bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical methodology for highly variable compounds: A novel design approach for the ofatumumab Phase 2 bioequivalence study
Authors: Jones Byron , Li Bingbing , Bagger Morten , Goodyear Alex , Ludwig Inga 
Published: May 2022

AbstractThis article describes a novel mixed‐scaling testing strategy, in combination with an adaptive parallel‐groups bioequivalence trial, to test pharmacokinetic equivalence of two formulations of a drug with highly variable pharmacokinetics. The methodology was applied to the Phase 2 APLIOS study in relapsing multiple sclerosis patients, where the bioequivalence of subcutaneous ofatumumab 20 mg administered via an autoinjector pen (test formulation) versus prefilled syringe (reference formulation) in the abdomen has been studied. Due to a high coefficient of variation (CV) of the relevant pharmacokinetic metrics (AUCtau and Cmax) for the reference formulation (>30%), a reference‐Scaled bioequivalence (RSABE) approach was applied but modified for a parallel‐groups design. In the absence of regulatory guidance for applying RSABE in parallel‐group designs, and in contrast to the available regulatory guidance for RSABE in cross‐over trials, the suggested testing strategy uses the between‐subject variability of the reference drug instead of the corresponding within‐subject variability that would be available if a standard cross‐over bioequivalence trial had been possible. Moreover, due to high uncertainty in the initial CV estimate for the sample size determination, a two‐stage adaptive design was used, allowing for a sample size adjustment based on the pharmacokinetic variability observed at an interim analysis. The interim analysis timing was pre‐specified based on simulations which included re‐estimation of the final sample size at the end of the first stage to ensure sufficient power of the RSABE test at the end of the second stage. Using this approach, bioequivalence was shown between the test and reference formulations.The APLIOS trial is registered at ClinicalTrials.gov: NCT03560739.
Apolipoprotein A1 is associated with pulmonary vascular resistance and adverse clinical outcomes in patients with pulmonary hypertension secondary to heart failure
Authors: Yu Wande , Dujiang Xie , Yi Wang , Guanwen Ding , Mengyu Zhang , Chang Pan , Aikai Zhang , Juan Zhang , Linlin Zhu , Hang Zhang 
Published: May 2022

AbstractPulmonary hypertension secondary to heart failure (HF‐PH) combined with pulmonary vascular remodeling has a high mortality rate. Apolipoprotein A1 (ApoA1) has been shown to adversely affect outcomes in patients with HF. A prospective follow‐up study was performed on 239 consecutive patients with HF‐PH who underwent right heart catheterization. Proteomics technology was used to analyze different proteins in plasma between post‐ and precapillary pulmonary hypertension (CpcPH) and isolated postcapillary pulmonary hypertension (IpcPH) filtered by propensity score matching. Ultimately, 175 patients were enrolled and followed for an average of 4.4 years. Lipoprotein components in plasma were measured, and the following clinical events were tracked. Proteomics data showed that lipid metabolism and inflammation were different between CpcPH and IpcPH. ApoA1 levels in HF‐PH patients with CpcPH were lower than those in HF‐PH patients with IpcPH. The patients with lower ApoA1 levels (≤1.025 g/L) were in a higher New York Heart Association class and had high levels of NT‐proBNP, mean pulmonary artery pressure, PVR, and diastolic pressure gradient. Besides, HF‐PH patients with lower ApoA1 levels had a 2.836‐fold higher relative risk of comorbid CpcPH compared with patients with higher ApoA1 levels. Moreover, patients with lower ApoA1 levels had a lower survival rate after adjusting for CpcPH. In conclusion, ApoA1 levels were negatively correlated with PVR levels. Lower ApoA1 levels were an independent risk factor for pulmonary vascular remodeling in HF‐PH patients. The survival of HF‐PH patients with lower ApoA1 levels was reduced.
Environmental drivers of cyanobacterial abundance and cyanotoxin production in backwaters of the Upper Mississippi River
Authors: Giblin Shawn M. , Larson James H. , King Jeremy D. 
Published: May 2022

AbstractHigh densities of cyanobacteria in aquatic ecosystems can cause impacts to ecosystem services because they serve as a poor‐quality food resource, produce toxins and can indirectly cause a variety of other negative impacts to water quality. There are many hypotheses about the potential environmental drivers of variation in cyanobacterial abundance and toxicity, but these hypotheses have rarely been considered in combination and rarely been examined in large river ecosystems. Here, we use monthly data from backwater habitats of the Upper Mississippi River (UMR) to evaluate associations between environmental conditions and cyanobacterial abundance and toxicity (microcystin and anatoxin‐a) that would be expected based on several hypotheses. Backwaters in the Mississippi River vary in flushing rate, temperature, turbidity, nutrient availability, water depth, and vegetative cover. We find support for hypotheses that suggest physical conditions in backwaters (flushing rate, temperature, turbidity, rooted vegetation cover, and water depth) and nutrient availability influence cyanobacterial abundance and toxicity. We then used structural equation modeling to incorporate several hypotheses into a causal modeling framework, which indicated that backwater connectivity (flushing) strongly influences cyanobacterial abundance via the regulation of water temperature, and that nutrient availability strongly influences the presence of microcystin concentrations above our detection limit. Our data suggest that management of backwater connectivity could influence cyanobacterial abundance and toxicity in UMR backwaters. Reconnecting backwaters (via alteration of levees) could serve as a local adaptation to minimize the effects of climate change and excessive nutrient loading.
Rapid Approach for Pharmaceutical Quality Evaluation and Comparison
Authors: Pettinau Francesca , Manca Ilaria , Manca Ilaria , Pittau Barbara 
Published: May 2022

AbstractA rapid approach, with the association of Fourier‐transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR), is proposed in order to provide a fast quality evaluation of pharmaceutical products. It offers an analytical screening tool also useful to compare drug products including generics. The approach requires a minimal amount of solvents and little sample preparation. In this paper characterization of pharmaceutical product samples containing telmisartan, allopurinol, anastrozole, metformin hydrochloride and lamivudine, active pharmaceutical ingredients (APIs) in solid dosage forms, are reported. The results show how this approach can provide useful data for a rapid screening of pharmaceutical composition and comparison of drugs with useful information also in terms of equivalence risk analysis.
A Naphthalimides‐Based Probe for Sequential Detection of Cu2+ and PPi and Its Application in Cells Imaging
Authors: Wang Wei , Wang Baihui , Liu Huimin , Liu Qinglei , Li Shanshan , Zhao Bing , Gao Yan 
Published: May 2022

AbstractA novel naphthalimides‐based fluorescent probe (NPHD) selectively detected Cu2+ and PPi through “strong yellow‐weak green‐strong yellow” photonic response in a sequential manner. The formation of NPHD‐Cu2+ resulted in obvious fluorescence decreased and wavelength shift from 595 nm to 525 nm by adding Cu2+ to NPHD solution. The mechanism could be attributed to d→π* electron transfer (ET) from Cu2+ to NPHD. Furthermore, the NPHD‐Cu2+ complex exhibited high selectivity toward PPi through via emission recovery of chemosensor NPHD. The detection limits of NPHD to Cu2+ and NPHD‐Cu2+ to PPi were estimated to be 5.72×10<M‐>8M and 2.39×10<M‐>8M. In addition, NPHD could be employed to detect exogenous Cu2+ and PPi in Hep G2 cells.
Sulfur‐Doped Hydrogen‐Bonded Organic Framework for Improved Oxygen Evolution Reaction
Authors: Wang Jiaji , Zhang Ling , Lin Shiwei 
Published: May 2022

AbstractDeveloping the efficient electrocatalysts for oxygen evolution reaction (OER) is highly required but still challenging, especially for hydrogen‐bonded organic framework (HOF) materials. Herein, we report a sulfur‐doped HOF material (S@HOF‐H2BDC) for improved OER performance for the first time. The prepared S@HOF‐H2BDC shows a greatly enhanced OER activity, lowing the overpotential of 48 mV at a current density of 10 mA cm−2relative to the undoped one, and even comparable to the benchmark IrO2. Results have shown that doping S atoms can induce more active sites, and accelerate the charge transfer kinetics. Moreover, the OOH*adsorption energy of S@HOF‐H2BDC can be remarkably modulated after introducing S atoms, thus increasing its catalyst performance.
Beyond the Paradox of Trust and Digital Platforms: Populism and the Reshaping of Internet Regulations
Authors: Flew Terry 
Published: May 2022

AbstractOne of the paradoxes of the misinformation and ‘fake news’ debates are that they require a greater degree of trust in media, digital platforms and governments in order to combat conspiracy theories, when in fact distrust of media, digital platforms and governments is part of a wider crisis of trust in institutions and expertise. This suggests that we need a more sophisticated analysis of the politics of expertise and how they intersect with both policies towards digital platforms and shifts in the political sphere. Drawing upon the work of Thomas Piketty on shifts in electoral politics, and Pippa Norris on the rise of populism, it is argued that debates about tech policy are largely played out between educated elites from ‘liberal’ and ‘cosmopolitan’ perspectives, which leaves them open to populist critique. One of the reasons why there are greater calls to regulate digital platforms is the rise of political populism, which can leave digital activists in a political bind: they favour measures to rein in the power of ‘Big Tech’ in principle, but are very wary of any measures perceived to increase the power of nation states with regards to the Internet.
Altwerden zwischen Speckgürtel und Peripherie – ein Blick auf das Land Brandenburg
Authors: Stellmacher Thorsten , Wolter Birgit 
Published: May 2022

ZusammenfassungGute Rahmenbedingungen für das Leben im Alter zu bieten, stellt insbesondere im ländlichen Raum die Kommunen vor große Herausforderungen. Der Anteil älterer Menschen an der Bevölkerung ist in den ländlichen Regionen meist höher als in den städtischen Ballungsräumen.
Steigende Wohnkosten im Alter – (k)ein Problem?
Authors: Vogel Claudia , Lozano Alcántara Alberto , Romeu Gordo Laura 
Published: May 2022

ZusammenfassungDie Wohnkosten sind in den letzten Jahren stärker gestiegen als die Alterseinkommen. Die Wohnkostenbelastung müsste somit bei den älteren Haushalten gestiegen sein. Auf Basis des Sozio-oekonomischen Panels (1996–2018) gehen wir den Fragen nach, wie sich die relative Wohnkostenbelastung seit Mitte der 1990er Jahre bei älteren Menschen entwickelt hat, und für welche Gruppen älterer Haushalte die hohen Wohnkosten zu einer finanziellen Überbelastung führen können. Die Ergebnisse zeigen, dass die relative Wohnkostenbelastung für ältere Menschen seit 1996 angestiegen ist, und zwar insbesondere für Mieterhaushalte. Zu den Gruppen, die durch Wohnkosten besonders überbelastet sind, gehören vor allem Mieterhaushalte und ältere Alleinlebende mit niedrigen Einkommen.
Wohnbedingungen und Pflegebedarf – Analysen von Erstbegutachtungen des Medizinischen Dienstes der Krankenversicherung
Authors: Stein Thomas , Schilling Ralph 
Published: May 2022

ZusammenfassungBei aktueller Lebenszeitprävalenz muss ein Großteil der Bevölkerung in Deutschland damit rechnen, im Laufe des Lebens pflegebedürftig zu werden. Etwa 75 % der im Jahr 2017 verstorbenen Frauen und 60 % der verstorbenen Männer waren zuvor pflegebedürftig.
Bauernhöfe als Orte für Menschen mit Demenz – Ergebnisse einer explorativen Studie aus Schleswig–Holstein
Authors: Schmidt Annika , Wolf-Ostermann Karin 
Published: May 2022

ZusammenfassungAufgrund der Bevölkerungsalterung, der Zunahme von altersspezifischen Erkrankungen und dem damit einhergehenden Anstieg der Pflegebedürftigkeit ist die Frage nach Versorgungserfordernissen und -bedarfen zunehmend von Bedeutung. Alternative und integrative Unterstützungsangebote gewinnen an Zuspruch. Als eine alternative Betreuungsform, auch für MmD leben, hat sich in vergangenen Jahren das Konzept der Green Care Farms international entwickelt. Der Beitrag thematisiert das in Deutschland angesiedelte Projekt „Bauernhöfe als Orte für MmD in Schleswig–Holstein“ vor und zeigt die Ressourcen und Barrieren des Angebotes auf.
Classic Theories of Distance Education
Authors: Evans Terry , Jakupec Viktor 
Published: May 2022

AbstractThis chapter explores the influence of three of distance education’s classic theorists—Otto Peters, Börje Holmberg, and Michael Moore—on its subsequent conceptualization and practice. The classic theorists’ understanding of theory and theorizing is discussed critically in the context of the articulation of each’s particular theory. This is then contextualized in terms of the history of the development of distance education and its institutions, from Pitman’s correspondence courses on shorthand, through correspondence schooling and higher education external studies, to the rise of the United Kingdom Open University in the 1960s. The latter’s subsequent powerful influence on the theory and practice of open and distance education internationally is described as stimulating a fertile context for the classic theorists’ endeavors. Finally, consideration is given to more recent scholars’ interpretations and adaptations of the classic theories of distance education. This leads to a concluding reflection on the authors’ engagement with distance education theorizing and the prospects for the future of distance education’s theorizing and practice.
Analyse steigender Behandlungskosten bei erhöhtem BMI von Patienten mit proximaler Femurfraktur
Authors: Gutwerk Alexander , Müller Michael , Crönlein Moritz , Kirchhoff Chlodwig , Biberthaler Peter , Pförringer Dominik , Braun Karl 
Published: May 2022

ZusammenfassungDie proximale Femurfraktur ist eine Frakturentität mit ansteigender Prävalenz, ein Effekt, welcher durch die zunehmende Alterung der Allgemeinbevölkerung noch zusätzlich verstärkt werden wird. In der Summe stellt sie sowohl die Operateure als auch das deutsche Gesundheitssystem als Ganzes vor Herausforderungen. Zudem führt ein stetiges Ansteigen des BMI in der Bevölkerung zu immer mehr adipösen Patienten mit proximaler Femurfraktur, was dann durch komplexere Operationen, längere Liegezeiten und eine wachsende Zahl postoperativer Komplikationen wiederum zu Herausforderungen führt.Ziel der vorliegenden Arbeit ist es, den monetären Aspekt dieser Entwicklung zu beleuchten. Hierzu wurden retrospektiv 950 Patientenfälle mit proximaler Femurfraktur analysiert. Hierbei konnte gezeigt werden, dass mit steigendem BMI höhere Kosten pro Fall entstanden (10.452 €, 11.505 €, 12.085 € bzw. 13.681 € für BMI < 18,5 kg/m2, BMI = 18,5–24,9 kg/m2, BMI = 25,0–29,9 kg/m2 bzw. BMI ≥ 30,0 kg/m2), da sowohl die Operationszeit als auch die Zeit des stationären Aufenthalts relevant verlängert waren.
Immune moral models? Pro-social rule breaking as a moral enhancement approach for ethical AI
Authors: Ramanayake Rajitha , Wicke Philipp , Nallur Vivek 
Published: May 2022

AbstractWe are moving towards a future where Artificial Intelligence (AI) based agents make many decisions on behalf of humans. From healthcare decision-making to social media censoring, these agents face problems, and make decisions with ethical and societal implications. Ethical behaviour is a critical characteristic that we would like in a human-centric AI. A common observation in human-centric industries, like the service industry and healthcare, is that their professionals tend to break rules, if necessary, for pro-social reasons. This behaviour among humans is defined as pro-social rule breaking. To make AI agents more human-centric, we argue that there is a need for a mechanism that helps AI agents identify when to break rules set by their designers. To understand when AI agents need to break rules, we examine the conditions under which humans break rules for pro-social reasons. In this paper, we present a study that introduces a ‘vaccination strategy dilemma’ to human participants and analyzes their response. In this dilemma, one needs to decide whether they would distribute COVID-19 vaccines only to members of a high-risk group (follow the enforced rule) or, in selected cases, administer the vaccine to a few social influencers (break the rule), which might yield an overall greater benefit to society. The results of the empirical study suggest a relationship between stakeholder utilities and pro-social rule breaking (PSRB), which neither deontological nor utilitarian ethics completely explain. Finally, the paper discusses the design characteristics of an ethical agent capable of PSRB and the future research directions on PSRB in the AI realm. We hope that this will inform the design of future AI agents, and their decision-making behaviour.
Wissenschaftliche Leistungen augenheilkundlicher Forschungseinrichtungen in Deutschland 2018 bis 2020
Authors: Schaub Friederike , Mele Birgit , Gass Philip , Ader Marius , Helbig Horst , Lagrèze Wolf A. , Schlötzer-Schrehardt Ursula , Ueffing Marius , Cursiefen Claus ,   das DOG Forschungslandkartenteam, Auffarth Gerd U. , Bartz-Schmidt Karl U. , Erb Carl , Eter Nicole , Fuchsluger Thomas A. , Geerling Gerd , Hattenbach Lars-Olof , Heiligenhaus Arnd , Hoerauf Hans , Hoffmann Michael B. , Holz Frank G. , Joachim Stephanie C. , Johnen Sandra , Joussen Antonia M. , Kellner Ulrich , Kohnen Thomas , Lytvynchuk Lyubomyr , Maier Mathias , Meller Daniel , Mueller Arthur , Nentwich Martin M. , Pfeiffer Norbert , Pillunat Lutz E. , Priglinger Siegfried , Ranjbar Mahdy , Reinhard Thomas , Roider Johann , Schrader Stefan , Seitz Berthold , Spitzer Martin S. , Stahl Andreas , Szurman Peter , Tode Jan , Viestenz Arne , Wagner Felix Mathias , Wiedemann Peter , Wolf Armin 
Published: May 2022

Zusammenfassung
Hintergrund
Die Deutsche Ophthalmologische Gesellschaft (DOG) erfasst regelmäßig die wissenschaftlichen Aktivitäten der augenheilkundlichen Forschungseinrichtungen in Deutschland.

Ziel der Arbeit
Mit dieser Publikation will die DOG die Leistungsfähigkeit der wissenschaftlichen Augenheilkunde in Deutschland transparent machen und die Optionen für zukünftige Forschungskooperationen mehren.

Methoden
Systematische Befragung deutscher Forschungszentren in der Augenheilkunde.

Ergebnisse
Die aktuelle Forschungslandkarte erfasst Daten aus 41 deutschen Forschungszentren für den Berichtszeitraum 2018 bis 2020. Im Vergleich zu vorangegangenen Auflagen der Forschungslandkarte ist ein deutlicher Anstieg wissenschaftlicher Aktivität zu verzeichnen. Unter anderem stieg die Zahl der gemeldeten Studien auf einen Wert von 496. Die Anzahl der hoheitlich geförderten Forschungsprojekte (n = 121) und der durch Stiftungen geförderten Projekte (n = 108) erhöhte sich ebenfalls. Und es ist nahezu eine Verdopplung der von Vertretern der deutschen Augenheilkunde vorgelegten wissenschaftlichen Publikationen zu verzeichnen: Wurden für den Zeitraum von 2012 bis 2014 1919 und im Zeitraum von 2015 bis 2017 2305 Publikationen veröffentlicht, so waren es im aktuellen Berichtszeitraum 4215. Die Landkarte berichtet darüber hinaus auch von einem kontinuierlichen Zuwachs des wissenschaftlichen Nachwuchses in der Augenheilkunde.

Diskussion
Die Forschungslandkarte demonstriert die Leistungsfähigkeit der deutschen wissenschaftlichen Augenheilkunde. Gleichzeitig ist der weitere Bedarf an Forschung in der Augenheilkunde ungebrochen sehr hoch, denn viele Erkrankungen, die die Augen betreffen, sind heute noch nicht oder noch nicht vollständig heilbar.
Maternal socioeconomic and lifestyle factors and life dissatisfaction associated with a small for gestational age infant. The Survey of Neonates in Pomerania (SNiP)
Authors: Pierdant Guillermo , Ittermann Till , Freyer-Adam Jennis , Siewert-Markus Ulrike , Grabe Hans Jörgen , Dörr Marcus , Heckmann Matthias , Zygmunt Marek , Lange Anja Erika , Markus Marcello Ricardo Paulista 
Published: May 2022

Abstract
Purpose
The aim is to investigate the associations of the mother’s socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant.

Methods
Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models.

Results
After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06–3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01).

Conclusions
Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates.
Living longer, working longer: analysing time trends in working life expectancy in Germany from a health perspective between 2002 and 2018
Authors: Heller Chiara , Sperlich Stefanie , Tetzlaff Fabian , Geyer Siegfried , Epping Jelena , Beller Johannes , Tetzlaff Juliane 
Published: May 2022

AbstractPopulation ageing poses growing challenges to social security systems, in particular to public pension funds. The study analyses how Working Life Expectancy (WLE) and Healthy Working Life Expectancy (HWLE) in terms of three health indicators developed in Germany. Based on the German Socio-Economic Panel (GSOEP) from 2002 to 2018 (n = 211,141), time trends in labour force rates, mental and physical Health-Related Quality of Life (HRQoL), self-rated health (SRH) and the respective combinations (health indicator*labour force) were analysed for all respondents aged 18–74. WLE and HWLE were calculated using the Sullivan method. WLE and HWLE in men and women at age 18 and 50 clearly increased over time. These increases in HWLE were found in terms of all three health indicators. This development was mainly driven by the clear increase of the labour force rates, since the shares of individuals with good and satisfactory SRH or average and good HRQoL remained largely stable over time. The results show that from a health perspective there have been potentials for increases in WLE during the past two decades and that increasingly more healthy life years are spent economically active. However, life years in the labour force but in poor health have increased, too. The absence of clear improvements in health emphasises the importance of current and future preventive measures to maintain health, especially among the middle-aged and older labour force.