bluuebunny/crossref_metadata_2025 huggingface dataset:
Future land-use change predictions using Dyna-Clue to support mosquito-borne disease risk assessment
Authors: Rakotoarinia Miarisoa Rindra , Seidou Ousmane , Lapen David R. , Leighton Patrick A. , Ogden Nicholas H. , Ludwig Antoinette
Published: June 2023

Mosquitoes are known vectors for viral diseases in Canada, and their distribution is driven by climate and land use. Despite that, future land-use changes have not yet been used as a driver in mosquito distribution models in North America. In this paper, we developed land-use change projections designed to address mosquito-borne disease (MBD) prediction in a 38 761 km2 area of Eastern Ontario. The landscape in the study area is marked by urbanization and intensive agriculture and hosts a diverse mosquito community. The Dyna-CLUE model was used to project land-use for three time horizons (2030, 2050, and 2070) based on historical trends (from 2014 to 2020) for water, forest, agriculture, and urban land uses. Five scenarios were generated to reflect urbanization, agricultural expansion, and natural areas. An ensemble of thirty simulations per scenario was run to account for land-use conversion uncertainty. The simulation closest to the average map generated was selected to represent the scenario. A concordance matrix generated using map pair analysis showed a good agreement between the simulated 2020 maps and 2020 observed map. By 2050, the most significant changes are predicted to occur mainly in the southeastern region’s rural and forested areas. By 2070, high deforestation is expected in the central west. These results will be integrated into risk models predicting mosquito distribution to study the possibility of humans’ increased exposure risk to MBDs.
No Reason to Worry About German Mortgages? An Analysis of Macroeconomic and Individual Drivers of Credit Risk
Authors: Barasinska Nataliya , Haenle Philipp , Koban Anne , Schmidt Alexander
Published: June 2023

This paper analyzes the macroeconomic and borrower-specific credit risk factors of residential real estate mortgages in Germany. Relying on a macroeconomic panel VAR model, we show a significant link between foreclosures, house price dynamics and unemployment. Using microeconomic regressions, we show that defaults are driven mostly by income and liquidity rather than loan-to-value (LTV) ratios. Based on those insights, we calibrate a structural model which predicts a significant increase in mortgage losses in a stress scenario, driven only partially by high-LTV loans. Hence, from a macroprudential perspective our findings support the need for a broad toolkit going beyond LTV-limits.
Evolutionary combination of connected event schemas into meaningful plots
Authors: Gervás Pablo , Méndez Gonzalo , Concepción Eugenio
Published: June 2023

Many of the stories we are exposed to are built from small schemas of connected events involving a set of characters–boy meets girl leads to a relationship or crime leads to revenge. The present paper proposes an evolutionary solution to the task of putting together a story by combining a set of such schemas. This approach presents three challenges: how to mix up the elements in the different schemas, how to instantiate the characters across the schemas and how to tell acceptable combinations from the rest. The present paper applies an evolutionary solution that relies on a genetic representation for these combinations of schemas, and applies as fitness functions a set of metrics on compatibility constraints across schema combinations. Outputs of this procedure are evaluated by human judges in comparison with baseline solutions in which the values for genes are assigned at random. The proposed solution generates a population of story drafts that resemble plot descriptions for simple stories. The results of the comparative evaluation by human judges are positive. The genetic representation of pattern combinations and the metrics on compatibility across pattern pairs provide a valid evolutionary solution for constructing simple plots.
Template-Based Generator for Single-Choice Questions
Authors: Willert Nico , Thiemann Jonathan
Published: June 2023

Manual composition of tasks and exams is a challenging and time-consuming task. Especially when exams are taken remotely without the personal monitoring by examiners, most exams can easily lose their integrity with the use of previously done exercises or student communication. This research introduces an approach that incorporates the principles of the generative software development and aspects of the feature-oriented product line engineering process into the field of question creation and generation. The resulting generator can be used to generate single-choice-question-families by means of written question templates. The generated questions within a question-family differ based on the set features and parameters and can be imported into the target learning management system ILIAS. Without much effort, examiners and educators can use the generator to create variants of their questions and deliver them to their students.
Repurposing Niclosamide as a plausible neurotherapeutic in autism spectrum disorders, targeting mitochondrial dysfunction: a strong hypothesis
Authors: Varma Manasi , Bhandari Ranjana , Kuhad Anurag
Published: June 2023

Autism Spectrum Disorders (ASD) are a complex set of neurodevelopmental manifestations which present in the form of social and communication deficits. Affecting a growing proportion of children worldwide, the exact pathogenesis of this disorder is not very well understood, and multiple signaling pathways have been implicated. Among them, the ERK/MAPK pathway is critical in a number of cellular processes, and the normal functioning of neuronal cells also depends on this cascade. As such, recent studies have increasingly focused on the impact this pathway has on the development of autistic symptoms. Improper ERK signaling is suspected to be involved in neurotoxicity, and the same might be implicated in autism spectrum disorders (ASD), through a variety of effects including mitochondrial dysfunction and oxidative stress. Niclosamide, an antihelminthic and anti-inflammatory agent, has shown potential in inhibiting this pathway, and countering the effects shown by its overactivity in inflammation. While it has previously been evaluated in other neurological disorders like Alzheimer’s Disease and Parkinson’s Disease, as well as various cancers by targeting ERK/MAPK, it’s efficacy in autism has not yet been evaluated. In this article, we attempt to discuss the potential role of the ERK/MAPK pathway in the pathogenesis of ASD, specifically through mitochondrial damage, before moving to the therapeutic potential of niclosamide in the disorder, mediated by the inhibition of this pathway and its detrimental effects of neuronal development.
Two types of ultrafast mode-locking operations from an Er-doped fiber laser based on germanene nanosheets
Authors: Xu Baohao , Jin Zhiyuan , Shi Lie , Zhang Huanian , Liu Qi , Qin Peng , Jiang Kai , Wang Jing , Tang Wenjing , Xia Wei
Published: June 2023

As a member of Xenes family, germanene has excellent nonlinear saturable absorption characteristics. In this work, we prepared germanene nanosheets by liquid phase exfoliation and measured their saturation intensity as 0.6 GW/cm2 with a modulation depth of 8%. Then, conventional solitons with a pulse width of 946 fs and high-energy noise-like pulses with a pulse width of 784 fs were obtained by using germanene nanosheet as a saturable absorber for a mode-locked Erbium-doped fiber laser. The characteristics of the two types of pulses were investigated experimentally. The results reveal that germanene has great potential for modulation devices in ultrafast lasers and can be used as a material for creation of excellent nonlinear optical devices to explore richer applications in ultrafast photonics.

Graphical Abstract
Improved oscillation criteria for second order quasilinear dynamic equations of noncanonical type
Authors: Grace Said R. , Chhatria G. N.
Published: June 2023

The present discussion is to study the following second order nonlinear delay dynamic equation of the form: $$\begin{aligned}{}[r(\theta )(\mathcal {W}^{\Delta }(\theta ))^{\alpha }]^{\Delta } +\mathcal {P}(\theta )\mathcal {W}^{\beta }(\eta (\theta ))=0,\;\theta \in \mathbb {T}_{0}=[\theta _{0},\infty )\cap \mathbb {T} \end{aligned}$$

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Advanced direct extrusion process with real-time controllable extrusion parameters for microstructure optimization of magnesium alloys
Authors: Azpiazu Leire Elorza , Egea Aritz , Letzig Dietmar , Ha Changwan
Published: June 2023

The extrusion speed and deformation temperature are important factors affecting the microstructure development during the deformation. Microstructure development plays a crucial role in the performance of the mechanical properties of materials. In direct extrusion, the homogeneous evolution of the microstructure in the length of the extruded bar could be affected due to its non-isothermal exit temperature evolution. Thus, a new set-up is suggested with real-time controllable speed and temperature to characterize the influence of temperature on the microstructure and obtain its homogeneous development for the magnesium alloy. During the extrusion, the temperature of the extruded bar is evaluated by using the infra-red camera, and the extrusion speed is simultaneously controlled in real-time depending on the temperature difference between a set temperature reference and the one obtained from the infra-red camera. This suggested set-up of extrusion is evaluated in terms of the microstructure and temperature evolution of the extruded bar.
The Predictive Role of the Posterior Cerebellum in the Processing of Dynamic Emotions
Authors: Malatesta Gianluca , D’Anselmo Anita , Prete Giulia , Lucafò Chiara , Faieta Letizia , Tommasi Luca
Published: June 2023

Recent studies have bolstered the important role of the cerebellum in high-level socio-affective functions. In particular, neuroscientific evidence shows that the posterior cerebellum is involved in social cognition and emotion processing, presumably through its involvement in temporal processing and in predicting the outcomes of social sequences. We used cerebellar transcranial random noise stimulation (ctRNS) targeting the posterior cerebellum to affect the performance of 32 healthy participants during an emotion discrimination task, including both static and dynamic facial expressions (i.e., transitioning from a static neutral image to a happy/sad emotion). ctRNS, compared to the sham condition, significantly reduced the participants’ accuracy to discriminate static sad facial expressions, but it increased participants’ accuracy to discriminate dynamic sad facial expressions. No effects emerged with happy faces. These findings may suggest the existence of two different circuits in the posterior cerebellum for the processing of negative emotional stimuli: a first-time-independent mechanism which can be selectively disrupted by ctRNS, and a second time-dependent mechanism of predictive "sequence detection" which can be selectively enhanced by ctRNS. This latter mechanism might be included among the cerebellar operational models constantly engaged in the rapid adjustment of social predictions based on dynamic behavioral information inherent to others’ actions. We speculate that it might be one of the basic principles underlying the understanding of other individuals’ social and emotional behaviors during interactions.
Analysis of Human Co-exposure to Lead and Cadmium Using Human Biomonitoring (HBM) Data in a Bayesian Copula-Based Regression Framework
Authors: Sy Moustapha , Conrad André , Jung Christian , Lindtner Oliver , Greiner Matthias
Published: June 2023

The identification of human co-exposure to industrial chemicals or environmental substances is of high interest in human health risk assessment. Due to their ubiquity and persistence in the environment, heavy metals such as cadmium (Cd) and lead (Pb) are of particular concern. Approaches to adequately investigating combinations of these and other often highly correlated variables are lacking. This study proposes a modeling approach to investigate the co-exposure to Cd and Pb, and better understanding the variations of blood Cd and Pb (CdB and PbB, respectively) together with potentially determinant factors. A copula-based regression model was built, using Bayesian inference and Markov Chain Monte Carlo simulation, to relate CdB and PbB of 3- to 14-year-old children participating in the German Environmental Survey for Children (GerES IV) with socio-demographic and ancillary exposure-relevant information. A minor to negligible dependence between CdB and PbB was observed, suggesting that Cd and Pb are subject to differing exposure sources/pathways or kinetics within human body. Despite the resulting low association between CdB and PbB, the developed approach provides methodological bases for enhancing the assessment of the cumulative exposure to multiple substances and for deepening the understanding of the determinants of these exposures.

Graphical Abstract
Use-wear analysis applied in a dissected palimpsest at the Middle Palaeolithic site of El Salt (eastern Iberia): working with lithic tools in a narrow timescale
Authors: Bencomo Mariel , Mayor Alejandro , Sossa-Ríos Santiago , Jardón Paula , Galván Bertila , Mallol Carolina , Hernández Cristo M.
Published: June 2023

Use-wear analyses are very useful to increase knowledge about the economic and subsistence dynamics carried out by Neanderthals. In general terms, functional results traditionally came from the analysis of tools belonging to stratigraphic units whose timescale refers to geological time. This is due to the fact that many Neanderthal sites are palimpsests of reiterated occupations over time, which must be dissected to approach us to human timescale. In the stratigraphic unit xa of El Salt (Alcoi, eastern Iberia), high temporal resolution archaeostratigraphic studies have been carried out. Diachronic material assemblages have been identified, allowing us to analyse more precisely the variability of Neanderthal behaviour over time. Amongst these assemblages, three have been selected (i.e. 5.3.1, 5.3.2 and 5.3.3) in order to analyse the lithic material functionality. The results obtained bring out the performance of different tasks within each analytical framework: woodworking in 5.3.1, woodworking and animal processing in 5.3.2, and butchering activity in 5.3.3. These results reflect the existence of a series of diachronic tasks carried out in overlapping activity areas. In this way, this work evidences flint use variability in a specific area of the site across time that could have been recognised only by means of high temporal resolution analytical frameworks.
Ambient vibrations-supported seismic assessment of the Saint Lawrence Cathedral’s bell tower in Genoa, Italy
Authors: Degli Abbati Stefania , Sivori Daniele , Cattari Serena , Lagomarsino Sergio
Published: June 2023

Post-earthquake damage surveys systematically highlight the seismic vulnerability of monumental structures, calling for simple assessment procedures to address the design of effective retrofitting interventions. The structural complexity characterizing monumental structures, however, makes a reliable prediction of their seismic response a relevant challenge of engineering interest. Ambient vibration tests (AVTs) provide valuable support to achieve such a task, improving the knowledge of the actual dynamic behavior of the structure and, consequently, the reliability of the seismic assessment. In this context, the paper illustrates the integration of AVTs outcomes with the evaluation of the seismic performance of historic masonry structures by presenting the comprehensive application to a case study, the bell tower of the Saint Lawrence’s Cathedral in Genoa, Italy. The research combines the assessment of the global seismic response of the tower, investigated through a simplified mechanical model, with the local verification of the pinnacles placed at its top, referring to a displacement-based approach on a macro-block model. An extensive ambient vibrations measurement campaign carried out in May 2020 allowed for a comprehensive operational identification of the bell tower and its pinnacles, clarifying the ongoing dynamic interaction with the main body of the church. This valuable information was successfully employed, first, to accurately reproduce the actual constraint conditions induced by the church on the bell tower, a determining factor in the modeling of its global seismic response and, second, to reliably quantify the seismic amplification caused by the tower filtering effect to be used as the seismic input for the local verification of the pinnacles.
Biomedical Ethical Aspects Towards the Implementation of Artificial Intelligence in Medical Education
Authors: Busch Felix , Adams Lisa C. , Bressem Keno K.
Published: June 2023

The increasing use of artificial intelligence (AI) in medicine is associated with new ethical challenges and responsibilities. However, special considerations and concerns should be addressed when integrating AI applications into medical education, where healthcare, AI, and education ethics collide. This commentary explores the biomedical ethical responsibilities of medical institutions in incorporating AI applications into medical education by identifying potential concerns and limitations, with the goal of implementing applicable recommendations. The recommendations presented are intended to assist in developing institutional guidelines for the ethical use of AI for medical educators and students.
Tailoring Food Biopolymers into Biogels for Regenerative Wound Healing and Versatile Skin Bioelectronics
Authors: Zeng Qiankun , Peng Qiwen , Wang Fangbing , Shi Guoyue , Haick Hossam , Zhang Min
Published: June 2023

An increasing utilization of wound-related therapeutic materials and skin bioelectronics urges the development of multifunctional biogels for personal therapy and health management. Nevertheless, conventional dressings and skin bioelectronics with single function, mechanical mismatches, and impracticality severely limit their widespread applications in clinical. Herein, we explore a gelling mechanism, fabrication method, and functionalization for broadly applicable food biopolymers-based biogels that unite the challenging needs of elastic yet injectable wound dressing and skin bioelectronics in a single system. We combine our biogels with functional nanomaterials, such as cuttlefish ink nanoparticles and silver nanowires, to endow the biogels with reactive oxygen species scavenging capacity and electrical conductivity, and finally realized the improvement in diabetic wound microenvironment and the monitoring of electrophysiological signals on skin. This line of research work sheds light on preparing food biopolymers-based biogels with multifunctional integration of wound treatment and smart medical treatment.
Analysis of Track Bending Stiffness and Loading Distribution Effect in Rail Support by Application of Bending Reinforcement Methods
Authors: Nabochenko Olga , Sysyn Mykola , Gerber Ulf , Krumnow Norman
Published: June 2023

Railway track is a linearly inhomogeneous object that consists of geometrical and elastic discontinuities such as bridges, transition zones, rail joints and crossings. The zones are subjected to the development of local instabilities due to quicker deterioration than the other tracks. Until now, there have been no efficient approaches that could fully exclude the problem of accelerated differential settlements in the problem zones. Many structural countermeasures are directed at controlling the sleeper/ballast loading with the help of fastenings/under-sleeper pad elasticities, sleeper forms and additional bending stiffness reinforcements. However, the efficiency of the methods is difficult to compare. The current paper presents a systematic approach in which the loading distribution effect in the rail support by application of two bending reinforcement methods is compared: auxiliary rail and under-sleeper beam. The study considers only the static effects to reach a clear understanding the influence of the main factors. The track equivalent bending stiffness criterion is proposed for comparing reinforcement solutions. The analysis shows that the activation of the bending stiffness of the reinforcement beams depends on the relative ratio of the rail fastenings stiffness and track support stiffness under sleepers (or under the under-sleeper beam). The comparison demonstrates that conventional auxiliary rail reinforcement solutions are ineffective due to their weak bending because of the high elasticity of fastening clips and the main rail fastenings. The share of an auxiliary rail is maximally 20% in the track bending stiffness and cannot be significantly improved by additional rails. The under-sleeper beam-based reinforcement solutions show noticeably higher efficiency. The highest effect can be achieved by the activation of the horizontal shear interaction between the under-sleeper beam and the rail. The additional track bending stiffness of the under-sleeper-based solutions is about 3.5 times more of the rail one and could be potentially increased to 6–10 times.
Real-Time Humidity Monitoring Using Distributed Optical Sensor for Water Asset Condition Assessment
Authors: Chow Christopher W. K. , Rameezdeen Raufdeen , Chen George Y. , Xu Haolan , Rahman Md Mizanur , Ma Xing , Zhuge Yan , Gorjian Nima , Gao Jing
Published: June 2023

It is well accepted that moisture ingress in concrete reduces durability and life span of water assets. Condition assessment is an important tool to inform decision for maintenance, retrofit or replacement. However, the most significant challenge is to obtain accurate condition information, particularly when the inspection points are physically difficult to access or inaccessible. Therefore, a reliable and cost-effective monitoring (sensor) system, preferably real-time with ability to streaming online, would be a useful management tool, particularly for water utilities. This paper describes an approach to develop a distributed optical fibre humidly sensor for condition assessment and environmental monitoring both inside and outside of infrastructures, such as inside the concrete and surrounding soil. A new polyelectrolyte multilayer (PEM) coating with higher sensitive was evaluated for relative humidity measurement in soil and concrete, respectively. In this study, two simulated conditions, in concrete and soil, were conducted to evaluate the sensing concept with the development of appropriate measuring methodologies including fibre installation and protection. The optical fibre sensor setup in laboratory environment showed that optical sensor can detect and indicate voltage change with the variation of moisture contents in both soil and concrete. The test results indicate a good correlation between high levels of relative humidity/moisture and transmitted optical power. A simple relative humidity (RH) calibration can be used to convert signal to RH in percentage for soil and concrete measurements and the procedure used to imbed the fibre in both samples is effective. Nevertheless, the sensor measures soil humidity (not moisture content); therefore, further investigation is required to identify the consequence for the variation of the measured parameter.
Bibo the Moving Cup for People Affected by Dementia: Design, Ethical Considerations, and First Observations in Use
Authors: Kollakidou Avgi , Lefeuvre Kevin , Zarp-Falden Christian Sønderskov , Malbois Elodie , Bodenhagen Leon , Krüger Norbert , Hornecker Eva
Published: June 2023

We present the concept and technical realisation for a cup that moves and lights up to bring itself to the attention of a person to trigger him/her taking a sip as a response. We then reflect on different ethical dimensions connected to the application of the cup in the context of people affected by dementia and describe first tests performed in elderly care homes. The concept is aimed at people with dementia in home or resident care who still have the ability to act, but tend to mentally drift away and thus require external impulses and triggers to drink. We found out that a substantial part of the residents fulfil these conditions. The cup moves and lights up in regular intervals if it has not been picked up recently. Once it is emptied, it alerts a caregiver to refill. Moreover, the degree or level of movement and light can be configured, depending on the person’s needs and reactions. This paper describes the core idea and the technical aspects of building the prototype. Finally, primary tests were conducted with the aim to construct a protocol and structure for an extended quantitative study.
Identifying Application Areas for Machine Learning in the Retail Sector
Authors: Brackmann Clemens , Hütsch Marek , Wulfert Tobias
Published: June 2023

Machine learning (ML) has the potential to take on a variety of routine and non-routine tasks in brick-and-mortar retail and e-commerce. Many tasks previously executed manually are amenable to computerization using ML. Although procedure models for the introduction of ML across industries exist, the tasks for which ML can be implemented in retail need to be determined. To identify these application areas, we followed a dual approach. First, we conducted a structured literature review of 225 research papers to identify possible ML application areas in retail, as well as develop the structure of a well-established information systems architecture. Second, we triangulated these preliminary application areas with the analysis of eight expert interviews. In total, we identified 21 application areas for ML in online and offline retail; these application areas mainly address decision-oriented and economic-operative tasks. We organized the application areas in a framework for practitioners and researchers to determine appropriate ML use in retail. As our interviewees provided information at the process level, we also explored the application of ML in two exemplary retail processes. Our analysis further reveals that, while ML applications in offline retail focus on the retail articles, in e-commerce the customer is central to the application areas of ML.
Red hair and pain sensitivity: insights into genomics of pain?
Authors: Williams Hannah R. , Pandit Jaideep J.
Published: June 2023

Purpose

To present a review of insights gained from investigating the question as to whether red haired individuals have altered sensitivity to pain.

Methods

A narrative review of the literature.

Results

Anecdotal observations from anaesthesiologists have suggested that individuals with red hair require more analgesia on average than members of the general population. This observation has been confirmed and the redheaded phenotype is associated with an altered sensitivity to pain across a wide range of different pain types. Through the use of mouse models, a central mechanism for this altered pain sensitivity has been proposed involving both the melanocortin and opioid receptor systems, despite the causative mutation for this phenotype occurring in melanocortin 1 receptors (MC1Rs) on peripheral melanocytes.

Conclusions

Understanding the endocrine imbalance caused by this loss of function mutation helps us to further explore the mechanisms behind pain sensitivity. It also facilitates a discussion about how pharmacogenomics can be exploited to personalise and subsequently optimise treatment.

Graphical Abstract
Oil discoveries and political windfalls: evidence on presidential support in Uganda
Authors: Paler Laura , Springman Jeremy , Grossman Guy , Pierskalla Jan
Published: June 2023

Oil discoveries, paired with delays in production, have created a new phenomenon: sustained post-discovery, pre-production periods. While research on the resource curse has debated the effects of oil on governance and conflict, less is known about the political effects of oil discoveries absent production. Using comprehensive electoral data from Uganda and a difference-in-differences design with heterogeneous effects, we show that oil discoveries increased electoral support for the incumbent chief executive in localities proximate to discoveries, even prior to production. Moreover, the biggest effects occurred in localities that were historically most electorally competitive. Overall, we show that the political effects of oil discoveries vary subnationally depending on local political context and prior to production, with important implications for understanding the roots of the political and conflict curses.
Status of terrestrial mammals in the Yangambi Landscape, Democratic Republic of the Congo
Authors: van Vliet Nathalie , Quintero Simón , Muhindo Jonas , Nyumu Jonas , Omar Cerutti Paolo , Nasi Robert , Rovero Francesco
Published: June 2023

In this study we provide the first comprehensive camera-trap assessment of terrestrial mammals in the Yangambi landscape, comprising the Yangambi Biosphere Reserve and a logging concession in the Democratic Republic of the Congo. The terrestrial mammal community in this area exhibits lower occupancy and species richness compared to other conservation areas in the Congo Basin. The community is dominated by four species: Emin's pouched rat Cricetomys emini (1.3 kg), African brush-tailed porcupine Atherurus africanus (2.8 kg), blue duiker Philantomba monticola (5 kg) and bay duiker Cephalophus dorsalis (12 kg), which are known to be highly resilient. Large ungulates and medium-sized carnivores have particularly low abundances. Our study also confirmed the presence of four species categorized as threatened on the IUCN Red List: the chimpanzee Pan troglodytes, giant ground pangolin Smutsia gigantea, black-bellied pangolin Phataginus tetradactyla and white-bellied pangolin Phataginus tricuspis. Our findings highlight the need to consider wildlife conservation at the landscape level, including the logging concession, where species showed higher occupancy levels compared to the Biosphere Reserve, and highlighting the need for planning infrastructure construction and developing mitigation schemes, reducing forest degradation from logging and developing permanent cash crop agriculture. Landscape-level conservation will only be possible if a collaborative management model steered by local communities is developed with the participation of all constituencies.
Crystal structure of 5-(3-methoxyphenyl)indoline-2,3-dione
Authors: Gorodnova Anastasia , Ivanov Vladimir N. , Kurkin Alexander V. , Dmitrienko Artem
Published: June 2023

The crystal structure of 5-(3-methoxyphenyl)indoline-2,3-dione (C15H11NO3) was solved and refined using laboratory powder diffraction data and optimized using density functional techniques. The title compound crystallizes in space group Pbca with a = 11.1772(3) Å, b = 7.92536(13) Å, c = 27.0121(7) Å, and V = 2392.82(10) Å3. The asymmetric unit contains one molecule. Isatin molecules are joined into almost flat chains along the a direction by N–H⋯O bonds. The chains are linked into layers by π-stacking interactions. Finally, the third dimension of the crystal is formed by weaker C–H⋯π and C–H⋯O contacts.
Welche Ärztinnen und Ärzte braucht es in der Zukunft?
Authors: Schmitz Christof
Published: June 2023

Zusammenfassung: Für Ideen zum ärztlichen Berufsbild der Zukunft müssen versorgungssystemische und gesellschaftliche Entwicklungen betrachtet werden. Erst daraus können konkrete Vorstellungen zum Berufsbild abgeleitet werden. Die folgenden Ausführungen zeigen, wie sich aufgrund gesellschaftlicher Entwicklungen eine Steigerung der Vielfalt bei den Patientinnen und Patienten, beim Personal und wohl auch eine Differenzierung von Versorgungssettings ergeben könnten. Die Konsequenz: Im Vergleich zu heute ist von fluideren und brüchigeren Berufsrollen auszugehen. Ärztliche Laufbahnen werden zukünftig mehr Rollenwechsel beinhalten, und die Frage der Ko-Evolution der Gesundheitsberufe wird deutlich relevanter werden. Das wirft grundsätzliche Fragen für die Aus- und Weiterbildung, aber auch für das professionelle Selbstverständnis auf.
Die Rolle des Elektrokardiogramms (EKG) in der Prävention des plötzlichen Herztods im Sport
Authors: Fuentes Artiles Ruben , van der Stouwe Jan Gerrit , Niederseer David
Published: June 2023

Zusammenfassung: Athlet_innen haben, verglichen mit der Normalbevölkerung, ein erhöhtes Risiko, einen plötzlichen Herztod beim Sport zu erleiden. Die Mehrheit dieser Athlet_innen leidet an einer bisher unerkannten kardiologischen Erkrankung, die für einen plötzlichen Herztod prädisponiert. Da körperliche Belastung einen wesentlichen Trigger für einen plötzlichen Herztod bei entsprechender Prädisposition darstellt, kann diese zugrundeliegende, meist erbliche Prädisposition dann zu einem plötzlichen Herztod während des Sports führen. Unterschiedliche Erkrankungen sind in verschiedenen Lebensabschnitten die Hauptursache für den plötzlichen Herztod während des Sports. Jedoch stellt das Screening mittels Elektrokardiogramm (EKG) unabhängig vom Alter eine allgemein etablierte Möglichkeit dar, Athlet_innen mit einer zugrundeliegenden, potenziell mit einem Sport-assoziierten plötzlichen Herztod vergesellschafteten Erkrankung zu identifizieren. Durch die Behandlung bzw. das entsprechende sportkardiologische Management der Erkrankung kann Leben gerettet werden.
CME: Ambulantes Management von Patientinnen und Patienten mit Leberzirrhose
Authors: Deuschle Florian , Semela David , Henz Samuel
Published: June 2023

Zusammenfassung: Viele Ursachen einer Zirrhose sind modifizierbar. Daher soll ätiologisch abgeklärt werden. Nach Diagnosesicherung wird die Grundkrankheit behandelt und die Betroffenen werden beraten (Alkoholabstinenz, Rauchstopp, gesunde Ernährung, Impfungen, körperliche Betätigung). Zum Varizenscreening wird eine Gastroskopie empfohlen. Patientinnen und Patienten mit Leberzirrhose haben ein erhöhtes Risiko für hepatozelluläre Karzinome, deshalb sollten sie halbjährlich eine Lebersonografie und die Bestimmung des Tumormarkers alpha-Foetoprotein machen (HCC Surveillance). Nach erster Dekompensation (z.B. Varizenblutung, Aszites, Enzephalopathie) oder Verschlechterung der Leberfunktion sollte eine Listung zur Lebertransplantation evaluiert werden. Die Kontrollhäufigkeit richtet sich nach Krankheitsstadium und eingetretenen Dekompensationen. Viele Komplikationen (z.B. Varizenblutung, spontan bakterielle Peritonitis, akutes Nierenversagen unter NSAR oder Diuretika) beginnen oligosymptomatisch und können rasch zu Multiorganversagen führen. Daher sollte bei Verschlechterung von Allgemeinzustand, Kognition oder Laborbefunden niedrigschwellig eine rasche Diagnostik erfolgen.
COPD – eine unterschätzte Erkrankung
Authors: Leuppi Jörg D. , Bridevaux Pierre-Olivier , Charbonnier Florian , Clarenbach Christian F. , Duchna Hans-Werner , Fellrath Jean-Marc , Gianella Pietro , Jochmann Anja , Kern Lukas , Pavlov Nikolay , Rothe Thomas , Steurer-Stey Claudia , von Garnier Christophe
Published: June 2023

Zusammenfassung: COPD ist eine heterogene Erkrankung mit komplexem Krankheitsbild. Die Diagnose ist nicht einfach zu stellen, denn COPD kann sich schleichend entwickeln und lange unbemerkt bleiben. Hausärztinnen und -ärzten kommt daher für die Früherkennung eine zentrale Rolle zu. Der COPD-Verdacht kann in Zusammenarbeit mit Pneumologen durch spezielle Untersuchungen abgesichert werden als Voraussetzung für das medikamentöse Therapiekonzept. Die neue GOLD-Guideline definiert drei COPD-Risikogruppen (A-B-E). Für Gruppe A wird ein kurz- oder langwirksamer Bronchodilatator (SAMA/SABA bzw. LAMA/LABA) empfohlen. Für Gruppe B und E wird eine Kombinationstherapie LABA+LAMA empfohlen. Bei Bluteosinophilie (≥300 Zellen/µl) und/oder kürzlicher Hospitalisierung aufgrund einer COPD-Exazerbation wird eine Dreifachtherapie (LABA+LAMA+ICS) empfohlen. Hausärztinnen und -ärzte sind wichtig bei der Umsetzung therapiebegleitender Massnahmen (Coaching von Patientinnen und Patienten, Impfungen, Rauchstopp, regelmässige Bewegung). Dies unterstreicht aber auch die hohen Anforderungen der Umsetzung der GOLD-Guideline in den Praxisalltag.
Making Andesite Through Shallow Hybridization of Magmas Derived From Variably Enriched Lithospheric Mantle
Authors: Wang Song‐Jie , Brown Michael
Published: June 2023

We integrate textural and in situ compositional information from plagioclase and clinopyroxene (Cpx) phenocrysts together with groundmass compositions in early Cretaceous andesite dykes within the Sulu belt of China to propose a new petrogenetic model for andesite. Plagioclase phenocrysts are mostly andesine; they are depleted in high field strength elements (HFSE). However, Cpx phenocrysts are either reversely zoned (type I) or homogeneous (type II), with the zoned Cpx divided into subtypes IA and IB. All Cpx has high Mg#, low Na2O and generally low Al2O3, with depletions in HFSE and variably high 87Sr/86Sr ratios, suggesting crystallization above the Moho from magmas derived from enriched lithospheric mantle. The cores of type IA/IB and type II Cpx have normal major‐ and trace‐element compositional variations and similar 87Sr/86Sr ratios to each other and to plagioclase, consistent with fractional crystallization from a common magma (magma 1). The rims of type IA and IB Cpx also have normal major‐ and trace‐element compositional variations, but these are not as evolved as the cores, and the rims have lower 87Sr/86Sr ratios, demonstrating crystallization from an isotopically distinct magma (magma 2). Based on modeled major and rare earth element compositions of magmas inferred to have been in equilibrium with different Cpx (±plagioclase) domains, the measured groundmass compositions can be reproduced by variable mixing between the two magmas. Our study demonstrates for the first time that andesite magma can be made through fractionation and shallow hybridization of magmas derived from variably enriched lithospheric mantle.
Skimming Flow and Sand Transport Within and Above Ammophila (Marram) Grass on a Foredune
Authors: Rotnicka Joanna , Dłużewski Maciej , Hesp Patrick A. , Tomczak Joanna O.
Published: June 2023

An investigation of wind flow and sand transport over a low to high density Ammophila dominated foredune on the Łeba barrier, Poland, utilizing multiple anemometers and sand traps is presented. The study provides the first high resolution data on modified saltation and suspended sand transport over a foredune under conditions of both canopy and skimming flow. Topographic acceleration of flow and topographic steering over the foredune were observed during oblique incident above threshold flow conditions. The concentration of sand in aeolian transport decreases with height to a minimum that is reached at different elevations above the ground, depending on Ammophila grass density. Of the three Ammophila (marram) grass densities investigated, nearly half (46%) of the total sand‐transport rate occurred above the lower density Ammophila grass, whereas up to 70% of the total transport occurred above the higher density marram grass. This likely results from both elastic collisions of sand grains with grass leaves over the Ammophila canopy and the different positions of the canopy rebounding surface, which is sensitive to even slight changes in wind speed. In addition, as plant density increases, there is less flow penetration into the canopy, vegetative forcing (similar to topographic forcing) of vertical flow is greater, and sand in both modified saltation and suspension is forced higher above the canopy in skimming flow. The maximum sand transport above the vegetation canopy increased in elevation from 32 to 48 to 53 cm as the vegetation density increased from low to moderate to high, respectively. The study also demonstrates that in skimming flow, relatively more sand is transported at higher elevations above a canopy surface than above a bare sand surface.
Silicon photonic Bessel–Gaussian beam generation unlocks new possibilities for long-range sensing
Authors: Kim Sangsik
Published: June 2023

Concentrically distributed silicon photonic grating arrays generate long-range Besse–Gaussian beams, enabling rotational and range measurements over obstacles. This compact and mass-producible chip unlocks new potentials for long-range sensing and applications.
Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem
Authors: Li Shibo , Li Chengpan , Khan Muhammad Imran , Liu Jing , Shi Zhengdi , Gao Dayong , Qiu Bensheng , Ding Weiping
Published: June 2023

Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus. However, the construction of hepatic sinusoids has always been a challenge for liver chips, especially for large-scale liver microsystems. Herein, we report an approach for the construction of hepatic sinusoids. In this approach, hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply. Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed. Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids, cell viability is witnessed to be considerably high, liver microstructure formation occurs, and hepatocyte metabolism is enhanced. In addition, this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing. This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.
The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users
Authors: Shram Megan J. , Henningfield Jack E. , Apseloff Glen , Gorodetzky Charles W. , De Martin Sara , Vocci Frank L. , Sapienza Frank L. , Kosten Thomas R. , Huston Jeff , Buchhalter August , Ashworth Judy , Lanier Ryan , Folli Franco , Mattarei Andrea , Guidetti Clotilde , Comai Stefano , O’Gorman Cedric , Traversa Sergio , Inturrisi Charles E. , Manfredi Paolo L. , Pappagallo Marco
Published: June 2023

Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (Emax) for Drug Liking, assessed using a bipolar 100-point visual analog scale (VAS). A total of 47 and 51 participants completed the Oxycodone Study and the Ketamine Study, respectively (Completer Population). In both studies, esmethadone doses ranging from therapeutic (25 mg) to 6 times therapeutic (150 mg) had a meaningful and statistically significantly (p < 0.001) lower Drug Liking VAS Emax compared with the positive control. Results were consistent for all secondary endpoints in both studies. In both studies, all doses of esmethadone were statistically equivalent to placebo on Drug Liking VAS Emax (p < 0.05). In the Ketamine Study, Drug Liking VAS Emax scores for esmethadone at all tested doses were significantly lower vs. dextromethorphan (p < 0.05) (exploratory endpoint). These studies indicate no meaningful abuse potential for esmethadone at all tested doses.
The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
Authors: Korn Sophie Marianne , Dhamotharan Karthikeyan , Jeffries Cy M. , Schlundt Andreas
Published: June 2023

The nucleocapsid protein (N) of SARS-CoV-2 plays a pivotal role during the viral life cycle. It is involved in RNA transcription and accounts for packaging of the large genome into virus particles. N manages the enigmatic balance of bulk RNA-coating versus precise RNA-binding to designated cis-regulatory elements. Numerous studies report the involvement of its disordered segments in non-selective RNA-recognition, but how N organizes the inevitable recognition of specific motifs remains unanswered. We here use NMR spectroscopy to systematically analyze the interactions of N’s N-terminal RNA-binding domain (NTD) with individual cis RNA elements clustering in the SARS-CoV-2 regulatory 5’-genomic end. Supported by broad solution-based biophysical data, we unravel the NTD RNA-binding preferences in the natural genome context. We show that the domain’s flexible regions read the intrinsic signature of preferred RNA elements for selective and stable complex formation within the large pool of available motifs.
Single-site decorated copper enables energy- and carbon-efficient CO2 methanation in acidic conditions
Authors: Fan Mengyang , Miao Rui Kai , Ou Pengfei , Xu Yi , Lin Zih-Yi , Lee Tsung-Ju , Hung Sung-Fu , Xie Ke , Huang Jianan Erick , Ni Weiyan , Li Jun , Zhao Yong , Ozden Adnan , O’Brien Colin P. , Chen Yuanjun , Xiao Yurou Celine , Liu Shijie , Wicks Joshua , Wang Xue , Abed Jehad , Shirzadi Erfan , Sargent Edward H. , Sinton David
Published: June 2023

Renewable CH4produced from electrocatalytic CO2reduction is viewed as a sustainable and versatile energy carrier, compatible with existing infrastructure. However, conventional alkaline and neutral CO2-to-CH4systems suffer CO2loss to carbonates, and recovering the lost CO2requires input energy exceeding the heating value of the produced CH4. Here we pursue CH4-selective electrocatalysis in acidic conditions via a coordination method, stabilizing free Cu ions by bonding Cu with multidentate donor sites. We find that hexadentate donor sites in ethylenediaminetetraacetic acid enable the chelation of Cu ions, regulating Cu cluster size and forming Cu-N/O single sites that achieve high CH4selectivity in acidic conditions. We report a CH4Faradaic efficiency of 71% (at 100 mA cm−2) with <3% loss in total input CO2that results in an overall energy intensity (254 GJ/tonne CH4), half that of existing electroproduction routes.
Coherent Stokes Raman scattering microscopy (CSRS)
Authors: Heuke Sandro , Rigneault Hervé
Published: June 2023

We report the first implementation of laser scanning coherent Stokes Raman scattering (CSRS) microscopy. To overcome the major challenge in CSRS imaging, we show how to suppress the fluorescence background by narrow bandpass filter and a lock-in based demodulation. Near background free CSRS imaging of polymer beads, human skin, onion cells, avocado flesh and the wing disc of a drosphila larva are presented. Finally, we explain and demonstrate numerically that CSRS solves a major obstacle of other coherent Raman techniques by sending a significant part (up to 100%) of the CSRS photons into the backward direction under tight focusing conditions. We believe that this discovery will pave the way for numerous technological advances, e.g., in epi-detected coherent Raman multi-focus imaging, real-time laser scanning based spectroscopy or efficient endoscopy.