. This involved checking the authorship of each paper and complementing this with information from websites, scientific social networks and other research endeavours whenever ambiguous situations arose. We observed that LIS departments produce barely a third of the research published in serial titles in the LIS subject category. Cross-disciplinary collaboration among all of the scientific fields involved is low, and even lower in LIS than in other fields. The low level of cross-disciplinary collaboration in LIS contradicts the interdisciplinary nature of LIS highlighted in the literature.
Organizational agility: ill-defined and somewhat confusing? A systematic literature review and conceptualization
Authors: Walter Anna-Theresa
Published: April 2020

Superior business performance is a central objective of any firm in an unpredictable environment. Organizational agility (OA) constitutes one option for prospering in this environment. Although research confirms a positive effect of OA on business performance, studies show conceptual imprecision. I systematically review and compile previous findings and provide a coherent view of OA. A search in three databases yielded a final sample of 75 articles. From a qualitative analysis, I identify four agility categories: agility drivers, agility enablers, agility capabilities, and agility dimensions. Based on findings from each category, I develop a conceptual map of OA that (i) connects the agility categories and clarifies how they work, and (ii) proposes a framework for the tasks and responsibilities of management within an agile organization. As part of the conceptualization, I also consider the business environment and the impact of an increased OA level. Viewed from a dynamic capability perspective, changing internal and external agility drivers necessitate the development of agility capabilities. These are realized by a specific set of interdependent enablers. Within this concept of an agile organization, management assumes various responsibilities, in particular, engaging in monitoring and decision-making functions. Conceptual clarity of OA at the organizational level facilitates a systematic development of agility research and provides guidance for practitioners. This article contributes to agility research by integrating insights from various research streams on OA. By highlighting the close ties to strategic management and the derivation of a model to agile management, this research also contributes to strategic management research.
Phylogeny and cultivation of the holocarpic oomycete Diatomophthora perforans comb. nov., an endoparasitoid of marine diatoms
Authors: Buaya Anthony T. , Ploch Sebastian , Kraberg Alexandra , Thines Marco
Published: April 2020

Oomycetes infecting diatoms are biotrophic parasitoids and live in both marine and freshwater environments. They are ubiquitous, but the taxonomic affinity of many species remains unclear and the majority of them have not been studied for their molecular phylogeny. Only recently, the phylogenetic and taxonomic placement of some diatom-infecting, early-diverging oomycetes was resolved, including the genera Ectrogella, Miracula, Olpidiopsis, and Pontisma. A group of holocarpic diatom parasitoids with zoospores swarming within the sporangium before release were found to be unrelated to the known genera with diatom-infecting species, and were re-classified to a new genus, Diatomophthora. However, about a dozen species of holocarpic diatom parasitoids with unclear affinity remained unsequenced, which includes a commonly occurring species so far identified as Ectrogella perforans. However, this assignment to Ectrogella is doubtful, as the species was not reported to feature a clear-cut diplanetism, a hallmark of Ectrogella s. str. and the whole class Saprolegniomycetes. It was the aim of the current study to clarify the phylogenetic affinities of the species and if the rather broad host range reported is correct or a reflection of cryptic species. By targeted screening, the parasitoid was rediscovered from Helgoland Roads, North Sea and Oslo Fjord, Southern Norway and investigated for its phylogenetic placement using small ribosomal subunit (18S) sequences. Stages of its life cycle on different marine diatoms were described and its phylogenetic placement in the genus Diatomophthora revealed. A stable host-parasite axenic culture from single spore strains of the parasitoid were established on several strains of Pleurosigma intermedium and Coscinodiscus concinnus. These have been continuously cultivated along with their hosts for more than 2 years, and cultural characteristics are reported. Cross-infection trials revealed the transferability of the strains between hosts under laboratory conditions, despite some genetic distance between the pathogen strains. Thus, we hypothesise that D. perforans might be in the process of active radiation to new host species.
Analysis of the species spectrum of the Diaporthe/Phomopsis complex in European soybean seeds
Authors: Hosseini Behnoush , El-Hasan Abbas , Link Tobias , Voegele Ralf Thomas
Published: April 2020

Phytopathogenic fungal species of theDiaporthe/Phomopsiscomplex (DPC) are associated with three highly destructive diseases on soybean: seed decay, pod and stem blight, and stem canker. They are responsible for poor seed quality and significant yield reduction in most soybean-producing areas. Precise identification and classification of DPC species are important in understanding the epidemiology of disease and to develop effective control measures. Although cultural and morphological characteristics of DPC-associated pathogens have been described, establishing a more accurate taxonomic framework seems necessary for a revaluation of the taxonomy and phylogeny of DPC species. In this study, we focused on morphological and molecular analyses of species from DPC-damaged European soybean seeds obtained from several locations throughout Europe. Colony characteristics, conidia dimensions, existence of α- and β-conidia, and formation of perithecia were evaluated in order to assign the isolates to a species morphologically. Phylogenetic relationships were determined based on sequences from beta-tubulin (TUB), translation elongation factor 1-alpha (TEF1), and nuclear ribosomal DNA internal transcribed spacers (ITS). All isolates were tested for pathogenicity on soybean with positive results. In this study, we present updated taxonomic data by combining morphological observations and molecular tools which placed 32Diaportheisolates into four DPC species:D. longicolla,D. caulivora,D. eres, andD. novem, which are well-known soybean pathogens.
Weight loss since early adulthood, later life risk of fracture hospitalizations, and bone mineral density: a prospective cohort study of 0.5 million Chinese adults
Authors:   on behalf of the China Kadoorie Biobank Collaborative Group, Shen Zewei , Yu Canqing , Guo Yu , Bian Zheng , Wei Yuxia , Du Huaidong , Yang Ling , Chen Yiping , Gao Yulian , Zhang Xukui , Chen Junshi , Chen Zhengming , Lv Jun , Li Liming
Published: April 2020

Summary

In a Chinese population from both urban and rural areas, weight loss of ≥ 5 kg from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.

Introduction

This study investigates the association of the long-term weight loss from young adulthood through the middle ages with the subsequent 10-year risk of hospitalized fracture and calcaneus bone mineral density (BMD).

Methods

China Kadoorie Biobank (CKB) was established during 2004–2008 in ten areas across China. Weight at age 25 years was self-reported at baseline, and weight at baseline and resurvey was measured by the calibrated equipment. Outcomes were hospitalized fracture during follow-up and calcaneus BMD measured at resurvey. Analysis for fracture risk included 411,812 participants who were free of fracture in the last 5 years before baseline, cancer, or stroke at any time before baseline. Analysis for BMD included 21,453 participants who participated in the resurvey of 2013–2014 with the same exclusion criteria as above.

Results

The mean age was 50.8 at baseline and 58.4 at resurvey. Median weight change from age 25 to baseline was 4.4 kg, with 20.7% losing weight and 58.5% gaining weight. During a median follow-up of 10.1 years, we documented 13,065 cases of first diagnosed fracture hospitalizations, including 1222 hip fracture. Compared with participants whose weight was stable (± 2.4 kg), the adjusted hazard ratios (95% CIs) for those with weight loss of ≥ 5.0 kg from age 25 to baseline was 1.39 (1.17 to 1.66) for hip fracture. Weight loss was not associated with fracture risk at other sites. Those with weight loss from age 25 to resurvey had the lowest BMD measures, with β (95% CIs) of − 4.52 (− 5.08 to − 3.96) for broadband ultrasound attenuation (BUA), − 4.83 (− 6.98, − 2.67) for speed of sound (SOS), and − 4.36 (− 5.22, − 3.49) for stiffness index (SI).

Conclusions

Weight loss from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.
Investigation of Surface Segregation in Fe-Cr-Si Alloys by XPS
Authors: Idczak K. , Idczak R.
Published: April 2020

The surface segregation of Fe-Cr-Si alloys was studied using the X-ray photoelectron spectroscopy (XPS). The experiment was performed in two stages, for the as-prepared samples and after oxidation process. Analysis of measured XPS spectra allowed one to characterize the changes in the surface chemical composition during the oxidation and thermal treatment procedures. According to the obtained results, it could be stated that the enhanced anti-corrosion properties of the Fe-Cr-Si alloys which contain more than 10 at. pct of Cr and 5 at. pct of Si in the bulk are mainly connected with the strong surface segregation process of both solutes. In the case of alloys which contain less solutes (Fe0.94Cr0.03Si0.03, Fe0.90Cr0.05Si0.05), the behavior of Cr atoms is different during the oxidation process. Chromium does not segregate to the surface, instead it diffuses into deeper parts of the material leaving the surface covered only by silicon and iron oxides. This effect is responsible for much worse corrosion resistance of the Fe0.94Cr0.03Si0.03 and Fe0.90Cr0.05Si0.05 alloys.
I care what you think: social image concerns and the strategic revelation of past pro-social behavior
Authors: von Siemens Ferdinand A.
Published: April 2020

This article studies whether people want to control what information on their own past pro-social behavior is revealed to others. Participants are assigned a color that depends on their past pro-social behavior. They can spend money to manipulate the probability with which their color is revealed to another participant. The data show that participants are more likely to reveal colors with more favorable informational content. This pattern is not found in a control treatment in which colors are randomly assigned, thus revealing nothing about past pro-social behavior. Regression analysis confirms these findings, also when controlling for past pro-social behavior. These results complement the existing empirical evidence, confirming that people strategically and, therefore, consciously manipulate their social image.
Ultimate shear response of ultra-high-performance steel fibre-reinforced concrete elements
Authors: Ţibea C. , Bompa Dan V.
Published: April 2020

This paper examines the experimental performance of ultra-high-performance steel fibre-reinforced concrete (UHPSFRC) beams subjected to loads at relatively low shear span-to-depth ratios. The results and observations from six tests provide a detailed insight into the ultimate response including shear strength and failure mode of structural elements incorporating various fibre contents. The test results showed that a higher fibre content results in an increase in ultimate capacity and some enhancement in terms of ductility. Detailed nonlinear numerical validations and sensitivity studies were also undertaken in order to obtain further insights into the response of UHPSFRC beams, with particular focus on the influence of the shear span-to-depth ratio, fibre content and flexural reinforcement ratio. The parametric investigations showed that a reduction in shear span-to-depth ratio results in an increase in the member capacity, whilst a reduction in the flexural reinforcement ratio produces a lower ultimate capacity and a relatively more flexible response. The test results combined with those from numerical simulations enabled the development of a series of design expressions to estimate the shear strength of such members. Validations were performed against the results in this paper, as well as against a collated database from previous experimental studies.
Twenty‐First Century Drought Projections in the CMIP6 Forcing Scenarios
Authors: Cook B. I. , Mankin J. S. , Marvel K. , Williams A. P. , Smerdon J. E. , Anchukaitis K. J.
Published: April 2020

There is strong evidence that climate change will increase drought risk and severity, but these conclusions depend on the regions, seasons, and drought metrics being considered. We analyze changes in drought across the hydrologic cycle (precipitation, soil moisture, and runoff) in projections from Phase Six of the Coupled Model Intercomparison Project (CMIP6). The multimodel ensemble shows robust drying in the mean state across many regions and metrics by the end of the 21st century, even following the more aggressive mitigation pathways (SSP1‐2.6 and SSP2‐4.5). Regional hotspots with strong drying include western North America, Central America, Europe and the Mediterranean, the Amazon, southern Africa, China, Southeast Asia, and Australia. Compared to SSP3‐7.0 and SSP5‐8.5, however, the severity of drying in the lower warming scenarios is substantially reduced and further precipitation declines in many regions are avoided. Along with drying in the mean state, the risk of the historically most extreme drought events also increases with warming, by 200–300% in some regions. Soil moisture and runoff drying in CMIP6 is more robust, spatially extensive, and severe than precipitation, indicating an important role for other temperature‐sensitive drought processes, including evapotranspiration and snow. Given the similarity in drought responses between CMIP5 and CMIP6, we speculate that both generations of models are subject to similar uncertainties, including vegetation processes, model representations of precipitation, and the degree to which model responses to warming are consistent with observations. These topics should be further explored to evaluate whether CMIP6 models offer reasons to have increased confidence in drought projections.
Manufacture and characterization of graphene membranes with suspended silicon proof masses for MEMS and NEMS applications
Authors: Fan Xuge , Smith Anderson D. , Forsberg Fredrik , Wagner Stefan , Schröder Stephan , Akbari Sayedeh Shirin Afyouni , Fischer Andreas C. , Villanueva Luis Guillermo , Östling Mikael , Lemme Max C. , Niklaus Frank
Published: April 2020

Graphene’s unparalleled strength, chemical stability, ultimate surface-to-volume ratio and excellent electronic properties make it an ideal candidate as a material for membranes in micro- and nanoelectromechanical systems (MEMS and NEMS). However, the integration of graphene into MEMS or NEMS devices and suspended structures such as proof masses on graphene membranes raises several technological challenges, including collapse and rupture of the graphene. We have developed a robust route for realizing membranes made of double-layer CVD graphene and suspending large silicon proof masses on membranes with high yields. We have demonstrated the manufacture of square graphene membranes with side lengths from 7 µm to 110 µm, and suspended proof masses consisting of solid silicon cubes that are from 5 µm × 5 µm × 16.4 µm to 100 µm × 100 µm × 16.4 µm in size. Our approach is compatible with wafer-scale MEMS and semiconductor manufacturing technologies, and the manufacturing yields of the graphene membranes with suspended proof masses were >90%, with >70% of the graphene membranes having >90% graphene area without visible defects. The measured resonance frequencies of the realized structures ranged from tens to hundreds of kHz, with quality factors ranging from 63 to 148. The graphene membranes with suspended proof masses were extremely robust, and were able to withstand indentation forces from an atomic force microscope (AFM) tip of up to ~7000 nN. The proposed approach for the reliable and large-scale manufacture of graphene membranes with suspended proof masses will enable the development and study of innovative NEMS devices with new functionalities and improved performances.
Ferroelectric polarization and thin-layered structure synergistically promoting CO2 photoreduction of Bi2MoO6
Authors: Li Shuguan , Bai Liqi , Ji Ning , Yu Shixin , Lin Sen , Tian Na , Huang Hongwei
Published: April 2020

Ferroelectric field and thin-layered structure greatly accelerate charge transfer from the bulk to the surface and enrich catalytic sites, synergistically boosting CO2 photoreduction activity of Bi2MoO6.
Anisotropic plasticity of nanocrystalline Ti: A molecular dynamics simulation*
Authors: An Minrong , Su Mengjia , Deng Qiong , Song Haiyang , Wang Chen , Shang Yu
Published: April 2020

Using molecular dynamics simulations, the plastic deformation behavior of nanocrytalline Ti has been investigated under tension and compression normal to the {0001},

{

1
¯

010
}

, and

{

1
¯

2

1
¯

0

}

planes. The results indicate that the plastic deformation strongly depends on crystal orientation and loading directions. Under tension normal to basal plane, the deformation mechanism is mainly the grain reorientation and the subsequent deformation twinning. Under compression, the transformation of hexagonal-close packed (HCP)-Ti to face-centered cubic (FCC)-Ti dominates the deformation. When loading is normal to the prismatic planes (both

{

1
¯

010
}

and

{

1
¯

2

1
¯

0
}

), the deformation mechanism is primarily the phase transformation among HCP, body-centered cubic (BCC), and FCC structures, regardless of loading mode. The orientation relations (OR) of {0001}HCP║{111}FCC and

〈

1
¯

210
〉

HCP

|
|

〈
110
〉

FCC

, and

{
10

1
¯

0
}

HCP

|
|

{
1

1
¯

0
}

FCC

and

〈
0001
〉

HCP

|
|

〈
010
〉

FCC

between the HCP and FCC phases have been observed in the present work. For the transformation of HCP → BCC → HCP, the OR is

0001

α
1

|
|

{
110
}

β

|
|

{
10

1
¯

0
}

α
2

(HCP phase before the critical strain is defined as α
1-Ti, BCC phase is defined as β-Ti, and the HCP phase after the critical strain is defined as α
2-Ti). Energy evolution during the various loading processes further shows the plastic anisotropy of nanocrystalline Ti is determined by the stacking order of the atoms. The results in the present work will promote the in-depth study of the plastic deformation mechanism of HCP materials.
Repolarization instability and arrhythmia by IKr block in single human-induced pluripotent stem cell-derived cardiomyocytes and 2D monolayers
Authors: Altrocchi Cristina , de Korte Tessa , Bernardi Joyce , Spätjens Roel L H M G , Braam Stefan R , Heijman Jordi , Zaza Antonio , Volders Paul G A
Published: April 2020

Aims

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have proven valuable for studies in drug discovery and safety, although limitations regarding their structural and electrophysiological characteristics persist. In this study, we investigated the electrophysiological properties of Pluricyte® CMs, a commercially available hiPSC-CMs line with a ventricular phenotype, and assessed arrhythmia incidence by IKr block at the single-cell and 2D monolayer level.

Methods and results

Action potentials were measured at different pacing frequencies, using dynamic clamp. Through voltage-clamp experiments, we determined the properties of INa, IKr, and ICaL. Intracellular Ca2+ measurements included Ca2+-transients at baseline and during caffeine perfusion. Effects of IKr block were assessed in single hiPSC-CMs and 2D monolayers (multi-electrode arrays). Action-potential duration (APD) and its rate dependence in Pluricyte® CMs were comparable to those reported for native human CMs. INa, IKr, and ICaL revealed amplitudes, kinetics, and voltage dependence of activation/inactivation similar to other hiPSC-CM lines and, to some extent, to native CMs. Near-physiological Ca2+-induced Ca2+ release, response to caffeine and excitation–contraction coupling gain characterized the cellular Ca2+-handling. Dofetilide prolonged the APD and field-potential duration, and induced early afterdepolarizations. Beat-to-beat variability of repolarization duration increased significantly before the first arrhythmic events in single Pluricyte® CMs and 2D monolayers, and predicted pending arrhythmias better than action-potential prolongation.

Conclusion

Taking their ion-current characteristics and Ca2+ handling into account, Pluricyte® CMs are suitable for in vitro studies on action potentials and field potentials. Beat-to-beat variability of repolarization duration proved useful to evaluate the dynamics of repolarization instability and demonstrated its significance as proarrhythmic marker in hiPSC-CMs during IKr block.
In patients undergoing dialysis who require a valve replacement is a bioprosthetic valve superior to a mechanical prosthesis in terms of long-term survival and morbidity?
Authors: Fong Laura S , Ang Zhen Hao , Wolfenden Hugh , Akhunji Zakir
Published: April 2020

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘In [dialysis patients undergoing a valve replacement] is [a bioprosthetic valve superior to a mechanical prosthesis] for [long-term survival and morbidity]’. Altogether more than 501 papers were found using the reported search, of which five represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There was limited high-quality evidence with all studies being retrospective. One meta-analysis and four cohort studies provided the evidence that there was no significant difference in long-term survival based on prosthesis type. However, the majority of studies demonstrated a significantly higher rate of valve-related complications including bleeding and thromboembolism, and readmission to hospital in the mechanical valve prosthesis group, likely related to the requirement for long-term anticoagulation. We conclude that overall long-term survival in dialysis-dependent patients is poor. While prosthesis type does not play a significant contributing role to long-term survival, bioprosthetic valves were associated with significantly fewer valve-related complications. Based on the available evidence, a bioprosthetic valve may be more suitable in this high-risk group of patients as it may avoid the complications associated with long-term anticoagulation without any reduction in long-term survival.
Application of Design Space, Uncertainty, and Risk Profile Strategies to the Development and Validation of UPLC Method for the Characterization of Four Authorized Phosphodiesterase Type 5 Inhibitors to Combat Counterfeit Drugs
Authors: Benchekroun Yassine Hameda , El Karbane Miloud , Ihssane Bouchaib , Haidara Hasnaa , Azougagh Mohamed , Saffaj Taoufiq
Published: April 2020

Background

Counterfeit medicines are an increasing scourge that are difficult to identify and they have become industrialized and widespread through highly organized illegal channels.

Objective

This research aims to develop a robust method to determine four phosphodiesterase type-5 inhibitors in counterfeit drugs based on ultra-performance liquid chromatography.

Method

Experimental design methodology (DOE) and design space (DS) recommended by ICH Q8 were used side-by-side in the development phase to define the optimal parameters as well as the robustness of the chromatographic method. Moreover, both the uncertainty and risk profile derived from the β-content and γ-confidence tolerance interval were investigated during the validation phase to examine the performance of this method.

Results

Successful chromatographic results, in a high resolution between the four active ingredients and an optimal analysis time of less than 1.6 min, were achieved at the end of the optimization phase. In addition, validation results show a low risk of future measurements outside acceptance limits set at 5%.

Conclusions

Our procedure was successfully applied in the routine phase to identify 23 illicit formulations of an erectile dysfunction drug.

Highlights

An efficient method for the characterization of 4 authorized phosphodiesterase in less than 1.6 min was established. A DS approach was applied to test the performance of this analytical method during analytical development. A risk profile was then carried out to approve the validity of the analytical method through the uncertainty profile approach.
Three cases of follicular pancreatitis: association between radiological findings and pathological features
Authors: Kondo Ryota , Wada Ryuichi , Matsushita Akira , Nakamura Yoshiharu , Yoshioka Masato , Shimizu Tetsuya , Kanda Tomohiro , Kaneya Yohei , Aoki Yuto , Shimizu Michio , Yoshida Hiroshi , Naito Zenya
Published: April 2020

Follicular pancreatitis (FP) is characterized by nodular mass composed of lymphoid hyperplasia and fibrosis. We here present radiological and pathological features of three cases of FP. The three patients were middle- or old-aged men, and nodular mass was pointed out at health examination. Computed tomography failed to demonstrate a mass. Magnetic resonance imaging demonstrated a mass in each case. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) demonstrated two nodular masses with high standardized uptake value (SUV) in two cases and single mass in one case. The pathological examination disclosed two lesions with fibrosis and hyperplastic lymphoid follicles in two cases and one lesion in one case. Masses with high SUV appeared to correspond with the lesions of FP. Compared with the features of FDG-PET images of pancreatic ductal carcinoma, multiple lesions with high SUV favor a diagnosis of FP rather than pancreatic cancer. FDG-PET is useful for the diagnosis of FP.
Osteosarcoma of the frontal bone: a study of a rare case in a 17-year-old female
Authors: Mohanna Farah , Slaibi Anas , Al-Shehabi Zuheir , Mahfoud Moufid
Published: April 2020

Head and neck osteosarcomas are infrequent and usually present in the third–fourth decades of life. However, they are extremely rare in the pediatric population. Primary involvement of the cranial vault, excluding the mandible and maxilla, is an exceedingly rare phenomenon; thus, the number of clinical studies published in the literature is limited. Because of the anatomy of the head, complete resection may be difficult to achieve. Furthermore, an aggressive surgical approach can cause a significant functional impairment or cosmetic defect. We report the case of a 17-year-old patient with an aggressive recurrence of multiple tumors in the left side of the skull accompanied with a severe headache and complete left-sided vision loss with no metastases at presentation. The recurrence of the tumor was preceded by pregnancy and delivery, which raised the question of whether pregnancy hormones were a provoking factor in the recurrence of the tumor or not.
Treatment with 2-methoxyestradiol increases endothelial nitric oxide synthase activity via scavenger receptor class BI in human umbilical vein endothelial cells
Authors: Dong Tao , Sato Seisuke , Lyu Jingya , Imachi Hitomi , Kobayashi Toshihiro , Fukunaga Kensaku , Saheki Takanobu , Iwama Hisakazu , Zhang Guoxing , Murao Koji
Published: April 2020

Concentrations of 2-methoxyestradiol (2ME2), a principal metabolite of estradiol, are significantly lower in women with severe preeclampsia. Nitric oxide (NO) released by endothelial nitric oxide synthase (eNOS) plays an important role in regulating cardiovascular homeostasis. Importantly, high-density lipoprotein (HDL) stimulates eNOS activity via endothelial human scavenger receptor class B type I (hSR-BI/CLA-1). Here, we aimed to determine the effect of 2ME2 on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). hSR-BI/CLA-1 expression was measured by real-time PCR, western blotting and reporter gene assays; eNOS activity was assessed by the measurement of eNOS phosphorylation. Both the mRNA and protein concentrations of hSR-BI/CLA-1 were significantly increased by 2ME2 in HUVECs. 2ME2 also dose-dependently increased the transcriptional activity of the hSR-BI/CLA-1 promoter. The effect of 2ME2 treatment on the promoter activity of hSR-BI/CLA-1 was abrogated by treatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, as was the increase in HDL-induced eNOS activation. Notably, constitutively active Akt increased the activity of the hSR-BI/CLA-1 promoter, whereas dominant-negative Akt abolished the effect of 2ME2 treatment on hSR-BI/CLA-1 promoter activity. The nuclear Sp1 protein concentration was significantly increased by exposure to 2ME2 and Sp1 overexpression increased the promoter activity of the hSR-BI/CLA gene. Furthermore, knockdown of Sp1 inhibited the effect of 2ME2 treatment on hSR-BI/CLA-1 protein expression. These results indicate that 2ME2 treatment increases HDL-dependent eNOS phosphorylation by upregulating endothelial hSR-BI/CLA-1 expression, suggesting that 2ME2 has a potential therapeutic value in the treatment of preeclampsia.
Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff
Authors: Lunell Erik , Fagerström Karl , Hughes John , Pendrill Robert
Published: April 2020

Introduction

The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation. Comparison is made to Swedish General snus and American Longhorn moist snuff and from literature 4 mg Nicorette gum and mean of 13 brands of e-cigarettes.

Aims and Methods

A single-dose randomized crossover design was used. In vivo extraction and PK parameters were determined.

Results

Part 1. The AUCinf of ZYN 3 mg was 27% smaller than that of 8 mg General and the AUCinf of ZYN 6 mg was 34% larger than that of 8 mg General. Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg General (32%).

Results

Part 2. Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN 8 mg and Longhorn Natural 18 mg moist snuff. The extracted amount of nicotine from ZYN 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg), but smaller than the extracted amount of nicotine from General 2 × 8 mg snus pouches (5.0 mg). The extracted fraction of nicotine for ZYN 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2 × 8 mg snus pouches (33%).

Conclusions

The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects.
Do Proxies for Informed Trading Measure Informed Trading? Evidence from Illegal Insider Trades
Authors: Ahern Kenneth R
Published: April 2020

This paper exploits hand-collected data on illegal insider trades to provide new evidence on the ability of a host of standard measures of illiquidity to detect informed trading. Controlling for unobserved cross-sectional and time-series variation, sampling bias, and strategic timing of insider trades, I find that when information is short-lived, only absolute order imbalance and effective spread are statistically and economically robust predictors of illegal insider trading. However, when information is long-lasting, insiders strategically time their trades to avoid illiquidity, and none of the standard measures considered are reliable predictors, including bid-ask spreads, order imbalance, Kyle’s λ, and Amihud illiquidity. (JEL D53D82G12G14K42)

Received: March 14, 2019; Editorial decision: February 18, 2020 by Editor Thierry Foucault. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Tn‐MUC1 Glycopeptides as Ligands: Detection of the Effect of Peptide Sequence, Site of Glycosylation, and Glycan Density on MGL Binding in H2O/D2O
Authors: Beckwith Donella M. , FitzGerald Forrest G. , Rodriguez Benavente Maria C. , Gabius Hans-Joachim , Cudic Mare
Published: April 2020

Objective

To apply synthetic Tn‐MUC1 glycopeptides for characterizing contributions of their structural parameters to affinity for the endogenous lectin MGL.

O‐Glycosylation of mucins is assumed to serve as a versatile signal via recognition by tissue lectins. Human macrophage galactose‐type lectin (hMGL, CD301 or CLEC10A), a C‐type lectin expressed by dendritic cells and macrophages, is a receptor of Ser/Thr‐linked a‐GalNAc (T antigen nouvelle: Tn, CD175) and its a2,6‐sialylated derivative (sTn). The relative contributions of the glycan and the peptide backbone to affinity are not well understood. In this study, the chemical synthesis of the tandem‐repeat sequence of mucin MUC1, i.e. HGVTSAPDTRPAPGSTAPPA, and site‐specific Thr‐based glycopeptides facilitated calorimetric study of lectin binding. First, CD spectroscopy revealed stabilization of the polyproline II (PPII) structure with increasing density of the glycan epitope. Binding is an enthalpy‐driven process, affinity enhancement occurred for glycopeptides relative to free GalNAc. Size of enthalpic gains were associated to valency, the monoglycosylated peptides had ΔH of about −10 kcal mol−1 and the triply glycosylated ligands had ΔH −30.4 kcal mol− 1. Increases in affinity (Kd) by one order of magnitude were determined for mono‐ (5.6 μM) to triglycosylated (588 nM) MUC1 peptides. Analysis of the kinetic profiles of binding of the MUC1 glycopeptides to hMGL appears to support involvement of a “bind and jump” mechanism. The lifetimes (lower koff values) increase as the density of GalNAc increases along the MUC1 20‐mer sequence. In order to assess a role of solvent reorganization to binding to a C‐type lectin, experiments were performed in parallel in D2O. Unlike GalNAc binding, H/D exchange resulted in more favorable enthalpic contributions, for the monoglycosylated analogs accompanied by compensating higher entropic penalty. Peptide backbone presence makes a difference, as glycan density was revealed to do. In summary, our results suggest that contact building of MUC1 glycopeptides with hMGL critically depends on structural characteristics in the vicinity of the glycan and its density.

Support or Funding Information

This work was supported by the National Institutes of Health Grant CA242351 M. C.
Hyperbaric fluorescence microscopy: imaging reactive O2 and N2 species in rat brain slices during exposure to normobaric and hyperbaric hyperoxia
Authors: Hinojo Christopher M. , Stavitzski Nicole , Dean Jay B.
Published: April 2020

Hyperbaric oxygen (HBO) is breathed in hyperbaric and undersea medicine. Protracted exposure to HBO, however, is toxic to the mammalian brain and results in central nervous system‐O2 toxicity (CNS‐OT; i.e., seizures). Thus, the use of HBO in military diving operations is limited by maximum time at depth; e.g., 10 min at 50 fsw on 100% O2. Our lab is interested in the mechanisms and mitigation of CNS‐OT for safer, longer dives. The present study reports our methods for measuring the rate of reactive species production in real time using fluorescence microscopy as a function of PO2 at normobaric and hyperbaric pressures. Our recent improvements in hyperbaric fluorescence microscopy include the following: 1) quantifying the effect of pressure on focal length of the microscope—during compression the focal length increases and during decompression the focal length shortens (“baro‐blurring”); 2) visual monitoring of the brain slice bath inside a sealed, dark pressure chamber without exciting fluorescent dyes (DHE ex/em: 525/590nm; DAF‐FM ex/em: 495/515nm) by continuous IR illumination (770nm) of the microscope objective and slice bath while imaging with a CCD camera (heat filter removed); 3) an internal pump for recirculating medium containing fluorescent dye; 4) addition of a Lumencor SPECTRA Light Engine; and 5) upgrades in remote controls for x‐y translation of the slice chamber. Experiments using hyperbaric fluorescence microscopy show that while normobaric hyperoxia (NBO; 0.4 – 0.95 ATA O2) and hyperbaric oxygen (HBO; 0.4 – 1.95 ATA O2) increase the rate of superoxide production (2.5uM DHE), not all cells produce superoxide at the same rate. Most DHE‐loaded cSC neurons exhibited varying fluorescence intensities initially in 0.4 ATA O2 that we labeled “Dim cells” (fluorescence intensity units (FIU) < average FIU at t=0) and “Bright cells” (FIU ≥ average FIU at t=0). O2‐ sensitive cells significantly increased superoxide production (by at least 25% ΔFIU/min) in both Dim and Bright cells after exposure to 0.95/1.95 ATA O2. Certain Bright and Dim cells, however, were O2‐insensitive cells (< 25% ΔFIU/min). After measuring the effects of NBO and HBO on superoxide production, we tested the effects of a 1:1 mixture of ketone salts (KS) on ΔFIU/min during increased background oxygenation. The rationale for this is that ketone metabolic therapy delays onset of CNS‐OT seizures. 5mM KS significantly decreased the production superoxide in O2‐sensitive Bright cells at 0.95/1.95 ATA O2. Our findings suggest that cells in the cSC are heterogeneous in their capacity for superoxide production and neuroprotection by ketone bodies during exposure to hyperoxia. Studies are underway to determine the effects of NBO & HBO ±KS on nitric oxide production in cSC cells using 1 uM DAF‐FM.

Support or Funding Information

Research funded by ONR Undersea Medicine Program