bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles
Authors: Wollmer Erik , Karkossa Frank , Freerks Lisa , Hetberg Anna-Elena , Neal Greg , Porter John , Whitaker Martin J. , Margetson Daniel , Klein Sandra 
Published: September 2020

Abstract
Purpose
The objective of the present work was to screen whether a novel pediatric hydrocortisone granule formulation can be co-administered with common food matrices and liquids.

Methods
Pediatric hydrocortisone granules were studied using a biopredictive in vitro approach. Experiments included an in situ chemical compatibility study of active ingredient and drug product with liquid dosing vehicles and soft foods commonly ingested by infants, pre-school- and school children. Drug solubility and stability experiments in the different vehicle types and, drug release/dissolution experiments mimicking age-related pediatric gastric conditions after administering the hydrocortisone granules together with the dosing vehicles and after different exposure/mixing times were performed.

Results
In the simulated dosing scenarios applied in dissolution experiments, in vitro dissolution in gastric conditions was rapid and complete. Results of the chemical compatibility/stability studies indicated that mixing with the different dosing vehicles studied should not be an issue regarding drug degradation products.

Conclusions
A novel in vitro approach ensuring a proper risk assessment of the use of dosing vehicles in the administration of pediatric dosage forms was established and applied to a novel pediatric hydrocortisone drug product. The studied dosing vehicles were shown to not alter performance of the drug product and are thus considered suitable for administration with hydrocortisone granules.
A Comprehensive Scientific Survey of Excipients Used in Currently Marketed, Therapeutic Biological Drug Products
Authors: Rao V. Ashutosh , Kim Jennifer J. , Patel Dipti S. , Rains Kimberly , Estoll Corey R. 
Published: September 2020

Abstract

Purpose

The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations.

Methods

Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020.

Results

We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug’s recommended pH range, concentration ranges for excipients, and route of administration.

Conclusions

The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.
The Gini index of demand imbalances in public transport
Authors: Hörcher Daniel , Graham Daniel J. 
Published: September 2020

AbstractThe paper studies a general bidirectional public transport line along which demand varies by line section. The length of line sections also varies, and therefore their contribution to aggregate (line-level) user and operational costs might be different, even if demand levels were uniform. The paper proposes the Gini index as a measure of demand imbalances in public transport. We run a series of numerical simulations with randomised demand patterns, and derive the socially optimal fare, frequency and vehicle size variables in each case. We show that the Gini coefficient is a surprisingly good predictor of all three attributes of optimal supply. These results remain robust with inelastic as well as elastic demand, at various levels of aggregate demand intensity. In addition, we find that lines facing severe demand imbalances generate higher operational cost and require more public subsidies under socially optimal supply, controlling for the scale of operations. The results shed light on the bias introduced by the assumption of homogeneous demand in several existing public transport models.
An artificial neural network based method to uncover the value-of-travel-time distribution
Authors: van Cranenburgh Sander , Kouwenhoven Marco 
Published: September 2020

AbstractThis study proposes a novel Artificial Neural Network (ANN) based method to derive the Value-of-Travel-Time (VTT) distribution. The strength of this method is that it is possible to uncover the VTT distribution (and its moments) without making assumptions about the shape of the distribution or the error terms, while being able to incorporate covariates and taking the panel nature of stated choice data into account. To assess how well the proposed ANN-based method works in terms of being able to recover the VTT distribution, we first conduct a series of Monte Carlo experiments. After having demonstrated that the method works on Monte Carlo data, we apply the method to data from the 2009 Norwegian VTT study. Finally, we extensively cross-validate our method by comparing it with a series of state-of-the-art discrete choice models and nonparametric methods. Based on the promising results we have obtained, we believe that there is a place for ANN-based methods in future VTT studies.
How to count biological minds: symbiosis, the free energy principle, and reciprocal multiscale integration
Authors: Sims Matthew 
Published: September 2020

AbstractThe notion of a physiological individuals has been developed and applied in the philosophy of biology to understand symbiosis, an understanding of which is key to theorising about the major transition in evolution from multi-organismality to multi-cellularity. The paper begins by asking what such symbiotic individuals can help to reveal about a possible transition in the evolution of cognition. Such a transition marks the movement from cooperating individual biological cognizers to a functionally integrated cognizing unit. Somewhere along the way, did such cognizing units simultaneously have cognizers as parts? Expanding upon the multiscale integration view of the Free Energy Principle, this paper develops an account of reciprocal integration, demonstrating how some coupled biological cognizing systems, when certain constraints are met, can result in a cognizing unit that is in ways greater than the sum of its cognizing parts. Symbiosis between V. Fischeri bacteria and the bobtail squid is used to provide an illustration this account. A novel manner of conceptualizing biological cognizers as gradient is then suggested. Lastly it is argued that the reason why the notion of ontologically nested cognizers may be unintuitive stems from the fact that our folk-psychology notion of what a cognizer is has been deeply influenced by our folk-biological manner of understanding biological individuals as units of reproduction.
Longer sleep duration may negatively affect renal function
Authors: Mazidi Mohsen , Shekoohi Niloofar , Katsiki Niki , Banach Maciej 
Published: September 2020

Abstract
Background
Observational studies evaluating the link between sleep duration and kidney function reported controversial results. In the present study, Mendelian randomization analysis was applied to obtain unconfounded estimates of the casual association of genetically determined sleep duration with estimated glomerular filtration rate and the risk of chronic kidney disease.

Methods
Data from the largest genome-wide association studies on self-reported and accelerometer-derived sleep duration, estimated glomerular filtration rate and chronic kidney disease were analysed in total, as well as separately in diabetic and non-diabetic individuals. Inverse variance weighted (IVW) method, weighted median-based method, MR-Egger and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were applied, as well as the leave-one-out method to rule out the impact of single single-nucleotide polymorphism.

Results
Individuals with genetically longer self-reported sleep duration had a higher chronic kidney disease risk (IVW: β = 0.358, p = 0.047). Furthermore, in non-diabetics, longer self-reported sleep duration was negatively associated with estimated glomerular filtration rate (IVW: β = − 0.024, p = 0.020). Similarly, accelerometer-derived sleep duration was negatively related to estimated glomerular filtration rate in the total population (IVW: β = − 0.019, p = 0.047) and then on-diabetic individuals. No significant association was found between self-reported sleep duration and estimated glomerular filtration rate in the whole population and type-2 diabetes mellitus patients. None of the estimated associations was subjected to a significant level of heterogeneity. MR-PRESSO analysis did not show any chance of outliers for all estimates. The pleiotropy test also indicated low chance of pleiotropy. The leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms.

Conclusions
For the first time, the present study shed a light on the potential harmful effects of longer sleep duration (measured both objectively and subjectively) on kidney function. This finding was observed in the total population and in non-diabetic individuals, but not in those with diabetes. Further research is needed to elucidate the links between sleep duration, estimated glomerular filtration rate and the risk of chronic kidney disease.
Potential reverse spillover of infectious bursal disease virus at the interface of commercial poultry and wild birds
Authors: Naggar Rania F. El , Rohaim Mohammed A. , Munir Muhammad 
Published: September 2020

AbstractRecently, multiple spillover events between domesticated poultry and wild birds have been reported for several avian viruses. This phenomenon highlights the importance of the livestock-wildlife interface in the possible emergence of novel viruses. The aim of the current study was to investigate the potential spillover and epidemiological links of infectious bursal disease virus (IBDV) between wild birds and domestic poultry. To this end, twenty-eight cloacal swabs were collected from four species of free-living Egyptian wild birds (i.e. mallard duck, bean goose, white-fronted goose and black-billed magpie). Genetic and phylogenetic analysis of three positive isolates revealed that the IBDV/USC-1/2019 strain clustered with previously reported very virulent IBDV (vvIBDV) Egyptian isolates. Interestingly, two other wild bird-origin isolates (i.e. IBDV/USC-2/2019 and IBDV/USC-3/2019) grouped with a vaccine strain that is being used in commercial poultry. In conclusion, our results revealed the molecular detection of vaccine and vvIBDV-like strains in Egyptian wild birds and highlighted the potential role of wild birds in IBDV epidemiology in disease-endemic regions.
‘Then You Will Know the Truth, and the Truth Will Set You Free’: An Interpretative Phenomenological Analysis of the Career Experiences of Gay Clergy in the Church of England
Authors: Connell Adam , Yates Julia 
Published: September 2020

AbstractThe career choices of Lesbian, Gay and Bisexual (LGB) employees are increasingly under the spotlight in academic research, but the experiences of LGB employees called to devote their careers to faith organisations remain largely unexplored in the literature. The Church of England does not fully condone same-sex relationships and this may pose a challenge for LGB people working for the Church, as they look for a way to reconcile their sexuality with their faith and their employer’s beliefs. This qualitative study explores the lived experiences of six gay clergymen in the Church of England, using data gathered through semi-structured interviews and analysed using Interpretative Phenomenological Analysis. Three master themes were identified: tensions between sexuality, calling, and career; coping strategies; and the institutionalisation of homophobia in the Church. The findings are discussed with reference to Work as Calling Theory and we offer practical recommendations.
CT-supported analysis of the destructive effects of Varroa destructor on the pre-imaginal development of honey bee, Apis mellifera
Authors: Keszthelyi Sándor , Sipos Tamás , Csóka Ádám , Donkó Tamás 
Published: September 2020

AbstractThe ectoparasitic mite, Varroa destructor, is a most important health risk for European honey bee subspecies (Apis mellifera) globally. There is a scarcity in experimental approaches addressing this issue by using computed tomography. Our purpose was to determine the decrease in the volume, surface, density and weight alteration triggered by V. destructor in pre-imaginal stages of A. mellifera using computer-based 3-D reconstruction technology. Computer tomography used in the current study proved to be sufficiently sensitive for the detection of V. destructor in comb cells. This non-invasive experimental setup revealed that the developing worker pupae have retained their volume and surface values, whereas the weight loss triggered by V. destructor was statistically confirmed. In addition, the disappearance of lower radiodensity tissues is shown to be due to mite parasitism, which can be primarily explained by haemolymph losses.
Adipositaschirurgie: Update 2020
Authors: Widmer Jeannette , Büter Marco , Thalheimer Andreas 
Published: September 2020

ZusammenfassungDie Anzahl übergewichtiger und adipöser Patienten steigt weltweit epidemisch an. Neben massiven sozioökonomischen Folgen sehen wir uns mit einer Vielzahl von adipositasassoziierten Begleiterkrankungen konfrontiert, die zum Teil eine massive Belastung für die betroffenen Patienten darstellen. Die Therapie sollte idealerweise so früh wie möglich durch ein interdisziplinäres Team begonnen werden und stufenweise erfolgen. Der konservative Therapieansatz ist jedoch weiterhin längerfristig kaum erfolgreich. Auch wenn in den letzten Jahren einige vielversprechende Medikamente zur Behandlung der Adipositas entwickelt wurden, ist die konservative Therapie für Patienten und Ärzte häufig frustran. Die langfristig erfolgreichste Therapie bleibt daher die bariatrische Chirurgie (operative Eingriffe, die zu einer Reduktion des Körpergewichts führen). In diesem Artikel werden die aktuellen operativen Verfahren der bariatrischen Chirurgie, die postoperativen Ergebnisse sowie die bisher bekannten Wirkungsmechanismen dargestellt.
Targeting Your Audience
Authors: Arksey Marieka , Peterson Marcia , Pierce Greg 
Published: September 2020

ABSTRACTThe Office of the Wyoming State Archaeologist has as one of its main objectives to actively engage the population of Wyoming in archaeological stewardship. To achieve this goal, in the past five years, we have launched the youth-oriented Summer Ventures program and the adult-oriented Wyoming Avocational Archaeology Training Program. Both programs were inspired by existing programs in other parts of the country and were launched following research and target audience surveys on how to best adapt them to Wyoming. Despite this preliminary research, our in-field experiences over the past few years have shown some patterns that are causing us to rethink both programs. This article discusses these initial in-field testing years, the issues we have encountered, and the ways we are redesigning both programs to better target the appropriate audiences in light of the different lifestyles of populations, particularly those of youths, in a rural state.
Ergodicity of affine processes on the cone of symmetric positive semidefinite matrices
Authors: Friesen Martin , Jin Peng , Kremer Jonas , Rüdiger Barbara 
Published: September 2020

AbstractThis article investigates the long-time behavior of conservative affine processes on the cone of symmetric positive semidefinite$d\times d$matrices. In particular, for conservative and subcritical affine processes we show that a finite$\log$-moment of the state-independent jump measure is sufficient for the existence of a unique limit distribution. Moreover, we study the convergence rate of the underlying transition kernel to the limit distribution: first, in a specific metric induced by the Laplace transform, and second, in the Wasserstein distance under a first moment assumption imposed on the state-independent jump measure and an additional condition on the diffusion parameter.
Community Organizations and Latin America’s Poorest Citizens: Voting, Protesting, and Contacting Government
Authors: Boulding Carew , Holzner Claudio A. 
Published: September 2020

ABSTRACTHow do Latin America’s poorest citizens participate in politics? This article explores the role that community organizations play in mobilizing individuals into three common modes of political participation: voting, protesting, and contacting government. It argues that community organizations help mobilize poor individuals both through the resources they provide for mobilization and because they serve as sites where political parties target individuals for mobilization. It analyzes survey data from LAPOP surveys for 18 Latin American countries and finds that overall, poor people are just as politically active as more affluent individuals; that involvement in community organizations is a very strong predictor of all types of political participation; and that membership in organizations has an especially strong effect on voting and protesting for poor people. By equalizing levels of political participation across income groups, organizations help erase class-based inequalities in participation that have plagued democracies in the region.
The effect of intra-striatal administration of GPR55 agonist (LPI) and antagonist (ML193) on sensorimotor and motor functions in a Parkinson’s disease rat model
Authors: Fatemi Iman , Abdollahi Abbas , Shamsizadeh Ali , Allahtavakoli Mohammad , Roohbakhsh Ali 
Published: September 2020

AbstractObjective:G protein-coupled receptor 55 (GPR55) is an orphan G protein-coupled receptor with various physiological functions. Recent evidence suggests that this receptor may be involved in the control of motor functions. Therefore, in the present study, we evaluated the effects of intra-striatal administration of GPR55 selective ligands in a rat model of Parkinson’s disease.Methods:Experimental Parkinson was induced by unilateral intra-striatal administration of 6-hydroxydopamine (6-OHDA, 10 µg/rat). L-α-lysophosphatidylinositol (LPI, 1 and 5 µg/rat), an endogenous GPR55 agonist, and ML193 (1 and 5 µg/rat), a selective GPR55 antagonist, were injected into the striatum of 6-OHDA-lesioned rats. Motor performance and balance skills were evaluated using the accelerating rotating rod and the ledged beam tests. The sensorimotor function of the forelimbs and locomotor activity were assessed by the adhesive removal and open field tests, respectively.Results:6-OHDA-lesioned rats had impaired behaviours in all tests. Intra-striatal administration of LPI in 6-OHDA-lesioned rats increased time on the rotarod, decreased latency to remove the label, with no significant effect on slip steps, and locomotor activity. Intra-striatal administration of ML193 also increased time on the rotarod, decreased latency to remove the label and slip steps in 6-OHDA-lesioned rats mostly at the dose of 1 µg/rat.Conclusions:This study suggests that the striatal GPR55 is involved in the control of motor functions. However, considering the similar effects of GPR55 agonist and antagonist, it may be concluded that this receptor has a modulatory role in the control of motor deficits in an experimental model of Parkinson.
Brain-derived neurotrophic factor, depressive symptoms and somatic comorbidity in patients with coronary heart disease
Authors: Tschorn Mira , Kuhlmann Stella Linnea , Rieckmann Nina , Beer Katja , Grosse Laura , Arolt Volker , Waltenberger Johannes , Haverkamp Wilhelm , Müller-Nordhorn Jacqueline , Hellweg Rainer , Ströhle Andreas 
Published: September 2020

AbstractObjective:Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF).Methods:The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment.Results:Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS.Conclusion:Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.
Spatial scaling of beta diversity in the shallow-marine fossil record
Authors: Womack Tom M. , Crampton James S. , Hannah Michael J. 
Published: September 2020

AbstractBeta diversity quantifies the spatial structuring of ecological communities and is a fundamental partition of biodiversity, central to understanding many macroecological phenomena in modern biology and paleobiology. Despite its common application in ecology, studies of beta diversity in the fossil record are relatively limited at regional spatial scales that are important for understanding macroevolutionary processes. The spatial scaling of beta diversity in the fossil record is poorly understood, but has significant implications due to temporal variation in the spatial distribution of fossil collections and the large spatiotemporal scales typically employed. Here we test the spatial scaling of several common measures of beta diversity using the Cenozoic shallow-marine molluscan fossil record of New Zealand and derive a spatially standardized time series of beta diversity. To measure spatial scaling, we use and compare grid-cell occupancy based on an equal-area grid and summed minimum spanning tree length, both based on reconstructed paleocoordinates of fossil collections. We find that beta diversity is spatially dependent at local to regional scales, regardless of the metric or spatial scaling utilized, and that spatial standardization significantly changes apparent temporal trends of beta diversity and, therefore, inferences about processes driving diversity change.