bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechanism and effects of remdesivir‐induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations
Authors: Li Ji‐tong , Zhang Yao‐dong , Song Xiao‐rui , Li Rui‐jing , Yang Wei‐li , Tian Ming , Zhang Shu‐feng , Cao Guang‐hai , Song Lu‐lu , Chen Yu‐ming , Liu Cui‐hua 
Published: May 2022

AbstractThe antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID‐19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non‐target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 μM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose‐dependent increases in mortality and malformation were observed in remdesivir‐treated embryos. Moreover, 10–100 μM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir‐treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir‐induced ecotoxicity to aquatic environments.
Mice Lacking Wnt9a or Wnt4 Are Prone to Develop Spontaneous Osteoarthritis With Age and Display Alteration in Either the Trabecular or Cortical Bone Compartment
Authors: Teufel Stefan , Wolff Lena , König Ulrich , Kobayashi Akio , Behringer Richard , Hartmann Christine 
Published: May 2022

ABSTRACTOsteoarthritis (OA) is a common degenerative disease of the joint, with a complex multifactorial not yet fully understood etiology. Over the past years, the Wnt signaling pathway has been implicated in osteoarthritis. In a recent genomewide association study (GWAS), the chromosomal location on chromosome 1, linked to the Wnt3a-Wnt9a gene locus, was identified as the most significant locus associated with a thumb osteoarthritis endophenotype. Previously, it was shown that WNT9a is involved in maintaining synovial cell identity in the elbow joint during embryogenesis. Here, we report that the conditional loss of Wnt9a in the Prx1-Cre expressing limb mesenchyme or Prg4-CreER expressing cells predispositions the mice to develop spontaneous OA-like changes with age. In addition, the trabecular bone volume is altered in these mice. Similarly, mice with a conditional loss of Wnt4 in the limb mesenchyme are also more prone to develop spontaneously OA-like joint alterations with age. These mice display additional alterations in their cortical bone. The combined loss of Wnt9a and Wnt4 increased the likelihood of the mice developing osteoarthritis-like changes and enhanced disease severity in the affected mice. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Bisphenol S favors hepatic steatosis development via an upregulation of liver MCT1 expression and an impairment of the mitochondrial respiratory system
Authors: Mornagui Bessem , Rezg Raja , Repond Cendrine , Pellerin Luc 
Published: May 2022

AbstractBisphenol S (BPS) is a common substitute of bisphenol A (BPA). Recent data suggest that BPS acts as an obesogenic endocrine disruptor with emerging implications in the physiopathology of metabolic syndrome. However, the effects of BPS on monocarboxylate transporters (acting as carriers for lactate, pyruvate, and ketone bodies) and the mitochondrial respiratory system in the liver remain limited. For this purpose, male Swiss mice were treated with BPS at 100 µg/kg/day for 10 weeks, in drinking water. An increase in body weight and food intake was observed with no increase in locomotor activity. Moreover, data show that BPS increases hepatic MCT1 (a key energetic fuel transporter) mRNA expression accompanied by hepatic steatosis initiation and lipid accumulation, while disrupting mitochondrial function and oxidative stress parameters. Furthermore, BPS produced a significant increase in lactate dehydrogenase and creatine kinase activities. We can suggest that BPS contributes to hepatic steatosis in mice by upregulating monocarboxylate transporters and affecting the bioenergetic status characterized by an impaired mitochondrial respiratory system. Thus, our data highlight a new mechanism putatively implicated in hepatic steatosis development during BPS‐induced obesity involving lactate metabolism.
Palaeoecological signals for Mesolithic land use in a Central European landscape?
Authors: Heidgen Shaddai , Marinova Elena , Nelle Oliver , Ebner Martin , Rotava Teresa , Tafelmaier Yvonne , Krauß Raiko , Bofinger Jörg , Junginger Annett 
Published: May 2022

ABSTRACTDuring the Early Holocene, climate was the major factor causing fires, but whether during the Mesolithic (~11.5–7.4 cal ka BP) people co‐shaped their environment by means of fire remains of debate. Few studies have tackled this question by linking high‐resolution multi‐proxy palaeoecological studies from near Mesolithic occupation sites. An Early Holocene sediment record from the Ammer Valley palaeo‐wetland in south‐west Germany was studied using pollen, micro‐ and macrocharcoal, and plant macroremains. Archaeological evidence from Early and Late Mesolithic sites of Rottenburg‐Siebenlinden allowed us to link this palaeoecological record with Mesolithic land use in the same catchment. Between 11.6 and 10.6 cal kabp,intensive wildfires reinforced the persistence of open and pioneer vegetation. A transition from a river‐dominated landscape towards a wetland with open stagnant waters at 10.6–9.5 cal ka
bpmade the region attractive to hunter‐gatherers, providing various plant resources (incl. hazel). From 10.1 cal ka
bponwards, Mesolithic communities may have shaped their environment by using fire as a tool to expand open areas, which were important for the implementation of their subsistence strategies. After 9.5 cal ka
bp, human control over fires cannot be excluded as Mesolithic occupation phases chronologically coincide with frequent low‐intensity fires and vegetation disturbance.
A Stress Test of Artificial Intelligence: Can Deep Learning Models Trained From Formal Echocardiography Accurately Interpret Point‐of‐Care Ultrasound?
Authors: Crockett David , Kelly Christopher , Brundage James , Jones Jamal , Ockerse Patrick 
Published: May 2022

ObjectivesTo test if a deep learning (DL) model trained on echocardiography images could accurately segment the left ventricle (LV) and predict ejection fraction on apical 4‐chamber images acquired by point‐of‐care ultrasound (POCUS).MethodsWe created a dataset of 333 videos from cardiac POCUS exams acquired in the emergency department. For each video we derived two ground‐truth labels. First, we segmented the LV from one image frame and second, we classified the EF as normal, reduced, or severely reduced. We then classified the media's quality as optimal, adequate, or inadequate. With this dataset we tested the accuracy of automated LV segmentation and EF classification by the best‐in‐class echocardiography trained DL model EchoNet‐Dynamic.ResultsThe mean Dice similarity coefficient for LV segmentation was 0.72 (N = 333; 95% CI 0.70–0.74). Cohen's kappa coefficient for agreement between predicted and ground‐truth EF classification was 0.16 (N = 333). The area under the receiver‐operating curve for the diagnosis of heart failure was 0.74 (N = 333). Model performance improved with video quality for the tasks of LV segmentation and diagnosis of heart failure, but was unchanged with EF classification. For all tasks the model was less accurate than the published benchmarks for EchoNet‐Dynamic.ConclusionsPerformance of a DL model trained on formal echocardiography worsened when challenged with images captured during resuscitations. DL models intended for assessing bedside ultrasound should be trained on datasets composed of POCUS images. Such datasets have yet to be made publicly available.
Three‐dimensional DEM simulation of the nonlinear crack closure behaviour of rocks
Authors: Ye Yang , Zeng Yawu , Cheng Shufan , Chen Xi , Sun Hanqing 
Published: May 2022

AbstractCrack‐closure behaviour of rock materials is well‐known, while the three‐dimensional discrete element method (DEM) simulation of crack‐closure behaviour is still a challenge. Hence, a numerical method was proposed through the combination of notional surface method and flat‐joint model. The pre‐existing microcracks with finite width can be inserted into the three‐dimensional numerical sample through the present method. Since the two physical mechanisms, that is, closure of pre‐existing microcracks and fracture of flat‐joint bonds, are included in the simulations, various evolution trends of crack‐closure stage can be captured through the present method. Due to the high computational efficiency of flat‐joint model, the three‐dimensional DEM simulations of crack‐closure behaviour can be achieved. The results of parametric study show that the crack intensity determines the crack‐closure behaviour and the crack width significantly influences the evolution trend of crack‐closure stage. The simulated unconfined compressive strength (UCS) and tensile strength (TS) significantly decrease with the increase of crack intensity. The crack width significantly influences the deformation parameters, such as elastic modulus, Poisson's ratio and crack closure strain. A calibration procedure was proposed to ease the calibration of mechanical parameters and crack‐closure behaviour. Through the proposed numerical method and calibration procedure, the basic mechanical parameters and crack‐closure behaviour of sandstone were well matched.
Mesh generation of complex three‐dimensional geometries for beam‐particle modeling of fracture
Authors: Rima Aya , Oliver‐Leblond Cécile , Ragueneau Frédéric , Bonhomme Marie‐Hélène , Guillet Thierry , Nahas Georges 
Published: May 2022

AbstractIn this article, we propose a three‐dimensional meshing algorithm for discrete models combining the lattice approach with the polyhedral particle approach. Our aim is to be able to leverage readily available, well‐supported meshers to handle various geometries. We use them to generate a tetrahedral mesh, which our mesher then converts to a polyhedral mesh. The input mesh serves as geometrical support to generate the nodes of the discrete mesh. The desired shape is obtained with an assembly of convex polyhedral particles—without having to clip them. We show that this approach enables meshing convex or concave geometries with sharp edges, curved features, and more. Several three‐dimensional geometries are presented to support this claim and illustrate the capabilities of the mesher. We provide a detailed analysis of its isotropy. The geometric isotropy is studied by analyzing the orientation of the generated beams. The mechanical isotropy is verified by assessing the properties of the elasticity tensor. Finally, we show that the new mesh retains its ability to be a good support for the generation of realistic cracking patterns.
Topology optimization design of multi‐material quasi‐periodic cellular structures for thermoelastic responses
Authors: Li Quhao , Xu Rui , Liu Shutian , Liang Guowei , Qu Yongxin 
Published: May 2022

AbstractThermal‐mechanical coupling environments extensively exist for engineering structures. How to effectively reduce thermoelastic deformation is distinctly important. Cellular structures have superior performances in stiffness and multi‐functionality with lightweight, and an excellent design can be expected by reasonably designing the microstructural topology and their distributions. However, existing studies are limited to designing homogenous cellular structures for thermoelastic response problems, although heterogeneous cellular structures have larger design spaces. This article intends to investigate the topology optimization problem for designing a special type of heterogeneous cellular structure, that is, quasi‐periodic cellular structure, for thermoelastic responses. The quasi‐periodic cellular structure is a composition of microstructures with similar but not the same topology across the macro domain, which ensures a good compromise between manufacturability and performance. By introducing the erode‐dilate operators to describe quasi‐periodic cellular structural topology, a simple single‐loop topology optimization model for minimizing the deformation variance of specific lines with multi‐material and multi‐constraint is established. Three types of design variables are included, and their sensitivity analyses are derived for using the gradient‐based optimization solver to obtain updates simultaneously. Designs with shape‐preserving and required stiffness under thermoelastic loadings can be obtained. The examples presented show the capabilities of the proposed procedure and validate the effectiveness of the quasi‐periodic cellular structures in improving structural performance for thermoelastic problems.
River rhythmicity: A conceptual means of understanding and leveraging the relational values of rivers
Authors: Jackson Sue , Anderson Elizabeth P. , Piland Natalia C. , Carriere Solomon , Java Lilia , Jardine Timothy D. 
Published: May 2022

Abstract

River rhythmicity refers to the periodic, recurrent phenomena of a riverscape that are synchronized with the rise and fall of river water, creating regimes of river time. River rhythmicity can serve as a lens into the temporal dimension of river formation and socio‐ecological dynamics that are of great interest to many disciplines.

In this paper, we introduce river rhythmicity as a conceptual and analytical framework to unify riparian human communities, academic disciplines and water agencies in approaching research and management of rivers. We also explore how the disruptions to riverine rhythms that are experienced by river‐dwelling communities, and are often visible in river discharge data through time, reconfigure, hinder or sever relationships between people and rivers.

To ground our discussion in practical, lived experience, we provide brief descriptions of regimes of river time to demonstrate how rhythmic patterns established with rivers in north‐central Canada and Amazonian Colombia shape the lives of two of our co‐authors. By prioritizing holistic accounts of river rhythms, we can elucidate a fuller range of phenomena and their dynamic interactions, revealing riverscape features that are highly valued by local communities yet not often visible to any one discipline.

Rhythmicity provides a conceptual framework to help address several challenges facing river conservation and water allocation dilemmas. By emphasizing relationality, it serves to (a) move beyond a biophysical framing of human‐nature connectedness by demonstrating that dynamic processes and relationships are constitutive of rivers, not derivative of them; (b) enhance understanding of how the temporal dimensions of riverine relationships and river dwelling are experienced; (c) highlight the socio‐cultural consequences of changes to river time and (d) centre socially embedded relationships with rivers forged from generations of observations of care and reciprocity.
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Pharmacological and clinical monitoring in children with acute lymphoblastic leukemia treated with a biogeneric PEG‐l‐asparaginase product
Authors: Matteo Cristina , Colombini Antonella , Bettini Laura Rachele , Porcu Luca , Barzaghi Silvia , Ceruti Tommaso , Silvestri Daniela , Amoroso Angela , Dell'Acqua Fabiola , Gotti Giacomo , Nastasi Claudia , Zucchetti Massimo , Rizzari Carmelo 
Published: May 2022

AbstractBackgroundl‐Asparaginase (ASP) plays a crucial role in the treatment of childhood acute lymphoblastic leukemia (ALL). Currently, different ASP products are available in the market, including both native and pegylated drugs. Several biogeneric Escherichia coli ASP (GEN‐ASP) products have been developed in response to shortages and expensiveness of the native E. coli ASP innovator compounds, but some concerns have been raised about their quality. Recently, a number of generic pegylated ASP products (GEN‐PEG‐ASP) have been marketed to substitute for the innovator product (PEG‐ASP).MethodsClinical courses and serum asparaginase activity (SAA) levels were monitored in 12 children with ALL, who were treated in our institution with two doses of a GEN‐PEG‐ASP product, given IV at 2500 IU/m2 during the remission induction phase. Results were compared with those obtained in a reference cohort of 35 patients treated in our institution, who received the innovator PEG‐ASP product at same dosage and within the same chemotherapy background.ResultsCompared to the reference cohort treated with PEG‐ASP, SAA levels were significantly lower in the 12 patients receiving GEN‐PEG‐ASP (p < .0001); a higher proportion of ASP‐associated hypersensitivity reactions (2/12 vs. 0/35; p = .061) and silent inactivation (3/12 vs. 0/35; p = .014) were observed in comparison with the reference cohort.ConclusionsOur results highlighted different pharmacological profiles and different rates of hypersensitivity reactions and silent inactivation in the GEN‐PEG‐ASP cohort compared to those treated with the innovator product. Our findings suggest that a rigorous clinical attention and a thorough pharmacological monitoring are advisable in patients treated with GEN‐PEG‐ASP products.
The simultaneous extraction of cellulose fiber and crystal biogenic silica from the same rice husk and evaluation in cellulose‐based composite bioplastic films
Authors: Karaca Arif Enes , Özel Cem , Özarslan Ali Can , Yücel Sevil 
Published: May 2022

AbstractBioplastics are environmental‐friendly materials that have been essentially required to reduce global pollution resulting from the accumulation of conventional plastics. The current study was focused on simultaneous extraction of cellulose fiber and crystal biogenic silica from the same rice husks and preparation of silica‐reinforced cellulose‐based composite bioplastic films via casting method to evaluate in packaging applications. Herein, ZnCl2 was utilized as a solvent for the extracted cellulose fiber for the first time. As the silica content increased, barrier properties of bioplastic films increased. The highest tensile strength value in bioplastic films was obtained at 1347 kN/m2 with 2% weight silica content. The biodegradability of bioplastic films in the soil after 21 days varied between 25.5% and 55.7%, which values were significantly higher than conventional plastics. After evaluating these properties, we strongly believe that composite bioplastic films have a high potential to be utilized as green packaging material.
Patterning meets gels: Advances in engineering functional gels at micro/nanoscales for soft devices
Authors: Wang Hongshang , Wang Wenjin , Xie Zhuang 
Published: May 2022

AbstractThe booming development of skin‐like soft devices with electronics, optical and interfacial functions have brought increasing attention on the engineering of functional gel materials with well‐defined patterned features. Such devices can greatly benefit from the excellent capability of ink‐ and light‐based lithographic techniques for miniaturization, high‐density and multiplexed integration, as well as design of microstructure‐based functionalities. In this review, recent advances in patterned gel‐based soft devices are provided, with the focus on how to exploit the capability of micro/nanopatterning in realizing high‐performance gel‐based soft electronic and optical devices. Both the development of new patterning strategies and the performance of the patterned functional gels in device applications are highlighted. Diverse patterned micro/nanoscale gel building blocks are first introduced, then the surface‐microstructured gels and gels with patterned inhomogeneity are discussed, in which their applications in soft devices are summarized, such as physio‐/chemo‐sensors, electroluminescent displays, transistors, shape‐morphing actuators, and optical/microfluidic platforms. In conclusion, perspectives on the future directions of this exciting field are presented.
Screening and identifying cucurbitacins and cucurbitacin glycosides in Cucumis sativus using high‐performance liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry combined with in‐source fragmentation and alkali adduct ions
Authors: Chen Si‐Yuan , Zhou Qing Yi‐Jun , Chen Lin , Li Jia‐Yu , Xie Tao , Zhang Shui‐Han 
Published: May 2022

RationaleCucumber, as a popular fruit and vegetable, has tremendously contributed to providing a sufficient and high‐quality food supply. However, the cucumber plant metabolites, which may possess potential benefits for human health, were rarely reported. In addition, rapid detection of these metabolites from the complex biological matrix of cucumber samples is a tremendous challenge.MethodsA rapid detection method was established to systematically screen cucurbitacins and cucurbitacin glycosides in cucumber plants by combining high‐performance liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry (HPLC‐Q‐TOF‐MS) with in‐source fragmentation (ISF). Moreover, the alkali cations, including acetic acid, 0.1% LiCl, 0.1% NH4Cl, 0.1% NaCl, and 0.1% KCl, were added to the mobile phase for improving the ion response.ResultsThe fragmentation pathways of seven cucurbitacins and cucurbitacin glycosides were primarily investigated. The characteristic ISF ions at m/z 501.3211 and 503.3367 were identified and employed to screen 40 cucurbitacins and cucurbitacin glycosides from the complex biological matrix. Their structures were identified by their tandem mass spectrometry (MS/MS) spectra and fragmentation pathways of references. Finally, the metabolic distribution and network of cucurbitacins and cucurbitacin glycosides in cucumber plants were also proposed.ConclusionsThis work marks the first systematic and comprehensive study of the metabolites in cucumber plants using HPLC‐Q‐TOF‐MS technology, providing a template for screening and identifying the triterpenoids from other plant‐derived medicines or food.