bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Low-Carbon Purchase from Social Norms Perspective
Authors: Liang Dapeng , Fu Yang , Liu Mengting , Sun Jiayin , Wang Hongyan
Published: October 2023

The importance of individual consumption behavior in a low-carbon economy is gradually recognized. Social norms have a significant effect on individual purchase behavior. However, the influence mechanism of social norms still needs more research. We conducted two behavioral experiments to explore the specific factors: first, the effect of descriptive norms on personal low-carbon consumption behavior through feedback information, and second, a comparison with injunctive norms, focusing on the impact of the normative focus shift brought by punishment represented by the policy implementation. The results show that social norms can effectively promote individual low-carbon consumption through feedback and high policy implementation efficiency. In particular, after effective policy implementation becomes an inherent element of injunctive norms, injunctive norms are activated and become the focus of norms, significantly improving the purchase rate of low-carbon goods.
Intercultural Friendships with International Students in China: Examining the Role of Intergroup Contact, Intercultural Communication Competence, Host Country Nationals’ Attitudes, and Perceived Intergroup Threats
Authors: Tang Lingjie , Zhang Chang’an
Published: October 2023

International students studying and living in a foreign context often complain about difficulties establishing friendships with host nationals. This study investigates host country nationals’ (HCNs) willingness to develop intercultural friendships with international students who are sojourning in China by exploring the effects of face-to-face and online intergroup contact, HCNs’ attitudes, intercultural communication competence (ICC), and perceived intergroup threats. Survey data from 469 HCNs indicate that (a) face-to-face and online contact are indirectly and positively related to their willingness to form intercultural friendships, (b) face-to-face contact can moderate the relationships of online contact with HCNs’ intergroup attitudes and perceived intergroup threats, and (c) both ICC and intergroup attitudes can positively predict friendship formation whereas perceived intergroup threats act as a negative predictor. The implications of our findings for future research and practice are presented.
Evaluation and Optimization of Urban Public Space Accessibility for Residents’ Satisfaction: A Case Study of Nanshan District, Shenzhen City
Authors: Wang Meng , Pei Xiaochen , Zhang Man , Tang Yuyang
Published: October 2023

In order to meet the people’s growing aspirations for a better life and to improve the efficient supply capacity of the citizens’ diversified needs, our government has made the optimization of the supply of public services in urban communities a key task in urban planning and construction and has taken the community living circle as a starting point to make up for the short boards of urban public services, which is of great practical significance in improving the quality of urban life and optimizing the spatial structure of the city. As an important carrier of urban residents’ public life, urban public open space plays an indispensable role in improving the quality of life of urban residents. Accessibility is an important indicator to characterize the publicity and service level of a public open space. This study focuses on the construction of the community living circle, optimizing the GIS-based, Gaussian, two-part mobile search method to quantitatively calculate and evaluate the accessibility of a public open space within a 500 m walking distance for the residents in Nanshan District, Shenzhen. On this basis, social survey methods, including the questionnaire survey method via a field survey and the interview method, were used to conduct field research on the residents’ accessibility satisfaction. Comparing the differences and correlations between the two results, the deep-seated reasons affecting the residents’ accessibility satisfaction are explored at the levels of the construction system, management services, and structural layout and spatial design of the public open space, and targeted guiding countermeasures are put forward to guide the development and construction of public open space in the future.
The Relationship between Cost Overruns and Modifications for Construction Projects: Spanish Public Works and Their Legal Framework
Authors: Alonso-Iglesias Guillermo , Ortega-Fernández Francisco , Rodríguez-Montequín Vicente , Skitmore Martin , Ogunmakinde Olabode Emmanuel
Published: October 2023

Cost overruns are a common problem for public works projects, often due to modifications to the original design. While the causes of these modifications have been studied, the legal framework’s impact and limitations on these modifications have received extensive treatment, with no specific case studies from different countries. This paper explores the relationship between modifications in Spanish public works projects and their compliance with legal limits, investigating the alignment between base bidding prices and eventual costs after adjustments. The study also delves into the strategic behaviour of construction companies in Spain, which frequently involves manipulating project costs to match the initially proposed bidding price. Statistical methods, such as the Spearman correlation test and graphical analysis, confirm a nearly exact relationship between base bid price and final price. Also, a modification costs comparison for two different legal periods highlights the legal framework’s influence, as a less restrictive framework leads into higher average cost overruns. It provides valuable information to avoid malpractice for tendering institutions, practitioners, and legal developers, as well as those interested in the Spanish public works sector, and opens the door for future research on solving this problem.
Integrated Platform-Based Tool to Improve Life Cycle Management and Circularity of Building Envelope Components
Authors: Morganti Luca , Demutti Marco , Fotoglou Ioakeim , Coscia Eva Alessandra , Perillo Paolo , Pracucci Alessandro
Published: October 2023

The construction industry impacts resource consumption and waste production and thus necessitates solutions that promote sustainable practices. In particular, it must address challenges surrounding data collection and digital management services that often hinder the recycling or reuse of materials. The purpose of this study is to develop an integrated platform-based digital tool that seamlessly incorporates circular economy principles into construction processes, with a particular focus on circular resource utilization in the building envelope components’ life cycle. This tool aims to address the challenges in the construction industry related to resource consumption, waste production, and sustainability by promoting sustainable practices and improving material management. This paper reports industrial joint research to develop an integrated platform-based digital tool that seamlessly incorporates circular economy principles into construction processes, focusing on circular resource utilization in the building envelope components life cycle. By combining different platforms and services from the previous research, this study’s results enhance and integrate comprehensive thinking approaches and services. These include promoting raw material substitution, reducing supply chain arrangement time, minimizing waste throughout the building component lifecycle, enhancing disassembly processes, and improving life cycle environmental assessments. The tool design was informed by user-driven narratives and requirements, and demo case testing procedures, ensuring usability and industry relevance. Furthermore, integration with product lifecycle management software and data management platforms enhanced data sharing and accuracy. This study highlights the potential of integrated tools to revolutionize supply chains and promote circular economy, transforming construction paradigms. They can contribute to the reshaping of material management towards environmental consciousness, fostering resource-efficient green building solutions, and enabling more circularity in the construction industry.
The Early Case for Stabilization and Sustainability of Korean G-SEED Based on Collaborative Governance: A Theoretical Review
Authors: Kim Myunghee
Published: October 2023

This article aims to identify the significance of collaborative governance in the initial stage of the system for stabilization and sustainability through a case study of the introduction of the Green Standard for Energy and Environmental Design (G-SEED) certification system. To this end, the collaborative governance model was examined, and how the initial drivers and collaborative dynamics contributed to the stabilization and sustainability of the G-SEED certification system were investigated. Based on a theoretical literature review, a descriptive case study was conducted by applying the Integrated Framework of Collaborative Governance framework to address how multi-stakeholder collaboration works in G-SEED. The results of this study demonstrate that the drivers and collaborative dynamics in the early G-SEED contributed to a major revision of green building certification regulations and standards as outcomes of collaborative actions and to a continued increase in the number of certifications. This article argues that the stabilization and sustainability of the certification system depend on how multiple stakeholders collaborate and establish collaborative governance in the early stage of system introduction. It suggests that in the case of G-SEED, it is necessary to consider the implications derived from the results based on collaboration among sectors to achieve qualitative growth rather than quantitative expansion.
Eye Lens Organoids Made Simple: Characterization of a New Three-Dimensional Organoid Model for Lens Development and Pathology
Authors: Duot Matthieu , Viel Roselyne , Viet Justine , Le Goff-Gaillard Catherine , Paillard Luc , Lachke Salil A. , Gautier-Courteille Carole , Reboutier David
Published: October 2023

Cataract, the opacification of the lens, is the leading cause of blindness worldwide. Although effective, cataract surgery is costly and can lead to complications. Toward identifying alternate treatments, it is imperative to develop organoid models relevant for lens studies and drug screening. Here, we demonstrate that by culturing mouse lens epithelial cells under defined three-dimensional (3D) culture conditions, it is possible to generate organoids that display optical properties and recapitulate many aspects of lens organization and biology. These organoids can be rapidly produced in large amounts. High-throughput RNA sequencing (RNA-seq) on specific organoid regions isolated via laser capture microdissection (LCM) and immunofluorescence assays demonstrate that these lens organoids display a spatiotemporal expression of key lens genes, e.g., Jag1, Pax6, Prox1, Hsf4 and Cryab. Further, these lens organoids are amenable to the induction of opacities. Finally, the knockdown of a cataract-linked RNA-binding protein encoding gene, Celf1, induces opacities in these organoids, indicating their use in rapidly screening for genes that are functionally relevant to lens biology and cataract. In sum, this lens organoid model represents a compelling new tool to advance the understanding of lens biology and pathology and can find future use in the rapid screening of compounds aimed at preventing and/or treating cataracts.
SMYD3 Modulates the HGF/MET Signaling Pathway in Gastric Cancer
Authors: De Marco Katia , Lepore Signorile Martina , Di Nicola Elisabetta , Sanese Paola , Fasano Candida , Forte Giovanna , Disciglio Vittoria , Pantaleo Antonino , Varchi Greta , Del Rio Alberto , Grossi Valentina , Simone Cristiano
Published: October 2023

Gastric cancer (GC) is the third most deadly cancer worldwide. Considerable efforts have been made to find targetable drivers in order to improve patient outcomes. MET is one of the most important factors involved in GC initiation and progression as it plays a major role in GC invasiveness and is related to cancer stemness. Unfortunately, treatment strategies targeting MET are still limited, with a proportion of patients responding to therapy but later developing resistance. Here, we showed that MET is a molecular partner of the SMYD3 methyltransferase in GC cells. Moreover, we found that SMYD3 pharmacological inhibition affects the HGF/MET downstream signaling pathway. Extensive cellular analyses in GC models indicated that EM127, a novel active site-selective covalent SMYD3 inhibitor, can be used as part of a synergistic approach with MET inhibitors in order to enhance the targeting of the HGF/MET pathway. Importantly, our data were confirmed in a 3D GC cell culture system, which was used as a surrogate to evaluate stemness characteristics. Our findings identify SMYD3 as a promising therapeutic target to impair the HGF/MET pathway for the treatment of GC.
Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
Authors: Biswas Deeptarup , Halder Ankit , Barpanda Abhilash , Ghosh Susmita , Chauhan Aparna , Bhat Lipika , Epari Sridhar , Shetty Prakash , Moiyadi Aliasgar , Ball Graham Roy , Srivastava Sanjeeva
Published: October 2023

Meningioma, a primary brain tumor, is commonly encountered and accounts for 39% of overall CNS tumors. Despite significant progress in clinical research, conventional surgical and clinical interventions remain the primary treatment options for meningioma. Several proteomics and transcriptomics studies have identified potential markers and altered biological pathways; however, comprehensive exploration and data integration can help to achieve an in-depth understanding of the altered pathobiology. This study applied integrated meta-analysis strategies to proteomic and transcriptomic datasets comprising 48 tissue samples, identifying around 1832 common genes/proteins to explore the underlying mechanism in high-grade meningioma tumorigenesis. The in silico pathway analysis indicated the roles of extracellular matrix organization (EMO) and integrin binding cascades in regulating the apoptosis, angiogenesis, and proliferation responsible for the pathobiology. Subsequently, the expression of pathway components was validated in an independent cohort of 32 fresh frozen tissue samples using multiple reaction monitoring (MRM), confirming their expression in high-grade meningioma. Furthermore, proteome-level changes in EMO and integrin cell surface interactions were investigated in a high-grade meningioma (IOMM-Lee) cell line by inhibiting integrin-linked kinase (ILK). Inhibition of ILK by administrating Cpd22 demonstrated an anti-proliferative effect, inducing apoptosis and downregulating proteins associated with proliferation and metastasis, which provides mechanistic insight into the disease pathophysiology.
Energy Prediction for Energy-Harvesting Wireless Sensor: A Systematic Mapping Study
Authors: Yuan Zhenbo , Ge Yongqi , Wei Jiayuan , Yuan Shuhua , Liu Rui , Mo Xian
Published: October 2023

Energy prediction plays a significant role in energy-harvesting wireless sensors (EHWS), as it helps wireless sensors regulate their duty cycles, achieve energy neutrality, and extend their lifespan. To explore and analyze advanced technologies and methods regarding energy prediction for EHWS, this study identifies future research directions and addresses the challenges faced based on the current research status, assisting with future literature research. This scholarly inquiry delineates future research prospects and addresses prevailing challenges within the context of the extant research landscape, thereby facilitating prospective scholarly endeavors. This study employed the systematic mapping study (SMS) approach to screen and further investigate the relevant literature. After searching and screening for papers from the ACM, IEEE Xplore, and Web of Science (WOS) databases from January 2007 to December 2022, 98 papers met the requirements of this study. Subsequently, the SMS was conducted for five research questions. The results showed that the solution proposal type category had the largest proportion among all research types, accounting for 58% of the total number, indicating that the research focusing on this field is placed on improving the existing methods or proposing new ones. Additionally, based on the SMS analysis, this study provides a systematic review of the technical utilization and improvement approaches, as well as the strengths and limitations of the selected prediction methods. Furthermore, by considering the current research landscape, this paper identifies the existing challenges and suggests future research directions, thereby offering valuable insights to researchers for making informed decisions regarding their chosen paths. The significance of this study lies in its contribution to driving advancements in the field of energy-harvesting wireless sensor networks. The importance of this study is underscored by its contribution to advancing the domain of energy-harvesting wireless sensor networks, thereby serving as a touchstone for forthcoming researchers in this specialized field.
A Method for Detecting Key Points of Transferring Barrel Valve by Integrating Keypoint R-CNN and MobileNetV3
Authors: Huang Canyu , Lei Zeyong , Li Linhui , Zhong Lin , Lei Jieheng , Wang Shuiming
Published: October 2023

Industrial robots need to accurately identify the position and rotation angle of the handwheel of chemical raw material barrel valves during the process of opening and closing, in order to avoid interference between the robot gripper and the handwheel. This paper proposes a handwheel keypoint detection algorithm for fast and accurate acquisition of handwheel position and rotation pose. The algorithm is based on the Keypoint R-CNN (Region-based Convolutional Neural Network) keypoint detection model, which integrates the lightweight mobile network MobileNetV3, the Coordinate Attention module, and improved BiFPN (Bi-directional Feature Pyramid Network) structure to improve the detection speed of the model, enhance the feature extraction performance of the handwheel, and improve the expression capability of small targets at keypoint locations. Experimental results on a self-built handwheel dataset demonstrate that the proposed algorithm outperforms the Keypoint R-CNN model in terms of detection speed and accuracy, with a speed improvement of 54.6%. The detection accuracy and keypoint detection accuracy reach 93.3% and 98.7%, respectively, meeting the requirements of the application scenario and enabling accurate control of the robot’s rotation of the valve handwheel.
Challenges and Opportunities for Multimedia Transmission in Vehicular Ad Hoc Networks: A Comprehensive Review
Authors: Okpok Mfon , Kihei Billy
Published: October 2023

This review paper delves into the challenges and opportunities associated with multimedia transmission in vehicular ad hoc networks (VANETs), with a particular focus on audio-visual transmission using IEEE 802.11p. The currently deployed message dictionaries for VANETs only allow for textual exchange. By examining current research in the field of multimedia transmission within transportation systems, we explore the technical issues, challenges, and opportunities involved in transmitting audio-visual-enhanced emergency notifications to transportation users. Additionally, we shed light on the challenges related to video transmission in VANETs and propose focused research areas where Artificial Intelligence can be applied to address the bandwidth constraints imposed by devices. This work makes three significant contributions. Firstly, it presents a detailed comparison between video and image transmission, highlighting their respective strengths and limitations. Secondly, it identifies and discusses the challenges associated with multimedia transmission, emphasizing the need for quality of service and resource availability. Lastly, it examines the opportunities for using intelligence at the edge for transmitting short clips of audio-visual emergency notifications within VANETs to support new services that can coexist with the currently deployed message dictionaries.
Interpretable Multi-Channel Capsule Network for Human Motion Recognition
Authors: Li Peizhang , Fei Qing , Chen Zhen , Liu Xiangdong
Published: October 2023

Recently, capsule networks have emerged as a novel neural network architecture for human motion recognition owing to their enhanced interpretability compared to traditional deep learning networks. However, the characteristic features of human motion are often distributed across distinct spatial dimensions and existing capsule networks struggle to independently extract and combine features across multiple spatial dimensions. In this paper, we propose a new multi-channel capsule network architecture that extracts feature capsules in different spatial dimensions, generates a multi-channel capsule chain with independent routing within each channel, and culminates in the aggregation of information from capsules in different channels to activate categories. The proposed structure endows the network with the capability to independently cluster interpretable features within different channels; aggregates features across channels during classification, thereby enhancing classification accuracy and robustness; and also presents the potential for mining interpretable primitives within individual channels. Experimental comparisons with several existing capsule network structures demonstrate the superior performance of the proposed architecture. Furthermore, in contrast to previous studies that vaguely discussed the interpretability of capsule networks, we include additional visual experiments that illustrate the interpretability of the proposed network structure in practical scenarios.
Inertial Measurement Unit-Based Real-Time Adaptive Algorithm for Human Walking Pattern and Gait Event Detection
Authors: Lu Yinxiao , Zhu Jun , Chen Wenming , Ma Xin
Published: October 2023

In this work, a lightweight adaptive hybrid gait detection method with two inertial measurement units (IMUs) on the foot and thigh was developed and preliminarily evaluated. An adaptive detection algorithm is used to eliminate the pre-training phase and to modify parameters according to the changes within a walking trial using an adaptive two-level architecture. The present algorithm has a two-layer structure: a real-time detection algorithm for detecting the current gait pattern and events at 100 Hz., and a short-time online training layer for updating the parameters of gait models for each gait pattern. Three typical walking patterns, including level-ground walking (LGW), stair ascent (SA), and stair descent (SD), and four events/sub-phases of each pattern, can be detected on a portable Raspberry-Pi platform with two IMUs on the thigh and foot in real-time. A preliminary algorithm test was implemented with healthy subjects in common indoor corridors and stairs. The results showed that the on-board model training and event decoding processes took 20 ms and 1 ms, respectively. Motion detection accuracy was 97.8% for LGW, 95.6% for SA, and 97.1% for SD. F1-scores for event detection were over 0.86, and the maximum time delay was steadily below 51 ± 32.4 ms. Some of the events in gait models of SA and SD seemed to be correlated with knee extension and flexion. Given the simple and convenient hardware requirements, this method is suitable for knee assistive device applications.
A Comprehensive Methodology for Assessing the Hazardousness of Waste Categorized in the European Union Legislation as “Mirror Entries”—Case Studies
Authors: Kim Lidia , Cuciureanu Adriana , Pascu Luoana Florentina , Tache (Țăpurică) Oana Cătălina , Catrina (Trăistaru) Gina Alina
Published: October 2023

In the European Union List of Wastes, the category of “mirror entry” waste refers to either hazardous or non-hazardous waste, depending on their composition and specificity. Classifying waste as hazardous or non-hazardous is essential because it influences the feasibility and economic viability of subsequent management methods. Thus, waste classification represents a challenge both for the scientific community and for the producers/holders of waste. The methodology presented in this paper describes the stages that are the basis for evaluating the dangerousness of “mirror entry” waste and the potential factors that influence the evaluation process. Three case studies that represented three types of industrial waste were selected: waste from the non-metallic minerals industry (W1), waste from glass manufacturing (W2), and waste from the iron and steel industry (W3). The case studies were characterized and evaluated according to hazardous properties and the assignment of a waste code. The W1 and W2 waste samples did not present the hazardous properties HP1–HP15 and were included in the non-hazardous waste list. The W3 waste sample exhibited five dangerous properties and was classified as hazardous waste. The assessed wastes maintain the classifications as long as there are no changes in the technological process generation and in their composition.
Naturmenschen? Alexander von Humboldt and Indigenous People
Authors: Eibach Joachim
Published: October 2023

In the numerous texts he wrote about his grand voyage to the Americas (1799–1804), the Berlin-born, highly influential, independent scholar Alexander von Humboldt (1769–1859) considers the people in Spanish America time and time again. While Humboldt was trained as a botanist, geologist, and mining engineer, he was nevertheless fascinated by indigenous actors who employed specific competencies as they operated in their natural environments and their own socio-cultural contexts, which were distinctly different from those in Europe. His perspectives on indigenous people are complex and refer back to various current discourses of his day. Although these texts address very different topics across a range of disciplines, they nevertheless clearly testify to his intense interest in Latin American society and culture. Humboldt repeatedly reconsiders his approaches to these topics; in a characteristically Humboldtian manner, he attempts to understand quite diverse phenomena by means of precise, on-site observation, comparison, and contextualization. In so doing, his argumentation oscillated between the poles established and defined by contemporary discourse, namely ‘savage’ and ‘barbarism’ on one side of the spectrum, and ‘civilization’ on the other.
Images of Nature: Introduction to the Special Issue
Authors: Mathieu Jon
Published: October 2023

This Special Issue on ‘Images of Nature’ in the longue durée has its origins in a historical conference on ‘Nature’ at the University of Geneva in the summer of 2022 (6th Swiss History Days, 29 June–1 July 2022) [...]
Expression and Characterization of a β-Galactosidase from the Pacific Oyster, Crassostrea gigas, and Evaluation of Strategies for Testing Substrate Specificity
Authors: Thoma Julia , Grabherr Reingard , Staudacher Erika
Published: October 2023

β-Galactosidases (EC 3.2.1.23) are exoglycosidases that catalyze the cleavage of glycoconjugates with terminal β-D-galactose residues in β1,3-, β1,4- or β1,6-linkage. Although this family of exoglycosidases has been extensively studied in vertebrates, plants, yeast, and bacteria, little information is available for mollusks. Mollusks are a diverse and highly successful group of animals that play many different roles in their ecosystems, including filter feeders and detritivores. Here, the first β-galactosidase from the Pacific oyster, Crassostrea gigas was discovered, biochemically characterized, and compared to our previously characterized slug enzyme from Arion vulgaris (UniProt Ref. Nr.: A0A0B7AQJ9). Overall, the mussel enzyme showed similar biochemical parameters to the snail enzyme. The enzyme from C. gigas was most active in an acidic environment (pH 3.5) and at a reaction temperature of 50 °C. Optimal storage conditions were up to 37 °C. In contrast to the enzyme from A. vulgaris, the supplementation of cations (Ni2+, Co2+, Mn2+, Mg2+, Ca2+, Cu2+, Ba2+) increased the activity of the enzyme from C. gigas. Substrate specificity studies of the β-galactosidases from the mussel, C. gigas, and the slug, A. vulgaris, revealed activity towards terminal β1,3- and β1,4-linked galactose residues for both enzymes. Using the same substrates in labeled and unlabeled form, we were able to detect the effect of labeling on the β-galactosidase activity using MALDI-TOF MS, HPTLC, and HPLC. While lactose was cleaved by the enzymes in an unlabeled or labeled state, galacto-N-biose was not cleaved as soon as a 2-amino benzoic acid label was added. In this study we present the biochemical characterization of the first recombinantly expressed β-galactosidase from the Pacific oyster, C. gigas, and we compare different analytical methods for the determination of β-galactosidase activity using the enzyme from C. gigas and A. vulgaris.
The W101C KCNJ5 Mutation Induces Slower Pacing by Constitutively Active GIRK Channels in hiPSC-Derived Cardiomyocytes
Authors: Kayser Anne , Dittmann Sven , Šarić Tomo , Mearini Giulia , Verkerk Arie O. , Schulze-Bahr Eric
Published: October 2023

Mutations in the KCNJ5 gene, encoding one of the major subunits of cardiac G-protein-gated inwardly rectifying K+ (GIRK) channels, have been recently linked to inherited forms of sinus node dysfunction. Here, the pathogenic mechanism of the W101C KCNJ5 mutation underlying sinus bradycardia in a patient-derived cellular disease model of sinus node dysfunction (SND) was investigated. A human-induced pluripotent stem cell (hiPSCs) line of a mutation carrier was generated, and CRISPR/Cas9-based gene targeting was used to correct the familial mutation as a control line. Both cell lines were further differentiated into cardiomyocytes (hiPSC-CMs) that robustly expressed GIRK channels which underly the acetylcholine-regulated K+ current (IK,ACh). hiPSC-CMs with the W101C KCNJ5 mutation (hiPSCW101C-CM) had a constitutively active IK,ACh under baseline conditions; the application of carbachol was able to increase IK,ACh, further indicating that not all available cardiac GIRK channels were open at baseline. Additionally, hiPSCW101C-CM had a more negative maximal diastolic potential (MDP) and a slower pacing frequency confirming the bradycardic phenotype. Of note, the blockade of the constitutively active GIRK channel with XAF-1407 rescued the phenotype. These results provide further mechanistic insights and may pave the way for the treatment of SND patients with GIRK channel dysfunction.
Unlocking the Complexity of Neuromuscular Diseases: Insights from Human Pluripotent Stem Cell-Derived Neuromuscular Junctions
Authors: Gazzola Morgan , Martinat Cécile
Published: October 2023

Over the past 20 years, the use of pluripotent stem cells to mimic the complexities of the human neuromuscular junction has received much attention. Deciphering the key mechanisms underlying the establishment and maturation of this complex synapse has been driven by the dual goals of addressing developmental questions and gaining insight into neuromuscular disorders. This review aims to summarise the evolution and sophistication of in vitro neuromuscular junction models developed from the first differentiation of human embryonic stem cells into motor neurons to recent neuromuscular organoids. We also discuss the potential offered by these models to decipher different neuromuscular diseases characterised by defects in the presynaptic compartment, the neuromuscular junction, and the postsynaptic compartment. Finally, we discuss the emerging field that considers the use of these techniques in drug screening assay and the challenges they will face in the future.
The Role of Carbon Nanoparticles as Lymph Node Tracers in Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Koimtzis Georgios , Geropoulos Georgios , Stefanopoulos Leandros , Chalklin Christopher Gwydion , Karniadakis Ioannis , Alexandrou Vyron , Tteralli Nikos , Carrington-Windo Eliot , Papacharalampous Andreas , Psarras Kyriakos
Published: October 2023

Colorectal malignancies are the third-most common malignancies worldwide, with a rising incidence. Surgery remains the treatment of choice and adequate lymph node dissection is required for accurate staging. The objective of this study is to assess the use of carbon nanoparticles in lymph node tracing and resection in cases of colorectal cancer. For that purpose, we conducted a systematic review and meta-analysis of studies included in Medline, Scopus, Embase, Cochrane Library, and Google Scholar databases. In the end, ten studies with a total number of 1418 patients were included in the final statistical analysis. The meta-analysis carried out showed that the use of carbon nanoparticles results in an increased number of lymph nodes harvested (WMD 6.15, 95% CI 4.14 to 8.16, p < 0.001) and a higher rate of cases with more than 12 lymph nodes harvested (OR 9.57, 95% CI 2.87 to 31.96, p = 0.0002). As a consequence, we suggest that carbon nanoparticles are used on a wider scale and that future research focuses on assessing the association between their use and overall patient survival. This study is limited by the fact that all included studies originate from China and by the fact that certain oncologic parameters and long-term outcomes have not been taken into account in the analysis.
Effect of the Functional VP1 Unique Region of Human Parvovirus B19 in Causing Skin Fibrosis of Systemic Sclerosis
Authors: Chen Der-Yuan , Tzang Chih-Chen , Liu Chuan-Ming , Chiu Tsu-Man , Lin Jhen-Wei , Chuang Pei-Hua , Kuo Chia-Wei , Tzang Bor-Show , Hsu Tsai-Ching
Published: October 2023

Human parvovirus B19 (B19V) is a single-stranded non-enveloped DNA virus of the family Parvoviridae that has been associated with various autoimmune disorders. Systemic sclerosis (SSc) is an autoimmune connective tissue disorder with high mortality and has been linked to B19V infection. However, the precise mechanism underlying the B19V contribution to the development of SSc remains uncertain. This study investigated the impacts of the functional B19V-VP1 unique region (VP1u) in macrophages and bleomycin (BLE)-induced SSc mice. Cell experimental data showed that significantly decreased viability and migration of both B19V-VP1u-treated U937 and THP-1 macrophages are detected in the presence of celastrol. Significantly increased MMP9 activity and elevated NF-kB, MMP9, IL-6, TNF-α, and IL-1β expressions were detected in both B19V-VP1u-treated U937 and THP-1 macrophages. Conversely, celastrol revealed an inhibitory effect on these molecules. Notably, celastrol intervened in this pathogenic process by suppressing the sPLA2 activity of B19V-VP1u and subsequently reducing the inflammatory response. Notably, the administration of B19V-VP1u exacerbated BLE-induced skin fibrosis in mice, with augmented expressions of TGF-β, IL-6, IL-17A, IL-18, and TNF-α, ultimately leading to α-SMA and collagen I deposits in the dermal regions of BLE-induced SSc mice. Altogether, this study sheds light on parvovirus B19 VP1u linked to scleroderma and aggravated dermal fibrosis.
Acute Kidney Injury by Ischemia/Reperfusion and Extracellular Vesicles
Authors: Nørgård Mikkel Ørnfeldt , Svenningsen Per
Published: October 2023

Acute kidney injury (AKI) is often caused by ischemia-reperfusion injury (IRI). IRI significantly affects kidney metabolism, which elicits pro-inflammatory responses and kidney injury. The ischemia/reperfusion of the kidney is associated with transient high mitochondrial-derived reactive oxygen species (ROS) production rates. Excessive mitochondrial-derived ROS damages cellular components and, together with other pathogenic mechanisms, elicits a range of acute injury mechanisms that impair kidney function. Mitochondrial-derived ROS production also stimulates epithelial cell secretion of extracellular vesicles (EVs) containing RNAs, lipids, and proteins, suggesting that EVs are involved in AKI pathogenesis. This literature review focuses on how EV secretion is stimulated during ischemia/reperfusion and how cell-specific EVs and their molecular cargo may modify the IRI process. Moreover, critical pitfalls in the analysis of kidney epithelial-derived EVs are described. In particular, we will focus on how the release of kidney epithelial EVs is affected during tissue analyses and how this may confound data on cell-to-cell signaling. By increasing awareness of methodological pitfalls in renal EV research, the risk of false negatives can be mitigated. This will improve future EV data interpretation regarding EVs contribution to AKI pathogenesis and their potential as biomarkers or treatments for AKI.
Expression Pattern of Trace Amine-Associated Receptors during Differentiation of Human Pluripotent Stem Cells to Dopaminergic Neurons
Authors: Katolikova Nataliia V. , Vaganova Anastasia N. , Shafranskaya Daria D. , Efimova Evgeniya V. , Malashicheva Anna B. , Gainetdinov Raul R.
Published: October 2023

Trace amine-associated receptors (TAARs), which were discovered only in 2001, are known to be involved in the regulation of a spectrum of neuronal processes and may play a role in the pathogenesis of a number of neuropsychiatric diseases, such as schizophrenia and others. We have previously shown that TAARs also have interconnections with the regulation of neurogenesis and, in particular, with the neurogenesis of dopamine neurons, but the exact mechanisms of this are still unknown. In our work we analyzed the expression of TAARs (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8 and TAAR9) in cells from the human substantia nigra and ventral tegmental areas and in human pluripotent stem cells at consecutive stages of their differentiation to dopaminergic neurons, using RNA sequencing data from open databases, and TaqMan PCR data from the differentiation of human induced pluripotent stem cells in vitro. Detectable levels of TAARs expression were found in cells at the pluripotent stages, and the dynamic of their expression had a trend of increasing with the differentiation and maturation of dopamine neurons. The expression of several TAAR types (particularly TAAR5) was also found in human dopaminergic neuron-enriched zones in the midbrain. This is the first evidence of TAARs expression during neuronal differentiation, which can help to approach an understanding of the role of TAARs in neurogenesis.
Hematologic Neoplasms Associated with Down Syndrome: Cellular and Molecular Heterogeneity of the Diseases
Authors: Peroni Edoardo , Gottardi Michele , D’Antona Lucia , Randi Maria Luigia , Rosato Antonio , Coltro Giacomo
Published: October 2023

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS via additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events, and the aberrant expression of CRLF2, JAK2 mutations, and RAS pathway-activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment’s role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.
Gender-Based Clinical, Therapeutic Strategies and Prognosis Differences in Atrial Fibrillation
Authors: Quesada Aurelio , Quesada-Ocete Javier , Quesada-Ocete Blanca , del Moral-Ronda Víctor , Jiménez-Bello Javier , Rubini-Costa Ricardo , Lavie Carl J. , Morin Daniel P. , de la Guía-Galipienso Fernando , Rubini-Puig Ricardo , Sanchis-Gomar Fabian
Published: October 2023

Background: There are limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. We aimed to examine gender-related differences in medical attention in an emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies, and long-term adverse events in this population. Methods: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010 to 2015, with a minimum FU of one year. Data on medical attention received, mortality, and other adverse outcomes were collected and analyzed. Results: Among the 2013 patients selected, 1232 (60%) were female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p = 0.001) and were less likely to be admitted (5.9% vs. 9.5%, p < 0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p = 0.001) and during FU (15.9% vs. 10.6%, p < 0.001), despite a lower AF recurrence rate in women (9.9% vs. 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p < 0.001). Conclusions: In patients with AF, although there were no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists, and showed a higher probability of hospitalization for heart failure. Being alert to these inequities should facilitate the adoption of measures to correct them.
Limitations in Contemporary Pharmacological Stroke Prevention Therapies in Atrial Fibrillation: A Descriptive Literature Review
Authors: Garot Philippe , Bergmann Martin W.
Published: October 2023

The most common arrhythmia, atrial fibrillation (AF), increases with age and is associated with a 5-fold increased risk of stroke. Although lifelong oral anticoagulation (OAC) is strongly recommended for stroke prevention in patients with AF and CHA2DS2-VASc ≥ 2 only 50–60% of patients in Western countries belonging to this group are treated with oral anticoagulants, and less than half of these adhere to therapy over time. Before 2010, the numerous limitations associated with vitamin K antagonists (VKAs) were considered to be the reason behind OAC underuse; however, the approval of direct oral anticoagulants (DOACs) that require once- or twice-daily intake, no regular blood tests and fewer drug–food interactions has resulted in only modest improvements in OAC use and adherence.
Clinical Benefit of First-Pass Recanalization Is Time-Dependent in Endovascular Treatment of Acute Ischemic Stroke
Authors: Baek Jang-Hyun , Heo Ji Hoe , Nam Hyo Suk , Kim Byung Moon , Kim Dong Joon , Kim Young Dae
Published: October 2023

Clinical benefit can be time-dependent even after first-pass recanalization (FPR) in endovascular treatment of acute stroke. This study aimed to evaluate the association between favorable outcome and FPR under a specific time frame. Patients who underwent mechanical thrombectomy were retrospectively reviewed. Recanalization status was categorized into four groups based on FPR and dichotomized time from groin puncture to recanalization (P-to-R time). Favorable outcomes were compared between groups. A total of 458 patients were included. As the cutoff of P-to-R time for favorable outcome was 30 min, recanalization status was categorized into FPR (+) with a P-to-R time ≤ 30 min (Group 1), FPR (–) with a P-to-R time ≤ 30 min (Group 2), FPR (+) with a P-to-R time > 30 min (Group 3), and FPR (–) with a P-to-R time > 30 min (Group 4). Favorable outcomes in Group 3 (37.5%) were significantly less frequent than those in Group 1 (60.4%, p = 0.029) and Group 2 (59.5%, p = 0.033) but were not significantly different from those in Group 4 (35.7%, p = 0.903). Compared to Group 1, Group 3 (adjusted odds ratio, 0.30 [95% confidence interval, 0.12–0.76]; p = 0.011) and Group 4 (0.25 [0.14–0.48]; p < 0.001) were adversely associated with favorable outcomes. FPR was associated with functional outcome in a time-dependent manner. Even for patients who have achieved FPR, their functional outcome might not be favorable if the P-to-R time is >30 min.
Clinical Presentation and Emergency Department Management Checkpoints of Acute Aortic Syndromes during the First Two Waves of the COVID-19 Pandemic
Authors: Bima Paolo , Giamello Jacopo Davide , Rubiolo Paolo , Risi Francesca , Balzaretti Paolo , Lauria Giuseppe , Vallino Domenico , Lupia Enrico , Morello Fulvio
Published: October 2023

The COVID-19 pandemic has deeply affected the activity and patient flows of Emergency Departments (EDs), and concern for the worsening outcome of cardiovascular emergencies has been raised. However, the impact of COVID-19 on all subtypes of acute aortic syndromes (AASs) has not been evaluated so far. Cases of AASs managed in the ED of three hub hospitals in a large area of Northern Italy were retrospectively analyzed, comparing those registered during the pandemic (March 2020 to May 2021) with corresponding pre-COVID-19 periods. A total of 124 patients with AAS were managed during the COVID-19 period vs. 118 pre-COVID-19 (p = 0.70), despite a −34.6% change in ED visits. Posterior chest pain at presentation was the only clinical variable with a different prevalence (46.0% vs. 32.2%, p = 0.03). Surgery and endovascular treatment rates were unchanged. Time intervals influenced by patient transfer to the hub center were longer during the COVID-19 period and longest during high viral circulation periods. Ninety-day mortality was unchanged, with a higher mortality trend during the pandemic surges. In conclusion, ED presentation and care of AASs were marginally affected by COVID-19, but efforts are needed to preserve efficient patient transfer to specialized centers and prevent mortality, especially during pandemic peaks.