bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rückgang der ambulanten Antibiotikaverordnungen bei Kindern und Jugendlichen in Deutschland 2010–2019. Regionale Entwicklung in den deutschen KV-Regionen
Authors: Holstiege J. , Bätzing J. , Akmatov M. K. , Tillmann R. , Hufnagel M. , Hübner J. , Berner R. , Simon A. 
Published: July 2021

ZusammenfassungIn den letzten 10 Jahren ist das Thema Antibiotic Stewardship (ABS) auch in der ambulanten Kinder- und Jugendmedizin immer stärker in den Vordergrund gerückt. Die vom Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik Deutschland regelmäßig ausgewerteten bundesweiten krankenkassenübergreifenden Arzneiverordnungsdaten gemäß § 300 Abs. 2 SGB V (gesetzlich Krankenversicherte) zeigen von 2010 bis 2019 eine starke Abnahme der Antibiotikaverordnungsraten bei Kindern und Jugendlichen (0 bis 14 Jahre) pro 1000 Versicherte, insbesondere bei Säuglingen (∆ −53 %) und Kleinkindern (∆ −46 %). Aus ABS-Perspektive werden weiterhin zu häufig Oralcephalosporine (v. a. Cefaclor und Cefuroxim) verordnet. Zudem persistieren starke regionale Unterschiede, die sich nicht durch Unterschiede in der Patientenpopulation oder im Erkrankungsspektrum erklären lassen.
Morc1 as a potential new target gene in mood regulation: when and where to find in the brain
Authors: Mundorf Annakarina , Koch Jennifer , Kubitza Nadja , Wagner Selina C. , Schmidt Michaela , Gass Peter , Freund Nadja 
Published: July 2021

AbstractRecent animal and human studies connected the Morc family CW-type zinc finger 1 (Morc1) gene with early life stress and depression. Moreover, the Morc superfamily is related to epigenetic regulation in diverse nuclear processes. So far, the Morc1 gene was mainly studied in spermatogenesis, whereas its distribution and function in the brain are still unknown. In a first attempt to characterize Morc1 in the brain, we performed a Western Blot analysis as well as a real-time PCR analysis during different stages of development. Additionally, we detected Morc1 mRNA using real-time PCR in different mood-regulating brain areas in adult rats. We found that MORC1 protein as well as Morc1 mRNA is already expressed in the brain at embryonic day 14 and is stably expressed until adulthood. Furthermore, Morc1 mRNA is present in many important brain areas of mood regulation like the medial prefrontal cortex, the nucleus accumbens, the hippocampus, the hypothalamus, and the amygdala. The ample distribution in the brain and its molecular structure as a zinc finger protein indicate that Morc1 might act as a transcription factor. This function and its expression in mood-regulating areas already in the early brain development turn Morc1 into a possible candidate gene for mediating early life stress and depression.
Co-clinical FDG-PET radiomic signature in predicting response to neoadjuvant chemotherapy in triple-negative breast cancer
Authors: Roy Sudipta , Whitehead Timothy D. , Li Shunqiang , Ademuyiwa Foluso O. , Wahl Richard L. , Dehdashti Farrokh , Shoghi Kooresh I. 
Published: July 2021

Abstract
Purpose
We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

Methods
TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A rank importance of predictors using ReliefF was used to identify predictive radiomic features in the preclinical PDX trial in conjunction with ML algorithms: classification and regression tree (CART), Naïve Bayes (NB), and support vector machines (SVM). The top four PDX-optimized image features, defined as radiomic signatures (RadSig), from each task were then used to predict or assess response to therapy. Performance of RadSig in predicting/assessing response was compared to SUVmean, SUVmax, and lean body mass-normalized SULpeak measures.

Results
Sixty-four out of 131 preclinical imaging features were identified as robust. NB-RadSig performed highest in predicting and assessing response to therapy in the preclinical PDX trial. In the clinical study, the performance of SVM-RadSig and NB-RadSig to predict and assess response was practically identical and superior to SUVmean, SUVmax, and SULpeak measures.

Conclusions
We optimized robust FDG-PET radiomic signatures (RadSig) to predict and assess response to therapy in the context of a co-clinical imaging trial.
Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience
Authors: Håkansson Claes , Tamaddon Ashkan , Andersson Henrik , Torisson Gustav , Mårtensson Gustav , Truong My , Annertz Mårten , Londos Elisabet , Björkman-Burtscher Isabella M. , Hansson Oskar , van Westen Danielle 
Published: July 2021

Abstract
Objectives
To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population.

Methods
Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens’ MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen’s κ (dichotomized data), Cohen’s κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65).

Results
Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen’s κ. All raters achieved adequate agreement expressed as Cohen’s κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists.

Conclusion
We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.

Key Points
• Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population.
• Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings.
• The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.
Approximation of SDEs: a stochastic sewing approach
Authors: Butkovsky Oleg , Dareiotis Konstantinos , Gerencsér Máté 
Published: July 2021

AbstractWe give a new take on the error analysis of approximations of stochastic differential equations (SDEs), utilizing and developing the stochastic sewing lemma of Lê (Electron J Probab 25:55, 2020. 10.1214/20-EJP442). This approach allows one to exploit regularization by noise effects in obtaining convergence rates. In our first application we show convergence (to our knowledge for the first time) of the Euler–Maruyama scheme for SDEs driven by fractional Brownian motions with non-regular drift. When the Hurst parameter is $$H\in (0,1)$$

H
∈
(
0
,
1
)

and the drift is $$\mathcal {C}^\alpha $$

C

α

, $$\alpha \in [0,1]$$

α
∈
[
0
,
1
]

and $$\alpha >1-1/(2H)$$

α
>
1
-
1
/
(
2
H
)

, we show the strong $$L_p$$

L
p

and almost sure rates of convergence to be $$((1/2+\alpha H)\wedge 1) -\varepsilon $$

(
(
1
/
2
+
α
H
)
∧
1
)
-
ε

, for any $$\varepsilon >0$$

ε
>
0

. Our conditions on the regularity of the drift are optimal in the sense that they coincide with the conditions needed for the strong uniqueness of solutions from Catellier and Gubinelli (Stoch Process Appl 126(8):2323–2366, 2016. 10.1016/j.spa.2016.02.002). In a second application we consider the approximation of SDEs driven by multiplicative standard Brownian noise where we derive the almost optimal rate of convergence $$1/2-\varepsilon $$

1
/
2
-
ε

of the Euler–Maruyama scheme for $$\mathcal {C}^\alpha $$

C

α

drift, for any $$\varepsilon ,\alpha >0$$

ε
,
α
>
0

.
Nonlocal wrinkling instabilities in bilayered systems using peridynamics
Authors: Laurien Marie , Javili Ali , Steinmann Paul 
Published: July 2021

AbstractWrinkling instabilities occur when a stiff thin film bonded to an elastic substrate undergoes compression. Regardless of the nature of compression, this phenomenon has been extensively studied through local models based on classical continuum mechanics. However, the experimental behavior is not yet fully understood and the influence of nonlocal effects remains largely unexplored. The objective of this paper is to fill this gap from a computational perspective by investigating nonlocal wrinkling instabilities in a bilayered system. Peridynamics (PD), a nonlocal continuum formulation, serves as a tool to model nonlocal material behavior. This manuscript presents a methodology to precisely predict the critical conditions by employing an eigenvalue analysis. Our results approach the local solution when the nonlocality parameter, the horizon size, approaches zero. An experimentally observed influence of the boundaries on the wave pattern is reproduced with PD simulations which suggests nonlocal material behavior as a physical origin. The results suggest that the level of nonlocality of a material model has quantitative influence on the main wrinkling characteristics, while most trends qualitatively coincide with predictions from the local analytical solution. However, a relation between the film thickness and the critical compression is revealed that is not existent in the local theory. Moreover, an approach to determine the peridynamic material parameters across a material interface is established by introducing an interface weighting factor. This paper, for the first time, shows that adding a nonlocal perspective to the analysis of bilayer wrinkling by using PD can significantly advance our understanding of the phenomenon.
Atypical HUS and Crohn’s disease—interference of intestinal disease activity with complement-blocking treatment
Authors: Horváth Orsolya , Kelen Kata , Prohászka Zoltán , Hosszú Ádám , Szabó Attila J , Reusz George S 
Published: July 2021

Abstract
Background
In atypical hemolytic-uremic syndrome (aHUS), various defects of the complement system have been reported to explain pathophysiology. Therapeutic options for complement inhibition are well-recognized; however, the links between various immune-derived diseases and aHUS are unclear, and their interference with treatment efficacy during long-term complement-blocking therapy is scarcely known.

Case-diagnosis/treatment
We present a pediatric patient who developed aHUS with acute kidney injury in parallel with the onset of Crohn’s disease (CD), and who required long-term complement-blocking therapy with eculizumab (ECU). Unexpectedly, during the 6-year ECU treatment, an important intra-patient variation of the degree of complement inhibition was observed. In spite of continuous and stable doses of complement-blocking therapy, periods of incomplete blockade were observed in strong association with relapses of CD. When conventional and later biological therapy with adalimumab was introduced, with CD going into remission, complement blockade became complete again. Despite periodically low ECU levels and insufficient complement inhibition, no clinical or hematological signs of aHUS recurrence were detected during CD relapses.

Conclusion
In aHUS cases secondary to CD, close monitoring of both complement inhibition and serum ECU levels is needed as intestinal disease can interfere with complement-blocking treatment. Increased doses of ECU may be necessary to maintain therapeutic blood levels of ECU and full complement blockade, especially if the intestinal disease is not under control.
Comparative study of a novel selective urate reabsorption inhibitor “dotinurad” among patient groups with different stages of renal dysfunction
Authors: Takahashi Toshinari , Beppu Takanobu , Hidaka Yuji , Hosoya Tatsuo 
Published: July 2021

Abstract
Background
Dotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction.

Methods
Patient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner.

Results
In the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period.

Conclusion
The efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.
Einsamkeit bei Leihgroßeltern
Authors: Haag Sophie , Niederberger Marlen 
Published: July 2021

Zusammenfassung
Hintergrund
Soziale Kontakte nehmen im Alter stetig ab. Kritische Lebensereignisse, gesundheitliche Einschränkungen oder weite Entfernungen zu Familienmitgliedern bedingen diese Entwicklung. Um in dieser Lebensphase möglichen Gefühlen der Einsamkeit entgegen zu wirken, engagieren sich Ältere mitunter in der Freiwilligenarbeit. So bleiben sie in gesellschaftlichen Strukturen eingebettet und sind sozial integriert.

Ziel
Eine Möglichkeit des freiwilligen Engagements ist die Tätigkeit als Leihoma bzw. Leihopa, wie es in einer Mittelstadt in Baden-Württemberg angeboten wird. Das Projekt verspricht eine Vernetzung der Generationen und einen Beitrag zur intergenerativen Gesundheitsförderung. Die vorliegende Studie untersucht, welche Rolle Einsamkeit als Motivation zur Übernahme und Aufrechterhaltung der Tätigkeit als Leihoma oder Leihopa spielt.

Methode
Zur Datenerhebung wurden leitfadengestützte Interviews mit vier Leihgroßeltern durchgeführt. Die Interviews wurden wörtlich transkribiert und induktiv mit der qualitativen Inhaltsanalyse nach Mayring ausgewertet.

Ergebnisse
Einsamkeit erweist sich als zentrales Motiv für die Übernahme und Aufrechterhaltung der Aufgabe als Leihgroßeltern. Insbesondere die Zeit mit den LeihenkelInnen wird positiv bewertet. Die Tätigkeit in der Leihfamilie schaffe Befriedigung und unterstütze ein Gefühl der Zufriedenheit. Die Leihgroßeltern sind dankbar für die Möglichkeit, etwas Sinnvolles zu machen, sich aktiv in die Familie einbringen zu können und sind bereit, sich in die familialen Strukturen zu integrieren.

Schlussfolgerungen
Das Projekt eröffnet SeniorInnen die Chance, neuen Familienanschluss zu finden und Sozialkontakte, auch zu anderen Leihgroßeltern, aufzubauen. Doch die familiale Integration beschränkt sich mitunter auf die Zeit mit den Kindern.
Spatial Approach to Contribution of Public Policies to the Dynamization of the Rural Population
Authors: Cienfuegos Oscar Luis Alonso , Sánchez Ana Isabel Otero 
Published: July 2021

AbstractIn this article we will analyze the results, in terms of population, of the Common Agricultural Policy of the European Union, in a small European region, of one million inhabitants, with geographical characteristics typical of mountain agriculture. We will use spatial econometric techniques to verify whether the hypothesis that public spending destined for direct subsidization contributes positively to the territorial dynamics of certain relevant economic variables is fulfilled, specifically we will study in our case the population variable. From a methodological point of view, we will use several complementary approaches that give solidity to the results, always from the focus of spatial econometrics, essential when working with territorial data at a low level of disaggregation. On the one hand, we will carry out an exploratory spatial data analysis, which will allow us to detect possible patterns of spatial dependence, and then move on to a confirmatory analysis that will consider both, autocorrelation (models of lag and spatial error) and spatial heterogeneity (switching regressions). In addition to this cross-sectional data approach, which is based on a method of estimating the particular to the general, we will also use the estimation of spatial models of panel data, to include a temporal approach, with a method of estimating the general to the particular. The best results are obtained with a Spatial Durbin Model.
Negotiating anthropomorphism in the Ai-Da robot
Authors: Romic Bojana 
Published: July 2021

AbstractThe central interest of this paper is the anthropomorphic social robot Ai-Da (Aidan Meller Gallery/Oxford University), perceived as an actor in the interplay of cultural and representational gestures. These gestures determine how this robot is presented—that is, how its activities are articulated, interpreted and promoted. This paper criticises the use of a transhistorical discourse in the presentational strategies around this robot, since this discourse reinforces the so-called “myth of a machine”. The discussion focuses on the individuation and embodiment of this drawing robot. It is argued that the choice to provide Ai-Da with an evocative silicone face, coupled with an anthropomorphic body, is a socio-political decision that shapes public imaginaries about social robots in general.
Close encounters with scientific analogies of the third kind
Authors: Nappo Francesco 
Published: July 2021

AbstractArguments from non-causal analogy form a distinctive class of analogical arguments in science not recognized in authoritative classifications by, e.g., Hesse (1963) and Bartha (2009). In this paper, I illustrate this novel class of scientific analogies by means of historical examples from physics, biology and economics, at the same time emphasizing their broader significance for contemporary debates in epistemology.
Cost-of-illness for non-underweight binge-eating disorders
Authors: Jenkins Paul E. 
Published: July 2021

AbstractPurposeThis study examined economic costs associated with untreated eating disorders (EDs) characterised by regular binge eating in the absence of low weight. Both direct and indirect costs were assessed, reporting a limited societal perspective of economic impact as some costs were not included.MethodsOne hundred and twenty six adults seeking treatment for recurrent binge eating were asked to report impairment associated with an ED. Costs were calculated using 2017 prices, including an examination of variables associated with costs.ResultsEstimated societal costs for the year preceding assessment were £3268.47 (€3758.54) per person. In multivariate analyses, no reliable baseline associates of cost were identified.ConclusionThe economic burden of EDs characterised by regular binge eating is significant, and underscores the need for efficacious and cost-effective treatments. Individuals with binge-eating disorders report work impairment and healthcare use that may cost the United Kingdom economy upwards of £3.5 billion (€4bn) per annum. Further studies should consider academic impairment and the economic impact of EDs on families.Level of evidenceIII: evidence obtained from well-designed cohort or case–control analytic studies.
Atomic-Scale Layer-by-Layer Deposition of FeSiAl@ZnO@Al2O3 Hybrid with Threshold Anti-Corrosion and Ultra-High Microwave Absorption Properties in Low-Frequency Bands
Authors: Tian Wei , Li Jinyao , Liu Yifan , Ali Rashad , Guo Yang , Deng Longjiang , Mahmood Nasir , Jian Xian 
Published: July 2021

AbstractDeveloping highly efficient magnetic microwave absorbers (MAs) is crucial, and yet challenging for anti-corrosion properties in extremely humid and salt-induced foggy environments. Herein, a dual-oxide shell of ZnO/Al2O3 as a robust barrier to FeSiAl core is introduced to mitigate corrosion resistance. The FeSiAl@ZnO@Al2O3 layer by layer hybrid structure is realized with atomic-scale precision through the atomic layer deposition technique. Owing to the unique hybrid structure, the FeSiAl@ZnO@Al2O3 exhibits record-high microwave absorbing performance in low-frequency bands covering L and S bands with a minimum reflection loss (RLmin) of -50.6 dB at 3.4 GHz. Compared with pure FeSiAl (RLmin of -13.5 dB, a bandwidth of 0.5 GHz), the RLmin value and effective bandwidth of this designed novel absorber increased up to ~ 3.7 and ~ 3 times, respectively. Furthermore, the inert ceramic dual-shells have improved 9.0 times the anti-corrosion property of FeSiAl core by multistage barriers towards corrosive medium and obstruction of the electric circuit. This is attributed to the large charge transfer resistance, increased impedance modulus |Z|0.01 Hz, and frequency time constant of FeSiAl@ZnO@Al2O3. The research demonstrates a promising platform toward the design of next-generation MAs with improved anti-corrosion properties.
Antimicrobial ethicists: Making ethics explicit in antimicrobial stewardship
Authors: Yen Christina F. , Cutrell James B. 
Published: July 2021

Abstract
Antimicrobial prescribing and the associated discipline of antimicrobial stewardship have inherent ethical and moral dimensions. We contend that the explicit, formal application of ethical principles and frameworks can strengthen and further justify the value of antimicrobial stewardship programs and their work. To illustrate the value of this process, we highlight 3 ethical scenarios that antimicrobial stewardship programs regularly encounter at the prescriber, institutional, and societal levels, and we analyze these scenarios using the Beauchamp and Childress biomedical ethics framework.