bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidating International Travelers’ Tourism Image of Taiwan: A Qualitative Approach
Authors: Lee Tsung-Hung , Fu Chung-Jen , Chen Mei-Hsiang
Published: January 2023

Although Western alien visitors to Taiwan have a unique, well-informed perspective of what appeals to tourists from their countries, little research has been conducted to assess their insights, representing a significant research gap. To fill this gap, this study aims to elucidate how international tourists perceive Taiwan as a tourist destination by collecting detailed qualitative data via in-depth interviews of twenty-four international expatriates. This study illustrated the image differences before and after the visit of international tourists by analyzing the dimensions of tourists’ consensus maps and the changes in their perception of the natural, social, cultural, gourmet food, and Aboriginal image of Taiwan. This study provides a better understanding of how international tourists in Taiwan view its current and potential appeal as a tourist destination, so as to identify ways of attracting new tourists from their cultures. Patterns emerged that suggest new approaches for promoting Taiwan tourism and tourism sustainability which might not occur to Taiwanese tourism professionals due to the interviewees’ unique points of view. This research concludes that the application of cultural promotion strategies, planned tour packages, and improvement of the image of nature, culture, society, food, and Aboriginal people in Taiwan will thereby improve the overall satisfaction of international tourists, building online image, and forming e-word-of-mouth.
Review of Rice–Fish–Duck Symbiosis System in China—One of the Globally Important Ingenious Agricultural Heritage Systems (GIAHS)
Authors: Zhang Yin , Guan Chunyun , Li Zhengyou , Luo Jun , Ren Bo , Chen Can , Xu Ying , Ding Jiaolong , Huang Huang
Published: January 2023

The Chinese rice–fish–duck symbiosis system is one of the globally important agricultural heritage systems, with a history of nearly a thousand years. It embodies the wisdom of the Chinese ancestors and has huge comprehensive value, which has extremely important references for the sustainable development of agriculture. The technological core for the rice–fish–duck symbiosis system lies in the selection of rice, fish, and duck varieties and the coupling of agricultural operation time. In the process of modern agriculture, many varieties with high comprehensive benefits have also been applied to the rice–fish–duck system, and the rice–fish–duck model has been further developed. What is worrying is that the transfer of rural labor, the promotion of modern agricultural technology, the low degree of marketization and industrialization, the weakening of cultural awareness, and the change in climate have posed huge threats and challenges to the traditional Chinese rice–fish–duck system. The protection and development of the system are urgently needed. Therefore, we recommend delimiting active protection areas, establishing scientific research bases, improving relevant systems, developing rural tourism markets, and innovating farming technology, which also provide guidance for protecting and developing other agricultural cultural heritages.
The Decorative Auspicious Elements of Traditional Bai Architecture in Shaxi Ancient Town, China
Authors: Zhao Hua , Huang Zongsheng , Deng Caijie , Ren Yuxin
Published: January 2023

The lucky cultural characteristics of traditional architecture are of importance. It shows what makes a place unique and the spiritual and material goals people have there. It is thus vital to understand the lucky cultural characteristics of traditional villages. This paper attempts to explore the auspicious cultural attributes of the town. We are aiming to reveal the current status of cultural integration in Shaxi’s ancient town so that we can find the problems arising from the development process. Moreover, the research subject is the lucky element of Shaxi Bai’s traditional architecture. Lucky themes include lotuses, unicorns, phoenixes, etc. The research was qualitative and quantitative, so we begin by identifying the lucky elements. Then, we used methods for analysing diversity and complex networks to determine their diversity indices and network model indicators. These findings show the old town’s diversified, lucky culture. However, Buddhist culture dominates the multicultural makeup. Furthermore, the native Bai culture is also conserved and preserved.
Understanding Rare Earth Elements as Critical Raw Materials
Authors: Leal Filho Walter Leal , Kotter Richard , Özuyar Pinar Gökçin , Abubakar Ismaila Rimi , Eustachio João Henrique Paulino Pires , Matandirotya Newton R.
Published: January 2023

The boom in technological advances in recent decades has led to increased demand for rare earth elements (REEs) (also known as rare earth metals) across various industries with wide-ranging industrial applications, including in the clean energy sector, but with some environmental, economic, and social footprint concerns. This paper reviews the complexities of the production, consumption, and reuse or recovery of REEs, presenting current trends in terms of potentials and challenges associated with this. This paper in particular focuses on the supply, demand, and (environmental and economic) sustainability of REEs, as a subset of critical raw materials. It does so via a critical stocktaking of key discussions and debates in the field over the past 15 years up until now, through a thematic analysis of the published and gray (policy) literature with a grounded theory approach. The paper finds that carefully balanced lifecycle sustainability assessments are needed for assessing the respective dimensions of the extraction, processing, and reuse or recovery methods for different types of REE sources and supplies to meet current and future demands. It furthermore diagnoses the need for taking into account some shifts and substitutions among REEs also for reasons of cost and locational supplies for the security of supply. Finally, the paper provides some overall policy recommendations for addressing current problems, with a conceptual framing of the UN Sustainable Development Goals.
Assessment of Building Energy Simulation Tools to Predict Heating and Cooling Energy Consumption at Early Design Stages
Authors: Del Ama Gonzalo Fernando , Moreno Santamaría Belén , Montero Burgos María Jesús
Published: January 2023

Recent developments in dynamic energy simulation tools enable the definition of energy performance in buildings at the design stage. However, there are deviations among building energy simulation (BES) tools due to the algorithms, calculation errors, implementation errors, non-identical inputs, and different weather data processing. This study aimed to analyze several building energy simulation tools modeling the same characteristic office cell and comparing the heating and cooling loads on a yearly, monthly, and hourly basis for the climates of Boston, USA, and Madrid, Spain. First, a general classification of tools was provided, from basic online tools with limited modeling capabilities and inputs to more advanced simulation engines. General-purpose engines, such as TRNSYS and IDA ICE, allow users to develop new mathematical models for disruptive materials. Special-purpose tools, such as EnergyPlus, work with predefined standard simulation problems and permit a high calculation speed. The process of reaching a good agreement between all tools required several iterations. After analyzing the differences between the outputs from different software tools, a cross-validation methodology was applied to assess the heating and cooling demand among tools. In this regard, a statistical analysis was used to evaluate the reliability of the simulations, and the deviation thresholds indicated by ASHRAE Guideline 14-2014 were used as a basis to identify results that suggested an acceptable level of disagreement among the outcomes of all models. This study highlighted that comparing only the yearly heating and cooling demand was not enough to find the deviations between the tools. In the annual analysis, the mean percentage error values showed a good agreement among the programs, with deviations ranging from 0.1% to 5.3% among the results from different software and the average values. The monthly load deviations calculated by the studied tools ranged between 12% and 20% in Madrid and 10% and 14% in Boston, which were still considered satisfactory. However, the hourly energy demand analysis showed normalized root mean square error values from 35% to 50%, which were far from acceptable standards.
Influence of Cooling Water Flow Rate on Start and Heat Transfer Performance of Pulsating Heat Pipe at Different Inclination Angles
Authors: Shi Weixiu , Liu Xuebing , Su Xiaoyang , Chen Hongdi , Pan Lisheng
Published: January 2023

Pulsating heat pipe (PHP) is an efficient heat transfer technology applied in the fields of heat dissipation and energy utilization. There are many factors affecting the heat transfer of PHP, including working fluid, filling ratio, inclination angle, etc. The cooling capacity of the cooling water system at the condensing section to the working fluid is also an important factor affecting the starting and operating of PHP. The research on PHP at different cooling water flow rates is of great significance for enhancing the operating performance. An experimental investigation of starting and running performance is carried out on a closed loop PHP with ultrapure water under different inclination angles of 90°, 60° and 30°. The starting and heat transfer performance of PHP with a filling ratio of 50% is obtained by adjusting the heat input in the range of 30–210 W at different cooling water flow rates of 6.7 g/s, 9.7 g/s and 13.9 g/s. The temperature and heat transfer resistance are used for analyzing the heat transfer performance. The results show that the starting mode, initial pulsating temperature and different heat transfer effects are brought about by different cooling water flow rates. It is observed that the cooling water flow rate has no obvious influence on the starting mode of PHP and that the starting mode of PHP is temperature progressive, starting with the increase in cooling water flow rates at a heating input of about 30 W. The influence of cooling water flow rates on the heat transfer performance of PHP is affected in a different way by inclination angles. The heat transfer performance of PHP with an inclination angle of 90° is similar at 6.7 g/s, 9.7 g/s and 13.9 g/s but, under the condition of 60° and 30°, the heat transfer resistance drops within a certain range effectively with an increasing cooling water flow rate from 6.7 g/s to 9.7 g/s and the heat transfer performance does not change significantly with the cooling water flow rate increasing to 13.9 g/s. Thus, there is an optimal value for the cooling water flow rate during the operating of PHP. The inclination angle also has an important effect on the temperature pulsating, and the temperature of PHP affected by gravity is stable with an inclination angle of 90°. However, the reduced influence of gravity on the backflow of the working fluid drops when the inclination angle decreases from 90° to 30°, and the wall temperature increases due to local overheating when the high heat input occurs.
Analysis of Factors Influencing Illegal Waste Dumping Generation Using GIS Spatial Regression Methods
Authors: Syafrudin Syafrudin , Ramadan Bimastyaji Surya , Budihardjo Mochamad Arief , Munawir Munawir , Khair Hafizhul , Rosmalina Raden Tina , Ardiansyah Septa Yudha
Published: January 2023

Illegal municipal waste dumping practices in developing countries may be impacted by many factors such as socioeconomic, demographic, availability of waste collection facilities, recycling sites, and spatial characteristics. This study uses spatial regression analysis to identify which factors primarily impact illegal waste dumping practices. For this purpose, 8 variables explain the data for the 177 subdistricts used in the spatial regression analysis. This study used ordinary least squares (OLS) and geographically weighted regression (GWR) methods to build a regression model of the factors identified. OLS analysis showed that only elevation and population density were found to become determinants of illegal waste dumping activity based on spatial regression methods. Elevation above sea level is positively correlated while population density is negatively correlated with the number of illegal dumping generations. GWR shows a better statistical value than OLS, where the significance of the adjusted R-square increased from 0.24 to 0.61. This study may help reduce the number of illegal waste dumping practices, especially in a metro city context.
Sustainable Management of Marine Biodiversity in Areas beyond National Jurisdiction by Establishing Protected Areas on the High Seas: A Chinese Perspective
Authors: Yu Minyou , Huang Yuwen , Fu Qinghua
Published: January 2023

Due to the several undiscovered and valuable gene and mineral resources, marine biodiversity is considered a strategic asset for socio-economic development. However, marine biodiversity is facing grave threats, particularly in areas beyond national jurisdiction (ABNJ), where sustainable management and effective implementation of governance is yet lacking. Here existing international legal regimes with the protection of marine biodiversity in areas beyond national jurisdiction are briefly summarized, focusing on potential factors influencing China’s policymaking on the construction of marine protected areas on the high seas. It is concluded that China should actively participate in international negotiations and seriously assess the impacts of establishing these protected areas before making its own decision in order to achieve the sustainable conservation and management of marine biodiversity in areas beyond national jurisdiction. In addition, the policy’s future research directions will be the practical challenges for China to establish and manage the marine protected areas on the high seas, especially in the selection of locations and the model of management.
The Spatial Pattern of Deprivations and Inequalities: The Case of Addis Ababa, Ethiopia
Authors: Gelet Gizachew Berhanu , Woldemichael Solomon Mulugeta , Beyene Ephrem Gebremariam
Published: January 2023

Addis Ababa is a metropolitan area faced with the challenges of Ethiopia’s urbanization, such as poverty, unemployment, informal settlements, an acute housing shortage, and environmental hazards. Yet, the non-practicality of area-based policy using the Multiple Deprivation Index (MDI) exacerbates the polarization of poverty and spatial inequality to create a divided city. The study developed the MDI for 2007 and 2016. The study’s objective was to justify the area-based policy by analyzing the overlaps of deprivations based on the relationship of pertinent indicators and components, the spatial pattern of inequality and deprivations, and the relationship of deprivation with population size and density. The findings of the study were triangulated and validated with the deductive theoretical, empirical, and SDG frameworks to replicate external validity. The research design included both descriptive and correlational methods. The inductively derived pattern using PCA (principal component analysis) and LISA (local spatial association index) of MDI components revealed spatial inequality and poverty polarization. The index of concentrated poverty was revealed by global spatial autocorrelation. The statistical and spatial trend analysis revealed concentrated poverty, especially in the inner-city slums and the peri-urban informal settlements. Most of the findings conformed to deductive theoretical and SDG frameworks, while the analysis of MDI indicators and components revealed additional slum indicators and the relevance of integrating other SDG indicators with SDG 11 for realizing sustainable urbanization. Due to spatial inequality, patterns of concentrated poverty, a large, deprived population, and easing future urbanization challenges, the study rationalized area-based policy for reducing inequality and poverty polarization.
The Impact Mechanism of Digital Transformation on the Risk-Taking Level of Chinese Listed Companies
Authors: Dai Debao , Han Shengnan , Zhao Min , Xie Jiaping
Published: January 2023

As the core engine of the digital economy, the digital transformation can make modern enterprises survive and develop better now. By the sample data of listed companies in the years from 2015 to 2020, this paper identifies the degree of enterprise digital transformation through text analysis, empirically examines the impact mechanism of digital transformation on corporate risk-taking, and fully considers the heterogeneity problems. The findings are as follows: (1) Digital transformation can improve the level of enterprise risk taking, especially the improvement of enterprise financial stability and strategic risk taking; (2) in terms of enterprise attribute structure, digital transformation can significantly enhance the risk-taking level of non-state-owned enterprises and high-tech enterprises; (3) the mechanism identification test finds that innovation-driven and enterprise value enhancement play a strengthening role in the role of digital transformation in promoting enterprise risk-taking level, and resource allocation efficiency as a mediating path weakens the role of digital transformation on enterprise risk-taking level. This study provides a basis for promoting the improvement of enterprises risk-taking: digital transformation can help enterprises maintain financial stability, improve innovation output capacity, enterprise value level, enterprise risk-taking capacity and sustainable development. At the same time, the Chinese government should take measures to further stimulate the willingness of state-owned enterprises to digital transformation.
Impact of Anti-Pandemic Policy Stringency on Firms’ Profitability during COVID-19
Authors: Labadze Lasha , Sraieb Mohamed M.
Published: January 2023

The coronavirus (COVID-19) pandemic devastated all economies across the world and triggered a deterioration in firms’ financial performance. However, some sectors turned out to be more vulnerable while others continued to perform well during the crisis period. Given this fact, we conducted a comprehensive study to estimate the impact of the COVID-19 pandemic on firms’ profitability in Europe. We used a dynamic panel data approach and a system generalized method of moment (System-GMM) model to investigate (i) which sectors were affected and what was the magnitude of the impact on firms’ profitability, and (ii) whether the stringency of anti-pandemic policies such as workplace closures and travel bans impacted firms unevenly. We find that COVID-19 caused about a 25% decline in the profitability of firms. The most impacted sectors were Consumer Discretionary, Consumer Staples, and Industrials, where profitability declined from 20 to 48%. We also find that firms in countries with high anti-pandemic policy stringency lost about 19% more in profitability than in the rest of the countries in Europe during 2020.
Assessing the Environmental Impacts of Household Water Supply: A Case Study Considering Consumption Patterns within a Life-Cycle Perspective
Authors: Zúñiga Valentina , Leiva Sofía , Riquelme Cristian , Gómez Gloria , Vidal Gladys , Neumann Patricio
Published: January 2023

Household water supply can cause different environmental impacts associated with the consumption of energy and materials, the generation of waste, and other inputs and outputs necessary to treat and distribute water. These impacts depend on the population’s consumption patterns, due to the potential availability of different water sources. In this work, the environmental impacts of water supply were evaluated from a production-consumption perspective, integrating life cycle assessment (LCA) and a survey for determining the end uses and sources of water at household level. The proposed method was applied in the city of Chillán (Chile), where three main sources exist: tap, bottled, and well water. Two household profiles were evaluated, differentiated by the presence of wells within the household. The results show that bottled water generates impacts up to three orders of magnitude greater than the other sources. Although it is the source with the lowest volumetric contribution (<1%), it accounts for 39–92% of the household impacts. Households with well access present greater per capita consumption of water, mainly associated with outdoor activities, but the environmental impacts are similar between profiles. Overall, this study demonstrates the importance of integrating a consumption perspective into LCA studies, generating better information for decision-making.
Proactive Operations Management: Staff Allocation with Competence Maintenance Constraints
Authors: Szwarc Eryk , Bocewicz Grzegorz , Golińska-Dawson Paulina , Banaszak Zbigniew
Published: January 2023

Highly qualified staff are the key to successful operations management in any organization. In this paper, the emphasis is put on the problem of planning the rotational assignment of work tasks to a multi-skilled staff to guarantee maintaining their competencies at the required level. The aim of this study is to propose a novel declarative model for proactive planning of staff allocation whilst taking into account the forgetting effect. Sufficient conditions are proposed that allow for the cyclical rotation of employees between different tasks in order to keep their competencies at a constant level. The numerical experiments prove that the presented approach allows for finding a trade-off between a robustness to absenteeism and maintaining staff competency levels. The proposed method is suitable for human resource-related decision making in an interactive mode.
Methodology for the Path Definition in Multi-Layer Gas Metal Arc Welding (GMAW)
Authors: Curiel David , Veiga Fernando , Suarez Alfredo , Villanueva Pedro
Published: January 2023

The reconstruction of the geometry of weld-deposited materials plays an important role in the control of the torch path in GMAW. This technique, which is classified as a direct energy deposition technology, is experiencing a new emergence due to its use in welding and additive manufacturing. Usually, the torch path is determined by computerised fabrication tools, but these software tools do not consider the geometrical changes along the case during the process. The aim of this work is to adaptively define the trajectories between layers by analysing the geometry and symmetry of previously deposited layers. The novelty of this work is the integration of a profiling laser coupled to the production system, which scans the deposited layers. Once the layer is scanned, the geometry of the deposited bead can be reconstructed and the symmetry in the geometry and a continuous trajectory can be determined. A wall was fabricated under demanding deposition conditions, and a surface quality of around 100 microns and mechanical properties in line with those previously reported in the literature are observed.
Multiwavelength Analysis of the IceCube Neutrino Source Candidate Blazar PKS 1424+240
Authors: Kun Emma , Medveczky Attila
Published: January 2023

The true nature of sources of cosmic neutrinos recorded by the Antarctic IceCube Neutrino Detector is still an enigma of high-energy astrophysics. Time-integrated neutrino source searches with the 10 years of IceCube data unfolded neutrino hot-spots of the sky; among them, one is associated with the blazar PKS 1424+240, which is the third most significant neutrino source candidate in the Northern sky. In this paper, we analyze VLBI radio data of PKS 1424+240 taken with the Very Large Baseline Array at 15 GHz as part of the MOJAVE Survey. We generate the adaptively binned gamma-ray light curve of the source, employing Fermi-LAT data between 100 MeV and 300 GeV. We find that the VLBI jet components maintain quasi-stationary core separations at 15 GHz. We find a quiescence and a perturbed phase of the VLBI core of PKS 1424+240, based on that its Doppler factor increased tenfold after 2016 compared to the quiescence phase. We do not find elevated gamma-ray activity after 2016, while archive Swift-XRT measurements show a highly increased 0.3–10 keV X-ray flux in the beginning of 2017. Substantial increase of the activity of the radio core might help us to identify episodes of particle acceleration in lepto-hadronic blazar jets that eventually lead to the emission of high-energy neutrinos.
Relativistic Fermion and Boson Fields: Bose-Einstein Condensate as a Time Crystal
Authors: Sbitnev Valeriy
Published: January 2023

In a basis of the space-time coordinate frame four quaternions discovered by Hamilton can be used. For subsequent reproduction of the coordinate frame these four quaternions are expanded to four 4 × 4 matrices with real-valued matrix coefficients −0 and 1. This group set is isomorphic to the SU(2) group. Such a matrix basis introduces extra six degrees of freedom of matter motion in space-time. There are three rotations about three space axes and three boosts along these axes. Next one declares the differential generating operators acting on the energy-momentum density tensor written in the above quaternion basis. The subsequent actions of this operator together with its transposed one on the above tensor lead to the emergence of the gravitomagnetic equations that are like the Maxwell equations. Wave equations extracted from the gravitomagnetic ones describe the propagation of energy density waves and their vortices through space. The Dirac equations and their reduction to two equations with real-valued functions, the quantum Hamilton-Jacobi equations and the continuity equations, are considered. The Klein-Gordon equations arising on the mass shell hints to the alternation of the paired fermion fields and boson ones. As an example, a Feynman diagram of an electron–positron time crystal is illustrated.
Harmonic Oscillator Coherent States from the Standpoint of Orbit Theory
Authors: Shapovalov Alexander , Breev Alexander
Published: January 2023

We study the known coherent states of a quantum harmonic oscillator from the standpoint of the originally developed noncommutative integration method for linear partial differential equations. The application of the method is based on the symmetry properties of the Schrödinger equation and on the orbit geometry of the coadjoint representation of Lie groups. We have shown that analogs of coherent states constructed by the noncommutative integration can be expressed in terms of the solution to a system of differential equations on the Lie group of the oscillatory Lie algebra. The solutions constructed are directly related to irreducible representation of the Lie algebra on the Hilbert space functions on the Lagrangian submanifold to the orbit of the coadjoint representation.
Enumerating Subtrees of Flower and Sunflower Networks
Authors: Li Long , Jia Zongpu , Yang Yu , Duan Fengge , Lv Hailian , Zhao Weiting
Published: January 2023

Symmetry widely exists in many complex and real-world networks, with flower networks and sunflower networks being two richly symmetric networks and having many practical applications due to their special structures. The number of subtrees (the subtree number index) is closely related to the reliable network design. Using a generating function, structural analysis techniques, and auxiliary structure introduction, this paper presents the subtree generating functions of flower networks Fln,m(n≥3,m≥2) and sunflower networks Sfn,m(n≥3,m≥2) and, thus, solves the computation of subtree number indices of Fln,m(n≥3,m≥2) and Sfn,m(n≥3,m≥2). The results provide a fundamental and efficient method for exploring novel features of symmetric complex cyclic networks from the structural subtree number index perspective. For instance, we conclude that under some parameter constraints, the flower networks are more reliable than sunflower networks.
Design and Performance Analysis of an In-Band Full-Duplex MAC Protocol for Ad Hoc Networks
Authors: Rahman Md. Abdur , Rahman Md. Mizanur , Alim Md. Abdul
Published: January 2023

This paper proposes a MAC protocol for ad hoc networks using In-band Full-duplex (IBFD) wireless communications, which are named as AdHoc-FDMAC. To utilize IBFD communications in ad hoc networks, this protocol modifies a number of control frames in the IEEE 802.11 Distributed Coordination Function (DCF) MAC standard. Here, the detailed time sequences for all types of IBFD communications are shown for the data transmission and routing. In this paper, the probability and throughput equations for IBFD communications in different situations have been derived. The performance of the proposed AdHoc-FDMAC has been analysed in terms of probability, throughput, and routing time. The Maximum throughput of AdHoc-FDMAC has been found to be 48.34 Mbps, and it is compared with a recently published ad hoc MAC as well as with the conventional HD MAC. The AdHoc-FDMAC outperforms the recently published ad hoc MAC and conventional HD MAC by 16.80% and 66.50% throughput gain, respectively. AdHoc-FDMAC incorporates the existing Ad hoc On-demand Distance Vector (AODV) routing protocol, but this AODV routing is utilized here using IBFD communications. This paper also compares the routing time of the IBFD-based AODV with the conventional AODV. The result shows that the IBFD-based AODV requires 33.33% less routing time than that of the conventional AODV for 3-hop distance between the transmitter and receiver. This paper suggests that the AdHoc-FDMAC protocol provides much more throughput in ad hoc networks by utilizing IBFD communications.
A Comprehensive Structural Analysis of Clostridium botulinum Neurotoxin A Cell-Binding Domain from Different Subtypes
Authors: Gregory Kyle S. , Acharya K. Ravi
Published: January 2023

Botulinum neurotoxins (BoNTs) cause flaccid neuromuscular paralysis by cleaving one of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex proteins. BoNTs display high affinity and specificity for neuromuscular junctions, making them one of the most potent neurotoxins known to date. There are seven serologically distinct BoNTs (serotypes BoNT/A to BoNT/G) which can be further divided into subtypes (e.g., BoNT/A1, BoNT/A2…) based on small changes in their amino acid sequence. Of these, BoNT/A1 and BoNT/B1 have been utilised to treat various diseases associated with spasticity and hypersecretion. There are potentially many more BoNT variants with differing toxicological profiles that may display other therapeutic benefits. This review is focused on the structural analysis of the cell-binding domain from BoNT/A1 to BoNT/A6 subtypes (HC/A1 to HC/A6), including features such as a ganglioside binding site (GBS), a dynamic loop, a synaptic vesicle glycoprotein 2 (SV2) binding site, a possible Lys–Cys/Cys–Cys bridge, and a hinge motion between the HCN and HCC subdomains. Characterising structural features across subtypes provides a better understanding of how the cell-binding domain functions and may aid the development of novel therapeutics.
Acknowledgment to the Reviewers of Toxins in 2022
Authors:   Toxins Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
PARP Inhibitors in the Management of BRCA-Positive Prostate Cancer: An Overview
Authors: Kourampi Islam , Tsetzan Ioannis-Panagiotis , Kappi Panagiota , Jain Nityanand
Published: January 2023

Prostate cancer is the second most common form of cancer in men and the fifth leading cause of death among men worldwide. Men with metastatic castration-resistant prostate cancer (mCRPC) often have BRCA-1 or BRCA-2 gene mutations which can make them sensitive to poly-(ADP-ribose) polymerase inhibitors or PARP inhibitors (PARPi), such as Olaparib, Rucaparib, and Niraparib. Although significant advances have been made with PARPi and the prognosis of patients with mCRPC has improved dramatically, resistance often constitutes a challenge that frequently results in tumor escape. This present communication paper explores the role of PARPi in BRCA-positive prostate cancer and sheds light on numerous published and ongoing clinical trials that will determine the future of PARPi at various tumor stages as a monotherapy or polytherapy regime.
Origin, Genetic Variation and Molecular Epidemiology of SARS-CoV-2 Strains Circulating in Sardinia (Italy) during the First and Second COVID-19 Epidemic Waves
Authors: Rocchigiani Angela Maria , Ferretti Luca , Ledda Alice , Di Nardo Antonello , Floris Matteo , Bonelli Piero , Loi Federica , Idda Maria Laura , Angioi Pier Paolo , Zinellu Susanna , Fiori Mariangela Stefania , Bechere Roberto , Capitta Paola , Coccollone Annamaria , Coradduzza Elisabetta , Dettori Maria Antonietta , Fattaccio Maria Caterina , Gallisai Elena , Maestrale Caterina , Manunta Daniela , Pedditzi Aureliana , Piredda Ivana , Palmas Bruna , Salza Sara , Sechi Anna Maria , Tanda Barbara , Madrau Maria Paola , Sanna Maria Luisa , Cherchi Simonetta , Ponti Nicoletta , Masala Giovanna , Sirica Roberto , Evangelista Eloisa , Oggiano Annalisa , Puggioni Giantonella , Ligios Ciriaco , Dei Giudici Silvia
Published: January 2023

Understanding how geography and human mobility shape the patterns and spread of infectious diseases such as COVID-19 is key to control future epidemics. An interesting example is provided by the second wave of the COVID-19 epidemic in Europe, which was facilitated by the intense movement of tourists around the Mediterranean coast in summer 2020. The Italian island of Sardinia is a major tourist destination and is widely believed to be the origin of the second Italian wave. In this study, we characterize the genetic variation among SARS-CoV-2 strains circulating in northern Sardinia during the first and second Italian waves using both Illumina and Oxford Nanopore Technologies Next Generation Sequencing methods. Most viruses were placed into a single clade, implying that despite substantial virus inflow, most outbreaks did not spread widely. The second epidemic wave on the island was actually driven by local transmission of a single B.1.177 subclade. Phylogeographic analyses further suggest that those viral strains circulating on the island were not a relevant source for the second epidemic wave in Italy. This result, however, does not rule out the possibility of intense mixing and transmission of the virus among tourists as a major contributor to the second Italian wave.
Immune and Metabolic Alterations in Children with Perinatal HIV Exposure
Authors: du Toit Louise D. V. , Prinsloo Andrea , Steel Helen C. , Feucht Ute , Louw Roan , Rossouw Theresa M.
Published: January 2023

With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed–and-uninfected (CHUU). Differences reported between these two groups include immune dysfunction and higher levels of inflammation, cognitive and metabolic abnormalities, as well as increased morbidity and mortality in CHEU. The reasons for these disparities remain largely unknown. The present review focuses on a proposed link between immunometabolic aberrations and clinical pathologies observed in the rapidly expanding CHEU population. By drawing attention, firstly, to the significance of the immune and metabolic alterations observed in these children, and secondly, the impact of their healthcare requirements, particularly in low- and middle-income countries, this review aims to sensitize healthcare workers and policymakers about the long-term risks of in utero exposure to HIV and ART.
The Importance of RSV Epidemiological Surveillance: A Multicenter Observational Study of RSV Infection during the COVID-19 Pandemic
Authors: Pruccoli Giulia , Castagno Emanuele , Raffaldi Irene , Denina Marco , Barisone Elisa , Baroero Luca , Timeus Fabio , Rabbone Ivana , Monzani Alice , Terragni Gian Maria , Lovera Cristina , Brach del Prever Adalberto , Manzoni Paolo , Barbaglia Michelangelo , Roasio Luca , De Franco Simona , Calitri Carmelina , Lupica Maddalena , Felici Enrico , Marciano Cinzia , Santovito Savino , Militerno Gaia , Abrigo Enrica , Curtoni Antonio , Quarello Paola , Bondone Claudia , Garazzino Silvia
Published: January 2023

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2–3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019–2020–2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity.
Differences in Genetic Diversity of Mammalian Tick-Borne Flaviviruses
Authors: Carpio Kassandra L. , Thompson Jill K. , Widen Steven G. , Smith Jennifer K. , Juelich Terry L. , Clements David E. , Freiberg Alexander N. , Barrett Alan D. T.
Published: January 2023

The genetic diversities of mammalian tick-borne flaviviruses are poorly understood. We used next-generation sequencing (NGS) to deep sequence different viruses and strains belonging to this group of flaviviruses, including Central European tick-borne encephalitis virus (TBEV-Eur), Far Eastern TBEV (TBEV-FE), Langat (LGTV), Powassan (POWV), Deer Tick (DTV), Kyasanur Forest Disease (KFDV), Alkhurma hemorrhagic fever (AHFV), and Omsk hemorrhagic fever (OHFV) viruses. DTV, AHFV, and KFDV had the lowest genetic diversity, while POWV strains LEIV-5530 and LB, OHFV, TBEV-Eur, and TBEV-FE had higher genetic diversities. These findings are compatible with the phylogenetic relationships between the viruses. For DTV and POWV, the amount of genetic diversity could be explained by the number of tick vector species and amplification hosts each virus can occupy, with low diversity DTV having a more limited vector and host pool, while POWV with higher genetic diversities has been isolated from different tick species and mammals. It is speculated that high genetic diversity may contribute to the survival of the virus as it encounters these different environments.
Tailoring the Host Range of Ackermannviridae Bacteriophages through Chimeric Tailspike Proteins
Authors: Gil Jose , Paulson John , Brown Matthew , Zahn Henriett , Nguyen Minh M. , Eisenberg Marcia , Erickson Stephen
Published: January 2023

Host range is a major determinant in the industrial utility of a bacteriophage. A model host range permits broad recognition across serovars of a target bacterium while avoiding cross-reactivity with commensal microbiota. Searching for a naturally occurring bacteriophage with ideal host ranges is challenging, time-consuming, and restrictive. To address this, SPTD1.NL, a previously published luciferase reporter bacteriophage for Salmonella, was used to investigate manipulation of host range through receptor-binding protein engineering. Similar to related members of the Ackermannviridae bacteriophage family, SPTD1.NL possessed a receptor-binding protein gene cluster encoding four tailspike proteins, TSP1-4. Investigation of the native gene cluster through chimeric proteins identified TSP3 as the tailspike protein responsible for Salmonella detection. Further analysis of chimeric phages revealed that TSP2 contributed off-target Citrobacter recognition, whereas TSP1 and TSP4 were not essential for activity against any known host. To improve the host range of SPTD1.NL, TSP1 and TSP2 were sequentially replaced with chimeric receptor-binding proteins targeting Salmonella. This engineered construct, called RBP-SPTD1-3, was a superior diagnostic reporter, sensitively detecting additional Salmonella serovars while also demonstrating improved specificity. For industrial applications, bacteriophages of the Ackermannviridae family are thus uniquely versatile and may be engineered with multiple chimeric receptor-binding proteins to achieve a custom-tailored host range.
Quinazolinone-Peptido-Nitrophenyl-Derivatives as Potential Inhibitors of SARS-CoV-2 Main Protease
Authors: Giang Huynh-Nguyet-Huong , Chou Feng-Pai , Chen Ching-Yun , Chou Shen-Chieh , Huang Sheng-Cih , Wu Tuoh , Hue Bui-Thi-Buu , Lin Hong-Cheu , Wu Tung-Kung
Published: January 2023

The severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2-Mpro) plays an essential role in viral replication, transcription, maturation, and entry into host cells. Furthermore, its cleavage specificity for viruses, but not humans, makes it a promising drug target for the treatment of coronavirus disease 2019 (COVID-19). In this study, a fragment-based strategy including potential antiviral quinazolinone moiety and glutamine- or glutamate-derived peptidomimetic backbone and positioned nitro functional groups was used to synthesize putative Mpro inhibitors. Two compounds, G1 and G4, exhibited anti-Mpro enzymatic activity in a dose-dependent manner, with the calculated IC50 values of 22.47 ± 8.93 μM and 24.04 ± 0.67 μM, respectively. The bio-layer interferometer measured real-time binding. The dissociation kinetics of G1/Mpro and G4/Mpro also showed similar equilibrium dissociation constants (KD) of 2.60 × 10−5 M and 2.55 × 10−5 M, respectively, but exhibited distinct association/dissociation curves. Molecular docking of the two compounds revealed a similar binding cavity to the well-known Mpro inhibitor GC376, supporting a structure−function relationship. These findings may open a new avenue for developing new scaffolds for Mpro inhibition and advance anti-coronavirus drug research.
Risk Factors and Spatiotemporal Analysis of Classical Swine Fever in Ecuador
Authors: Acosta Alfredo , Dietze Klaas , Baquero Oswaldo , Osowski Germana Vizzotto , Imbacuan Christian , Burbano Alexandra , Ferreira Fernando , Depner Klaus
Published: January 2023

Classical swine fever (CSF) is one of the most important re-emergent swine diseases worldwide. Despite concerted control efforts in the Andean countries, the disease remains endemic in several areas, limiting production and trade opportunities. In this study, we aimed to determine the risk factors and spatiotemporal implications associated with CSF in Ecuador. We analysed passive surveillance and vaccination campaign datasets from 2014 to 2020; Then, we structured a herd-level case–control study using a logistic and spatiotemporal Bayesian model. The results showed that the risk factors that increased the odds of CSF occurrence were the following: swill feeding (OR 8.53), time until notification (OR 2.44), introduction of new pigs during last month (OR 2.01) and lack of vaccination against CSF (OR 1.82). The spatiotemporal model showed that vaccination reduces the risk by 33%. According to the priority index, the intervention should focus on Morona Santiago and Los Rios provinces. In conclusion, the results highlight the complexity of the CSF control programs, the importance to improve the overall surveillance system and the need to inform decision-makers and stakeholders.
Immunogenicity and Safety of Anti-SARS-CoV-2 mRNA Vaccines in a Cohort of Patients with Hereditary Angioedema
Authors: Mormile Ilaria , Gigliotti Maria , Petraroli Angelica , Cocchiaro Antonio , Furno Alessandro , Granata Francescopaolo , Rossi Francesca , Portella Giuseppe , de Paulis Amato
Published: January 2023

Many factors may trigger hereditary angioedema (HAE) attacks. This study aims to gain insights into the benefits and potential risks of COVID-19 vaccination in HAE patients, focusing particularly on the possibility of triggering attacks. We enrolled 31 patients with HAE undergoing two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine. To evaluate the possible influence of the vaccine on disease control and attack frequency, we administered the angioedema control test (AECT) 4-week version before (T0), 21 days after the first dose (T1), and between 21 and 28 days after the second dose (T2). Despite 5 patients (16.1%) experiencing attacks within 72 h of the first dose administration, no significant variation in attack frequency was observed before and after vaccination [F(2,60) = 0.123; p = 0.799]. In addition, patients reported higher AECT scores at T1 and T2 compared to T0 [F(2,44) = 6.541; p < 0.05; post hoc p < 0.05)], indicating that the disease was rather more controlled after vaccinations than in the previous period. All patients showed a positive serological response to the vaccine without significant differences from healthy controls (U = 162; p = 0.062). These observations suggest that the vaccine administration is safe and effective in HAE patients.
Immunoinformatics Approaches for Vaccine Design: A Fast and Secure Strategy for Successful Vaccine Development
Authors: Rawat Suraj Singh , Keshri Anand Kumar , Kaur Rimanpreet , Prasad Amit
Published: January 2023

Vaccines are major contributors to the cost-effective interventions in major infectious diseases in the global public health space [...]
A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529)
Authors: Mohammed Hassen , Pham-Tran Dan Duy , Yeoh Zi Yi Michelle , Wang Bing , McMillan Mark , Andraweera Prabha H. , Marshall Helen S.
Published: January 2023

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1–28.7%) and 23.4% (95%CI: 13.5–33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1–37.1%) at three months to 3.9% (95%CI: −24.8–32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8–58.3%) and 57.3% (95%CI: 54.0–60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8–48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5–69.7%) at three months, decreased to 49% (95%CI: 35.7–63.4%) within six months, and increased to 86% after the first or second booster dose.