bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiologically‐based pharmacokinetic pharmacodynamic parent‐metabolite model of edoxaban to predict drug–drug‐disease interactions: M4 contribution
Authors: Xu Ruijuan , Liu Wenyuan , Ge Weihong , He Hua , Jiang Qing
Published: April 2023

This study aimed to develop a physiologically‐based pharmacokinetic pharmacodynamic (PBPK/PD) parent‐metabolite model of edoxaban, an oral anticoagulant with a narrow therapeutic index, and to predict pharmacokinetic (PK)/PD profiles and potential drug–drug‐disease interactions (DDDIs) in patients with renal impairment. A whole‐body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extrapolated to situations including renal impairment and drug‐drug interactions (DDIs). Observed PK and PD data in adults were compared with predicted data. The effect of several model parameters on the PK/PD response of edoxaban and M4 was investigated in sensitivity analysis. The PBPK/PD model successfully predicted PK profiles of edoxaban and M4 as well as anticoagulation PD responses with or without the influence of interacting drugs. For patients with renal impairment, the PBPK model successfully predicted the fold change in each impairment group. Inhibitory DDI and renal impairment had a synergistic effect on the increased exposure of edoxaban and M4, and their downstream anticoagulation PD effect. Sensitivity analysis and DDDI simulation show that renal clearance, intestinal P‐glycoprotein activity, and hepatic OATP1B1 activity are the major factors affecting edoxaban‐M4 PK profiles and PD responses. Anticoagulation effect induced by M4 cannot be ignored when OATP1B1 is inhibited or downregulated. Our study provides a reasonable approach to adjust the dose of edoxaban in several complicated scenarios especially when M4 cannot be ignored due to decreased OATP1B1 activity.
State Manipulation via the All‐Microwave Protocol in the Superconducting Qutrits
Authors: Liu Qiang , Song Xiaofeng , Liu Tao , Li Ruidong , Chen Jiasong , Ma Zhuang , Tan Xinsheng
Published: April 2023

The quantum gate is the foundation of quantum computation and simulation in superconducting circuits. In recent years, quantum systems with three energy levels have attracted much attention. Therefore, it is essential to study the protocol of the quantum‐state transfer in qutrits. Herein, the all‐microwave schemes are studied to realize the state transfer and quantum gates. First, the ∣fg>–∣ge> transition is designed in a superconducting circuit with a relatively large coupling. We measured the Stark shift in cases where the experimental parameters did not satisfy the dispersive condition. Then, by carefully calibrating the pulse parameters, the regular Rabi oscillation and the state transfer are realized between the second excited state of two qubits via stimulated Raman adiabatic passage.
Efficient global optimization with co‐evolutionary strategy for asymmetric minimax problem in robust design
Authors: Yang Wenying , Mei Fabin , Zhai Guofu
Published: April 2023

Minimax optimization (MMO), which aims at pursuing the solutions with the best performances in the worst case, is widely used in the robust design. However, there are still fundamental limitations for MMO to converge to the optimum when solving asymmetric problems. Moreover, when MMO is employed in robust design where the objective function is evaluated through costly simulations, the efficiency of the optimization becomes crucial. To address these issues, in this paper, A novel efficient global optimization algorithm based on co‐evolutionary strategy is proposed to solve the asymmetry MMO problem with satisfactory efficiency. Furthermore, the new algorithm is tested on eight analytical benchmark problems and compared with the state‐of‐the‐art methods. Lastly, the methodology has been successfully applied to the robust design of a practical engineering product.
Characteristics of research into professional learning across professions: A mapping review
Authors: Baumfield Vivienne , Bethel Alison , Dowek Aimee , Walshe Karen , Mattick Karen
Published: April 2023

Given the importance of their roles in society, the education of professionals is a central concern for providers and recipients of public services. In this article we consider the contribution of research on professional learning to current debate on the form and content of professional education. This mapping review asked, ‘What does the research literature tell us about the characteristics of research into professional learning across professions?’ We identified and synthesised primary research involving post‐qualification professionals' professional learning. We searched seven databases using terms such as ‘professional learning’, ‘professional development’ and ‘continuing education’ from 2000 to date. We carefully screened articles against agreed criteria, extracted data and mapped the findings. After removing duplicates, 20,616 records remained. After full text screening, 356 articles were included: 266 from teaching (75%), 77 from healthcare (22%) and 13 from another profession or cross‐professional (4%). Three included papers that spanned professions. Only 6% of articles studied the institution as the unit of analysis (rather than the individual). Around half of the included papers (49%) included an intervention. Most teaching interventions were proximal to the workplace whereas most healthcare/other studies were distal to the workplace, perhaps reflecting stage of development of the research field. Our study synthesised a heterogeneous literature to indicate the types or research that are needed to progress the debate. The clear differences in ‘style’ between professions suggested that collaboration could provide mutual benefit. Future research requires studies that report research in ways that lend themselves to evidence synthesis or replication.
Human iPSC‐Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System
Authors: Qi Lin , Matsuo Koji , Pereira Ashley , Lee Yue Tung , Zhong Fenmiao , He Yuchen , Zushin Peter‐James H. , Gröger Marko , Sharma Aditi , Willenbring Holger , Hsiao Edward C. , Stahl Andreas
Published: April 2023

Chronic white adipose tissue (WAT) inflammation has been recognized as a critical early event in the pathogenesis of obesity‐related disorders. This process is characterized by the increased residency of proinflammatory M1 macrophages in WAT. However, the lack of an isogenic human macrophage‐adipocyte model has limited biological studies and drug discovery efforts, highlighting the need for human stem cell‐based approaches. Here, human induced pluripotent stem cell (iPSC) derived macrophages (iMACs) and adipocytes (iADIPOs) are cocultured in a microphysiological system (MPS). iMACs migrate toward and infiltrate into the 3D iADIPOs cluster to form crown‐like structures (CLSs)‐like morphology around damaged iADIPOs, recreating classic histological features of WAT inflammation seen in obesity. Significantly more CLS‐like morphologies formed in aged and palmitic acid‐treated iMAC‐iADIPO‐MPS, showing the ability to mimic inflammatory severity. Importantly, M1 (proinflammatory) but not M2 (tissue repair) iMACs induced insulin resistance and dysregulated lipolysis in iADIPOs. Both RNAseq and cytokines analyses revealed a reciprocal proinflammatory loop in the interactions of M1 iMACs and iADIPOs. This iMAC‐iADIPO‐MPS thus successfully recreates pathological conditions of chronically inflamed human WAT, opening a door to study the dynamic inflammatory progression and identify clinically relevant therapies.
High Selectivity and Sensitivity in Chemiresistive Sensing of Co(II) Ions with Liquid‐Phase Exfoliated Functionalized MoS2: A Supramolecular Approach
Authors: Zhuravlova Anna , Ricciardulli Antonio Gaetano , Pakulski Dawid , Gorczyński Adam , Kelly Adam , Coleman Jonathan N. , Ciesielski Artur , Samorì Paolo
Published: April 2023

Chemical sensing of water contamination by heavy metal ions is key as it represents a most severe environmental problem. Liquid‐phase exfoliated two‐dimensional (2D) transition metal dichalcogenides (TMDs) are suitable candidates for chemical sensing thanks to their high surface‐to‐volume ratio, sensitivity, unique electrical characteristics, and scalability. However, TMDs lack selectivity due to nonspecific analyte‐nanosheet interactions. To overcome this drawback, defect engineering enables controlled functionalization of 2D TMDs. Here, ultrasensitive and selective sensors of cobalt(II) ions via the covalent functionalization of defect‐rich MoS2 flakes with a specific receptor, 2,2′:6′,2″‐terpyridine‐4′‐thiol is developed. A continuous network is assembled by healing of MoS2 sulfur vacancies in a tailored microfluidic approach, enabling high control over the assembly of thin and large hybrid films. The Co2+ cations complexation represents a powerful gauge for low concentrations of cationic species which can be best monitored in a chemiresisitive ion sensor, featuring a 1 pm limit of detection, sensing in a broad concentration range (1 pm ‐ 1 µm) and sensitivity as high as 0.308 ± 0.010 lg([Co2+])−1 combined with a high selectivity towards Co2+ over K+, Ca2+, Mn2+, Cu2+, Cr3+, and Fe3+ cations. This supramolecular approach based on highly specific recognition can be adapted for sensing other analytes through specific ad‐hoc receptors.
Manipulating the Interfacial Band Bending For Enhancing the Thermoelectric Properties of 1T′‐MoTe2/Bi2Te3 Superlattice Films
Authors: Zhang Cheng , Chen Zhe , Bai Hui , Lin Weixiao , Yang Ming , Hong Min , Zhan Fangyang , Xie Sen , Zhang Min , Li Ziwei , Wang Zhaohui , Luo Yubo , Yang Junyou , Wang Rui , Wu Jinsong , Zhang Hang , Zhang Qingjie , Liu Wei , Tang Xinfeng
Published: April 2023

Interfacial charge effects, such as band bending, modulation doping, and energy filtering, are critical for improving electronic transport properties of superlattice films. However, effectively manipulating interfacial band bending has proven challenging in previous studies. In this study, (1T′‐MoTe2)x(Bi2Te3)y superlattice films with symmetry‐mismatch were successfully fabricated via the molecular beam epitaxy. This enables to manipulate the interfacial band bending, thereby optimizing the corresponding thermoelectric performance. These results demonstrate that the increase of Te/Bi flux ratio (R) effectively tailored interfacial band bending, resulting in a reduction of the interfacial electric potential from ≈127 meV at R = 16 to ≈73 meV at R = 8. It is further verified that a smaller interfacial electric potential is more beneficial for optimizing the electronic transport properties of (1T′‐MoTe2)x(Bi2Te3)y. Especially, the (1T′‐MoTe2)1(Bi2Te3)12 superlattice film displays the highest thermoelectric power factor of 2.72 mW m−1 K−2 among all films, due to the synergy of modulation doping, energy filtering, and the manipulation of band bending. Moreover, the lattice thermal conductivity of the superlattice films is significantly reduced. This work provides valuable guidance to manipulate the interfacial band bending and further enhance the thermoelectric performances of superlattice films.
Characterization of Corn Starch Granules Modified by Glucan 1,4‐α‐Maltotriohydrolase from Microbacterium imperiale
Authors: Wu Chunsen , Zhang Yan , Gao Fan , Zhang Jian , Qian Jian‐Ya
Published: April 2023

In this study, glucan 1,4‐α‐maltotriohydrolase (AMTS) is used to modify corn starch granules to elucidate the structural and physical property changes following AMTS modification. The degree of hydrolysis (DH) of granular corn starch is modulated by adding various amounts of AMTS. Pore structures with more pores, deep channels, and cavities in starch granules with extended hydrolysis are observed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The short‐range ordered structure, lamellar structure, and crystalline structure are significantly enhanced under moderate AMTS modification, and then slightly decreased with further modification. These structural changes significantly improve oil and water absorption capacities, decrease solubility and swelling power, diminish pasting properties, and lower the digestibility of granular corn starch. When AMTS interferes with the starch system, the specific surface area of granular starch gradually increases with extended hydrolysis, with the maximum being almost 4.6‐fold that of native starch. All these results suggest AMTS hydrolysises of corn starch granules through an “inside‐out” pattern, preferential hydrolysis of the amorphous region, and subsequent alternate hydrolysis of the amorphous and crystalline regions. Overall, AMTS is a potential granular starch hydrolase for producing porous starch used as the carrier material in a variety of food applications.
Developmental immunotoxicity of maternal exposure to yttrium nitrate on BALB/c offspring mice
Authors: Yuan Yuese , Wang Xiaoyun , Ge Jianhong , Jiang Wanyu , Li Zekang , Wang Zhenyu , Xiao Qianqian , Meng Qinghe , Jiang Jianjun , Hao Weidong , Wei Xuetao
Published: April 2023

Yttrium is a typical heavy rare earth element with widespread use in numerous sectors. Only one previous study has indicated that yttrium has the potential to cause developmental immunotoxicity (DIT). Therefore, there remains a paucity of evidence on the DIT of yttrium. This study aimed to explore the DIT of yttrium nitrate (YN) and the self‐recovery of YN‐induced DIT. Dams were treated with 0, 0.2, 2, and 20 mg/kg bw/day YN by gavage during gestation and lactation. No significant changes were found in innate immunity between the control and YN‐treated groups in offspring. In female offspring at postnatal day 21 (PND21), YN markedly inhibited humoral and cellular immune responses, the proliferative capacity of splenic T lymphocytes, and the expression of costimulatory molecules in splenic lymphocytes. Moreover, the inhibitory effect on cellular immunity in female offspring persisted to PND42. Unlike females, YN exposure did not change the adaptive immune responses in male offspring. Overall, maternal exposure to YN showed a strong DIT to offspring, with the lowest effective dose of 0.2 mg/kg in the current study. The toxicity of cellular immunity could persist throughout development into adulthood. There were sex‐specific differences in YN‐induced DIT, with females being more vulnerable.
Interacting effects of climate change and invasions by alien plant species on the morphodynamics of temperate rivers
Authors: O'Briain Rossa , Corenblit Dov , Gurnell Angela
Published: April 2023

This review explores the implications of climate change for the functioning of plant species as biogeomorphic engineers of temperate river systems, including the potential for an increasing role of invasive alien plant species (IAPS). First, we introduce engineer plants as important controls, along with flowing water and transported sediments, on the morphodynamics of river systems and the likelihood that climate change may affect the contributions of species within their native habitats. We then examine through the prism of the fluvial biogeomorphic succession model how climate change may accelerate the establishment of IAPS, the possible consequences for the performance and/or persistence of native engineer plant species, and thus the potential pathways of influence for IAPS on river morphodynamics. Finally, we present examples of the impacts of invasions by specific plant species along particular river systems and consider their potential biogeomorphic impact against a backdrop of climate change. Loss, replacement, or displacement of native plant species in the river corridor by IAPS can potentially alter biogeomorphic phenomena by directly increasing or decreasing erosion and/or sedimentation and the associated development of fluvial landforms. In the shorter term, increased climate disturbance may provide more establishment opportunities for opportunistic IAPS. In the longer term, under heavy establishment, IAPS may alter the coupled assembly of plant communities, fluvial landforms and ecosystem development, potentially resulting in river landscape metamorphosis and significantly changed habitat conditions.

This article is categorized under:

Science of Water > Water and Environmental Change

Water and Life > Nature of Freshwater Ecosystems

Water and Life > Stresses and Pressures on Ecosystems

Water and Life > Conservation, Management, and Awareness
Building a Fine-Grained Analytical Performance Model for Complex Scientific Simulations
Authors: van Dijk Jelle , Zavodszky Gabor , Varbanescu Ana-Lucia , Pimentel Andy D. , Hoekstra Alfons
Published: April 2023

Analytical performance models are powerful for understanding and predicting the performance of large-scale simulations. As such, they can help identify performance bottlenecks, assess the effect of load imbalance, or indicate performance behavior expectations when migrating to larger systems. Existing automated methods either focus on broad metrics and/or problems - e.g., application scalability behavior on large scale systems and inputs - or use black-box models that are more difficult to interpret e.g., machine-learning models.

In this work we propose a methodology for building per-process analytical performance models relying on code analysis to derive a simple, high-level symbolic application model, and using empirical data to further calibrate and validate the model for accurate predictions.

We demonstrate our model-building methodology on HemoCell, a high-performance framework for cell-based bloodflow simulations. We calibrate the model for two large-scale systems, with different architectures. Our results show good prediction accuracy for four different scenarios, including load-balanced configurations (average error of 3.6%, and a maximum error below 13%), and load-imbalanced ones (with an average prediction error of 10% and a maximum error below 16%).
Proactive Task Offloading for Load Balancing in Iterative Applications
Authors: Chung Minh Thanh , Weidendorfer Josef , Fürlinger Karl , Kranzlmüller Dieter
Published: April 2023

Load imbalance is often a challenge for applications in parallel systems. Static cost models and pre-partitioning algorithms distribute the load at the beginning. Nevertheless, dynamic changes during execution or inaccurate cost indicators may lead to imbalance at runtime. Reactive work-stealing strategies can help monitor the execution and perform task migration to balance the load. However, the benefits depend on migration overhead and assumption about future execution.

Our proactive approach further improves existing solutions by applying machine learning to online load prediction. Following that, we propose a fully distributed algorithm for adapting the prediction result to guide task offloading. The experiments are performed with an artificial test case and a realistic application named Sam(oa)$$^2$$2on three systems with different communication overhead. Our results confirm improvements for important use cases compared to previous solutions. Furthermore, this approach can support co-scheduling tasks across multiple applications.
Die Erforschung geschriebener und gesprochener Hassrede im Deutschen: bisherige Erkenntnisse zu Prosodie und Kontext
Authors: Neitsch Jana , Niebuhr Oliver
Published: April 2023

Dass Hassrede (hate speech) zunehmend als Problem gilt, geht nicht allein auf ein steigendes Vorkommen zurück, sondern auch auf eine erhöhte Sensibilität für dieses Thema. Da die sprachliche Struktur von Hassrede sehr vielfältig und ihre Wahrnehmung sehr komplex ist, rückt ihre Erforschung zudem verstärkt in den Fokus der Linguistik und der Prosodieforschung. In unserem Beitrag fassen wir die Untersuchung unterschiedlicher geschriebener und gesprochener Hassredetypen im Deutschen über die letzten drei Jahre zusammen. Wir zeigen, dass geschriebene Hassrede anders wahrgenommen wird, sobald man sie laut ausspricht. Dabei werden lexikalisch vormarkierte Typen von Hassrede, etwa Imperative oder solche mit Holocaust-Bezug, in ihrer negativen Wirkung verstärkt, während Hassrede, die auf stimmlichen Faktoren basiert, wie Ironie oder rhetorische Fragen, an negativer Wirkung verliert. Wir zeigen außerdem, wie sich diese Urteile in menschlichen Biosignalen wiederfinden, z. B. in EEG-Messungen zu Stress und Emotionen im präfrontalen Kortex. In diesem Zusammenhang beschreibt der Beitrag auch ein neues EEG-Experiment, das die Rolle des sozialen Kontextes auf die Wirkung von Hassrede untersucht. Unsere Ergebnisse zeigen ein höheres EEG-Stresslevel, wenn Rezipienten alleine mit Hassrede konfrontiert sind im Vergleich zur Hassrede-Konfrontation in Gesellschaft eines bekannten Menschen. Abschließend leitet der Beitrag aus allen Ergebnissen Ansatzpunkte für den praktischen Umgang mit Hassrede und deren weitere Erforschung ab.
Automatische Klassifikation offensiver deutscher Sprache in sozialen Netzwerken
Authors: Demus Christoph , Labudde Dirk , Pitz Jonas , Probol Nadine , Schütz Mina , Siegel Melanie
Published: April 2023

Der Umgang mit Hatespeech ist bereits seit mehreren Jahren ein Problem im Internet, insbesondere in sozialen Netzwerken. Da die enorme Menge an Kommentaren nicht mehr manuell moderiert werden kann, ist es essenziell, automatische Methoden zur Detektion offensiver Kommentare unterstützend einzusetzen. Doch speziell in Bezug auf die deutsche Sprache bringt die Erforschung von Methoden zur Hatespeech-Erkennung einige Schwierigkeiten mit sich: zum einen sprachliche Besonderheiten und zum anderen die Knappheit geeigneter Datensätze. Deshalb soll mit diesem Kapitel ein Überblick über die Forschungsentwicklung gegeben werden, die wir insbesondere anhand von Shared Tasks darstellen. Außerdem werden geeignete Datensätze, Methoden und Ergebnisse zusammenfassend dargestellt und diskutiert.
Hate Speech behandeln: Diagnosewerkzeuge aus der Computerlinguistik
Authors: Schäfer Johannes
Published: April 2023

Hate Speech stellt in sozialen Medien ein offenkundiges Problem dar, welches in der Forschung in den letzten Jahren zunehmend interdisziplinär untersucht wird. In diesem Artikel beleuchte ich das Phänomen aus computerlinguistischer Sicht und beschreibe näherungsweise erprobte Herangehensweisen für Lösungsansätze. Durch eine Diskussion von Anwendungsmöglichkeiten ordne ich das Problem in die computerlinguistische Forschung ein, wobei sich hier die automatische Erkennung von Hate Speech in Kurznachrichten vordergründig als Hauptaufgabe herausgestellt hat. Ich zeige jedoch, dass damit nur ein Teil des Problems untersucht wird. Beispielsweise der Kontext von Nachrichten bleibt in den meisten Forschungen zur Hate-Speech-Erkennung außen vor, was eine Diskrepanz zum realen Vorkommen des Phänomens darstellt. Auch zeige ich, dass es weitere, wenig untersuchte Forschungsrichtungen zum Phänomen Hate Speech gibt, wie zum Beispiel die Analyse von Teiläußerungen. Schließlich schlage ich eine Einteilung von Lösungsansätzen zur Erkennung von Hate Speech in drei Kategorien vor, zu denen ich jeweils einen einleitenden Überblick gebe: Lexikonbasierte Systeme, erklärbare maschinelle Lernsysteme und neuronale Netzwerke.
Emotionsklassifikation in Texten unter Berücksichtigung des Komponentenprozessmodells
Authors: Klinger Roman
Published: April 2023

Ein wichtiger Bestandteil unserer alltäglichen Kommunikation, neben der Mitteilung und Beschreibung von Ereignissen und Fakten, ist der Ausdruck von Emotionen, welcher auch Bestandteil von Hassrede ist: Es wird zum Beispiel Wut zum Ausdruck gebracht, was wiederum bei den Betroffenen Angst, Traurigkeit oder vielleicht auch Überraschung auslösen kann. In der maschinellen Verarbeitung von Sprache haben sich in der letzten Zeit einige konkrete Aufgaben, welche Teil der Emotionsanalyse in Text sind, herauskristallisiert. Diese sind zum einen Klassifikationsaufgaben (welche Emotion drückt ein Text aus?) und zum anderen relationale Strukturlernaufgaben (welche Wörter bezeichnen die Person, die eine Emotion fühlt und welche Wörter lassen auf die Ursache der Emotion schließen?). Wir verschaffen uns in diesem Kapitel einen kurzen Überblick über das Feld und diskutieren im Anschluss etwas genauer, wie sich die Beschreibungen von Emotionen in verschiedenen Domänen unterscheiden und wie Ereignisbeschreibungen mit Hilfe psychologischer Theorien mit Emotionen zusammengebracht werden können. Insbesondere analysieren wir auf Basis des Emotions-Komponenten-Prozessmodells, auf welche Komponenten von Emotionen (subjektives Gefühl, kognitive Evaluation, Körperreaktion, Ausdruck, Motivation) Autor:innen zugreifen, und stellen fest, dass diese Verteilung zwischen sozialen Medien und Literatur unterschiedlich ist. In beiden Domänen spielt aber die kognitive Komponente zur Interpretation von Emotionen eine wichtige Rolle. Dies zeigt auf, dass insbesondere der Ereignisinterpretation Aufmerksamkeit geschenkt werden muss, um implizit kommunizierte Emotionen aufzudecken. Dies motiviert uns, Emotionen mit Hilfe der Appraisaltheorien zu analysieren, welche den Zusammenhang zwischen kognitiven Prozessen und Emotionen erklären. Zu beiden Konzepten – dem Komponentenmodell und den Appraisaltheorien – präsentieren wir Textkorpora und Klassifikationsmodelle.
The Rights of Nature as a Legal Response to the Global Environmental Crisis? A Critical Review of International Law’s ‘Greening’ Agenda
Authors: Gilbert Jérémie , Macpherson Elizabeth , Jones Emily , Dehm Julia
Published: April 2023

Over the past decade and a half, various natural entities have been recognised as having rights or legal personhood in certain domestic jurisdictions. The idea of nature as rights-bearing is seen by advocates to be a new and improved response to environmental threats. While rights of nature approaches are increasingly evident in transnational law, orthodox international law has yet to engage seriously with such approaches, despite increasing calls to recognise the rights of nature in international law. In this contribution we consider the potential and limitations of rights-based protections of nature as part of the ‘greening’ of international law. We argue that attempts to incorporate the rights of nature into international law need to be understood within the wider context and history of international law, including trajectories of colonialism and economic resource exploitation. Although rights of nature approaches may offer a path towards a greener international law, this path should not be followed in a way that reproduces problematic, homogenising aspects of international law, but instead centres human relationality with nature in place. Instead, we argue that there are important lessons to be learnt from transnational attempts to protect and implement rights of nature and legal personhood, especially where models are informed by Indigenous peoples’ relationships with nature.
Systematics of boundary actions in gauge theory and gravity
Authors: Kim Seolhwa , Kraus Per , Myers Richard M.
Published: April 2023

Abstract

We undertake a general study of the boundary (or edge) modes that arise in gauge and gravitational theories defined on a space with boundary, either asymptotic or at finite distance, focusing on efficient techniques for computing the corresponding boundary action. Such actions capture all the dynamics of the system that are implied by its asymptotic symmetry group, such as correlation functions of the corresponding conserved currents. Working in the covariant phase space formalism, we develop a collection of approaches for isolating the boundary modes and their dynamics, and illustrate with various examples, notably AdS3 gravity (with and without a gravitational Chern-Simons terms) subject to assorted boundary conditions.
The Vaults of the Church of St. Michael the Archangel in Brixen Between Geometry, History and Missed Space
Authors: Luigini Alessandro , Brusaporci Stefano , Kofler Waltraud , Basso Alessandro , Maiezza Pamela , Tata Alessandra , Rossi Maria Laura
Published: April 2023

Through the analysis of the vaulted system, the study aims to research the spatialities enclosed in the church of St. Michael the Archangel in Brixen (Bz): the current one surveyed, the gothic one and the painted baroque one, grafted onto the late-Gothic structure.
Fruit and vegetable consumption and the risk of hypertension: a systematic review and meta-analysis of prospective studies
Authors: Madsen Helga , Sen Abhijit , Aune Dagfinn
Published: April 2023

Purpose

A high fruit and vegetable intake has been associated with reduced risk of hypertension; however, results have been inconsistent and it is unclear whether specific types of fruits and vegetables are particularly beneficial. This systematic review and meta-analysis aimed to summarize the published prospective studies on fruit and vegetable consumption and risk of hypertension.

Methods

Embase and PubMed databases were searched for relevant prospective studies up to 15th May 2022. Random effects models were used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) for the association between fruit and vegetable intake and risk of hypertension. Strength of evidence was assessed using World Cancer Research Fund (WCRF) criteria.

Results

Eighteen prospective studies (451 291 participants, 145 492 cases) were included. The summary RR (95% CI) of hypertension per 200 g/day was 0.97 (0.95–0.99, I2 = 68%, n = 8) for fruits and vegetables, 0.93 (0.89–0.98, I2 = 77%, n = 10) for fruits, and 1.00 (0.98–1.02, I2 = 38%, n = 10) for vegetables. Reductions in risk were observed up to 800 g/day for fruits and vegetables, and 550 g/day for fruits, and these two associations were considered probably causal using WCRF criteria. Inverse associations were observed for apples or pears, blueberries, raisins or grapes, avocado, broccoli, carrots and lettuce, while positive associations were observed for cantaloupe, Brussels sprouts, cruciferous vegetables, and total and fried potatoes (n = 2–5).

Conclusion

A high intake of fruit and vegetables combined, and total fruit was associated with reduced risk of hypertension, while results for fruit and vegetable subtypes were mixed and need further study.
Akzeptanz einer telemetrischen Versorgung bei Patienten mit sICD-Sicherheitshinweis
Authors: König Leonie , Grünberg Elisabeth , Xynogalos Panagiotis , Thomas Dierk , Rivinius Rasmus , Frey Norbert , Ullrich Charlotte , Rahm Ann-Kathrin
Published: April 2023

Hintergrund

Telemonitoring dient der Überwachung von implantierbaren Kardioverter-Defibrillatoren (ICD). Trotz der wissenschaftlich nachgewiesenen Effektivität und Sicherheit der telemetrischen Versorgung zeigen Studien, dass das Angebot nicht bei allen Patienten mit der Nutzung und Akzeptanz des Telemonitorings einhergeht.

Fragestellung

Ziel dieses Forschungsvorhabens ist die Untersuchung der Einstellungen von ICD-Patienten zum Telemonitoring. Dabei ist von Interesse, welche Aspekte Einfluss auf die Haltung und Entscheidungsfindung nehmen.

Methode

Die Datenerhebung erfolgte anhand teilstrukturierter leitfadengestützter Einzelinterviews. Es wurden insgesamt 14 Patienten mit subkutanem ICD und sowohl primär als auch sekundärprophylaktischer Indikation rekrutiert. Die Datenauswertung erfolgte nach inhaltlich strukturierender qualitativer Vorgehensweise.

Ergebnis

Die Studie hat gezeigt, dass die Patienten mit Telemonitoring einen hohen Nutzen sehen, bei geringem Bedenken hinsichtlich der digitalen Technik. Bei Patienten ohne Telemonitoring verhält es sich umgekehrt. Die medizinischen Vorerfahrungen der Patienten haben einen wesentlichen Einfluss auf die Akzeptanz des Telemonitorings. Die technische Umsetzung und die praktische Handhabung des Telemonitorings wurden von Patienten aller Altersgruppen als einfach und unkompliziert angesehen.

Diskussion

Die Ergebnisse lassen darauf schließen, dass die primär- und sekundärprophylaktische Indikation für eine ICD-Implantation einen Einfluss auf die Einstellung zum Telemonitoring und somit auf dessen Akzeptanz haben. Die Ergebnisse geben Anlass zu weiterer qualitativer Forschung im Hinblick auf die Nutzerakzeptanz zum Telemonitoring anderer ICD-Systeme.
Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension
Authors: Meisel Andreas , Annane Djillali , Vu Tuan , Mantegazza Renato , Katsuno Masahisa , Aguzzi Rasha , Frick Glen , Gault Laura , Howard James F. ,   the CHAMPION MG Study Group
Published: April 2023

Introduction

Ravulizumab demonstrated efficacy and an acceptable safety profile versus placebo in the randomized controlled period (RCP) of the phase 3 CHAMPION MG trial in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. We report an interim analysis of the ongoing open-label extension (OLE) designed to evaluate long-term treatment effects.

Methods

Following completion of the 26-week RCP, patients could enter the OLE; patients who received ravulizumab in the RCP continued the drug; patients who previously received placebo switched to ravulizumab. Patients receive body-weight-based maintenance dosing of ravulizumab every 8 weeks. Efficacy endpoints up to 60 weeks included Myasthenia Gravis–Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores, with least-squares (LS) mean change and 95% confidence intervals (95% CI) reported.

Results

Long-term efficacy and safety in the OLE were analyzed in 161 and 169 patients, respectively. Improvements in all scores were maintained through 60 weeks in patients who received ravulizumab during the RCP; LS mean change from RCP baseline in MG-ADL score was − 4.0 (95% CI: − 4.8, − 3.1; p < 0.0001). Rapid (within 2 weeks) and sustained improvements occurred in patients previously receiving placebo; LS mean change in MG-ADL score from OLE baseline to Week 60 was − 1.7 (95% CI: − 2.7, − 0.8; p = 0.0007). Similar trends were seen in QMG scores. Ravulizumab treatment was associated with a decreased rate of clinical deterioration events compared with placebo. Ravulizumab was well tolerated; no meningococcal infections were reported.

Conclusion

Findings support the sustained efficacy and long-term safety of ravulizumab, administered every 8 weeks, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

ClinicalTrials.gov identifier: NCT03920293; EudraCT: 2018-003243-39.
Carimas: An Extensive Medical Imaging Data Processing Tool for Research
Authors: Rainio Oona , Han Chunlei , Teuho Jarmo , Nesterov Sergey V. , Oikonen Vesa , Piirola Sauli , Laitinen Timo , Tättäläinen Marko , Knuuti Juhani , Klén Riku
Published: April 2023

Carimas is a multi-purpose medical imaging data processing tool, which can be used to visualize, analyze, and model different medical images in research. Originally, it was developed only for positron emission tomography data in 2009, but the use of this software has extended to many other tomography imaging modalities, such as computed tomography and magnetic resonance imaging. Carimas is especially well-suited for analysis of three- and four-dimensional image data and creating polar maps in modeling of cardiac perfusion. This article explores various parts of Carimas, including its key features, program structure, and application possibilities.
Documenting resistance, conflict and violence: a scoping review of the role of participatory digital platforms in the mobilisation of resistance
Authors: Fife Kirsty , Flinn Andrew , Nyhan Julianne
Published: April 2023

In recent years, grassroots movements have gained traction and significant numbers globally. Against longer histories of resistance and protest movements’ mobilisation of documentation, mechanisation and digital technologies, this scoping literature review seeks to understand how resistance and social movements have drawn upon the participatory and easily accessible nature of social media and digital platforms to mobilise new generations of activists, create new archives, document activities and abuses, call for accountability and overwrite or challenge the narratives put forward by mainstream media outlets and state archives. We identify relevant projects, explore the activist potential and threats of the combination of digital technologies, social movements, and documentary or archival practice, before concluding by identifying open research questions in relation to digital technologies, social movements and archival practice.
Feasibility of introducing a smartphone navigation application into the care of breast cancer patients (The FIONA Study)
Authors: Isakoff Steven J. , Said Maya R. , Kwak Agnes H. , Glieberman Eva , O’Rourke Emily A. , Stroiney Amanda , Spring Laura M. , Moy Beverly , Bardia Aditya , Horick Nora , Peppercorn Jeffrey M.
Published: April 2023

Purpose

Patients with breast cancer (BC) face complex medical information and decisions. The Outcomes4Me mobile app provides evidence-based BC education, symptom management tracking and clinical trial matching. This study sought to evaluate the feasibility of introducing this app into routine BC care.

Methods

In this pilot study among BC patients undergoing therapy at an academic cancer center, patients were followed for 12 weeks with survey administration and electronic health record (EHR) abstraction at baseline and completion. Feasibility was defined as 40% of patients engaging with the app 3 or more times during the study. Additional endpoints included app usability (system usability scale), patient care experience, symptom evaluation, and clinical trial matching.

Results

The study enrolled 107 patients from 6/01/2020 to 3/31/2021. Utilization of the app was deemed feasible with 60% of patients engaging with the app at least 3 times. SUS score of 70 indicated above average usability. New diagnosis and higher education level was associated with greater app engagement, with usability similar across all age groups. 41% of patients found the app helped track symptoms. Cognitive and sexual symptoms were infrequently reported, but were more frequently captured in the app than in the EHR. After using the app, 33% of patients reported increased interest in clinical trial enrollment.

Conclusion

Introducing the Outcomes4Me patient navigation app into routine BC care is feasible and may improve the patient experience. These results support further evaluation of this mobile technology platform to improve BC education, symptom management, and decision making.

Clinical trial registry

Clinicaltrials.gov registration #: NCT04262518
Advances in the prevention and treatment of breast cancer-related lymphedema
Authors: Donahue Paula M. C. , MacKenzie Adrien , Filipovic Aleksandra , Koelmeyer Louise
Published: April 2023

Purpose

Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies.

Findings

Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful.

Conclusion

Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.
The value of case reports in rare oncological scenarios: mixed method analysis of colorectal metastases from breast cancer
Authors: Nagtegaal I. D. , Snoek J. A. A. , Bult P. , Tol J. , Siesling S. , Voorham Q. J. , Hugen N.
Published: April 2023

With improved survival of cancer patients, we increasingly encounter infrequent metastatic locations. While for the common metastatic locations both prognostic information as well as evidence-based guidelines are available, for rare locations we have to rely on anecdotal case reports, the value of which is currently unknown. Therefore, we performed a systemic literature review and compare the results with a large national real-life cohort focussed on breast cancer patients with colorectal metastases. We performed a systematic literature search for breast cancer patients with colorectal metastases. Autopsy studies were excluded. Data on stage, histological factors, treatment and outcome were extracted. All identified cases were analysed as individual patients. The real-life cohort was extracted from the nationwide Dutch pathology databank. Linkage with the Netherlands Cancer Registry provided clinical characteristics, treatment and outcome data. Survival analyses and univariate regression were performed to identify relevant features for future treatment decisions. We identified 308 patients from 207 studies in the literature, and 454 patients in the real-life cohort. Colorectal metastases were the first metastatic event in 42.5% and 47.0% respectively. Cohorts were comparable for age, gender, location and hormone status, but differed in tumour type, stage and treatment. The time to colorectal metastases was similar in both cohorts (median of 68 months), and was dependent on presence of other metastases, nodal status, and primary breast surgery. The median overall survival after development of colorectal metastases was 20.6 months (95%CI 18.0–23.1 months). Despite a potential publication bias and lack of complete data for patients in the case report series, we have shown that an extensive systematic review can provide data that are comparable to real-life data, which can be used for decision-making and informing patients. Colorectal metastases are a late event in breast cancer patients, that is not associated with a detrimental survival.
Computer vision syndrome-related symptoms in presbyopic computer workers
Authors: Galindo-Romero Caridad , Rodríguez-Zamora Celia L. , García-Ayuso Diego , Di Pierdomenico Johnny , Valiente-Soriano Francisco J.
Published: April 2023

Purpose

To evaluate the prevalence of computer vision syndrome (CVS)-related symptoms in a presbyopic population using the computer as the main work tool, as well as the relationship of CVS with the electronic device use habits and the ergonomic factors.

Methods

A sample of 198 presbyopic participants (aged 45–65 years) who regularly work with a computer completed a customised questionnaire divided into: general demographics, optical correction commonly used and for work, habits of electronic devices use, ergonomic conditions during the working hours and CVS-related symptoms during work performance. A total of 10 CVS-related symptoms were questioned indicating the severity with which they occurred (0–4) and the median total symptom score (MTSS) was calculated as the sum of the symptoms.

Results

The MTSS in this presbyopic population is 7 ± 5 symptoms. The most common symptoms reported by participants are dry eyes, tired eyes and difficulties in refocusing. MTSS is higher in women (p < 0.05), in laptop computer users (p < 0.05) and in teleworkers compared to office workers (p < 0.05). Regarding ergonomic conditions, MTSS is higher in participants who do not take breaks while working (p < 0.05), who have an inadequately lighting in the workspace (p < 0.05) and in the participants reporting neck (p < 0.01) or back pain (p < 0.001).

Conclusion

There is a relationship between CVS-related symptoms, the use of electronic devices and the ergonomic factors, which indicates the importance of adapting workplaces, especially for home-based teleworkers, and following basic visual ergonomics rules.
Transdiagnostic Symptoms in Children with Neurodevelopmental Disabilities and Perceived Parent-Child Relationship Quality: A Pilot Study
Authors: Vashi Nisha , Bohr Yvonne , Weiss Jonathan A.
Published: April 2023

This pilot study examined associations between transdiagnostic symptoms and parent-perceived parent-child relationship quality in treatment-seeking families of children with neurodevelopmental disabilities, and interactions among clinical symptoms and cognitive functioning. Sixty-three children between 8 to 13 years of age and their caregivers were assessed at baseline while seeking cognitive behaviour therapy for emotion regulation and mental health difficulties. Diagnoses included autism, ADHD, cerebral palsy, and learning disability, with 52% of children having multiple diagnoses. Parent-perceived parent-child relationship quality was assessed by the Positive Affect Index, autism symptoms (e.g., social communication, repetitive behaviours) by the Social Responsiveness Scale, Second Edition, mental health (i.e., internalizing problems, externalizing problems, behavioural symptoms) by the Behaviour Assessment Scale for Children, Third Edition, and IQ by the Weschler Abbreviated Scale of Intelligence, Second Edition. Results revealed that higher IQ scores and greater social communication challenges, externalizing problems, and behavioural symptoms, were associated with lower parent-child relationship quality. Interaction effects were found between IQ and social communication challenges, reflecting significantly stronger relationships between social communication challenges and lower parent-child relationship quality in the context of higher IQ. Understanding the interactions between cognitive functioning and social communication challenges can help to inform individualized supports, and advocate for a transdiagnostic approach to intervention.