bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Changes that Occurred on the European Continent Due to the War in Ukraine
Authors: KOVTUNYK Inna , ISHCHENKO Yevhenii , YUVSECHKO Yaroslav , TYCHYNA Viktoriia , DATSO Taras
Published: October 2023

The objective of this research is to examine the social changes in European countries resulting from the Russian war against Ukraine and to understand their implications for the future functioning of social institutions. The research is grounded in the theoretical framework that recognizes the significant impact of the war in Ukraine on various aspects of European societies, including emotional state, daily life, public opinion, interpersonal relationships, socio-economic status, employment, and public activity. The study aims to identify and analyze the main trends of social changes in European countries in response to the war. The research utilizes the analytic-bibliographic method to review relevant scientific literature on social changes in European countries over the past year. Additionally, it employs various analytical methods such as induction, deduction, analysis, synthesis of information, systemic-structural, comparative, logical-linguistic methods, as well as abstraction and idealization for data study and processing. An online survey conducted by the researchers was used to gather practical insights on key questions related to changes in the social status quo in Europe due to the resolution of the war in Ukraine. The research findings highlight the most important theoretical aspects of societal development trends in European countries affected by the war in Ukraine. It also investigates the perspectives of scientists and sociologists studying the international social sphere regarding critical aspects of this issue. The conclusion drawn from the research provides a comprehensive understanding of the social changes that have occurred in European countries as a result of the war in Ukraine. This research contributes to the broader understanding of the far-reaching impacts of the Russian war against Ukraine on European societies. The implications of this research can guide post-war European society research and aid in planning transformative changes to address the societal shifts brought about by the conflict.
The Relationship between Aesthetic Cognition and Aesthetic Behaviour in University Students: The Mediating Role of Aesthetic Emotion
Authors: QIAO Qiao , JIANG Yongzhi
Published: October 2023

This paper discusses the relationships among aesthetic cognition, aesthetic emotion and college students’ aesthetic behaviour in light of three questionnaires including an aesthetic cognition scale, an aesthetic emotion scale, and an aesthetic behaviour scale. A survey including these three structured scales was administered to 1060 university students at general undergraduate institutions. Their responses were scored on a 5-point Likert scale. Structural equation modelling was used to construct the measurement model and structural model. The survey results indicated positive correlations among these three variables. In addition, aesthetic emotion played a mediating role in the influence of aesthetic cognition on aesthetic behaviour. The results of this study can enhance the daily lives of college students by improving their levels of aesthetic and creative behaviour.
A Post-Keynesian Critique on Mainstream Financial Education
Authors: Batista Pereira Fernando , Cavalcante Anderson Tadeu Marques , Crocco Marco
Published: October 2023

Financial education has attracted increased attention from governments, think tanks and international institutions in the past years. Nonetheless, the prevalent policies and practices in the field usually assume a very narrow analytical framework. This paper analyses financial education policy proposals from a post-Keynesian theoretical perspective. Most practices assume that financial education, by transferring knowledge and information to people, promotes financial capability, improving individual decisions. Our analysis shows, however, that a disregard for basic elements related to the functioning of the financial system, such as uncertainty and Minsky’s financial cycles, may compromise any financial decision. The conclusion is that financial education policies require the acknowledgement of the uncertain and imbalanced environment in which the financial decisions are made and cannot be restricted solely to the qualification of individuals.
O caráter induzido e autônomo dos investimentos em construção civil: uma avaliação para o período de 2012 a 2020 da economia brasileira
Authors: Dos Santos Rômulo Bernardo , Kaio Glauber Vital da Costa  , Julia de Medeiros Braga
Published: October 2023

O trabalho contribui à escassa literatura empírica e teórica a respeito do setor de construção civil no Brasil a partir de uma perspectiva agregada. Em primeiro lugar é feito um levantamento das políticas públicas direcionadas ao setor. É então calculado o impulso de crédito a obras em infraestrutura e analisado sua relação com a atividade econômica brasileira e os investimentos em construção. Em seguida são estimadas as relações de longo prazo entre a formação bruta de capital fixo em construção com variáveis econômicas e são testadas as causalidades com base na formulação de Toda e Yamamoto (1995) com dados mensais disponibilizados pelo Banco Central do Brasil e IBGE para o período de 2012 e 2020. Os resultados apontam que investimentos em construção civil são impactados pela concessão de crédito e taxas de juros destinadas ao setor imobiliário. Além disso, foi identificada a presença de um efeito acelerador, de forma que esses investimentos são dinamizados pelas expectativas de aumento de demanda agregada, conforme sugerido na abordagem do supermultiplicador sraffiano. Os resultados sinalizam que medidas específicas de política monetárias e creditícias, em particular, e de estímulo de demanda agregada, em geral, têm eficácia na dinamização dos investimentos em construção civil.
Ciclos De Liquidez Mundial Nos Anos 2000-2019: análise e proposição de um indicador
Authors: Ferreira de Souza Henrique , Petrelli Corrêa Vanessa
Published: October 2023

Partindo da perspectiva de que os mercados não são perfeitamente eficientes na alocação de recursos, não há motivos para esperar que a total abertura e integração financeira das economias proporcione o maior crescimento econômico. Muito pelo contrário, esses movimentos podem elevar o grau de vulnerabilidade dos países periféricos a acontecimentos externos. No presente trabalho destaca-se a vulnerabilidade externa financeira ligada à hierarquia das moedas. Do mesmo modo, os fluxos internacionais de capitais são vetores centrais de efetivação dessa vulnerabilidade, comportando-se de maneira coordenada, ligados, preponderantemente, aos ciclos de liquidez mundial (LM). Assim, o objetivo desse artigo é adicionar elementos para o entendimento da periodicidade da liquidez mundial nos anos 2000, por meio do cálculo de um indicador – relacionado aos fluxos de capitais para os países periféricos – e análise histórica do período retratado, examinando a conjuntura internacional e alguns trabalhos ligados a essa, como os relatórios do Fundo Monetário Internacional (FMI) e da Conferência das Nações Unidas sobre Comércio e Desenvolvimento (UNCTAD).
Desenvolvimento e Estagnação: O debate entre desenvolvimentistas e liberais neoclássico
Authors: Feijó Carmem
Published: October 2023

Resenha - Desenvolvimento e Estagnação: O debate entre desenvolvimentistas e liberais neoclássico
RANCANG BANGUN SISTEM KEAMANAN JARINGAN MIKROTIK MENGGUNAKAN FIREWALL FILTERING DAN PORT KNOCKING DENGAN NOTIFIKASI TELEGRAM PADA EVENT VIRTUAL
Authors: Febri Febri , Hutabri Ellbert
Published: October 2023

Network security is a very important aspect in maintaining information security. In network management using proxy devices, use of firewall filtering and port knocking in an effort to increase security and control network access and hide services that are not needed. In addition to obtaining information on suspicious network activity in real-time with telegram notifications. The method used includes analysis of network security needs, system architecture design, firewall filtering and port knocking configurations on the proxy and integration with the telegram API to send notifications. The results of this study show that using firewall filtering and port knocking on Mikrotik can effectively improve network security by limiting unauthorized access and reducing the risk of attacks from outside. The system is also capable of providing notifications via telegram when suspicious activity is detected, thus enabling a network administrator to respond quickly to these threats
ANALISIS RISIKO KESELAMATAN DAN KESEHATAN KERJA (K3) PADA PENGOPERASIAN MESIN PIERCING MILL DI PT RAINBOW TUBULARS MANUFACTURE
Authors: Astanto Ardi , Zetli Sri
Published: October 2023

The piercing mill machine is one of the machines used by the company PT Rainbow Tubulars Manufacturing in producing Oil country Tubular Goods (OCTG) seamless pipes. The work process in operating the piercing mill machine includes sprinkling salt and pushing the pipe directly exposed to high heat, noise, smoke and extreme dust. The company has established controls such as Personal Protective Equipment (PPE) and Occupational Safety and Health (OSH) training, but these control efforts have not been maximized, due to a lack of awareness and compliance in using Personal Protective Equipment (PPE). The purpose of this study is to identify the risks of operating a piercing mill machine using the Job Safety Analysis (JSA) method, calculate and analyze the value of the risk, and provide recommendations to the company. Research data was obtained by documentation, observation, interviews, and discussions with production supervisors and OSH experts. The results of this study obtained four job structures and 27 work stages and 31 sources of risk. There are three very high risks, including splashing of billet material with high temperatures, exposure to heat, dust and high noise. providing tools such as replacing tools that are no longer suitable for use.
ANALISIS PENGARUH PENGAWASAN MANAJEMEN SERTA MOTIVASI KERJA TERHADAP KINERJA PEKERJA DI PT ABC
Authors: Novendra Muhammad Racha , Zetli Sri
Published: October 2023

This research is to find out and analyze the impact of Management Supervision and Work Motivation on Employee Performance. This research was conducted at PT ABC from March 2023 to July 2023. In this study, the population was all employees, totaling 150 people. The independent variables in this study: Management Supervision (X1) and Work Motivation (X2) and the dependent variable is Employee Performance (Y). Data analysis method used in this research is simple linear analysis. The results of the study are Management Supervision and Work Motivation have an influence on Worker Performance of 18.1%.
Vascular deficits contributing to skeletal fragility in type 1 diabetes
Authors: Draghici Adina E. , Zahedi Bita , Taylor J. Andrew , Bouxsein Mary L. , Yu Elaine W.
Published: October 2023

Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.
The antivirulence activity, transcriptomics of EGCG and its protective effects on zebrafish infected by Aeromonas hydrophila
Authors: Yin Hongmei , Yan Qiaohua , Cheng Guoqiang , Zhang Li , Li Meiqing , Hu Tingting , Gao Sihui , Chen Yuanhang , Tang Huaqiao , Luo Jie
Published: October 2023

Background

Aeromonas hydrophila is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on the virulence factors of A.hydrophila and its impact on adhesion, invasion, and cytotoxicity in Caco-2 cells. The potential mechanism of antibacterial activity of EGCG was investigated by transcriptomic analysis.

Results

EGCG not only inhibited the production of biofilm, hemolytic activity, motility, and protease activity of A.hydrophila, but also reduced its adhesion, invasion, and cytotoxicity in Caco-2 cells. Transcriptomic analysis indicated that the antimicrobial activity of EGCG may be achieved by weakening the chemotaxis and stress response of the bacteria, as well as inhibiting the TonB system. Animal studies demonstrated that EGCG can significantly improve the survival rate and organs damage of zebrafish infected with A.hydrophila.

Conclusion

EGCG would be a potential alternative drug for the prevention and treatment of A. hydrophila infections by anti-virulence mechanism.
Using the Implementation Centric Evolving Climate Change Adaptation Process to bridge the gap between policy and action
Authors: Wells Cathie A. , Saggioro Elena , Petty Celia , Cornforth Rosalind
Published: October 2023

With climate impacts increasing in both frequency and intensity and unprecedented climate events having devastating results, the need for timely policy and action to support adaption is not in doubt. However, the gap between policy and action leaves many communities exposed to extreme events and vulnerable to loss of life and livelihoods. This is partly due to the difficulty policymakers face when confronted by climate projections with their inherent uncertainties. Competing sectoral interests and a lack of resources often compound such challenges. To address these issues, the Implementation Centric Evolving Climate Change Adaptation Process (ICECCAP) encases the climate risk assessment in an enabling framework to track resource, knowledge and regulatory needs. This process was applied as part of a UNEP project to support the National Adaptation Plan in Pakistan. A range of climate storylines, describing plausible climate futures and their potential environmental and socio-economic impacts, were developed and discussed with local stakeholders, including policy makers from across levels of governance. The process allowed us to translate complex physical science into narratives that could be communicated clearly to non-technical national stakeholders, forming a basis for subsequent negotiation and decision-making at a local level to address multiple risks and respond to adaptation needs at this finer resolution. This reflects our aim, as part of the My Climate Risk network, to amalgamate bottom-up climate risk assessment with climate projection data that remains meaningful at a local scale. We show how the integration of scientific research and local expert stakeholder views can promote buy-in to adaptation planning. Grounded in a systemic and comprehensive understanding of potential impacts of climate change, this process has implications across socio-economic, environmental and governance spheres.
Assessment of the activities physiological cost of the defense forces officers in Ukraine using miniature ECG device
Authors: Bocharov Mykhailo , Stasiuk Vasyl , Osyodlo Vasyl , Ryzhenko Tetyana , Malanin Vlad , Chumachenko Dmytro , Chaikovsky Illya
Published: October 2023

Introduction

In the principles of the organization of armed struggle of the defense forces of most developed countries of the world, considerable attention is paid to the evaluation of combat readiness of the military personnel. This procedure is conditioned by such interconnected goals of the armed struggle as the maximum realization of the combat potential and the minimization of personnel losses. The purpose of the work is to determine the physiological cost of the activities of the soldiers of the Defense Forces of Ukraine with the help of miniature electrocardiographic hardware and software complexes.

Methods

In the research, ultra-miniature ECG devices worn on the body for a long time, so-called wearable “on-body” ECG patch devices, were used in various combat conditions. When analyzing the data, the principle of multi-faceted ECG analysis was implemented, which allows you to obtain complete and physiologically based information, which includes 4 blocks: heart rate variability (HRV), amplitude-time indicators of the ECG, heart rhythm disorders, and psycho- emotional state.

Results

In this study, a complex index of the functional state formed based on estimates of generally accepted and original indicators of heart rhythm variability, the shape of the teeth and complexes of the electrocardiogram, as well as an index of the psycho-emotional state formed according to the same principles based on the analysis of heart rhythm variability according to the modified McCraty algorithm (USA) was evaluated. Examination with the help of the complex is carried out in a state of rest, sitting or lying down.

Discussion

The sensitivity of the developed monitoring system is good enough to detect the changes in the functional state both in the case of short-term (for hours) intense physical or psycho-emotional stress and more chronic (for days and weeks) stress depending on the nature of the task being done. The proposed methods and means can be considered an important tool to support the commander's decision-making regarding the ability of personnel from the point of view of their functional state to perform combat tasks.
Using RNA-based therapies to target the kidney in cardiovascular disease
Authors: Palmer Trecia C. , Hunter Robert W.
Published: October 2023

RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular homeostasis, many extant drugs used for preventing cardiovascular disease act predominantly on renal tubular cells. Moreover, kidney disease is a major independent risk factor for cardiovascular disease and a global health problem. Chronic kidney disease is projected to become the fifth leading cause of death by 2040, with around half of affected individuals dying from cardiovascular disease. The most promising strategies for delivering therapeutic RNA selectively to kidney cells make use of synthetic polymers and engineered extracellular vesicles to deliver an RNA cargo. Future research should focus on establishing the safety of these novel delivery platforms in humans, on developing palatable routes of administration and on prioritising the gene targets that are likely to have the biggest impact in cardiovascular disease.
“And then I check to see if it looks legit” – digital critical competence in teacher education
Authors: Leming Tove , Johanson Lisbeth Bergum
Published: October 2023

This study investigates pre-service teachers’ understanding and use of their own digital critical competence. In the Norwegian teacher training programmes, pre-service teachers at all levels are required to develop critical reflection skills and learn basic digital skills. They have to be able to communicate digitally and at the same time be able to reflect on how developments in technology entail a growing need for critical assessment of digital media. Through a qualitative approach, we interviewed 17 social studies pre-service teachers at UiT The Arctic University of Norway and asked how they understand and use digital critical competence. Our study shows that the students’ understanding of digital critical competence as a concept in the early stage of their education is mainly linked to source criticism and can largely be classified as a procedural understanding. A procedural approach means acting without any consideration of the underlying intentions; it requires little thought, and cognitive operations are ignored. More experienced pre-service teachers can link digital critical competence more clearly to the teaching profession and the school context and can reflect on didactic perspectives. They have a more norm-critical approach and question how information and knowledge are established. We find that they have developed a more critical and reflexive approach. The implication for teacher education is that digital critical competence should have a space in all subjects, not just social studies. This will help improve the quality of education and equip the pre-service teachers for everyday life as critical and reflexive teachers.
Advancing our understanding of the influence of drug induced changes in the gut microbiome on bone health
Authors: Bailey Stacyann , Fraser Keith
Published: October 2023

The gut microbiome has been implicated in a multitude of human diseases, with emerging evidence linking its microbial diversity to osteoporosis. This review article will explore the molecular mechanisms underlying perturbations in the gut microbiome and their influence on osteoporosis incidence in individuals with chronic diseases. The relationship between gut microbiome diversity and bone density is primarily mediated by microbiome-derived metabolites and signaling molecules. Perturbations in the gut microbiome, induced by chronic diseases can alter bacterial diversity and metabolic profiles, leading to changes in gut permeability and systemic release of metabolites. This cascade of events impacts bone mineralization and consequently bone mineral density through immune cell activation. In addition, we will discuss how orally administered medications, including antimicrobial and non-antimicrobial drugs, can exacerbate or, in some cases, treat osteoporosis. Specifically, we will review the mechanisms by which non-antimicrobial drugs disrupt the gut microbiome’s diversity, physiology, and signaling, and how these events influence bone density and osteoporosis incidence. This review aims to provide a comprehensive understanding of the complex interplay between orally administered drugs, the gut microbiome, and osteoporosis, offering new insights into potential therapeutic strategies for preserving bone health.
Combination optimization method of grid sections based on deep reinforcement learning with accelerated convergence speed
Authors: Zhao Huashi , Wu Zhichao , He Yubin , Fu Qiujia , Liang Shouyu , Ma Guang , Li Wenchao , Yang Qun
Published: October 2023

A modern power system integrates more and more new energy and uses a large number of power electronic equipment, which makes it face more challenges in online optimization and real-time control. Deep reinforcement learning (DRL) has the ability of processing big data and high-dimensional features, as well as the ability of independently learning and optimizing decision-making in complex environments. This paper explores a DRL-based online combination optimization method of grid sections for a large complex power system. In order to improve the convergence speed of the model, it proposes to discretize the output action of the unit and simplify the action space. It also designs a reinforcement learning loss function with strong constraints to further improve the convergence speed of the model and facilitate the algorithm to obtain a stable solution. Moreover, to avoid the local optimal solution problem caused by the discretization of the output action, this paper proposes to use the annealing optimization algorithm to make the granularity of the unit output finer. The proposed method in this paper has been verified on an IEEE 118-bus system. The experimental results show that it has fast convergence speed and better performance and can obtain stable solutions.
Dynamic reconfiguration of distribution network considering the uncertainty of distributed generation and loads
Authors: Liu Qi , Zhang Lihong , Ji Xingquan , Shi Huizhe
Published: October 2023

This study presents a new methodology to perform the distribution network dynamic reconfiguration (DNDR), taking into consideration the stochastic variations of loads and distributed generation (DG) of power. To solve the heavy computational burden that exists in traditional algorithms of the DNDR, this study first establishes the nodal sensitivity models to calculate the nodal variations caused by nodal power variations. Then, the DNDR is executed utilizing a co-evolutionary algorithm with the goal of loss minimization. The stochastic power flow calculations (PFCs) based on the nodal sensitivity are performed in the DNDR to handle the power fluctuations of the DGs and loads. Finally, the modified IEEE 33-bus test system and a practical distribution system are used for simulations. The simulation results validate the quickness and effectiveness of the proposed DNDR method.
A cross-sectional survey on mother-to-child transmission of HIV among the migrant population in Dongguan, China
Authors: Pan Congcong , Pan Haiyan , Liang Dongmei , Liu Yuanyuan , Yin Sichun , Zhong Jianbo , He Songmei
Published: October 2023

Introduction

The migrant population, consisting of individuals who relocate from rural to urban areas, faces unique challenges that heighten their vulnerability to HIV infection. These challenges stem from a combination of sociodemographic factors and limited access to healthcare services. Understanding the dynamics of HIV transmission within this population is crucial for the development of effective prevention strategies.

Methods

To investigate the factors contributing to HIV vulnerability among migrants, we conducted a cross-sectional study at Dongguan People's Hospital from January 1, 2018, to December 31, 2021. Our study focused on pregnant women living with HIV and their infants, with a particular emphasis on sociodemographic characteristics, HIV testing and treatment profiles, and neonatal clinical data. Data were systematically collected using standardized forms.

Results

Analysis of data from 98 participants revealed noteworthy findings. No significant associations were observed between age, marital status, and educational background regarding HIV vulnerability. Similarly, factors such as the status of sexual partners, spousal therapy, and the number of children had no significant impact. However, our analysis highlighted the critical role of treatment strategies for HIV-positive women and the timing of antiretroviral therapy initiation for women with HIV, both of which were associated with HIV transmission (P < 0.05). Additionally, factors such as feeding type, neonatal antiretroviral prophylaxis, and preventive treatment strategies showed significant associations, while the preventive treatment program for neonates demonstrated no significant impact.

Discussion

These findings provide valuable insights into the specific risk factors and barriers to HIV prevention faced by the migrant population in Dongguan. They underscore the importance of targeted interventions and policies aimed at curtailing mother-to-child HIV transmission. By addressing the unique challenges experienced by migrant mothers and their infants, this study contributes significantly to broader efforts in controlling the spread of HIV, ultimately enhancing the health outcomes and well-being of Dongguan's migrant population. Furthermore, our research introduces a distinctive perspective within the extensively examined domain of Prevention of Mother-to-Child Transmission (PMTCT) programs, focusing on the internally migrant Chinese population, an understudied demographic group in this context. This study, conducted in Dongguan, China, represents one of the pioneering investigations into pregnant women with HIV and their infants within this migrant community.
Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia
Authors: Zhang Yi , Li Zheng , Huang Ying , Zou Bingwen , Xu Yong
Published: October 2023

In the quest for cancer treatment modalities with greater effectiveness, the combination of tumor immunotherapy and nanoparticle-based hyperthermia has emerged as a promising frontier. The present article provides a comprehensive review of recent advances and cutting-edge research in this burgeoning field and examines how these two treatment strategies can be effectively integrated. Tumor immunotherapy, which harnesses the immune system to recognize and attack cancer cells, has shown considerable promise. Concurrently, nanoparticle-based hyperthermia, which utilizes nanotechnology to promote selective cell death by raising the temperature of tumor cells, has emerged as an innovative therapeutic approach. While both strategies have individually shown potential, combination of the two modalities may amplify anti-tumor responses, with improved outcomes and reduced side effects. Key studies illustrating the synergistic effects of these two approaches are highlighted, and current challenges and future prospects in the field are discussed. As we stand on the precipice of a new era in cancer treatment, this review underscores the importance of continued research and collaboration in bringing these innovative treatments from the bench to the bedside.
A humanized orthotopic mouse model for preclinical evaluation of immunotherapy in Ewing sarcoma
Authors: Luo Wen , Hoang Hai , Liao Yanling , Pan Jian , Ayello Janet , Cairo Mitchell S.
Published: October 2023

The advent of novel cancer immunotherapy approaches is revolutionizing the treatment for cancer. Current small animal models for most cancers are syngeneic or genetically engineered mouse models or xenograft models based on immunodeficient mouse strains. These models have been limited in evaluating immunotherapy regimens due to the lack of functional human immune system. Development of animal models for bone cancer faces another challenge in the accessibility of tumor engraftment sites. Here, we describe a protocol to develop an orthotopic humanized mouse model for a bone and soft tissue sarcoma, Ewing sarcoma, by transplanting fresh human cord blood CD34+ hematopoietic stem cells into young NSG-SGM3 mice combined with subsequent Ewing sarcoma patient derived cell engraftment in the tibia of the humanized mice. We demonstrated early and robust reconstitution of human CD45+ leukocytes including T cells, B cells, natural killer cells and monocytes. Ewing sarcoma xenograft tumors successfully orthotopically engrafted in the humanized mice with minimal invasive procedures. We validated the translational utility of this orthotopic humanized model by evaluating the safety and efficacy of an immunotherapy antibody, magrolimab. Treatment with magrolimab induces CD47 blockade resulting in significantly decreased primary tumor growth, decreased lung metastasis and prolonged animal survival in the established humanized model. Furthermore, the humanized model recapitulated the dose dependent toxicity associated with the CD47 blockade as observed in patients in clinical trials. In conclusion, this orthotopic humanized mouse model of Ewing sarcoma represents an improved platform for evaluating immunotherapy in bone and soft tissue sarcoma, such as Ewing sarcoma. With careful design and optimization, this model is generalizable for other bone malignancies.
Causal association between adiposity and hemorrhoids: a Mendelian randomization study
Authors: Huang Jian , Gui Ying , Qin Hongping , Xie Yubo
Published: October 2023

Background

Hemorrhoids are a very common anorectal disorder affecting a large number of individuals throughout the world. This study aimed to evaluate the causal effects of four adiposity traits including body mass index (BMI), body fat percentage, waist circumference, and waist-to-hip ratio on hemorrhoids by Mendelian randomization (MR).

Methods

We used summary statistics of BMI (N = 461,460), body fat percentage (N = 454,633), waist circumference (N = 462,166), waist-to-hip ratio (N = 212,244), and hemorrhoids (N = 337,199) from large-scale genome wide association studies of European ancestry. Univariable and multivariable MR were carried out to infer causality. The MR Steiger directionality test was used to test the causal direction.

Results

The primary MR analysis using the inverse variance weighted (IVW) method showed that there were positive effects of genetically determined BMI [odds ratio (OR) = 1.005, 95% confidence interval (CI): 1.003–1.008, per standard deviation (SD), p = 7.801 × 10−5], body fat percentage (OR = 1.005, 95% CI: 1.001–1.008, per SD, p = 0.008), waist circumference (OR = 1.008, 95% CI: 1.005–1.011, per SD, p = 1.051 × 10−6), and waist-to-hip ratio (OR = 1.010, 95% CI: 1.003–1.017, per SD, p = 0.003) on hemorrhoids. These findings were robust in multivariable MR adjusting for physical activity. The Steiger directionality test showed evidence against reverse causation.

Conclusion

Our MR study supports a causal role of adiposity in the development of hemorrhoids. Adiposity prevention may be an important strategy for reducing hemorrhoids risk.
Effect of epidural block on surgical conditions during pediatric subumbilical laparoscopic surgery involving a supraglottic airway: a randomized clinical trial
Authors: Wu Lei , Wei Siwei , Xiang Zhen , Yu Eryou , Chen Zheng , Du Zhen , Qu Shuang Quan
Published: October 2023

Background

Few studies have examined the effect of epidural block on surgical conditions during pediatric subumbilical laparoscopic surgery involving a supraglottic airway (SGA). This study investigated the surgical condition scores for such procedures in cases where neuromuscular block, epidural block, or neither was used.

Methods

A total of 150 patients aged 3–12 years undergoing laparoscopic orchiopexy with a ProSeal SGA device were randomly allocated to one of three groups: the control group (did not receive neuromuscular block and epidural block), the NMB group [received a neuromuscular block (train-of-four 1–2 twitches) using rocuronium], or the EDB group (received an epidural block using ropivacaine). The primary outcome was the quality of surgical conditions evaluated with the Leiden-Surgical Rating Scale by the blinded surgeon. The secondary outcome measures included intraoperative hemodynamic data (including mean arterial pressure and heart rate), the SGA device removal time, the PACU discharge time, the pain score in the PACU and intraoperative adverse events (including bradycardia, hypotension, peak airway pressure > 20 cmH2O, and poor or extremely poor surgical conditions occurred during the operation). Statistical analysis was performed with one-way analysis of variance, the Kruskal–Wallis test, the chi-square test or Fisher’s exact test. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes.

Results

Surgical condition scores were significantly higher in the NMB and EDB groups than in the control group (median difference: 0.8; 95% confidence interval [CI], 0.5–1.0; p < 0.0001; and median difference: 0.7; 95% CI, 0.5–0.8; p < 0.0001, respectively). Blood pressure and heart rate were significantly lower in the EDB group than in the other two groups (p < 0.0001 and p = 0.004). Patients in the EDB group had significantly lower pain scores during PACU than those in the other two groups (p < 0.0001). The sufentanil dose was lower in the EDB group than in the other two groups (p = 0.001).

Conclusion

Epidural block can improve surgical conditions during pediatric subumbilical laparoscopic surgery involving a SGA to a degree comparable to that with moderate neuromuscular block.
Translational evaluation of gait behavior in rodent models of arthritic disorders with the CatWalk device – a narrative review
Authors: Ritter Jana , Menger Maximilian , Herath Steven C. , Histing Tina , Kolbenschlag Jonas , Daigeler Adrien , Heinzel Johannes C. , Prahm Cosima
Published: October 2023

Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases.
Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death
Authors: Zhang Xin-yu , Li Yu-ying , Huang Hai-xin , Zhao Chen-chen , Lei Xiao-xiao , Zhao Bao-peng , Lu Jing-yi , Lan Tian , Sun Wen-chao
Published: October 2023

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host’s innate immune response by targeting the interferon pathway’s principal factor and enhance virus replication by modulating the host’s RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.
Regulations of phage therapy across the world
Authors: Yang Qimao , Le Shuai , Zhu Tongyu , Wu Nannan
Published: October 2023

Phage therapy, a century-long treatment targeting bacterial infection, was widely abandoned after the clinical availability of antibiotics in the mid-20th century. However, the crisis of antimicrobial resistance today led to its revival in many countries. While many articles dive into its clinical application now, little research is presenting phage therapy from a regulatory perspective. Here, we focus on the regulations of phage therapy by dividing sections into Eastern Europe where it was never abandoned and Western Europe, Australia, the United States, India, and China where it only re-attracted researchers’ attention in recent decades. New insights about its regulations in China are provided as little English literature has specifically discussed this previously. Ultimately, by introducing the regulations in phage therapy for human health across representative countries, we hope to provide ideas of how countries may borrow each other’s adapting legislation in phage therapy to best overcome the current regulatory hurdles.
Insights into the function of ESCRT and its role in enveloped virus infection
Authors: Wang Chunxuan , Chen Yu , Hu Shunlin , Liu Xiufan
Published: October 2023

The endosomal sorting complex required for transport (ESCRT) is an essential molecular machinery in eukaryotic cells that facilitates the invagination of endosomal membranes, leading to the formation of multivesicular bodies (MVBs). It participates in various cellular processes, including lipid bilayer remodeling, cytoplasmic separation, autophagy, membrane fission and re-modeling, plasma membrane repair, as well as the invasion, budding, and release of certain enveloped viruses. The ESCRT complex consists of five complexes, ESCRT-0 to ESCRT-III and VPS4, along with several accessory proteins. ESCRT-0 to ESCRT-II form soluble complexes that shuttle between the cytoplasm and membranes, mainly responsible for recruiting and transporting membrane proteins and viral particles, as well as recruiting ESCRT-III for membrane neck scission. ESCRT-III, a soluble monomer, directly participates in vesicle scission and release, while VPS4 hydrolyzes ATP to provide energy for ESCRT-III complex disassembly, enabling recycling. Studies have confirmed the hijacking of ESCRT complexes by enveloped viruses to facilitate their entry, replication, and budding. Recent research has focused on the interaction between various components of the ESCRT complex and different viruses. In this review, we discuss how different viruses hijack specific ESCRT regulatory proteins to impact the viral life cycle, aiming to explore commonalities in the interaction between viruses and the ESCRT system.
A bacterial quorum sensing signal is a potent inhibitor of de novo pyrimidine biosynthesis in the globally abundant Emiliania huxleyi
Authors: Garrett Oscar , Whalen Kristen E.
Published: October 2023

Interactions between marine phytoplankton, viruses, and bacteria drive biogeochemical cycling, shape marine trophic structures, and impact global climate. Microbially produced compounds have emerged as key players in influencing eukaryotic organismal physiology, and in turn, remodel microbial community structure. This work aimed to reveal the molecular mechanism by which the bacterial quorum sensing molecule 2-heptyl-4-quinolone (HHQ), produced by the marine gammaproteobacterium Pseudoalteromonas spp., arrests cell division and confers protection from virus-induced mortality in the bloom-forming coccolithophore Emiliania huxleyi. Previous work has established alkylquinolones as inhibitors of dihydroorotate dehydrogenase (DHODH), a fundamental enzyme catalyzing the fourth step in pyrimidine biosynthesis and a potential antiviral drug target. An N-terminally truncated version of E. huxleyi DHODH was heterologously expressed in E. coli, purified, and kinetically characterized. Here, we show HHQ is a potent inhibitor (Ki of 2.3 nM) of E. huxleyi DHODH. E. huxleyi cells exposed to brequinar, the canonical human DHODH inhibitor, experienced immediate, yet reversible cellular arrest, an effect which mirrors HHQ-induced cellular stasis previously observed. However, brequinar treatment lacked other notable effects observed in HHQ-exposed E. huxleyi including significant changes in cell size, chlorophyll fluorescence, and protection from virus-induced lysis, indicating HHQ has additional as yet undiscovered physiological targets. Together, these results suggest a novel and intricate role of bacterial quorum sensing molecules in tripartite interdomain interactions in marine ecosystems, opening new avenues for exploring the role of microbial chemical signaling in algal bloom regulation and host-pathogen dynamics.
Coexistence of muscle atrophy and high subcutaneous adipose tissue radiodensity predicts poor prognosis in hepatocellular carcinoma
Authors: Ohara Masatsugu , Suda Goki , Kohya Risako , Sasaki Takashi , Yoda Tomoka , Yoshida Sonoe , Fu Qingjie , Yang Zijian , Hosoda Shunichi , Maehara Osamu , Ohnishi Shunsuke , Tokuchi Yoshimasa , Kitagataya Takashi , Kawagishi Naoki , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Ogawa Koji , Sakamoto Naoya
Published: October 2023

Introduction

We aimed to assess the prognostic implications of muscle atrophy and high subcutaneous adipose tissue (SAT) radiodensity in patients with hepatocellular carcinoma (HCC).

Methods

In this retrospective study, muscle atrophy was assessed using the psoas muscle index (PMI) obtained from computed tomography. SAT radiodensity was evaluated based on radiodensity measurements. Survival and multivariate analyses were performed to identify factors associated with prognosis. The impact of muscle atrophy and high SAT radiodensity on prognosis was determined through survival analysis.

Results

A total of 201 patients (median age: 71 years; 76.6% male) with HCC were included. Liver cirrhosis was observed in 72.6% of patients, and the predominant Child–Pugh grade was A (77.1%). A total of 33.3% of patients exhibited muscle atrophy based on PMI values, whereas 12.9% had high SAT radiodensity. Kaplan–Meier survival analysis demonstrated that patients with muscle atrophy had significantly poorer prognosis than those without muscle atrophy. Patients with high SAT radiodensity had a significantly worse prognosis than those without it. Muscle atrophy, high SAT radiodensity, the Barcelona Clinic Liver Cancer class B, C, or D, and Child–Pugh score ≥ 6 were significantly associated with overall survival. Further classification of patients into four groups based on the presence or absence of muscle atrophy and high SAT radiodensity revealed that patients with both muscle atrophy and high SAT radiodensity had the poorest prognosis.

Conclusion

Muscle atrophy and high SAT radiodensity are significantly associated with poor prognosis in patients with HCC. Identifying this high-risk subgroup may facilitate the implementation of targeted interventions, including nutritional therapy and exercise, to potentially improve clinical outcomes.