bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Transporters for Drug Delivery to the Brain: Can We Do Better?
Authors: Puris Elena , Fricker Gert , Gynther Mikko 
Published: March 2022

AbstractLimited drug delivery to the brain is one of the major reasons for high failure rates of central nervous system (CNS) drug candidates. The blood–brain barrier (BBB) with its tight junctions, membrane transporters, receptors and metabolizing enzymes is a main player in drug delivery to the brain, restricting the entrance of the drugs and other xenobiotics. Current knowledge about the uptake transporters expressed at the BBB and brain parenchymal cells has been used for delivery of CNS drugs to the brain via targeting transporters. Although many transporter-utilizing (pro)drugs and nanocarriers have been developed to improve the uptake of drugs to the brain, their success rate of translation from preclinical development to humans is negligible. In the present review, we provide a systematic summary of the current progress in development of transporter-utilizing (pro)drugs and nanocarriers for delivery of drugs to the brain. In addition, we applied CNS pharmacokinetic concepts for evaluation of the limitations and gaps in investigation of the developed transporter-utilizing (pro)drugs and nanocarriers. Finally, we give recommendations for a rational development of transporter-utilizing drug delivery systems targeting the brain based on CNS pharmacokinetic principles.
Local trade-off between information and disturbance in quantum measurements
Authors: Terashima Hiroaki 
Published: March 2022

AbstractThis study confirms a local trade-off between information and disturbance in quantum measurements. It is represented by the correlation between the changes in these two quantities when the measurement is slightly modified. The correlation indicates that when the measurement is modified to increase the obtained information, the disturbance also increases in most cases. However, the information can be increased while decreasing the disturbance because the correlation is not necessarily perfect. For measurements having imperfect correlations, this paper discusses a general scheme that raises the amount of information while decreasing the disturbance.
Mental health conditions and academic burnout among medical and non-medical undergraduates during the mitigation of COVID-19 pandemic in China
Authors: Yang Qian , Liu Yueheng , Yang Winson Fuzun , Peng Pu , Chen Shubao , Wang Yunfei , Wang Xin , Li Manyun , Wang Yingying , Hao Yuzhu , He Li , Wang Qianjin , Zhang Junhong , Ma Yuejiao , He Haoyu , Zhou Yanan , Long Jiang , Qi Chang , Tang Yi-Yuan , Liao Yanhui , Tang Jinsong , Wu Qiuxia , Liu Tieqiao 
Published: March 2022

Abstract
The outbreak of the novel coronavirus disease 2019 (COVID-19) has posed a great impact on people’s mental health, especially for undergraduate students. This study aimed to compare the mental health conditions and academic burnout between medical and non-medical undergraduates in China when the COVID-19 pandemic is mitigating. A cross-sectional online survey was conducted among 4,972 undergraduates between October 2020 and April 2021, when the pandemic was basically under control. The survey included basic demographics information and standardized scales to evaluate depression, anxiety, perceived stress, daytime sleepiness, alcohol abuse/dependence, quality of life, fatigue, and academic burnout. Compared with medical undergraduates, non-medical undergraduates had higher rates of moderate to severe depression symptoms (29.1% vs. 17.9%, P < 0.001), moderate to severe anxiety symptoms (19.7% vs. 8.9%, P < 0.001), alcohol abuse/dependence (16.3% vs.10.3%, P < 0.001), excessive daytime sleepiness (47.4% vs. 43.4%, P = 0.018), high perceived stress (34.7% vs. 22.2%, P < 0.001), high level of fatigue (51.8% vs. 42.2%, P < 0.001), low QOL (35.8% vs. 21.4%, P < 0.001), and higher academic burnout score (59.4 vs. 57.5, P < 0.001). Being non-medical undergraduates, depression, alcohol abuse/dependence, excessive daytime sleepiness, and high perceived stress were positively associated with academic burnout, while high QOL was negatively associated with the burnout (all P < 0.001). Excessive daytime sleepiness was the strongest predictor for academic burnout.
Automated 3D thorax model generation using handheld video-footage
Authors: Dussel Nadine , Fuchs Reinhard , Reske Andreas W. , Neumuth Thomas 
Published: March 2022

Abstract
Purpose
For the visualization of pulmonary ventilation with Electrical Impedance Tomography (EIT) most devices use standard reconstruction models, featuring common thorax dimensions and predetermined electrode locations. Any discrepancies between the available model and the patient in terms of body shape and electrode position lead to incorrectly displayed impedance distributions. This work addresses that problem by presenting and evaluating a method for 3D model generation of the thorax and any affixed electrodes based on handheld video-footage.

Methods
Therefore, a process was developed, providing users with the ability to capture a patient's chest and the attached electrodes via smartphone. Once data is collected, extracted images are used to generate a 3D model with a structure from motion approach and locate electrodes with ArUco markers. For the evaluation of the developed method, multiple tests were performed in laboratory environments, which were compared with manually created reference models and differences quantified based on mean distance, standard deviation, and maximum distance.

Results
The implemented workflow allows for automated model reconstruction based on videos or selected images captured with a handheld device. It generates sparse point clouds from which a surface mesh is reconstructed and returns relative coordinates of any identified ArUco marker. The average value for the mean distance error of two model generations was 5.4 mm while the mean standard deviation was 6.0 mm. The average runtime of twelve reconstructions was 5:17 min, with a minimal runtime of 3:22 min and a maximal runtime of 7:29 min.

Conclusion
The presented methods and results show that model reconstruction of a patient’s thorax and applied electrodes at an emergency site is feasible with already available devices. This is a first step toward the automated generation of patient-specific reconstruction models for Electrical Impedance Tomography based on images recorded with handheld devices.
Multiphysics Simulation of Seebeck Coefficient Measurement
Authors: Huang K. , Edler F. 
Published: March 2022

AbstractUsing the finite element method (FEM), we developed a simulation model based on our actual apparatus, which is used for measuring the Seebeck coefficient and the electrical conductivity of thermoelectric materials. In terms of geometry, materials, and physics, our simulation model corresponds to the essential details of the experimental device. This article describes the model in detail and highlights key technical characteristics. By comparing it with actual measurement results, the accuracy of the model has been verified. Based on this accurate model, a simulation comparison study on the changes of certain parameters was carried out. Finally, the results of these comparisons are discussed to gain a deeper understanding of the actual experimental process and to improve the accuracy of the measurement.
Dissolved methane in anaerobic effluent: Emission or recovery?
Authors: Zhang Xiaoyuan , Gu Jun , Meng Shujuan , Liu Yu 
Published: March 2022

AbstractVarious anaerobic processes have been explored for the energy-efficient treatment of municipal wastewater. However, dissolved methane in anaerobic effluent appears to be a barrier towards the energy and carbon neutrality of wastewater treatment. Although several dissolved methane recovery methods have been developed, their engineering feasibility and economic viability have not yet been assessed in a holistic manner. In this perspective, we thus intend to offer additional insights into the cost-benefit of dissolved methane recovery against its emission.
Language of Religion, Religions as Languages. Introduction to the Special Issue ‘Religions and Languages: A Polyphony of Faiths’
Authors: Vestrucci Andrea 
Published: March 2022

AbstractReligions use linguistic and non-linguistic codes of meaning to express their contents: natural tongues, music, sculpture, poetry, rituals, practices... Also, religions provide the semantic context and the rules to produce, validate, and interpret their expressions: as such, religions can be considered languages. TheSophiaSpecial Issue ‘Religions and Languages: A Polyphony of Faiths’ explores the multifaceted relationships of world religions with languages broadly construed, intended as other religious codes, natural tongues, artistic forms, digital media, and even science. Do natural languages modify themselves in order to convey a divine message? How do artistic means of expression accommodate religious contents? What are the aspects of interaction between religions, technological advances, and scientific methods? The five contributions in this issue offer innovative, compelling, and engaging perspectives regarding this complex and fascinating issue.
Activation and Stabilization of Lipase B from Candida antarctica by Immobilization on Polymer Brushes with Optimized Surface Structure
Authors: Wunschik Dennis Sebastian , Lorenz André , Ingenbosch Kim Nadine , Gutmann Jochen Stefan , Hoffmann-Jacobsen Kerstin 
Published: March 2022

AbstractA reusable support system for the immobilization of lipases is developed using hybrid polymer-inorganic core shell nanoparticles. The biocatalyst core consists of a silica nanoparticle. PMMA is grafted from the nanoparticle as polymer brush via ARGET ATRP (activator regenerated by electron transfer atom transfer radical polymerization), which allows defining the surface properties by chemical synthesis conditions. Lipase B from Candida antarctica is immobilized on the hybrid particles. The activity and stability of the biocatalyst are analyzed by spectroscopic activity analysis. It is shown that the hydrophobic PMMA brushes provide an activating surface for the lipase giving a higher specific activity than the enzyme in solution. Varying the surface structure from disordered to ordered polymer brushes reveals that the reusability of the biocatalyst is more effectively optimized by the surface structure than by the introduction of crosslinking with glutaraldehyde (GDA). The developed immobilization system is highly suitable for biocatalysis in non-native media which is shown by a transesterification assay in isopropyl alcohol and an esterification reaction in n-heptane.
GLP-1R Agonist Exendin-4 Protects Against Hemorrhagic Transformation Induced by rtPA After Ischemic Stroke via the Wnt/β-Catenin Signaling Pathway
Authors: Liu Chengli , Sun Shanshan , Xie Jie , Li Hui , Li Tianyu , Wu Qiqi , Zhang Yongsheng , Bai Xiangjun , Wang Jian , Wang Xin , Li Zhanfei , Wang Wei 
Published: March 2022

AbstractTissue plasminogen activator (tPA) is recommended by the FDA to dissolve intravascular clots after acute ischemic stroke (AIS). However, it may contribute to hemorrhagic transformation (HT). The Wnt/β-catenin signaling pathway plays an important role in regulating the blood–brain barrier (BBB) formation in the central nervous system. We explored whether glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4) reduces the risk of HT after rtPA treatment via the Wnt/β-catenin pathway by using a rat transient middle cerebral artery occlusion (MCAO) modelin vivoand an oxygen–glucose deprivation plus reoxygenation (OGD/R) model in vitro. Our results showed that EX-4 attenuated neurological deficits, brain edema, infarct volume, BBB disruption, and rtPA-induced HT in ischemic stroke. EX-4 suppressed the production of ROS and the activation of MMP-9 to protect the integrity of the BBB by activating the Wnt/β-catenin signaling pathway. PRI-724, a selective inhibitor of β-catenin, was able to reverse the therapeutic effect of EX-4 in vivo and in vitro. Therefore, our results indicate that the GLP-1R agonist may be a potential therapeutic agent to decrease the risk of rtPA-induced HT after ischemic stroke via the Wnt/β-catenin signaling pathway.
Optimized Identification of Triacylglycerols in Milk by HPLC-HRMS
Authors: Imperiale Sebastian , Morozova Ksenia , Ferrentino Giovanna , Scampicchio Matteo 
Published: March 2022

AbstractThis work has developed an optimized workflow for the targeted analysis of triacylglycerols (TAGs) in milk by liquid chromatography coupled with a Q-Exactive Orbitrap mass spectrometer. First, the effects of resolution (17,500; 35,000; 70,000; 140,000) and automatic gain control target (AGC, from 2×104, 2×105, 1×106, and 3×106) have been optimized with the goal to minimize the injection time, maximize the number of scans, and minimize the mass error. Then, the flow rate of the liquid chromatography system was also optimized by maximizing the number of theoretical plates. The resulting optimized parameters consisted of a flow rate of 200 μL/min, mass resolution of 35,000, and AGC target of 2×105. Such optimal conditions were applied for targeted TAG analysis of milk fat extracts. Up to 14 target triglycerides in milk fat were identified performing a data-dependent HPLC-HRMS-MS2 experiment (t-SIM-ddMS2). The findings reported here can be helpful for MS-based lipidomic workflows and targeted milk lipid analysis.
Serial Homology
Authors: Fusco Giuseppe 
Published: March 2022

AbstractSerial homology, i.e., homology between repetitive structures in the same individual organism, is a debated concept in evolutionary developmental biology. The central question is the evolutionary interpretation of “sameness” in the context of the same body. This essay provides a synthetic analysis of the main issues involved in the debate, connecting conceptual problems with current experimental research. It is argued that a concept of serial homology that is not of the all-or-nothing kind can smooth several theoretical inconsistencies, while being more in line with what we know about evolutionary change and the way we investigate it.
Quality of cost evaluations of physician continuous professional development: Systematic review of reporting and methods
Authors: Cook David A. , Wilkinson John M. , Foo Jonathan 
Published: March 2022

Introduction We sought to evaluate the reporting and methodological quality of cost evaluations of physician continuing professional development (CPD).
Methods We conducted a systematic review, searching MEDLINE, Embase, PsycInfo, and the Cochrane Database for studies comparing the cost of physician CPD (last update 23 April 2020). Two reviewers, working independently, screened all articles for inclusion. Two reviewers extracted information on reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), and on methodological quality using the Medical Education Research Study Quality Instrument (MERSQI) and a published reference case.
Results Of 3338 potentially eligible studies, 62 were included. Operational definitions of methodological and reporting quality elements were iteratively revised. Articles reported mean (SD) 43% (20%) of CHEERS elements for the Title/Abstract, 56% (34%) for Introduction, 66% (19%) for Methods, 61% (17%) for Results, and 66% (30%) for Discussion, with overall reporting index 292 (83) (maximum 500). Valuation methods were reported infrequently (resource selection 10 of 62 [16%], resource quantitation 10 [16%], pricing 26 [42%]), as were descriptions/discussion of the physicians trained (42 [68%]), training setting (42 [68%]), training intervention (40 [65%]), sensitivity analyses of uncertainty (9 [15%]), and generalizability (30 [48%]). MERSQI scores ranged from 6.0 to 16.0 (mean 11.2 [2.4]). Changes over time in reporting index (initial 241 [105], final 321 [52]) and MERSQI scores (initial 9.8 [2.7], final 11.9 [1.9]) were not statistically significant (p ≥ 0.08).
Nutzungsverhalten von Lehrkräften bei der Implementierung einer physikdidaktisch innovativen Unterrichtskonzeption
Authors: Breuer Judith , Vogelsang Christoph , Reinhold Peter 
Published: March 2022

ZusammenfassungEine zentrale Aufgabe fachdidaktischer Forschung stellt die Verbesserung schulischen Unterrichts dar. Die freie Bereitstellung wirksamer Unterrichtskonzeptionen zur Unterstützung des Selbststudiums von Lehrkräften bildet eine Strategie für eine flächendeckende Implementierung fachdidaktischer Innovationen. Allerdings etablieren sich zahlreiche, empirisch erfolgreich evaluierte Unterrichtskonzeptionen nicht nachhaltig an Schulen. Daher untersucht das vorliegende Forschungsvorhaben den Implementationsprozess solcher Materialien unter authentischen Bedingungen. Dazu wurde kriteriengeleitet eine evidenzbasierte, fachdidaktisch innovative Unterrichtskonzeption ausgewählt: das Münchener Unterrichtskonzept zur Quantenmechanik (MILQ). Diese wurde den teilnehmenden Lehrkräften fakultativ zur Verfügung gestellt. Mittels Fallstudien wurde die Implementierung von MILQ von elf Lehrkräften durch halbstandardisierte Interviews zu Beginn und am Ende einer Unterrichtsreihe zur Quantenmechanik sowie zwei Unterrichtsbeobachtungen mit je einem anschließendenstimulated recallexplorativ erfasst. Die Probanden setzten sich überwiegend heuristisch mit MILQ auseinander und implementierten vor allem Elemente auf Sichtstrukturebene im Unterricht, die konform zu ihren bisherigen Vorstellungen waren. Dadurch wurde das fachdidaktische Innovationspotential nicht ausgeschöpft. Bezeichnend ist, dass der empirische Wirksamkeitsnachweis von MILQ für die Beurteilung der Lehrkräfte nicht relevant war, was aus theoretischer Sicht bislang als ein zentrales Argument der Bereitstellungsstrategie zur Implementierung fachdidaktischer Innovation angenommen wurde.
Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY
Authors: Grottoli S. , Bianchi A. , Bogazzi F. , Bona C. , Carlsson M. O. , Colao A. , Dassie F. , Giampietro A. , Gomez R. , Granato S. , Maffei P. , Pivonello R. , Prencipe N. , Ragonese M. , Urbani C. , Cannavò S. 
Published: March 2022

Abstract
Objective
A comprehensive picture of pegvisomant use for treating acromegaly in routine clinical practice in different countries is lacking. We aimed, therefore, to document country-specific behaviors in real-life pegvisomant use, and the main safety and effectiveness outcomes in the ACROSTUDY.

Design
ACROSTUDY is an open-label, non-interventional, post-marketing safety surveillance study.

Methods
A descriptive analysis was performed using data from the six top-recruiter ACROSTUDY countries, i.e., Germany (n = 548 patients), Italy (n = 466), France (n = 312), USA (n = 207), Spain (n = 200) and the Netherlands (n = 175). These nations accounted for > 85% of the ACROSTUDY cases.

Results
The mean pegvisomant dose at treatment start was lowest in the Netherlands (9.4 mg/day), whereas it ranged between 10.9 and 12.6 mg/day in the other countries. At year 5, the mean pegvisomant dose was around 15 mg/day in all countries, except France (18.1 mg/day). At starting pegvisomant, patients treated with monotherapy ranged between 15% in the Netherlands and 72% in Spain. Monotherapy remained lowest over time in the Netherlands. In all countries, the percentage of patients with normal IGF-1 increased steeply from < 20% at baseline to 43–58% at month 6 and 51–67% at year 1. After that, we observed minor changes in the rate of acromegaly control in all countries. The Netherlands peaked in disease control at year 2 (72%). The proportion of patients reporting changes in pituitary tumor size was generally low. Serious treatment-related adverse events were < 5% in all countries.

Conclusions
Our study provided a detailed summary of real-life use of pegvisomant in the six top-recruiter ACROSTUDY nations.
Large-Scale Fatigue Testing Based on the Rotating Beam Method
Authors: Isakov M. , Rantalainen O. , Saarinen T. , Lehtovaara A. 
Published: March 2022

Abstract
A large-scale fatigue testing machine based on the rotating beam method in a four-point bending configuration was designed and built. With the device, high-strength metal specimens with a 32-mm gauge diameter and a 100-mm gauge length can be tested at a cyclic frequency of up to 48 Hz. In this work, particular attention was paid to evaluating the spatial and temporal uniformity of the loading within the large specimen; methods for quantitative evaluation of these effects were developed. The developed test methodology allows for the fatigue testing of specimens with size, microstructure, and surface conditions that are similar to actual machine parts.
The crisis of nuclear arms control
Authors: Kühn Ulrich 
Published: March 2022

AbstractThe politics of nuclear arms control between the United States and Russia are in a protracted state of crisis, which is in need of explanation. This article provides an overview of bilateral contractual milestones from 1972 to 2001 and analyzes instances of cooperation through the lens of three key factors that have influenced the process. It then considers the changes that these factors have undergone over twenty years of crisis in bilateral arms control from 2001 to 2021 and gauges the possible consequences of a continuation of the current situation. It concludes that during the first period, a shared willingness to shield the bilateral process from political disruption, U.S. bipartisan support, and cooperatively addressing the vertical diffusion of offensive and defensive missile capabilities were both possible and necessary for ensuring success. During the second period, these key factors underwent significant changes and ultimately had a negative effect on the bilateral process, which makes the current crisis unique compared to earlier episodes of regression. Most importantly, both sides were no longer willing to shield the bilateral process in its entirety during this period, including defensive and sub-strategic offensive elements. With a view to future consequences, these findings point to reduced arms race stability, weaker negotiated outcomes, and an erosion of the global nonproliferation regime.
Using and Abusing the Arts with ‘At-Risk’ Youth
Authors: Howard Frances 
Published: March 2022

AbstractArts programmes are frequently provided for youth who are deemed unfortunate or unruly. Globally, arts programmes for at-risk youth have been widely recognised as beneficial; however, there has been a lack of criticality on how arts experiences can have an adverse impact. Research into a UK-based programme—the Arts Award—is presented to highlight the different, and lower quality, offer for at-risk youth. Multi-sited ethnography captured the experiences of participants accessing the programme through five diverse youth settings. My research demonstrated that often the most disadvantaged young people receive the weakest arts programmes, that are deficit-oriented, mechanistic and instrumentalised. This article offers a unique perspective on the ways in which the arts can fail at-risk youth.