bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab
Authors: Hummel Matthew , Bosje Tjerk , Shaw Andrew , Liu Mark Shiyao , Barve Abhijit , Kothekar Mudgal , Socinski Mark A. , Waller Cornelius F. 
Published: April 2021

Abstract
Purpose
Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar.

Methods
The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration–time curve from 0 extrapolated to infinity (AUC0–∞). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability.

Results
Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC0–∞ were close to 1, and 90% CIs were within the equivalence range (0.80–1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC0–t], peak serum concentration [Cmax], time to Cmax, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC0–t and Cmax within 80–125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab.

Conclusion
MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).
Three species of Echinococcus granulosus sensu lato infect camels on the Arabian Peninsula
Authors: Al-Hizab Fahad A. , Mohamed Nouh S. , Wassermann Marion , Hamouda Mahmoud A. , Ibrahim Abdelazim M. , El-Ghareeb Waleed R. , Abdel-Raheem Sherief M. , Romig Thomas , Omer Rihab A. 
Published: April 2021

AbstractWe report on the genetic identity of 36 Echinococcus cysts that were collected during a recent slaughterhouse survey of 810 locally bred camels (dromedaries) in the Eastern Province of the Kingdom of Saudi Arabia. Analysis of a partial nad1 gene sequence showed that the majority (n = 29) belonged to E. granulosus sensu stricto, four to E. canadensis G6/7, and three to E. ortleppi. Eight of the 29 E. granulosus s.s. cysts contained protoscoleces; all other cysts were calcified and non-viable. This is the first report of the presence E. ortleppi from the Arabian Peninsula, a parasite that is typically transmitted via cattle. The results indicate widespread infection of camels with CE in eastern Saudi Arabia and an active role of camels in the lifecycles of at least E. granulosus s.s.. Complete cox1 haplotype analysis of 21 E. granulosus s.s. isolates shows that the majority of variants circulating in eastern Saudi Arabia is distinct from but closely related to haplotypes from neighboring countries in the Middle East, which indicates the presence of this parasite in KSA for a longer period of time. All isolates of E. granulosus s.s. in this study belonged to the G1 cluster, although the G3 genotype has previously also been reported from the Middle East.
Proteolysis and inflammation of the kidney glomerulus
Authors: Demir Fatih , Troldborg Anne , Thiel Steffen , Lassé Moritz , Huesgen Pitter F. , Tomas Nicola M. , Wiech Thorsten , Rinschen Markus M. 
Published: April 2021

AbstractProteases play a central role in regulating renal pathophysiology and are increasingly evaluated as actionable drug targets. Here, we review the role of proteolytic systems in inflammatory kidney disease. Inflammatory kidney diseases are associated with broad dysregulations of extracellular and intracellular proteolysis. As an example of a proteolytic system, the complement system plays a significant role in glomerular inflammatory kidney disease and is currently under clinical investigation. Based on two glomerular kidney diseases, lupus nephritis, and membranous nephropathy, we portrait two proteolytic pathomechanisms and the role of the complement system. We discuss how profiling proteolytic activity in patient samples could be used to stratify patients for more targeted interventions in inflammatory kidney diseases. We also describe novel comprehensive, quantitative tools to investigate the entirety of proteolytic processes in a tissue sample. Emphasis is placed on mass spectrometric approaches that enable the comprehensive analysis of the complement system, as well as protease activities and regulation in general.
The effectiveness of a virtual reality attention task to predict depression and anxiety in comparison with current clinical measures
Authors: Voinescu Alexandra , Petrini Karin , Stanton Fraser Danaë , Lazarovicz Radu-Adrian , Papavă Ion , Fodor Liviu Andrei , David Daniel 
Published: April 2021

AbstractPrevious studies have revealed that attention and inhibition are impaired in individuals with elevated symptoms of depression and anxiety. Virtual reality (VR)-based neuropsychological assessment may be a valid instrument for assessing attention and inhibition given its higher ecological validity when compared to classical tests. However, it is still unclear as to whether a VR assessment can predict depression and anxiety with the same or higher level of effectiveness and adherence as classical neuropsychological measures. The current study examined the effectiveness of a new VR test, Nesplora Aquarium, by testing participants with low (N = 41) and elevated (N = 41) symptoms of depression and anxiety. Participants completed a continuous performance test where they had to respond to stimuli (species of fish) in a virtual aquarium, as well as paper-and-pencil and computerised tests. Participants’ performance in Nesplora Aquarium was positively associated with classic measures of attention and inhibition, and effectively predicted symptoms of depression and anxiety above and beyond traditional cognitive measures such as psychomotor speed and executive functioning, spatial working memory span. Hence, VR is a safe, enjoyable, effective and more ecological alternative for the assessment of attention and inhibition among individuals with elevated anxiety and depression symptoms.
Body mass index and leptin levels in serum and cerebrospinal fluid in relation to delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage
Authors: Veldeman Michael , Weiss Miriam , Simon Tim Philipp , Hoellig Anke , Clusmann Hans , Albanna Walid 
Published: April 2021

AbstractAneurysmal subarachnoid hemorrhage (SAH) is associated with a high mortality rate and may leave surviving patients severely disabled. After the initial hemorrhage, clinical outcome is further compromised by the occurrence of delayed cerebral ischemia (DCI). Overweight and obesity have previously been associated with protective effects in the post-bleeding phase. The aim of this study was to assess the effects of a patient’s body mass index (BMI) and leptin levels on the occurrence of DCI, DCI-related cerebral infarction, and clinical outcome. In total, 263 SAH patients were included of which leptin levels were assessed in 24 cases. BMI was recorded along disease severity documented by the Hunt and Hess and modified Fisher scales. The occurrence of clinical or functional DCI (neuromonitoring, CT Perfusion) was assessed. Long-term clinical outcome was documented after 12 months (extended Glasgow outcome scale). A total of 136 (51.7%) patients developed DCI of which 72 (27.4%) developed DCI-related cerebral infarctions. No association between BMI and DCI occurrence (P = .410) or better clinical outcome (P = .643) was identified. Early leptin concentration in serum (P = .258) and CSF (P = .159) showed no predictive value in identifying patients at risk of unfavorable outcomes. However, a significant increase of leptin levels in CSF occurred from 326.0 pg/ml IQR 171.9 prior to DCI development to 579.2 pg/ml IQR 211.9 during ongoing DCI (P = .049). In our data, no association between obesity and clinical outcome was detected. After DCI development, leptin levels in CSF increased either by an upsurge of active transport or disruption of the blood-CSF barrier. This trial has been registered at ClinicalTrials.gov (NCT02142166) as part of a larger-scale prospective data collection. BioSAB: https://clinicaltrials.gov/ct2/show/NCT02142166
Browser-in-the-Middle (BitM) attack
Authors: Tommasi Franco , Catalano Christian , Taurino Ivan 
Published: April 2021

AbstractMan-in-the-Middle (MitM), one of the best known attacks in the world of computer security, is among the greatest concerns for professionals in the field. Main goal of MitM is to compromise confidentiality, integrity and availability of data flowing between source and destination. However, most of its many variants involve difficulties that make it not always possible. The present paper aims at modelling and describing a new method of attack, named Browser-in-the-Middle (BitM) which, despite the similarities with MitM in the way it controls the data flow between a client and the service it accesses, bypasses some of MitM’s typical shortcomings. It could be started by phishing techniques and in some cases coupled to the well-known Man-in-the-Browser (MitB) attack. It will be seen how BitM expands the range of the possible attacker’s actions, at the same time making them easier to implement. Among its features, the absence of the need to install malware of any kind on the victim’s machine and the total control it allows the attacker are to be emphasized.
Improving Baltic Sea wave forecasts using modelled surface currents
Authors: Kanarik Hedi , Tuomi Laura , Björkqvist Jan-Victor , Kärnä Tuomas 
Published: April 2021

AbstractCurrents in the Baltic Sea are generally weak, but during strong winds they can grow high enough to affect the surface wave propagation and evolution. To evaluate the significance of wave-current interactions in the Baltic Sea, we conducted a study using the wave model WAM, comparing a run without surface currents to one with current forcing from a NEMO hydrodynamical model simulation. The overall changes to the wave field caused by currents were quite small. Changes of over 10 cm in significant wave height (SWH) or 1 s in the peak period (Tp) occurred only in some areas and typically less than 3% of the time. Current refraction changed the SWH annual mean by up to 2 cm, but changes up to 60 cm were seen in the maximum values. Tp had occasionally large changes due to shifts in the peak energy in two-peaked swell and wind-sea spectra. Including currents typically led to a stronger changes in swell energy compared to the changes in wind sea energy. A comparison with a wave buoy in the Gulf of Finland showed that this change in the swell energy improved the accuracy of the simulation in this narrow gulf. Current-induced refraction was most prominent near the coastal areas, where current speed occasionally exceeded 0.3 m/s. In general, SWH decreased in the coastal areas with strong currents and slightly increased in adjacent open sea areas. The current effects were most frequent in the Gulf of Finland, the Western Gotland Basin and the Åland Sea.
Corona-Impfstoffe im Überfluss — was dann?
Authors: Cassel Dieter , Ulrich Volker 
Published: April 2021

ZusammenfassungSeit Beginn der Corona-Impfkampagne in Deutschland am 27. Dezember 2020 waren knapp drei Monate später 10,5 Mio. Dosen verimpft. Das waren durchschnittlich 126.000 Dosen pro Tag mit steigender Tendenz: Am 15. März 2021 waren es schon mehr als 250.000 täglich. Damit konnten aber erst 3,2 Mio. Personen vollständig immunisiert werden. Um Herdenimmunität zu erreichen, die wegen der hoch infektiösen Mutanten eine Immunisierungsquote der Bevölkerung von etwa 80 % erfordern dürfte, müssten aber gut 65 Mio. Personen mit 130 Mio. Dosen geimpft sein. Beim jetzigen Impftempo würde es noch bis in den Sommer 2022 dauern, um das Immunitätsziel zu erreichen. Kommt es nach dem Impfstoffmangel bald zu einer Knappheit der Impfkapazitäten? Könnte die Herdenimmunität an mangelnder Impfbereitschaft scheitern?
Der verdrängte Keynes
Authors: Horn Gustav A. 
Published: April 2021

ZusammenfassungIn diesen Tagen jährt sich der Tod von John Maynard Keynes zum 75. Mal. Er war einer der bedeutendsten Ökonomen des 20. Jahrhunderts, wenn nicht gar der bedeutendste überhaupt. Dabei waren seine Lehren und seine Ratschläge schon zu seinen Lebzeiten teilweise heftigst umstritten. Das galt erst recht für die Zeit nach seinem Tod. Zwar dominierte keynesianisches Gedankengut die Wirtschaftspolitik der Nachkriegszeit. Doch spätestens seit den 1970er Jahren begann deren intellektuelle Anziehungskraft angesichts gleichzeitig steigender Arbeitslosigkeit, Staatsverschuldung und Inflation merklich zu schwinden. In jüngster Zeit ist allerdings eine Trendwende erkennbar, die mit Fehlern der Wirtschaftspolitik, aber auch mit neuen Herausforderungen im Zusammenhang steht.
Does corruption matter for FDI flows in the OECD? A gravity analysis
Authors: Zander Tobias 
Published: April 2021

AbstractIn this paper, the effect of corruption on foreign direct investment (FDI) flows is analyzed. The literature is thus far divided regarding the effects of corruption: One hypothesis argues that corruption greases the wheels of government and is therefore beneficial while the other hypothesis argues that it sands the wheels of government leading to suboptimal results in an economy. For the empirical analysis, a dataset consisting of bilateral FDI data from the OECD and the control of corruption measure from the World Governance Indicators of the World Bank is compiled. To further analyze the effects of corruption the Panama Papers revelation is used as a corruption increasing event and the implementation into law of the OECD Anti-Bribery Convention is used as a corruption decreasing event. Finally, the difference between corruption levels in the target and the origin country, will be examined. Then, a gravity model with dyadic and time-fixed effects is employed to analyze the data. Findings are ambiguous in that corruption is positively correlated with FDI inflows in the target country and negatively correlated with FDI inflows in the origin country. The Panama Papers variable shows strong evidence, that the release of the Panama Papers resulted in a drop in FDI flows. Therefore, it seems that corruption has complex country specific effects and that target and source countries have to adopt varying policies with regards to corruption. The general effect of corruption harms FDI flows, as shown by the Panama Papers revelation.
Seventy Years of Pottery Studies in the Archaeology of Mesolithic and Neolithic Sudan
Authors: D’Ercole Giulia 
Published: April 2021

AbstractThis review article examines seventy years of research and methodological approaches to the analysis of Mesolithic and Neolithic pottery in Sudan. It begins with the studies done by A. J. Arkell at the end of the 1940s, leading to the definition of the Khartoum Mesolithic and Khartoum Neolithic ceramic traditions. The article then discusses the application of the concepts of ware, fabric, decorative technique, andchaîne opératoireto the analysis of pottery and the use of new classification tools and archaeometric methodologies. The implication of the concepts of cultural encounter and the communicative role of material culture for ceramic studies and the insights that ceramics can provide for understanding the interrelationships between humans and the landscape are also discussed.
Classifier-based constraint acquisition
Authors: Prestwich S. D. , Freuder E. C. , O’Sullivan B. , Browne D. 
Published: April 2021

AbstractModeling a combinatorial problem is a hard and error-prone task requiring significant expertise. Constraint acquisition methods attempt to automate this process by learning constraints from examples of solutions and (usually) non-solutions. Active methods query an oracle while passive methods do not. We propose a known but not widely-used application of machine learning to constraint acquisition: training a classifier to discriminate between solutions and non-solutions, then deriving a constraint model from the trained classifier. We discuss a wide range of possible new acquisition methods with useful properties inherited from classifiers. We also show the potential of this approach using a Naive Bayes classifier, obtaining a new passive acquisition algorithm that is considerably faster than existing methods, scalable to large constraint sets, and robust under errors.
The emergency (crisis) e-learning as a challenge for teachers in Poland
Authors: Tomczyk Łukasz , Walker Christopher 
Published: April 2021

AbstractThe article was written as a consequence of the COVID-19 pandemic in Poland, which had an impact not only on public health, but also on the functioning of the educational sector. The text is an attempt to summarize the challenges of crisis e-learning from the perspective of the challenges faced by teachers in Poland in the period of March-December 2020. The article reveals a number of new phenomena not present in the literature in the context of e-learning implemented in an intuitive, non-linear way, without methodological support, and thus referred to as crisis e-learning. The aim of the research was to explore the characteristics of crisis e-learning in Poland from the perspective of teachers' experiences. Due to epidemiological limitations, the research area was narrowed down to cyberspace. This text presents the results of research relating to statements made by teachers posting in the largest Polish discussion group on education. The group currently consists of over four thousand people. The study uses an analysis of several thousand posts and then identifies and categorizes statements related to crisis e-learning along with a phenomenological interpretation. The analyses made it possible to identify seven categories of challenges attributed to crisis e-learning, such as: technical problems, use of non-standard solutions, the search for solutions to increase the effectiveness of e-learning, the transfer of proven applications and programmes, problems with students, problems with parents, and the modernisation of workstations. The data presented show teacher micro-worlds in the time of the pandemic in Poland. The article is a response to the need to understand the processes occurring in the Polish educational system under the influence of crisis events related to the pandemic. The text may prove valuable for educating future generations of teachers in the field of e-learning and increasing the effectiveness of training activities aimed at strengthening the digital competence of current teachers.
Group Analytic Hierarchy Process Sorting II Method: An Application to Evaluate the Economic Value of a Wine Region Landscape
Authors: Assumma Vanessa , Bottero Marta , Ishizaka Alessio , Tasiou Menelaos 
Published: April 2021

AbstractIn the ongoing context of climate change, there is an increasing need to support decision-making processes in the domain of landscape planning and management. Suitable evaluation techniques are needed to take into account the interests of actors and stakeholders in shared policy decisions. An important methodological contribution to the field is given by the Multicriteria Decision Analysis (MCDA), due to its ability to combine multiple aspects of a decision problem with the values and opinions expressed by different Decision Makers. The present paper develops the “Group Analytic Hierarchy Process Sorting II method” (GAHPSort II), which aims to sort a group of municipalities included in the UNESCO site “Vineyard Landscape of Piedmont: Langhe-Roero, and Monferrato” (Italy) according to the economic attractiveness of the landscape. Extending the previous versions AHPSort I, AHPSort II and GAHPSort, the GAHPSort II optimizes multi-stakeholder evaluations on large databases by reducing the number of comparisons. Moreover, the GAHPSort II method is proposed as a novel spatial decision support system because it combines a set of economic indicators for landscape and GIS methods for aiding the Decision Makers to better understand the case study and to support the definition and localization of policies and strategies of landscape planning and management.
Distinctively Political Normativity in Political Realism: Unattractive or Redundant
Authors: Erman Eva , Möller Niklas 
Published: April 2021

AbstractPolitical realists’ rejection of the so-called ‘ethics first’ approach of political moralists (mainstream liberals), has raised concerns about their own source of normativity. Some realists have responded to such concerns by theorizing a distinctively political normativity. According to this view, politics is seen as an autonomous, independent domain with its own evaluative standards. Therefore, it is in this source, rather than in some moral values ‘outside’ of this domain, that normative justification should be sought when theorizing justice, democracy, political legitimacy, and the like. For realists the question about a distinctively political normativity is important, because they take the fact that politics is a distinct affair to have severe consequences for both how to approach the subject matter as such and for which principles and values can be justified. Still, realists have had a hard time clarifying what this distinctively political normativity consists of and why, more precisely, it matters. The aim of this paper is to take some further steps in answering these questions. We argue that realists have the choice of committing themselves to one of two coherent notions of distinctively political normativity: one that is independent of moral values, where political normativity is taken to be a kind of instrumental normativity; another where the distinctness still retains a justificatory dependence on moral values. We argue that the former notion is unattractive since the costs of commitment will be too high (first claim), and that the latter notion is sound but redundant since no moralist would ever reject it (second claim). Furthermore, we end the paper by discussing what we see as the most fruitful way of approaching political and moral normativity in political theory.