bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Butterfly‐Like Shaped Gold Nanomaterial: For the Regulation of Liquid–Liquid Phase‐Separated Biomacromolecule Droplets
Authors: Nobeyama Tomohiro , Tataka Koji , Mori Megumi , Murakami Tatsuya , Yamada Yoichi , Shiraki Kentaro
Published: August 2023

Nanotechnology is a critical tool to manipulate the sophisticated behavior of biological structures and has provided new research fields. Liquid–liquid phase‐separated (LLPS) droplets gather attention as basic reaction fields in a living cell. Droplets play critical roles in regulating protein behavior, including enzyme compartmentalization, stress response, and disease pathogenesis. The dynamic manipulation of LLPS droplet formation/deformation has become a crucial target in nanobiotechnology. However, the development of nanodevices specifically designed for this purpose remains a challenge. Therefore, this study presents butterfly‐shaped gold nanobutterflies (GNBs) as novel nanodevices for manipulating LLPS droplet dynamics. The growth process of the GNBs is analyzed via time‐lapse electroscopic imaging, time‐lapse spectroscopy, and additives assays. Interestingly, GNBs demonstrate the ability to induce LLPS droplet formation in systems such as adenosine triphosphate/poly‐l‐lysine and human immunoglobulin G, whereas spherical and rod‐shaped gold nanoparticles exhibit no such capability. This indicates that the GNB concave surface interacts with the droplet precursors facilitating the LLPS droplet formation. Near‐infrared‐laser irradiation applied to GNBs enables on‐demand deformation of the droplets through localized heat effects. GNB regulates the enzymatic reaction of lysozymes. The innovative design of GNBs presents a promising strategy for manipulating LLPS dynamics and offers exciting prospects for future research.
3D Hollow Hierarchical Porous Carbon with Fe‐N4‐OH Single‐Atom Sites for High‐Performance Zn‐Air Batteries
Authors: Zhou Shilong , Chen Chao , Xia Jiawei , Li Le , Qian Xingyue , Arif Muhammad , Yin Fengxiang , Dai Guohong , He Guangyu , Chen Qun , Chen Haiqun
Published: August 2023

The development of innovative and efficient Fe‐N‐C catalysts is crucial for the widespread application of zinc‐air batteries (ZABs), where the inherent oxygen reduction reaction (ORR) activity of Fe single‐atom sites needs to be optimized to meet the practical application. Herein, a three‐dimensional (3D) hollow hierarchical porous electrocatalyst (ZIF8@FePMPDA‐920) rich in asymmetric Fe‐N4‐OH moieties as the single atomic sites is reported. The Fe center is in a penta‐coordinated geometry with four N atoms and one O atom to form Fe‐N4‐OH configuration. Compared to conventional Fe‐N4 configuration, this unique structure can weaken the adsorption of intermediates by reducing the electron density of the Fe center for oxygen binding, which decreases the energy barrier of the rate‐determining steps (RDS) to accelerate the ORR and oxygen evolution reaction (OER) processes for ZABs. The rechargeable liquid ZABs (LZABs) equipped with ZIF8@FePMPDA‐920 display a high power density of 123.11 mW cm−2 and a long cycle life (300 h). The relevant flexible all‐solid‐state ZABs (FASSZABs) also display outstanding foldability and cyclical stability. This work provides a new perspective for the structural design of single‐atom catalysts in the energy conversion and storage areas.
Chirality‐Dependent Angiogenic Activity of MoS2 Quantum Dots toward Regulatable Tissue Regeneration
Authors: Liang Kangqiang , Xue Yumeng , Zhao Bin , Wen Mengyao , Xu Ziqi , Sukhorukov Gleb , Zhang Lianbing , Shang Li
Published: August 2023

Despite great advances in understanding the biological behaviors of chiral materials, the effect of chirality‐configured nanoparticles on tissue regeneration‐related biological processes remains poorly understood. Herein, the chirality of MoS2 quantum dots (QDs) is tailored by functionalization with l‐/d‐penicillamine, and the profound chiral effects of MoS2 QDs on cellular activities, angiogenesis, and tissue regeneration are thoroughly investigated. Specifically, d‐MoS2 QDs show a positive effect in promoting the growth, proliferation, and migration of human umbilical vein endothelial cells. The expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and fibroblast growth factor (FGF) in d‐MoS2 QDs group is substantially up‐regulated, resulting in enhanced tube formation activity. This distinct phenomenon is largely due to the higher internalization efficiency of d‐MoS2 QDs than l‐MoS2 QDs and chirality‐dependent nano‐bio interactions. In vivo angiogenic assay shows the expression level of angiogenic markers in newly‐formed skin tissues of d‐MoS2 QDs group is higher than that in l‐MoS2 QDs group, leading to an accelerated re‐epithelialization and improved skin regeneration. The findings of chirality‐dependent angiogenesis activity of MoS2 QDs provide new insights into the biological activity of MoS2 nanomaterials, which also opens up a new path to the rational design of chiral nanomaterials for tissue regeneration application.
Soft Phonon Mode Triggering Fast Ag Diffusion in Superionic Argyrodite Ag8GeSe6
Authors: Shen Xingchen , Koza Michael Marek , Tung Yung‐Hsiang , Ouyang Niuchang , Yang Chun‐Chuen , Wang Chen , Chen Yue , Willa Kristin , Heid Rolf , Zhou Xiaoyuan , Weber Frank
Published: August 2023

The structural coexistence of dual rigid and mobile sublattices in superionic Argyrodites yields ultralow lattice thermal conductivity along with decent electrical and ionic conductivities and therefore attracts intense interest for batteries, fuel cells, and thermoelectric applications. However, a comprehensive understanding of their underlying lattice and diffusive dynamics in terms of the interplay between phonons and mobile ions is missing. Herein, inelastic neutron scattering is employed to unravel that phonon softening on heating to Tc ≈ 350 K triggers fast Ag diffusion in the canonical superionic Argyrodite Ag8GeSe6. Ab initio molecular dynamics simulations reproduce the experimental neutron scattering signals and identify the partially ultrafast Ag diffusion with a large diffusion coefficient of 10−4 cm−2 s−1. The study illustrates the microscopic interconnection between soft phonons and mobile ions and provides a paradigm for an intertwined interaction of the lattice and diffusive dynamics in superionic materials.
In Situ Synthesis Method of Approaching High Surface Capacity Sulfur and the Role of Cobalt Sulfide as Lithium–Sulfur Battery Materials
Authors: Lim Yew Von , Vafakhah Sareh , Li Xue Liang , Jiang Zhuoling , Fang Daliang , Huang Shaozhuan , Wang Ye , Ang Yee Sin , Ang Lay Kee , Yang Hui Ying
Published: August 2023

Lithium–sulfur batteries (Li–S) are potentially applicable in electrification and the replacement of fossil fuels due to the high energy density and the economy of sulfur. However, effectively an insulator, sulfur is known to suffer from inert electrochemical and poor conductivity. By synthetically incorporating conductive, low‐dimensional carbonaceous composites acting as both containment hosts and catalysts to active materials, this work entails an effective and straightforward materials engineering approach in fundamentally remodeling active materials utilization and activation. This synthetic‐based approach highlights direct processing capabilities than traditional thermal infusion processes without compromising performance and addresses the low activation, poor conductivity as well as alleviating side reactions due to polysulfide species. Motivated by recent efforts in excellent catalytic properties of cobalt sulfide (CoS)‐based materials, in this work, high‐performance CoS‐based carbonaceous composites are designed and employed, alleviating side reactions. These sulfide‐based catalysts are further elucidated in their role in facilitating charge/discharge of active materials, and assessed on practical polysulfide and side reaction alleviation with respect to various discharge/charge states. Proof‐of‐concept devices demonstrate the following performance highlights: 1) high‐performance stability, 2) strong polysulfide adsorption capability and kinetic characteristics, 3) large and workable areal capacity, and active materials loading.
1 nm‐Resolution Sorting of Sub‐10 nm Nanoparticles Using a Dielectric Metasurface with Toroidal Responses
Authors: Luo Hong , Fang Xiang , Li Chengfeng , Dai Xinhua , Ru Ning , You Minmin , He Tao , Wu Pin Chieh , Wang Zhanshan , Shi Yuzhi , Cheng Xinbin
Published: August 2023

Sorting nanoparticles is of paramount importance in numerous physical, chemical, and biomedical applications. Current technologies for sorting dielectric nanoparticles have a common size limit and resolution approximately of 20 and 10 nm, respectively. It remains a grand challenge to push the limit. Herein, the new physics that deploys toroidal and multipole responses in a dielectric metasurface to exert strong and distinguishable optical forces on sub‐10 nm nanoparticles is unravelled. The electric toroidal dipole, electric dipole, and quadrupole emerge with distinct light and force patterns, which can be leveraged to promise unprecedented high‐precision manipulations, such as sorting sub‐10 nm polystyrene nanoparticles at 1 nm resolution, sorting 20 nm proteins/exsomes at 3 nm resolution, conveying, and concentrating 100 nm gold nanoparticles. Remarkably, the design can also be employed to screen out medium‐sized nanoparticles from a mixture of nanoparticles with over three sizes. This optofluidic manipulation platform opens the new way to explore intriguing optical modes for the powerful manipulation of nanoparticles with nanometer precisions and low laser powers.
A validated high‐performance liquid chromatography method for the determination of brassinin, an indoleamine 2,3‐dioxygenase inhibitor in rat plasma
Authors: Dhurjad Pooja , Gupta Kajal , Sakla Akash P. , Shankaraiah Nagula , Sonti Rajesh
Published: August 2023

Brassinin, a phytochemical in cruciferous vegetables, is an indoleamine 2,3‐dioxygenase inhibitor and possesses a therapeutic opportunity in cancer immunotherapy. Here, we have developed and validated a novel, specific, and rapid bioanalytical method in rat plasma that is unavailable in the literature for preclinical studies. The method development involved single‐step protein precipitation as an extraction method using acetonitrile with an absolute and relative mean recovery of 79.32% and 93.59%, respectively. The method is accurate and precise over the linearity range of 1.0–50.0 μg/mL with a retention time of 5.3 and 3.5 min of brassinin and telmisartan, an internal standard. The intra‐day and inter‐day precision of the method expressed as a %coefficient of variation, ranging from 0.03% to 2.82% and 0.39% to 5.82%, whereas intra‐day and inter‐day accuracy ranged from 99.75% to 103.40% and 99.76% to 104.25%, respectively. The high‐performance liquid chromatography bioanalytical method was successfully validated as per Food and Drug Administration guidelines, and it can be applied in routine bioanalysis and pharmacokinetic studies.
Anisotropic, Strong, and Thermally Insulating 3D‐Printed Nanocellulose–PNIPAAM Aerogels
Authors: Nagel Yannick , Sivaraman Deeptanshu , Neels Antonia , Zimmermann Tanja , Zhao Shanyu , Siqueira Gilberto , Nyström Gustav
Published: August 2023

Cellulose is a promising candidate for the fabrication of superinsulating materials, which would be of great interest for thermal management applications as well as for the scientific community. Until now, the production of strong cellulose‐based aerogels has been dominated by traditional manufacturing processes, which have limited the possibilities to achieve the structural control and mechanical properties seen in natural materials such as wood. In this work, we show a simple but versatile method to fabricate cellulose aerogels in intricate geometries. We take advantage of the 3D printing technique direct ink writing to control both the shape and the thermal‐mechanical properties of the printed cellulose‐based hydrogel inks. Moreover, the shear forces involved in the extrusion process allow us to impart an anisotropic nanostructure to the printed samples. By solvent exchange and supercritical drying, the hydrogel parts are then transformed into stable aerogels. Using X‐ray diffraction analysis, mechanical tests and thermal conductivity tests, our 3D printed aerogels are shown to exhibit directionally dependent thermal‐mechanical properties higher than those reported for earlier cellulose‐based aerogels. These characteristics enable us to fabricate customized structures that can be precisely tailored for their application as load‐bearing insulating materials for thermal management.
The Physicochemical, Morphological, Functional, Thermal Properties, and Digestibility of Amaranthus paniculatus (Rajgeera) Starch and Flour
Authors: Yadav Pooja , Bharathi Uma , John Don Bosco Sowriappan
Published: August 2023

The present study aims to characterize the physicochemical, morphological, functional, thermal properties and in vitro digestibility of Amaranthus paniculatus flour (APF) and A. paniculatus starch (APS). A significant difference (p ≤ 0.05) is observed in the chemical composition of A. paniculatus flour and starch; the amylose content of the starch (3.91%) is found to be significantly higher (p ≤ 0.05) than flour (2.35%). Morphology of APS reveals that the starch granules are polygonal, have a smooth surface, and have no fissures. A. paniculatus flour and starch exhibit A‐type crystallinity; however, the relative crystallinity of APS (15.75%) is significantly higher (p ≤ 0.05) than flour (12.76%). The functional properties, including solubility, water and oil absorption capacity of APF are significantly higher (p ≤ 0.05) than APS. The enthalpy of gelatinization (ΔH) of APS is found to be significantly higher (p ≤ 0.05) than APF. A. paniculatus starch has a significantly higher (p ≤ 0.05) amount of rapid digestible starch (RDS) than flour, however, the flour of A. paniculatus has significantly higher (p ≤ 0.05) resistant starch (RS) and slowly digestible starch (SDS). The study reveals that A. paniculatus flour and starch are significantly different from each other and can be used in various food and non‐food industries due to their physicochemical, functional, and structural properties.
New damage evolution law in plastic damage models for fiber‐reinforced cementitious composites
Authors: Júnior Edmir José dos Santos , Krahl Pablo Augusto , Monteiro Francisco Alex Correia , Cordeiro Sérgio Gustavo Ferreira
Published: August 2023

Nowadays, fiber‐reinforced cement‐based composites (FRCC) can develop ductile behavior with high toughness when the matrix, fibers, and interface are optimally designed. These materials are promising solutions for constructing more resilient structures. In this context, the widespread use in large‐scale applications requires reliable models to predict the performance of FRCC structures. Usually, the studies on numerical modeling of FRCC apply the damage laws developed for quasi‐brittle concrete, making damage increase faster than really occurs in the presence of fibers. Therefore, the present paper proposes a new damage evolution model for FRCC based on energy dissipation concepts. It is assumed that the dissipated energy contributes fully to the evolution of the scalar damage and plastic strain variables, which is a technical advance from the previous works. The damage evolution is obtained with experimental envelopes of uniaxial stress–strain tests and the focal point from loading–unloading cycles. The results showed that the model accurately predicted experimental results using the damage‐plasticity framework. Furthermore, there are no empirical constants in the proposal, which means that it can be applied to any class of FRCC. An application regarding damage evaluation near a load transfer device in jointed plain cementitious pavements is presented. The damage distribution reveals that using FRCC materials has induced smaller damage values when compared with using conventional concrete. Consequently, cracking is reduced in such zones, increasing the structural life of the pavement.
Freestanding MXene‐based macroforms for electrochemical energy storage applications
Authors: Lu Qiongqiong , Liu Congcong , Zhao Yirong , Pan Wengao , Xie Kun , Yue Pengfei , Zhang Guoshang , Omar Ahmad , Liu Lixiang , Yu Minghao , Mikhailova Daria
Published: August 2023

Freestanding MXene‐based macroforms have gained significant attention as versatile components in electrochemical energy storage applications owing to their interconnected conductive network, strong mechanical strength, and customizable surface chemistries derived from MXene nanosheets. This comprehensive review article encompasses key aspects related to the synthesis of MXene nanosheets, strategies for structure design and surface medication, surface modification, and the diverse fabrication methods employed to create freestanding MXene‐based macroform architectures. The review also delves into the recent advancements in utilizing freestanding MXene macroforms for electrochemical energy storage applications, offering a detailed discussion on the significant progress achieved thus far. Notably, the correlation between the macroform's structural attributes and its performance characteristics is thoroughly explored, shedding light on the critical factors influencing efficiency and durability. Despite the remarkable development, the review also highlights the existing challenges and presents future perspectives for freestanding MXene‐based macroforms in the realms of high‐performance energy storage devices. By addressing these challenges and leveraging emerging opportunities, the potential of freestanding MXene‐based macroforms can be harnessed to enable groundbreaking advancements in the field of energy storage.
Presence of Saccharomyces eubayanus in fermentative environments reveals a new adaptive scenario in Patagonia
Authors: Gonzalez‐Flores Melisa , Delfino Ana V. , Rodríguez María E. , Lopes Christian A.
Published: August 2023

Patagonia (Argentina and Chile) harbors the highest Saccharomyces eubayanus genomic diversity and its widest predominance in natural environments. In this work, S. eubayanus was isolated for the first time from a fermentative environment. This species was found dominating both a traditional apple chicha fermentation as well as feral apple trees in the Andean region of Aluminé (Argentina). S. eubayanus was the only Saccharomyces species found in the isolation substrates, although it coexisted with other non‐Saccharomyces species. The absence of strong fermentative competitors of the Saccharomyces genus (like Saccharomyces uvarum or Saccharomyces cerevisiae) in the feral apples could promote the development and implantation of S. eubayanus in a spontaneous apple must fermentation. Phylogeographic analyses revealed a high intraspecific diversity in S. eubayanus, enabling the characterization of strains belonging to the genomic subpopulations PA1, PA2, and PB1 according to the sequences obtained for the intFR gene region. This result evidence that the studied sampling area represents a natural habitat for the species. Being a novel finding, studying the causes that allowed this species to prosper in a fermentative environment becomes essential. Hence, the physiological profile of the new isolates, including their ability to grow at different temperature, nitrogen, and ethanol concentrations was evaluated in comparison with a set of S. eubayanus strains previously isolated from natural environment and representing different genomic subpopulations. Greater physiological diversity was evidenced when strains isolated from both natural and fermentative environments were analyzed overall. Furthermore, no direct relationship between genomic population and physiological behavior was observed; on the opposite, strains appeared to exhibit similar behavior, primarily grouped by isolation origin.
Crystal Structure and Magnetic Properties of High‐Pressure Phases RESi3 (RE=Tb, Dy, Er, Tm)
Authors: Neziraj Teuta , Akselrud Lev , Wirth Steffen , Schwarz Ulrich
Published: August 2023

The new metastable binary rare‐earth metal trisilicides RESi3 (RE=Tb, Dy, Er, and Tm) are obtained by high‐pressure high‐temperature synthesis (9.5 GPa, 823–923 K). Powder diffraction data refinements reveal that their crystal structure is isotypic to that of YbSi3, and the values of cell parameters and cell volumes decrease from Tb to Tm. Magnetic measurements on the compounds indicate Curie‐Weiss paramagnetic behavior and antiferromagnetic ordering at low temperatures. The values for TN follow a de Gennes scaling pointing towards Ruderman‐Kittel‐Kasuya‐Yosida (RKKY) interaction. Upon heating at ambient pressure, the RESi3 compounds decompose into Si and RESi2‐x.

The new high‐pressure phases TbSi3, DySi3, ErSi3 and TmSi3 adopt atomic arrangements in which two‐dimensional building units of silicon are separated by rare‐earth metal atoms. The silicon environment with five short Si‐Si contacts in connection with the formal charge Si− is incompatible with the classical 8‐N rule. This is confirmed by earlier quantum chemical methods evidencing a mixture of two‐atomic Si‐Si bonds and multiatomic interactions involving lone‐pairs located at silicon atoms. Consequently, the rare‐earth metal trisilicides do not belong to the class of electron‐precise Zintl phases, which is consistent with their earlier observed character of covalent metals. This result is in concert with the present study revealing that compounds RESi3 (RE=Gd‐Tm) follow a de Gennes scaling, which is based on a magnetic coupling via conduction electrons.
Domain-Specific Evaluation of Visual Explanations for Application-Grounded Facial Expression Recognition
Authors: Finzel Bettina , Rieger Ines , Kuhn Simon , Schmid Ute
Published: August 2023

Research in the field of explainable artificial intelligence has produced a vast amount of visual explanation methods for deep learning-based image classification in various domains of application. However, there is still a lack of domain-specific evaluation methods to assess an explanation’s quality and a classifier’s performance with respect to domain-specific requirements. In particular, evaluation methods could benefit from integrating human expertise into quality criteria and metrics. Such domain-specific evaluation methods can help to assess the robustness of deep learning models more precisely. In this paper, we present an approach for domain-specific evaluation of visual explanation methods in order to enhance the transparency of deep learning models and estimate their robustness accordingly. As an example use case, we apply our framework to facial expression recognition. We can show that the domain-specific evaluation is especially beneficial for challenging use cases such as facial expression recognition and provides application-grounded quality criteria that are not covered by standard evaluation methods. Our comparison of the domain-specific evaluation method with standard approaches thus shows that the quality of the expert knowledge is of great importance for assessing a model’s performance precisely.
Human-in-the-Loop Integration with Domain-Knowledge Graphs for Explainable Federated Deep Learning
Authors: Holzinger Andreas , Saranti Anna , Hauschild Anne-Christin , Beinecke Jacqueline , Heider Dominik , Roettger Richard , Mueller Heimo , Baumbach Jan , Pfeifer Bastian
Published: August 2023

We explore the integration of domain knowledge graphs into Deep Learning for improved interpretability and explainability using Graph Neural Networks (GNNs). Specifically, a protein-protein interaction (PPI) network is masked over a deep neural network for classification, with patient-specific multi-modal genomic features enriched into the PPI graph’s nodes. Subnetworks that are relevant to the classification (referred to as “disease subnetworks”) are detected using explainable AI. Federated learning is enabled by dividing the knowledge graph into relevant subnetworks, constructing an ensemble classifier, and allowing domain experts to analyze and manipulate detected subnetworks using a developed user interface. Furthermore, the human-in-the-loop principle can be applied with the incorporation of experts, interacting through a sophisticated User Interface (UI) driven by Explainable Artificial Intelligence (xAI) methods, changing the datasets to create counterfactual explanations. The adapted datasets could influence the local model’s characteristics and thereby create a federated version that distils their diverse knowledge in a centralized scenario. This work demonstrates the feasibility of the presented strategies, which were originally envisaged in 2021 and most of it has now been materialized into actionable items. In this paper, we report on some lessons learned during this project.
Communities of Inquiry
Authors: Scott-Baumann Alison
Published: August 2023

Before diving into Ricœur’s historical and conceptual experiences of free speech about Algeria, Nanterre and USA in Chaps. 4, 5 and 6, I provide in this chapter a clear working definition of ‘free speech’ as a negotiated process and explore how, by using the Communities of Inquiry approach, young people can learn the art of discussion as they progress through university. As an antidote to the chilling effects of the culture wars, this develops a politics of pedagogy that entails mutual recognition of each other’s arguments and helps us to share the risk with each other of causing offence. There are significant differences between this approach and the communicational ethicsof Habermas. This chapter and Chaps. 4 and 6 end with sample Communities of Inquiry.
Media made from brown-rotted elm and pine wood for rearing Reticulitermes termites
Authors: Mitaka Y. , Vargo E. L.
Published: August 2023

Termites are not only decomposers in forest and savanna ecosystems, but also major pests of wooden buildings worldwide. Therefore, termites have long been of interest to researchers, and there has been a need for media for maintaining termites in the laboratory. Recently, a "brown-rotted pinewood mixed cellulose" (BPC) medium using the Japanese red pine (Pinus densiflora) was developed as a medium for long-term stable rearing of the subterranean termite Reticulitermes speratus. It is unclear whether the method of preparing the BPC medium can be applied to other termite species using different types of wood. Here, we developed two media for rearing two American termite species (Reticulitermes flavipes and R. virginicus): "brown-rotted elm wood mixed cellulose" (BEC) medium using winged elm (Ulmus alata) and BPC medium using loblolly pine (P. taeda). In colony foundation by R. flavipes dealates, about 80% of the incipient colonies on BEC and BPC media successfully produced larvae and workers, whereas less than 21% of the colonies on cellulose media did so. Long-term rearing of R. flavipes workers showed that the food consumption rate was higher on the BEC and BPC media than on the cellulose medium. On the other hand, long-term rearing of R. virginicus workers showed that the apparent digestibility coefficient was higher on the BPC medium than on the other media. These results indicate that the BEC and BPC media can be used for both colony foundation by dealates and rearing workers in R. flavipes, and that the BPC medium is more suitable for rearing R. virginicus workers. These new media and others made using the same process will contribute to the maintenance of termite colonies in the laboratory for a variety of experiments.
Empfehlungen zur Versorgung von Patient:innen mit FOP
Authors: Seefried L. , Banholzer D. , Fischer R. , Grafe I. , Hüning I. , Morhart R , Oheim R. , Semler O. , Siggelkow H. , Stockklausner C. , Hoyer-Kuhn H.
Published: August 2023

Hintergrund

Bei der Fibrodysplasia ossificans progressiva (FOP) handelt es sich um eine sehr seltene, genetisch bedingte Erkrankung, ausgelöst durch eine „Gain-of-function“-Mutation im ACVR1-Gen, welches den Typ-I-Bone-Morphogenetic-Protein(BMP)-Rezeptor ACVR1 („activin A receptor type 1“) – auch bekannt als ALK2 („activin receptor-like kinase 2“) kodiert. Diese Mutation führt zum Auftreten und Fortschreiten heterotoper Ossifikationen (HO) im Weich- und Bindegewebe. Der HO gehen oft Episoden von Weichteilschwellungen, sogenannte Flare-ups voraus. Die für FOP charakteristischen Flare-ups können durch Traumata, Infektionen, Impfungen oder andere medizinische sowie chirurgische Eingriffe induziert werden oder spontan auftreten. Mit fortschreitendem Alter der Patient:innen kommt es bei den Betroffenen aufgrund zunehmender HO zu schwerwiegenden Bewegungseinschränkungen bis hin zur Bewegungsunfähigkeit, die mit einer verkürzten Lebenserwartung einhergeht. Ein erstes charakteristisches klinisches Anzeichen für FOP ist die angeborene Fehlbildung der Großzehen [25] mit valgischer Achsabweichung, die bei fast allen Patient:innen auftritt. Um die Diagnose zu sichern, ist eine molekulargenetische Analyse des ACVR1-Gens möglich.

Ziel der Empfehlungen

Ziel der vorliegenden Handlungsempfehlungen ist es, einen Überblick über die notwendigen Voraussetzungen und Bedingungen für die Versorgung von Patient:innen mit FOP zu geben und durch eine bessere Verfügbarkeit von Wissen insgesamt einen positiven Beitrag für Patient:innen mit FOP zu leisten. Um dies zu erreichen, werden relevante Aspekte bei der Versorgung der sehr seltenen Erkrankung FOP vorgestellt, von der initialen Diagnose bis zur Betreuung in der Regelversorgung, basierend auf dem Wissen der Autor:innen (deutsches FOP-Netzwerk) und den internationalen FOP Treatment Guidelines. Die hier vorgestellten Empfehlungen richten sich an alle Akteur:innen und Entscheidungsträger:innen im Gesundheitswesen und sollen darüber hinaus der Information von Betroffenen und der Öffentlichkeit dienen.
Almost complex structures on hyperbolic manifolds
Authors: Kotschick D.
Published: August 2023

We discuss the existence of almost complex structures on closed hyperbolic manifolds of even dimension at least four. We prove that for $$n=2$$

n
=
2

and for all odd n every hyperbolic 2n-manifold has a finite covering admitting an almost complex structure. Conjecturally this should be true for all n. For $$n=4$$

n
=
4

we prove it for arithmetic manifolds.
Reductions in Motor Unit Firing are Associated with Clinically Meaningful Leg Extensor Weakness in Older Adults
Authors: Wages Nathan P. , Mousa Mohamed H. , Clark Leatha A. , Tavoian Dallin , Arnold W. David , Elbasiouny Sherif M. , Clark Brian C.
Published: August 2023

Weakness, one of the key characteristics of sarcopenia, is a significant risk factor for functional limitations and disability in older adults. It has long been suspected that reductions in motor unit firing rates (MUFRs) are one of the mechanistic causes of age-related weakness. However, prior work has not investigated the extent to which MUFR is associated with clinically meaningful weakness in older adults. Forty-three community-dwelling older adults (mean: 75.4 ± 7.4 years; 46.5% female) and 24 young adults (mean: 22.0 ± 1.8 years; 58.3% female) performed torque matching tasks at varying submaximal intensities with their non-dominant leg extensors. Decomposed surface electromyographic recordings were used to quantify MUFRs from the vastus lateralis muscle. Computational modeling was subsequently used to independently predict how slowed MUFRs would negatively impact strength in older adults. Bivariate correlations between MUFRs and indices of lean mass, voluntary activation, and physical function/mobility were also assessed in older adults. Weak older adults (n = 14) exhibited an approximate 1.5 and 3 Hz reduction in MUFR relative to non-weak older adults (n = 29) at 50% and 80% MVC, respectively. Older adults also exhibited an approximate 3 Hz reduction in MUFR relative to young adults at 80% MVC only. Our model predicted that a 3 Hz reduction in MUFR results in a strength decrement of 11–26%. Additionally, significant correlations were found between slower MUFRs and poorer neuromuscular quality, voluntary activation, chair rise time performance, and stair climb power (r’s = 0.31 to 0.43). These findings provide evidence that slowed MUFRs are mechanistically linked with clinically meaningful leg extensor weakness in older adults.
Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension
Authors: Mulas Olga , Mola Brunella , Costa Alessandro , Pittau Francesca , Mantovani Daniela , Dessì Samuele , Fronteddu Antonella , La Nasa Giorgio , Caocci Giovanni
Published: August 2023

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08–3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928–6.451, p < 0.001 and HR = 1.8; 95%CI 0.983–3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92–10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21–0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24–1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07–1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.
Assignment games with population monotonic allocation schemes
Authors: Solymosi Tamás
Published: August 2023

We characterize the assignment games which admit a population monotonic allocation scheme (PMAS) in terms of efficiently verifiable structural properties of the nonnegative matrix that induces the game. We prove that an assignment game is PMAS-admissible if and only if the positive elements of the underlying nonnegative matrix form orthogonal submatrices of three special types. In game theoretic terms it means that an assignment game is PMAS-admissible if and only if it contains either a veto player or a dominant veto mixed pair, or the game is a composition of these two types of special assignment games. We also show that in PMAS-admissible assignment games all core allocations can be extended to a PMAS, and the nucleolus coincides with the tau-value.
Retrospective real-world analysis of adherence and persistence to lipid-lowering therapy in Germany
Authors: Koenig Wolfgang , Lorenz Elke S. , Beier Lea , Gouni-Berthold Ioanna
Published: August 2023

Background

Cardiovascular disease is the leading cause of mortality in Germany. Cardiovascular risk can be mitigated with long-term lipid-lowering therapies (LLTs) that reduce levels of low-density lipoprotein cholesterol. Although effective, risk mitigation is hindered by poor persistence and adherence.

Objective

To investigate real-world persistence and adherence to LLTs through 36 months post-initiation.

Methods

This retrospective cohort study included patients with dyslipidemia who were newly prescribed LLTs between July and December 2017, using anonymized prescription data from the Insight Health™ Patient Insight Tool, and followed up until March 2021. Persistence and adherence to the therapies were stratified by age and sex. The proportion of days covered (PDC) was used to measure adherence.

Results

Patients with dyslipidemia and newly prescribed statins (n = 865,732), ezetimibe (n = 34,490), or anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (anti-PCSK9 mAbs; n = 1940) were included. Persistence to LLTs declined gradually across all treatment subgroups and was lower in women than men. Adherence, calculated as the mean PDC at the end of the analysis period (July 2017‒March 2021) was 0.84, 0.92, and 0.93 for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Among patients who discontinued treatment, mean treatment duration was 265, 255, and 387 days for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Only ~ 10% of patients persisted between 201 and 300 days. By Day 300, 71% of patients on statins had discontinued treatment. At 36 months, overall persistence rates were lowest with statins (20.6%), followed by ezetimibe (22.3%) and anti-PCSK9 mAbs (50.9%).

Conclusions

High non-persistence rates were observed across all LLT regimens analyzed, with the lowest persistence rates observed with statins.

Graphical Abstract
Long-term results and quality of life after vibrant soundbridge implantation (VSBs) in children and adults with aural atresia
Authors: Gantner Sophia , Epp Alexandra , Pollotzek Marlene , Hempel John Martin
Published: August 2023

Purpose

The aim of this study was to evaluate the long-term effectiveness and acceptance of the active middle ear implant system Vibrant Soundbridge (VSB®, MED-EL, Austria) in patients with aural atresia or aplasia (children and adults).

Methods

Data from 51 patients (mean age 13.9 ± 11.3 years), 42 (79.2%) children and adolescents, and 11 (20.8%) adults) who received a VSB implant between 2009 and 2019 at the Department of Otolaryngology at LMU Clinic Großhadern, Munich were included in the study. Pure-tone audiometry, speech recognition in a quiet environment and in a noisy environment were performed preoperatively, during the first fitting of the audio processor, after 1–3 years, after 3–5 years, and after 5 years (if possible). The follow-up period ranged from 11 to 157 months with a mean of 58.6 months (4.8 years). Furthermore, the benefit of the VSB was evaluated by self-assessment questionnaires (Speech, Spatial, and Qualities of Hearing Scale, respectively, for parents).

Results

Significant improvements were observed in hearing and speech comprehension immediately after the initial fitting of the VSB system (mean hearing gain 38.4 ± 9.4 dB HL) and at follow-up intervals (1–3, 3–5 and after 5 years) for children and adults (p < 0.01). The values remained stable over the long-term, indicating a sustained functional gain from the VSB (mean hearing gain 38.9 ± 9.2 dB HL). The results of the self-assessments affirm the positive influence on hearing and speech comprehension with the VSB. With the VSB, there was an improvement of 41.3 ± 13.7% in the Freiburg monosyllable test.

Conclusion

These results (a stable hearing gain over the long term, a good tolerance of the implant and an improvement in quality of life) affirm the recommendation for using the active middle ear implant VSB as early as permitted for aural atresia and aplasia patients. This study represents the audiometric results with the (to date) largest collective of aural atresia patients and with a long follow-up period.
Supportive care interventions for men with urological cancers: a scoping review
Authors: Saab Mohamad M. , McCarthy Megan , Murphy Mike , Medved Katarina , O’Malley Maria , Bambury Richard M. , Gleeson Jack P. , Noonan Brendan
Published: August 2023

Purpose

To identify supportive care interventions for men with urological cancers.

Methods

Experimental studies conducted among men with any urological cancer were eligible for inclusion. Academic Search Complete, CINAHL Plus with Full Text, MEDLINE, APA PsycArticles, APA PsycInfo, Social Sciences Full Text (H.W. Wilson), SocINDEX with Full Text, ERIC, Google Scholar and ClinicalTrials.gov were searched on 6 December 2022. No database limits were applied. The included studies were methodologically appraised. A narrative synthesis of the results was conducted.

Results

Thirty studies were included with 10 categories of interventions identified. Over 300 outcomes were measured, and more than 100 instruments were used. Multicomponent interventions generally led to positive changes in physiological outcomes like body mass index, as well as exercise tolerance and quality of life. This change, however, was not sustained in the long term. Cognitive-behavioural interventions significantly improved psychological symptoms but seldom physical symptoms. Telephone and web-based interventions showed great promise in improving outcomes like depression, positive affect, negative affect, perceived stress, spiritual wellbeing and fatigue. Findings from physical activity/exercise-based interventions were promising for both, physical and psychological outcomes. Rehabilitative interventions were associated with significant improvements in quality of life, urinary symptoms and psychological symptoms, albeit in the short term. Mixed results were reported for nurse-led interventions, family-based interventions and nutritional interventions.

Conclusion

All but one study focused exclusively on prostate cancer. The included studies were significantly heterogeneous. Multicomponent, cognitive-behavioural, telephone and web-based, physical activity/exercise-based and rehabilitative interventions showed great promise in improving various outcomes. This improvement, however, was often short-lived.
Esketamin-Behandlung im akut-tagesklinischen Setting
Authors: Stefan Romy , Fugger Gernot
Published: August 2023

Die unipolare Depression betrifft weltweit über 300 Mio. Menschen und ist die führende Ursache für Suizide mit einer jährlichen Suizidrate von etwa 800.000 Personen. Bei adäquater Behandlung ist die Prognose sehr gut, jedoch entwickeln 10–30 % der Betroffenen eine therapieresistente Depression, welche durch ein unzureichendes oder fehlendes Ansprechen auf die antidepressive Behandlung gekennzeichnet ist. Der Add-on-Behandlung mit Esketamin wird ein immer höherer Stellenwert in der leitliniengerechten Therapie der therapieresistenten Depression beigemessen. Es wird empfohlen, die Induktionsphase im stationären Setting zu starten und bei guter Verträglichkeit die Behandlung ambulant oder teilstationär fortzusetzen. Über die teilstationäre Handhabung der Induktionsphase von Esketamin ist noch wenig bekannt. In diesem Fallbericht wird über eine effektive Depressionstherapie mit Esketamin im multidisziplinären Setting einer Akut-Tagesklinik berichtet.
Investigation of three common centrifugation protocols for platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam: a prospective trial
Authors: Straub Anton , Utz Chiara , Stapf Maximilian , Vollmer Andreas , Kasper Sylvia , Kübler Alexander C. , Brands Roman C. , Hartmann Stefan , Lâm Thiên-Trí
Published: August 2023

Objectives

Different platelet-rich fibrin (PRF) protocols exist and are known to differ in resulting mechanical and bioactive properties. Centrifugation parameters may also influence drug release, in particular antibiotics, when using PRF as a bio-carrier. We thus evaluated three common protocols regarding effects on the bio-carrier properties.

Materials and methods

In a prospective trial comprising 33 patients, we compared different protocols for PRF as a bio-carrier for ampicillin/sulbactam (SAM). Blood samples were taken shortly after a single dose of ampicillin/sulbactam (2 g/1 g) was administered to patients intravenously. PRF was obtained by centrifugation and three protocols were used: protocol A (1300 rpm, 8 min, RCF-max = 208 g), B (2300 rpm, 12 min, RCF-max = 652 g), and C (1500 rpm, 14 min, RCF-max = 276 g). The antibacterial activity of PRF was investigated against five oral species in vitro, based on agar diffusion methodology.

Results

The study demonstrates that a single dose of SAM is sufficient to reach high concentrations in PRF in all protocols (150 µg/ml), which is comparable to the plasma SAM concentration. Antibacterial activity was inferred from the diameter of inhibition zones seen in agar diffusion tests using PRF discs. Protocol B resulted in the largest inhibition zones. One-way ANOVA revealed statistically improved results for protocol B for some bacteria.

Conclusions

The study provides valuable data on PRF antibiotic enrichment, notably SAM. A single dose of SAM is sufficient to reach clinically relevant concentrations in PRF.

Clinical relevance

These findings potentially extend the application of PRF, for example in patients with osteonecrosis of the jaw or in oral surgery (e.g., stick bone).
Associations of polygenic inheritance of physical activity with aerobic fitness, cardiometabolic risk factors and diseases: the HUNT study
Authors: Tynkkynen Niko Paavo , Törmäkangas Timo , Palviainen Teemu , Hyvärinen Matti , Klevjer Marie , Joensuu Laura , Kujala Urho , Kaprio Jaakko , Bye Anja , Sillanpää Elina
Published: August 2023

Physical activity (PA), aerobic fitness, and cardiometabolic diseases (CMD) are highly heritable multifactorial phenotypes. Shared genetic factors may underlie the associations between higher levels of PA and better aerobic fitness and a lower risk for CMDs. We aimed to study how PA genotype associates with self-reported PA, aerobic fitness, cardiometabolic risk factors and diseases. PA genotype, which combined variation in over one million of gene variants, was composed using the SBayesR polygenic scoring methodology. First, we constructed a polygenic risk score for PA in the Trøndelag Health Study (N = 47,148) using UK Biobank single nucleotide polymorphism-specific weights (N = 400,124). The associations of the PA PRS and continuous variables were analysed using linear regression models and with CMD incidences using Cox proportional hazard models. The results showed that genotypes predisposing to higher amount of PA were associated with greater self-reported PA (Beta [B] = 0.282 MET-h/wk per SD of PRS for PA, 95% confidence interval [CI] = 0.211, 0.354) but not with aerobic fitness. These genotypes were also associated with healthier cardiometabolic profile (waist circumference [B = -0.003 cm, 95% CI = -0.004, -0.002], body mass index [B = -0.002 kg/m2, 95% CI = -0.004, -0.001], high-density lipoprotein cholesterol [B = 0.004 mmol/L, 95% CI = 0.002, 0.006]) and lower incidence of hypertensive diseases (Hazard Ratio [HR] = 0.97, 95% CI = 0.951, 0.990), stroke (HR = 0.94, 95% CI = 0.903, 0.978) and type 2 diabetes (HR = 0.94, 95 % CI = 0.902, 0.970). Observed associations were independent of self-reported PA. These results support earlier findings suggesting small pleiotropic effects between PA and CMDs and provide new evidence about associations of polygenic inheritance of PA and intermediate cardiometabolic risk factors.