bluuebunny/crossref_metadata_2025 huggingface dataset:
Games over Probability Distributions Revisited: New Equilibrium Models and Refinements
Authors: Rass Stefan , König Sandra , Schauer Stefan
Published: December 2022

This article is an overview of recent progress on a theory of games, whose payoffs are probability distributions rather than real numbers, and which have their equilibria defined and computed over a (suitably restricted yet dense) set of distributions. While the classical method of defining game models with real-valued utility functions has proven strikingly successful in many domains, some use cases from the security area revealed shortcomings of the classical real-valued game models. These issues motivated the use of probability distributions as a more complex object to express revenues. The resulting class of games displays a variety of phenomena not encountered in classical games, such as games that have continuous payoff functions but still no equilibrium, or games that are zero-sum but for which fictitious play does not converge. We discuss suitable restrictions of how such games should be defined to allow the definition of equilibria, and show the notion of a lexicographic Nash equilibrium, as a proposed solution concept in this generalized class of games.
Photosensitive Hydrogel-Based Embolic Agent Treatment of Wide-Necked Aneurysms: Preliminary Animal Results
Authors: Ku Jerry C. , Dobashi Yuta , Pasarikovski Christopher R. , Ramjist Joel , Hamani Clement , Heyn Chinthaka , Walus Konrad , Yang Victor X. D.
Published: December 2022

Background: The endovascular treatment of cerebral aneurysms has become widespread but may still be limited by recurrence rates or complications. The discovery of novel embolic strategies may help mitigate these concerns. Methods: We formulated a Photosensitive Hydrogel Polymer (PHP) embolic agent which is low-viscosity, shear-thinning, and radio-opaque. After the filling of an aneurysm with PHP with balloon assistance, we utilized photopolymerization to induce solidification. Different methods of light delivery for photopolymerization were assessed in silicone models of aneurysms and in four acute animal trials with venous anastomosis aneurysms in pigs. Then, balloon-assisted embolization with PHP and photopolymerization was performed in three aneurysms in pigs with a one-month follow-up. Filling volume, recurrence rates, and complications were recorded. Results: The PHP was found to be suitable for the intravascular delivery and treatment of cerebral aneurysms. It was found that light delivery through the balloon catheter, as opposed to light delivery through the injection microcatheter, led to higher rates of filling in the 3D model and acute animal model for cerebral aneurysms. Using the balloon-assisted embolization and light delivery strategy, three wide-necked aneurysms were treated without complication. One-month follow-up showed no recurrence or neck remnants. Conclusions: We demonstrated a novel method of balloon-assisted photosensitive hydrogel polymer embolization and photopolymerization, leading to complete aneurysm filling with no recurrence at 1 month in three wide-necked aneurysms in pigs. This promising methodology will be investigated further with longer-term comparative animal trials.
Responses of Bilevel Ventilators to Unintentional Leak: A Bench Study
Authors: Lebret Marius , Fresnel Emeline , Prouvez Nathan , Zhu Kaixian , Kerfourn Adrien , Richard Jean-Christophe , Patout Maxime
Published: December 2022

Background: The impact of leaks has mainly been assessed in bench models using continuous leak patterns which did not reflect real-life leakage. We aimed to assess the impact of the pattern and intensity of unintentional leakage (UL) using several respiratory models. Methods: An active artificial lung (ASL 5000) was connected to three bilevel-ventilators set in pressure mode; the experiments were carried out with three lung mechanics (COPD, OHS and NMD) with and without upper airway obstruction. Triggering delay, work of breathing, pressure rise time, inspiratory pressure, tidal volume, cycling delay and the asynchrony index were measured at 0, 6, 24 and 36 L/min of UL. We generated continuous and inspiratory UL. Results: Compared to 0 L/min of UL, triggering delays were significantly higher with 36 L/min of UL (+27 ms) and pressure rise times were longer (+71 ms). Cycling delays increased from −4 [−250–169] ms to 150 [−173–207] ms at, respectively 0 L/min and 36 L/min of UL and work of breathing increased from 0.15 [0.12–0.29] J/L to 0.19 [0.16–0.36] J/L. Inspiratory leakage pattern significantly increased triggering delays (+35 ms) and cycling delays (+263 ms) but decreased delivered pressure (−0.94 cmH2O) compared to continuous leakage pattern. Simulated upper airway obstruction significantly increased triggering delay (+199 ms), cycling delays (+371 ms), and decreased tidal volume (−407 mL) and pressure rise times (−56 ms). Conclusions: The pattern of leakage impacted more the device performances than the magnitude of the leakage per se. Flow limitation negatively reduced all ventilator performances.
Prevalence, Knowledge, and Attitudes among Health Professions Students toward the Use of Electronic Cigarettes
Authors: AlMuhaissen Suha , Mohammad Haneen , Dabobash Afnan , Nada Marya Q. , Suleiman Zahra M.
Published: December 2022

Healthcare professionals are standing against the widespread use of e-cigarettes among the population, especially young adults. E-cigarettes are generally introduced, especially via social media platforms, as a safer alternative to conventional cigarette smoking. The aim of this study was to measure the prevalence of e-cigarette use among healthcare professions students at the University of Jordan, as well as to explore their knowledge and attitudes toward the use of e-cigarettes. An anonymous Google-Form®-based cross-sectional questionnaire was presented to potential participants at the University of Jordan. Students’ responses were analyzed using SPSS® 23.0 software. A total of 679 online surveys were completed. About 37.4% of students reported using e-cigarettes at least once in their lifetime and about 20% of students were current e-cigarette users. The multivariate analysis showed that the factors associated with E-cigarette smoking are being male, having mothers, siblings, or friends using e-cigarettes, having easy access to e-cigarettes, and having social media as the main source of knowledge regarding e-cigarettes. The relatively high acceptance level and use of e-cigarettes among health professions students should be an alarming sign to decision-makers to give more attention to legislation that controls tobacco products including e-cigarette selling and advertising.
The Apple Mobility Trends Data in Human Mobility Patterns during Restrictions and Prediction of COVID-19: A Systematic Review and Meta-Analysis
Authors: Strzelecki Artur
Published: December 2022

The objective of this systematic review with PRISMA guidelines is to discover how population movement information has epidemiological implications for the spread of COVID-19. In November 2022, the Web of Science and Scopus databases were searched for relevant reports for the review. The inclusion criteria are: (1) the study uses data from Apple Mobility Trends Reports, (2) the context of the study is about COVID-19 mobility patterns, and (3) the report is published in a peer-reviewed venue in the form of an article or conference paper in English. The review included 35 studies in the period of 2020–2022. The main strategy used for data extraction in this review is a matrix proposal to present each study from a perspective of research objective and outcome, study context, country, time span, and conducted research method. We conclude by pointing out that these data are not often used in studies and it is better to study a single country instead of doing multiple-country research. We propose topic classifications for the context of the studies as transmission rate, transport policy, air quality, re-increased activities, economic activities, and financial markets.
Can Exercise Affect the Pain Characteristics in Patients with Fibromyalgia? A Randomized Controlled Trial
Authors: Vrouva Sotiria , Sopidou Varvara , Koutsioumpa Evangelia , Chanopoulos Konstantinos , Nikolopoulou Alexandra , Papatsimpas Vasileios , Koumantakis George A.
Published: December 2022

Exercise is often recommended for fibromyalgia. The aim of this study was to investigate the possible influence and change in the pain characteristics of fibromyalgia patients when breathing exercises were added to their exercise program. A total of 106 patients were included and randomly divided into two groups. Τhe first group of patients followed a program of active exercises up to the limits of pain, lasting 30 min with a repetition of two times a week. Patients of the second group followed the same program with the addition of diaphragmatic breaths when they reached the pain limit. The patients completed three questionnaires: the Fibromyalgia Rapid Screening Tool (FiRST), the Brief Pain Inventory (BPI), and the Pain Quality Assessment Scale (PQAS)—once at the beginning, once again after three weeks of exercise, and again 3 months since the beginning of the program. Independent t-tests for the mean total change scores in pain scales demonstrated that for the second group there was a greater improvement in all pain scales, except for the PQAS Deep Pain subscale (p = 0.38). In conclusion, both groups showed significant improvement in all characteristics of the pain scales; however, the improvement of the second group was significantly higher.
Ecological and Socioeconomic Factors in the Occurrence of Rabies: A Forgotten Scenario
Authors: Subedi Deepak , Chandran Deepak , Subedi Sanju , Acharya Krishna Prasad
Published: December 2022

In many third world countries, where rabies is endemic in dog populations, humans continue to be at risk of contracting the disease. Vaccination is the most effective form of prophylaxis for people, yet it often fails to adequately protect dogs. The most major implications are the costs of post-exposure prophylaxis (PEP) after an exposure occurs and the loss of human life and productivity due to early mortality from rabies (about 60,000 deaths annually). The largest rabies death tolls can be found in the world’s poorest regions, where rabies vaccinations for domestic dogs are uncommon and PEP is scarce. Mass vaccination of dogs, neutering programs, patient PEP, strengthening laboratory and human resources, education and awareness, and animal and human rabies surveillance are all common methods used to prevent, control, and ultimately eradicate dog-mediated human rabies. Current rabies control initiatives, however, pay little attention to the role that ecological and socioeconomic variables play in the disease’s occurrence and spread. To help better inform rabies control strategies, we address in this work the ways in which ecological and socioeconomic factors affect the occurrence and spread of rabies.
Space Analysis of School Violence in the Educational Setting of Peru, 2019
Authors: Arhuis-Inca Wendy , Ipanaqué-Zapata Miguel , Bazalar-Palacios Janina , Gaete Jorge
Published: December 2022

Background: Schools are increasingly experiencing physical, psychological, and sexual violence, which impacts students’ academic achievement and physical and emotional health. Our objective was to identify regional prevalence rates, average prevalence by aggressor type, and provincial spatial conglomerates with higher rates for each type of school violence reported in educational settings in Peru during 2019. Methods: An analysis was made of 12,132 cases reported through Peru’s Specialized School Violence System (SíseVe). The Moran indices were calculated using provincial prevalence rates to identify conglomerates with high prevalence. Results: In the coast region, the Department of Tacna reported the highest prevalence rates for physical (99.7) and psychological (107); the Department of Amazonas, which is in the jungle, reported the highest prevalence rate for sexual violence (74.6), with teachers in public schools accounting for the majority of sexual assaults against students (56%). Conclusions: Sexual violence predominated in the jungle zone, with a significant percentage of teachers participating in violence with sexual connotations. Physical and psychological violence prevailed in the coastal region.
Land Degradation Caused by Construction Activity: Investigation, Cause and Control Measures
Authors: Dai Shubing , Ma Yulei , Zhang Kuandi
Published: December 2022

The rapid expansion of construction land has been a common phenomenon worldwide, which resulted in the loss of high-quality arable land and severe land degradation. Here, a statistical analysis, together with a field investigation, was carried out in China to address the challenges. This study has gathered data on the reduction of land amount and quality caused by construction activities and has collected the relevant policies to control land deterioration caused by those activities. The increasing amount of farmland and open space are occupied by construction use. The annual growth of construction land from 2001 to 2017 was 43.64 × 104 hm2, with an annual average of about 38 × 104 hm2 of cultivated land being converted to construction land in China. Construction activities usually cause a deterioration of the physico-chemical properties in and around construction site soils. The organic matter of post-construction soil was lower than the pre-construction by 257.4~879.8%. A lack of strong economic incentives for developers, limited effectiveness of measures to control land degradation, and weak requirements and enforcement of relevant laws and regulations allow land degradation from construction activities to remain at a significant level. For more efficiency and success, the study proposes effective measures to control the hazards that occur so widely in China.
A Blockchain Technology Introduction Strategy for Asymmetric Sharing Platforms under Different Homing Behaviors of Both Sides
Authors: Guo Libin , Guo Xiangtian
Published: December 2022

To address user privacy concerns and improve user trust levels, sharing platforms are commencing to focus on investing in blockchain technology. This study focuses on blockchain technology investment and pricing strategies for two asymmetric sharing platforms. By constructing a Hotelling model, we investigate the investment strategies of the two asymmetric platforms regarding blockchain technology under different user attribution behaviours, i.e., single-homing or multi-homing, and the optimal pricing under different investment decisions. Afterwards, we compare and analyse the investment strategies under different conditions, obtain the influence of relevant market factors on the pricing strategies of the platforms, and finally determine the optimal timing of blockchain technology investment for asymmetric sharing platforms. The results indicate that when users’ perception of blockchain value is high, both platforms are motivated to introduce blockchain technology, and, conversely, a stronger platform exits the blockchain market. In multi-homing markets, platforms are more likely to implement blockchain strategies and the cost of technology investment is significantly higher than in a single-homing market. In addition, we also find that the degree of differentiation has a significant impact on the blockchain strategies of weaker platform under multi-homing market.
Spatiotemporal Differentiation of the Coupling and Coordination of Production-Living-Ecology Functions in Hubei Province Based on the Global Entropy Value Method
Authors: Liu Yujie , Xu Jie , Zhou Yong , Muhtar Amat , Wang Li
Published: December 2022

Rapid urbanization and industrialization have brought about regional prosperity and pressure on the ecological environment, and the disorder of development has led to competition among the production-living-ecology functions. How to build livable cities, optimize the spatial layout of land, and promote the coordinated development of the production-living-ecology functions in various regions has become an important issue in the sustainable development and utilization of land space. In order to study the spatiotemporal conflict and coordination of the production-living-ecology functions with respect to the dramatic developments associated with the 21st century, this study took Hubei Province, which is the top-ranking economic region in China in recent years, as the study area and adopted the global entropy value method, triangle model, and coupled evaluation model to delineate an index system to measure the degree of conflict and coordination of the production-living-ecology functions in Hubei Province from 2000 to 2020, and also delineate zoning management based on statistical yearbook data. The results showed the following: (1) With respect to the time scale, the indices of the production-living-ecology functions in Hubei Province increased year by year, and the degree of coordination also increased yearly, from the stage of disorder with certain conflict to the stage of coordination with a high level of coupling. (2) On the spatial scale, the development of production-living-ecology functions in Hubei Province was unbalanced, which may be related to the overall development strategy of “two circles and one belt” in Hubei Province, with the eastern part of the province having a higher degree of coordination of the production-living-ecology functions and the western part having a lower degree of coordination. (3) Among the production-living-ecology functions, the ecological function of Hubei Province as a whole exhibited minimal change and maintained stable development, while the living and production functions underwent considerable development, indicating that Hubei Province has protected the orderly development of the ecological environment in the process of urbanization and new industrialization. (4) According to the development and coordination of the production-living-ecology functions in each region of Hubei Province, four development management zones were created: high-quality development zone, secondary development zone, balanced development zone, and development potential zone. Finally, policy suggestions are given for each zone.
Habituation of Fear—Israeli-Jewish Population during Protracted Belligerence
Authors: Eran-Jona Meytal , Tiargan-Orr Roni , Levine Stephen Z. , Limor Yehiel , Schenhav Mordechai , Ben-Shalom Uzi
Published: December 2022

The identification of demographic factors of vulnerability and resilience in communities facing belligerent conflicts is increasingly relevant today. This representative study aims to examine the effect of protracted violence on the level of fear of the overall Israeli-Jewish population, and the role of the conflict on the connection between socio-economic factors and fears. Sixty-six representative samples were identified and surveyed from 2001 to 2019 (n = 37,190) that occurred during (n = 14,362) and between (n = 22,828) seven conflicts and non-conflict periods. Results show that during military conflicts, civilians declared less fears of physical injury comparing routine time; a slow trend of decline in the level of fears over time was observed; during routine periods, fear was associated with female-gender and with the lowest income level group. Ultra-orthodox and Religious respondents had significantly less fear than the secular and traditional respondents. During military conflicts, the results changed significantly, mainly for the lowest income group, women and ultra-orthodox.
Impact of Government Intervention in Response to Coronavirus Disease 2019
Authors: Won Jin-Young , Lee Yu-Rim , Cho Myeong-Heum , Kim Yoon-Tae , Heo Bo-Young
Published: December 2022

Coronavirus disease 2019 (COVID-19) led to the loss of lives and had serious social and economic effects. Countries implemented various quarantine policies to reduce the effects. The countries were divided into low- and high-risk groups based on the differences in quarantine policies and their levels of infection. Quarantine policies that significantly contributed to risk reduction were determined by analyzing 11 quarantine indicators for reducing the spread of COVID-19. The cross-tabulation and Chi-square tests were used to compare the quarantine policies by the groups. Multivariate logistic regression was used to determine the useful quarantine policies implemented by the low-risk group to verify quarantine policies for minimizing the negative effects. The analysis showed that the low- and medium-risk groups showed significant differences for 9 of the 11 indicators, and 4 of these differentiated the low- from the medium-risk group. Countries with strict quarantine policies related to workplace closure and staying at home were more likely to be included in the low-risk group. These policies had a significant impact in the low-risk countries and could contribute to reducing the spread and effects of COVID-19 in countries included in the high-risk group.
Urban Land-Cover Changes in Major Cities in China from 1990 to 2015
Authors: Ding Qian , Pan Tao , Lin Tao , Zhang Chi
Published: December 2022

The accelerated urbanization process in China has led to land-cover changes, triggering a series of environmental issues as one of the major drivers of global change. We studied the land-cover changes in the built-up areas of 50 major cities in China from 1990 to 2015 with Landsat data combined with spectral unmixing methods and decision tree classification. The overall accuracy of urban land-cover type products with 30 m resolution was obtained as 84%, which includes impervious surfaces, bare soil, vegetation, and water bodies. Based on these land-cover type products, the results show that the urbanization of major cities in China manifests itself as a steep expansion of impervious surfaces (+32.91%) and vegetation (+36.93%), while the proportion of bare soil (−68.64%) and water bodies (−1.20%) decreases. The increase in vegetation indicates an increasing emphasis on greening during urbanization, which is especially vital for the sustainability of urban ecosystems. Increasing economic standards and population sizes are significantly correlated with impervious surface expansion and may be the main drivers of urbanization. Nationwide, there is a decreasing trend of shape complexity among different large cities, which indicates that landscape shapes will gradually become regular when cities grow to a certain level. Greenspace areas in the cities increased significantly during 1990–2015 and became more fragmented and tended to disperse across cities. These changes reflect the government’s efforts to enhance urban ecosystem functions to serve the rapidly increasing urban population in China over the past three decades.
How Are Bystanders Involved in Cyberbullying? A Latent Class Analysis of the Cyberbystander and Their Characteristics in Different Intervention Stages
Authors: Jia Yanru , Wu Yuntena , Jin Tonglin , Zhang Lu
Published: December 2022

Background: Cyberbullying is a phenomenon that occurs by means of digital devices in virtual environments. Although research reveals the relevant role played by bystanders in stopping cyberbullying, the patterns of cyberbullying bystanders among Chinese college students is not clear. Data: Participants were 1025 Chinese college students (62.0% girls, 38.0% boys). The present analyses empirically explored the roles of cyberbystanders (passive outsider online, defender of the cybervictim online, reinforcer of the cyberbully online, passive face-to-face outsider, face-to-face defender of the cybervictim, and face-to-face reinforcer of the cyberbully) using latent class analysis. Results: (1) Five latent classes were identified: defensive bystander (17.9%), indifferent bystander (10.1%), low-involved bystander (10.2%), medium-involved bystander (45.7%), and high-involved bystander (16.0%). (2) The cyberbystander patterns varied significantly for all stages of bullying intervention, among which the defensive bystander had the lowest score in the notice stage but the highest scores in the other stages. (3) There was a graded relationship between the five latent classes and the level of social network site use and cyber-victimization experience. College students with high usage of social network sites and high cyber-victimization experience were more likely to engage in diverse bystander behaviors.
Should I Help? Prosocial Behaviour during the COVID-19 Pandemic
Authors: Wider Walton , Lim Mei Xian , Wong Ling Shing , Chan Choon Kit , Maidin Siti Sarah
Published: December 2022

The Movement Control Order (MCO) enacted during the COVID-19 pandemic has profoundly altered the social life and behaviour of the Malaysian population. Because the society is facing huge social and economic challenges that need individuals to work together to solve, prosocial behaviour is regarded as one of the most important social determinants. Because it is related with individual and societal benefits, participating in prosocial activities may be a major protective factor during times of global crisis. Rather than focusing only on medical and psychiatric paradigms, perhaps all that is necessary to overcome the COVID-19 risks is for individuals to make personal sacrifices for the sake of others. In reality, a large number of initiatives proven to be beneficial in decreasing viral transmission include a trade-off between individual and collective interests. Given its crucial importance, the purpose of this concept paper is to provide some insight into prosocial behaviour during the COVID-19 period. Understanding prosocial behaviour during the COVID-19 pandemic is crucial because it may assist in the establishment of a post-COVID society and provide useful strategies for coping with future crises.
Development and Piloting of a Web-Based Tool to Teach Relative and Absolute Risk Reductions
Authors: Zacher Sandro , Berger-Höger Birte , Lühnen Julia , Steckelberg Anke
Published: December 2022

Interpreting study results is an essential component of decision-making. Both laypeople and healthcare professionals often misinterpret treatment effects that are presented as relative risk reduction. Therefore, we developed and piloted a web-based tool to teach the difference between relative and absolute risk reductions. This project follows the UKMRC-guidance for complex interventions. The tool was developed based on adult learning and design theories. This was followed by a qualitative feasibility study focusing on acceptance, applicability, and comprehensibility with healthcare professionals and laypersons. We conducted think-aloud and semi-structured interviews and analysed them using qualitative content analysis. In addition, we explored calculation skills. Between January 2020 and April 2021, we conducted 22 interviews with 8 laypeople and 14 healthcare professionals from different settings. Overall, the tool proved to be feasible and relevant. With regard to comprehension, we observed an awareness of the interpretation of risk reduction, presented therapy effects were questioned more critically, and the influence of relative effects was recognized. Nevertheless, there were comprehension problems in some of the participants, especially with calculations in connection with low mathematical skills. The tool can be used to improve the interpretation of risk reductions in various target groups and to supplement existing educational programs.
Genomic Survey of Heat Shock Proteins in Liriodendron chinense Provides Insight into Evolution, Characterization, and Functional Diversities
Authors: Ke Yongchao , Xu Mingyue , Hwarari Delight , Chen Jinhui , Yang Liming
Published: December 2022

Heat shock proteins (HSPs) are conserved molecular chaperones whose main role is to facilitate the regulation of plant growth and stress responses. The HSP gene family has been characterized in most plants and elucidated as generally stress-induced, essential for their cytoprotective roles in cells. However, the HSP gene family has not yet been analyzed in the Liriodendron chinense genome. In current study, 60 HSP genes were identified in the L. chinense genome, including 7 LchiHSP90s, 23 LchiHSP70s, and 30 LchiHSP20s. We investigated the phylogenetic relationships, gene structure and arrangement, gene duplication events, cis-acting elements, 3D-protein structures, protein–protein interaction networks, and temperature stress responses in the identified L. chinense HSP genes. The results of the comparative phylogenetic analysis of HSP families in 32 plant species showed that LchiHSPs are closely related to the Cinnamomum kanehirae HSP gene family. Duplication events analysis showed seven segmental and six tandem duplication events that occurred in the LchiHSP gene family, which we speculated to have played an important role in the LchiHSP gene expansion and evolution. Furthermore, the Ka/Ks analysis indicated that these genes underwent a purifying selection. Analysis in the promoter region evidenced that the promoter region LchiHSPs carry many stress-responsive and hormone-related cis-elements. Investigations in the gene expression patterns of the LchiHSPs using transcriptome data and the qRT-PCR technique indicated that most LchiHSPs were responsive to cold and heat stress. In total, our results provide new insights into understanding the LchiHSP gene family function and their regulatory mechanisms in response to abiotic stresses.
Studies on the Requirement of Transthyretin Protein (BxTTR-52) for the Suppression of Host Innate Immunity in Bursaphelenchus xylophilus
Authors: Wen Tong-Yue , Zhang Yan , Wu Xiao-Qin , Ye Jian-Ren , Qiu Yi-Jun , Rui Lin
Published: December 2022

The pinewood nematode, Bursaphelenchus xylophilus, has been determined as one of the world’s top ten plant-parasitic nematodes. It causes pine wilt, a progressive disease that affects the economy and ecologically sustainable development in East Asia. B. xylophilus secretes pathogenic proteins into host plant tissues to promote infection. However, little is known about the interaction between B. xylophilus and pines. Previous studies reported transthyretin proteins in some species and their strong correlation with immune evasion, which has also been poorly studied in B. xylophilus. In this study, we cloned and functionally validated the B. xylophilus pathogenic protein BxTTR-52, containing a transthyretin domain. An in situ hybridization assay demonstrated that BxTTR-52 was expressed mainly in the esophageal glands of B. xylophilus. Confocal microscopy revealed that BxTTR-52-RFP localized to the nucleus, cytoplasm, and plasma membrane. BxTTR-52 recombinant proteins produced by Escherichia coli could be suppressed by hydrogen peroxide and antioxidant enzymes in pines. Moreover, silencing BxTTR-52 significantly attenuated the morbidity of Pinus thunbergii infected with B. xylophilus. It also suppressed the expression of pathogenesis-related genes in P. thunbergii. These results suggest that BxTTR-52 suppresses the plant immune response in the host pines and might contribute to the pathogenicity of B. xylophilus in the early infection stages.
Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells
Authors: Ma Qingwen , Li Xue , Wang Sisi , Wang Qi , Li Yu , Li Kuan , Wang Jianhai , Zhang Qiuyang , Wu Junping , Chen Huaiyong
Published: December 2022

Lung homeostasis and regeneration depend on lung epithelial progenitor cells. Lkb1 (Liver Kinase B1) has known roles in the differentiation of airway epithelial cells during embryonic development. However, the effects of Lkb1 in adult lung epithelial progenitor cell regeneration and its mechanisms of action have not been determined. In this study, we investigated the mechanism by which Lkb1 regulates lung epithelial progenitor cell regeneration. Organoid culture showed that loss of Lkb1 significantly reduced the proliferation of club cells and alveolar type 2 (AT2) cells in vitro. In the absence of Lkb1, there is a slower recovery rate of the damaged airway epithelium in naphthalene-induced airway epithelial injury and impaired expression of surfactant protein C during bleomycin-induced alveolar epithelial damage. Moreover, the expression of autophagy-related genes was reduced in club cells and increased in AT2 cells, but the expression of Claudin-18 was obviously reduced in AT2 cells after Lkb1 knockdown. On the whole, our findings indicated that Lkb1 may promote the proliferation of lung epithelial progenitor cells via a niche-dependent pathway and is required for the repair of the damaged lung epithelium.
A Rapid and Specific Real-Time PCR Assay for the Detection of Clinically Relevant Mucorales Species
Authors: Bergallo Massimiliano , Tullio Vivian , Roana Janira , Allizond Valeria , Mandras Narcisa , Daprà Valentina , Dini Maddalena , Comini Sara , Cavallo Lorenza , Gambarino Stefano , Cuffini Anna Maria , Banche Giuliana
Published: December 2022

Infections triggered by filamentous fungi placed in the order Mucorales, phylum Zygomycota, can cause serious harm to immunocompromised patients. Since there is lack of a standardized PCR (polymerase chain reaction) assay for early diagnosis of this fungal infection, this work was aimed to develop a new PCR assay able to detect the presence of Mucorales genera in clinical specimens. Here, we describe a novel diagnostic TaqMan MGB probe assay for precise and rapid detection of the most common clinical species of Mucorales. Zygomycete-specific oligonucleotides were designed to specifically amplify and bind highly conserved sequences of fungal 28S rRNA gene. Additionally, we succeeded in differentiating Mucorales species (i.e., Rhizopus, Lichtheimia, Mucor, and Rhizomucor) in artificially infected serum samples, suggesting that the quantitative capability of this real-time PCR assay could potentially optimize the diagnosis of mucormycosis.
The Interplay of Lung Cancer, COVID-19, and Vaccines
Authors: Trivanović Dragan , Peršurić Željka , Agaj Andrea , Jakopović Marko , Samaržija Miroslav , Bitar Lela , Pavelić Krešimir
Published: December 2022

Patients with cancer are more susceptible to a higher risk of coronavirus infection and its severe complications than the general population. In addition, these patients were not included in the pivotal clinical trials for COVID-19 vaccines. Therefore, considerable uncertainty remains regarding the management of cancer patients during the COVID-19 pandemic and the safety of COVID-19 vaccinations in cancer patients. In this review, we summarize the current knowledge generated from the beginning of the COVID-19 pandemic on the vulnerability of cancer patients to the coronavirus disease, as well as the effectiveness of COVID-19 vaccines in this population. We also discuss the available data on the effects of anticancer treatment with immune checkpoint inhibitors on the immune responses to SARS-CoV-2 in cancer patients. Special attention in this review will be given to patients with lung cancer, as such patients are at an increased risk for severe effects from COVID-19.
Molecular Characteristics of Subgenomic RNAs and the Cap-Dependent Translational Advantage Relative to Corresponding Genomic RNAs of Tomato spotted wilt virus
Authors: Yang Chen , Yu Chengming , Zhang Zhenjia , Wang Deya , Yuan Xuefeng
Published: December 2022

Tomato spotted wilt virus (TSWV) causes severe viral diseases on many economically important plants of Solanaceae. During the infection process of TSWV, a series of 3′-truncated subgenomic RNAs (sgRNAs) relative to corresponding genomic RNAs were synthesized, which were responsible for the expression of some viral proteins. However, corresponding genomic RNAs (gRNAs) seem to possess the basic elements for expression of these viral proteins. In this study, molecular characteristics of sgRNAs superior to genomic RNAs in viral protein expression were identified. The 3′ ends of sgRNAs do not cover the entire intergenic region (IGR) of TSWV genomic RNAs and contain the remarkable A-rich characteristics. In addition, the 3′ terminal nucleotides of sgRNAs are conserved among different TSWV isolates. Based on the eIF4E recruitment assay and subsequent northern blot, it is suggested that the TSWV sgRNA, but not gRNA, is capped in vivo; this is why sgRNA is competent for protein expression relative to gRNA. In addition, the 5′ and 3′ untranslated region (UTR) of sgRNA-Ns can synergistically enhance cap-dependent translation. This study further enriched the understanding of sgRNAs of ambisense RNA viruses.
Revisiting AGAMOUS-LIKE15, a Key Somatic Embryogenesis Regulator, Using Next Generation Sequencing Analysis in Arabidopsis
Authors: Joshi Sanjay , Awan Hadia , Paul Priyanka , Tian Ran , Perry Sharyn E.
Published: December 2022

AGAMOUS-like 15 (AGL15) is a member of the MADS-domain transcription factor (TF) family. MADS proteins are named for a conserved domain that was originally from an acronym derived from genes expressed in a variety of eukaryotes (MCM1-AGAMOUS-DEFICIENS-SERUM RESPONSE FACTOR). In plants, this family has expanded greatly, with more than one-hundred members generally found in dicots, and the proteins encoded by these genes have often been associated with developmental identity. AGL15 transcript and protein accumulate primarily in embryos and has been found to promote an important process called plant regeneration via somatic embryogenesis (SE). To understand how this TF performs this function, we have previously used microarray technologies to assess direct and indirect responsive targets of this TF. We have now revisited this question using next generation sequencing (NGS) to both characterize in vivo binding sites for AGL15 as well as response to the accumulation of AGL15. We compared these data to the prior microarray results to evaluate the different platforms. The new NGS data brought to light an interaction with brassinosteroid (BR) hormone signaling that was “missed” in prior Gene Ontology analysis from the microarray studies.
Selective Silencing of Disease-Associated B Lymphocytes from Hashimoto’s Thyroiditis Patients by Chimeric Protein Molecules
Authors: Ralchev Nikola Ralchev , Markovski Aleksandar Mishel , Yankova Inna Angelova , Manoylov Iliyan Konstantinov , Doytchinova Irini Atanas , Mihaylova Nikolina Mihaylova , Shinkov Alexander Dimitrov , Tchorbanov Andrey Ivanov
Published: December 2022

Hashimoto’s thyroiditis is one of the most common endocrine disorders, affecting up to 20% of the adult population. No treatment or prevention exists except hormonal substitution for hypothyroidism. We hypothesize that it may be possible to selectively suppress anti-thyroglobulin (Tg) IgG antibody-producing B lymphocytes from HT patients by a chimeric protein molecule containing a monoclonal antibody specific for the human inhibitory receptor CR1, coupled to peptide epitopes derived from Tg protein. We expect that this treatment will down-regulate B-cell autoreactivity by delivering a strong inhibitory signal. Three peptides—two epitope-predicted ones derived from Tg and another irrelevant peptide—were synthesized and then coupled with monoclonal anti-human CR1 antibody to construct three chimeric molecules. The binding to CD35 on human B cells and the effects of the chimeric constructs on PBMC and TMC from patients with HT were tested using flow cytometry, ELISpot assay, and immunoenzyme methods. We found that after the chemical conjugation, all chimeras retained their receptor-binding capacity, and the Tg epitopes could be recognized by anti-Tg autoantibodies in the patients’ sera. This treatment downregulated B-cell autoreactivity and cell proliferation, inhibited Tg-specific B-cell differentiation to plasmablasts and promoted apoptosis to the targeted cells. The treatment of PBMCs from HT patients with Tg-epitope-carrying chimeric molecules affects the activity of Tg-specific autoreactive B lymphocytes, delivering to them a strong suppressive signal.
Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections
Authors: Strharsky Tomas , Pindjakova Dominika , Kos Jiri , Vrablova Lucia , Smak Pavel , Michnova Hana , Gonec Tomas , Hosek Jan , Oravec Michal , Jendrzejewska Izabela , Cizek Alois , Jampilek Josef
Published: December 2022

A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15–5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34–44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.
A Self-Forming Hydrogel from a Bactericidal Copolymer: Synthesis, Characterization, Biological Evaluations and Perspective Applications
Authors: Alfei Silvana , Zorzoli Alessia , Marimpietri Danilo , Zuccari Guendalina , Russo Eleonora , Caviglia Debora , Schito Anna Maria
Published: December 2022

Objects touched by patients and healthcare workers in hospitals may harbor pathogens, including multi-drug resistant (MDR) staphylococci, enterococci (VRE), Escherichia coli, Acinetobacter, and Pseudomonas species. Medical devices contaminated by these pathogens may also act as a source of severe and difficult-to-treat human infections, thus becoming a critical public health concern requiring urgent resolutions. To this end, we recently reported the bactericidal effects of a cationic copolymer (CP1). Here, aiming at developing a bactericidal formulation possibly to be used either for surfaces disinfection or to treat skin infections, CP1 was formulated as a hydrogel (CP1_1.1-Hgel). Importantly, even if not cross-linked, CP1 formed the gel upon simple dispersion in water, without requiring gelling agents or other additives which could be skin-incompatible or interfere with CP1 bactericidal effects in possible future topical applications. CP1_1.1-Hgel was characterized by attenuated-total-reflectance Fourier transform infrared (ATR-FTIR) and UV-Vis spectroscopy, as well as optic and scanning electron microscopy (OM and SEM) to investigate its chemical structure and morphology. Its stability was assessed by monitoring its inversion properties over time at room temperature, while its mechanical characteristics were assessed by rheological experiments. Dose-dependent cytotoxicity studies performed on human fibroblasts for 24 h with gel samples obtained by diluting CP_1.1-Hgel at properly selected concentrations established that the 3D network formation did not significantly affect the cytotoxic profile of CP1. Also, microbiologic investigations carried out on two-fold serial dilutions of CP1-gel confirmed the minimum inhibitory concentrations (MICs) previously reported for the not formulated CP1.Selectivity indices values up to 12 were estimated by the values of LD50 and MICs determined here on gel samples.
Structural Basis of Cysteine Ligase MshC Inhibition by Cysteinyl-Sulfonamides
Authors: Pang Luping , Lenders Stijn , Osipov Evgenii M. , Weeks Stephen D. , Rozenski Jef , Piller Tatiana , Cappoen Davie , Strelkov Sergei V. , Van Aerschot Arthur
Published: December 2022

Mycothiol (MSH), the major cellular thiol in Mycobacterium tuberculosis (Mtb), plays an essential role in the resistance of Mtb to various antibiotics and oxidative stresses. MshC catalyzes the ATP-dependent ligation of 1-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol (GlcN-Ins) with l-cysteine (l-Cys) to form l-Cys-GlcN-Ins, the penultimate step in MSH biosynthesis. The inhibition of MshC is lethal to Mtb. In the present study, five new cysteinyl-sulfonamides were synthesized, and their binding affinity with MshC was evaluated using a thermal shift assay. Two of them bind the target with EC50 values of 219 and 231 µM. Crystal structures of full-length MshC in complex with these two compounds showed that they were bound in the catalytic site of MshC, inducing dramatic conformational changes of the catalytic site compared to the apo form. In particular, the observed closure of the KMSKS loop was not detected in the published cysteinyl-sulfamoyl adenosine-bound structure, the latter likely due to trypsin treatment. Despite the confirmed binding to MshC, the compounds did not suppress Mtb culture growth, which might be explained by the lack of adequate cellular uptake. Taken together, these novel cysteinyl-sulfonamide MshC inhibitors and newly reported full-length apo and ligand-bound MshC structures provide a promising starting point for the further development of novel anti-tubercular drugs targeting MshC.