bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-synuclein expression in neurons modulates Japanese encephalitis virus infection
Authors: Gupta Anjali , Bohara Vijay Singh , Chauhan Aditya Singh , Mohapatra Anshuman , Kaur Harpreet , Sharma Ajanta , Chaudhary Nitin , Kumar Sachin 
Published: November 2024

ABSTRACT

Japanese encephalitis virus (JEV) stands as a prominent vector-borne zoonotic pathogen, displaying neurotropism and eliciting Parkinson’s disease (PD)-like symptoms among most symptomatic survivors. A characteristic feature of PD is the aggregation of mutated α-synuclein (α-syn) that damages the dopaminergic neurons. Considering this link between JEV-induced PD-like symptoms and α-syn pathogenesis, we explored the role of α-syn in JEV infectivity in neuronal cells. Our investigation revealed a significant increase in endogenous α-syn expression in JEV-infected cells. In addition, exogenous α-syn (Exoα-syn) treatment substantially reduced JEV replication, suggesting its anti-JEV effect. Furthermore, Exoα-syn treatment led to the upregulation of superoxide dismutase 1 (SOD1) and reduction in reactive oxygen species (ROS). The results were validated by endogenous α-syn-silencing, which decreased SOD1 and raised ROS levels in neuronal cells. Similarly, the SOD1 inhibition
via
LCS-1 also intensified ROS and JEV infection. Silencing of SOD1 in α-syn overexpressing neuro2a cells exhibited increased JEV replication. Overall, our results suggest that α-syn exerts an anti-JEV effect by regulating protein involved in oxidative stress inside neuronal cells. This study contributes valuable insights into the interplay between α-syn expression and JEV infectivity, shedding light on avenues further to investigate the potential role of α-syn in JEV pathogenesis.

IMPORTANCE
Japanese encephalitis virus (JEV) poses a significant threat, particularly to children. Despite extensive research efforts, the development of effective treatments against JEV has been impeded. One of the major setbacks is a lack of comprehensive understanding of neurotropism. The study focuses on alpha-synuclein (α-syn), a neuronal protein, and aims to determine its role in JEV pathogenesis. The present study reveals that the host cell upregulates α-syn in response to JEV infection. α-syn restrains JEV propagation by modulating superoxide dismutase 1 (SOD1) expression which further blocks JEV-induced ROS generation. Endogenous α-syn silencing led to a decrease in SOD1 expression and increased viral titer. α-syn plays a crucial role in counteracting oxidative stress through SOD1, which is essential for limiting JEV replication. This study provides broader implications for antiviral strategies and their possible role in neurodegenerative diseases; however, there is still much to explore, particularly regarding α-syn aggregation kinetics in JEV infection.
Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein
Authors: Xiong Yingcai , Tao Keyu , Li Tao , Zhou Yinghui , Zhang Zhaowei , Ou Weiying , Wang Zhao , Wang Shouchuan , Hou Yayi , Cao Peng , Ji Jianjian 
Published: November 2024

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication.
In vitro
dose–response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an
in vivo
study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.

IMPORTANCE

A significant challenge in developing anti-respiratory syncytial virus (RSV) agents is the rapid emergence of resistant viral strains. Designing drugs that target multiple viral components can effectively reduce the likelihood of developing resistant strains. In this study, we screened compounds from the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to simultaneously targe the RSV fusion (F) protein, glycoprotein (G), and host heparan sulfate proteoglycans (HSPGs). Our findings revealed that chebulagic acid (CHLA) and punicalagin (PUG) significantly inhibited RSV replication both
in vitro
and
in vivo
and interacted with all three targets. Both CHLA and PUG were able to disrupt RSV attachment and membrane fusion. Mechanistically, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with CHLA also enhancing the conformational stability of the RSV-F protein before fusion. In conclusion, our study suggests that CHLA and PUG hold promise as therapeutic agents against RSV infection.
Vaccine candidates based on MVA viral vectors expressing VP2 or VP7 confer full protection against Epizootic hemorrhagic disease virus in IFNAR(−/−) mice
Authors: Jiménez-Cabello Luis , Utrilla-Trigo Sergio , Rodríguez-Sabando Karen , Carra-Valenzuela Alejandro , Illescas-Amo Miguel , Calvo-Pinilla Eva , Ortego Javier 
Published: November 2024

ABSTRACT

Epizootic hemorrhagic disease (EHD), caused by Epizootic hemorrhagic disease virus (EHDV), is an emerging and severe livestock disease. Recent incursion and distribution of EHDV in Europe have outlined the need for vaccine research against this viral disease. In this work, we report modified vaccinia virus Ankara (MVA)-vectored vaccines designed to express protein VP2 of EHDV-8 or protein VP7 of EHDV-2. Prime boost immunization of adult IFNAR(−/−) mice with the MVA-VP2 vaccine candidate induced high titers of EHDV-8-specific neutralizing antibodies (NAbs) and conferred full protection against homologous lethal challenge with EHDV-8. However, no heterologous protection was observed after lethal challenge with EHDV-6. In contrast, the MVA-VP7 vaccine candidate elicited strong cytotoxic CD8+ T-cell responses against VP7 and conferred complete protection against lethal challenge with either EHDV-8 or EHDV-6 in IFNAR(−/−) mice in the absence of NAbs, being the first multiserotype vaccine candidate against EHDV. Moreover, we expressed recombinant proteins VP2 and VP7 of EHDV in the baculovirus expression system, which were used to analyze the potential DIVA (differentiating infected from vaccinated animals) character of these vaccine candidates.

IMPORTANCE
Emergence and re-emergence of arthropod-borne viruses are major concerns for both human and animal health. The most recent example is the fast expansion of EHDV-8 through Europe. Besides, EHDV-8 relates with a high prevalence of pathologic cases in cattle populations. No vaccine is currently available in Europe, and vaccine research against this arboviral disease is negligible. In this work, we present novel DIVA vaccine candidates against EHDV, and most importantly, we identified the protein VP7 of EHDV as an antigen capable of inducing multiserotype protection, one of the major challenges in vaccine research against orbiviruses.
Anthrax lethal toxin exerts potent metabolic inhibition of the cardiovascular system
Authors: Liu Jie , Zuo Zehua , Fattah Rasem , Finkel Toren , Leppla Stephen H. , Liu Shihui 
Published: November 2024

ABSTRACT

Bacillus anthracis
causes anthrax through a combination of bacterial infection and toxemia. As a major virulence factor of
B. anthracis
, anthrax lethal toxin (LT) is a zinc-dependent metalloproteinase, exerting its cytotoxicity through proteolytic cleavage of the mitogen-activated protein kinase kinases, thereby shutting down the MAPK pathways. Anthrax lethal toxin induces host lethality mostly by targeting the cardiovascular system. Although the enzymatic activity and the molecular targets of LT have long been known, the detailed mechanisms underlying cellular/tissue/organ toxicity are still poorly understood. In this work, we sought to investigate the mechanism of LT-induced cellular damage in the cardiovascular system. We demonstrate for the first time that anthrax lethal toxin has potent inhibitory effects on the central metabolism of cardiomyocytes and endothelial cells. This is likely due to the observed downregulating of c-Myc expression through the toxin-induced inhibition of the ERK pathway. Since c-Myc is a master transcription factor controlling the expression of many rate-limiting metabolic enzymes in glycolysis and the tricarboxylic acid cycle, LT’s downregulation of c-Myc may lead to the observed bioenergetic collapse, particularly, in cardiomyocytes. Since cardiac cell contraction requires continuous production of large amounts of ATP, potent inhibition of the bioenergetics of cardiomyocytes would be incompatible with life. Thus, LT-induced lethality through targeting cardiomyocytes and endothelial cells appears to be a consequence of a bioenergetic collapse, likely due to the toxin’s potent inhibitory activity on the MEK-ERK-c-Myc-metabolic/bioenergetic axis within these target cells of cardiovascular system.

IMPORTANCE

Anthrax lethal toxin (LT) is a major virulence factor of
Bacillus anthracis
, the causative pathogen of anthrax disease. Anthrax lethal toxin is a metalloproteinase that cleaves and inactivates MEKs, thereby shutting down MAPK pathways, leading to host mortality primarily through targeting of the cardiovascular system. However, the detailed mechanisms underlying the toxin’s cellular and tissue toxicity are still poorly understood. Here, we found that anthrax lethal toxin has potent inhibitory activity on glycolysis and oxidative phosphorylation of cardiomyocytes and endothelial cells. These effects appear to be the consequence of downregulation of c-Myc, a master transcription factor that controls many rate-limiting enzymes of glycolysis and the tricarboxylic acid cycle. With the high demand on energy for cardiac contraction, the potent inhibition of cardiomyocyte metabolism by LT would be incompatible with life. This work provides critical insights into why the cardiovascular system is the major
in vivo
target of LT-induced lethality.
Threats from the
Candida parapsilosis
complex: the surge of multidrug resistance and a hotbed for new emerging pathogens
Authors: Gabaldón Toni 
Published: November 2024

SUMMARY

Candida parapsilosis
is a common agent of candidiasis that has gained increased attention in recent years, culminating with its recent consideration as a high-priority fungal pathogen by the World Health Organization. Reasons for this classification are the recent surge in incidence and the alarmingly growing rates of drug and multidrug resistance. In addition, several closely related species such as
Candida metapsilosis
and
Candida orthopsilosis
may represent recently emerged opportunistic pathogens originated from environmental niches through interspecies hybridization. Here, I review recent research focused on the potential origin and spread of drug resistance and of emerging species in this complex. I will also discuss open questions regarding the possible implications of human activities in these two epidemiological phenomena.
Two-Layer Equilibrium Model of Miscible Inhomogeneous Fluid Flow
Authors: Liapidevskii V. Yu. 
Published: November 2024

Abstract
Two-layer flow of a density-stratified fluid with mass transfer between the layers is considered. In the Boussinesq approximation, the equations of motion are reduced to a homogeneous quasilinear system of partial differential equations of mixed type. The flow parameters in the intermediate mixed layer are determined from the equilibrium conditions in a more general model of three-layer flow of a miscible fluid. In particular, the equilibrium conditions imply the constancy of the interlayer Richardson number in velocity-shift flows. A self-similar solution to the problem of breakdown of an arbitrary discontinuity (the lock-exchange problem) in the domain of hyperbolicity of the system under consideration is constructed. The transcritical flow regimes over a local obstacle are studied and the conditions under which the obstacle determines the upstream flow are determined. A comparison of steady-state and time-dependent solutions with the solutions obtained for the original three-layer models of miscible fluid flow is carried out.
Postoperative pain management practice and associated factors among nurses working at public hospitals, in Oromia region, Ethiopia, 2021: an institution-based cross-sectional study
Authors: Amena Nimona , Dechasa Abebe , Kurke Abdo , Abdisa Desalegn , Dugasa Yonas Gurmu 
Published: November 2024

BackgroundManagement of postoperative pain leads to positive patient progress and shortens the duration of hospital stay. There is a lack of information on nurse’s postoperative pain management practice and its associated factors.ObjectiveTo assess postoperative pain management practice and associated factors among nurses working in public hospitals of West Shoa Zone, Oromia, Ethiopia, 2021.DesignAn institutional-based cross-sectional study was employed.SettingStudy was conducted among eight public hospitals (two tertiary hospitals and six secondary hospitals), which were located in West Shoa Zone in Oromia, Ethiopia.ParticipantsTotally 377 participants were selected by using simple random sampling. From this, 277 were men and 100 participants were women. All nurses who were worked in surgical ward, medical wards, minor operation room and major operation room, recovery rooms, emergency, obstetrics and gynaecology wards were included.MethodsData were collected by distributing structured self-administered questionnaires that adapted from different literatures and were entered into Epi data V.3.1 and exported to SPSS V.22 for analysis. Variables with significant association in the bivariate analyses were entered into a multivariable regression analysis to identify the independent factors associated with nurses’ postoperative pain management practice. Significant factors were declared at p<0.05.ResultThe result showed that 66% of nurses had good pain management practice. Nurses favourable attitude towards postoperative pain management (adjusted OR (AOR): 4.698, 95% CI (2.725 to 8.100)), having access to read pain management guideline (AOR: 3.112, 95% CI (1.652 to 5.862)), adequate knowledge of postoperative pain management (AOR: 2.939, 95% CI (1.652 to 5.227)), working at operation room (AOR: 2.934, 95% CI (1.27 to 6.795)) and received training on pain management (AOR: 3.289, 95% CI (1.461 to 7.403)) were significantly associated with the practices of postoperative pain management.Conclusion and recommendation65% of participants (nurses) have a good level of practice of postoperative pain management. Training, access to pain management guidelines, knowledge and attitude are significant factors in postoperative pain management practice. Governmental and other bodies concerned to postoperative care quality needs to show commitment on availing needed training and infrastructures.
A multi-method feasibility trial of a multi-component behaviour change intervention to reduce sedentary behaviour and increase physical activity among ethnically diverse older adults
Authors: Meghani Naureen Akber Ali , Hudson Joanne , Stratton Gareth , Mullins Jane , Sahoo Deepak 
Published: November 2024

IntroductionEvidence suggests that sedentary behaviour (SB) and physical activity (PA) are important indicators of well-being and quality of life in older adults (OAs). However, OAs are the least active and highly sedentary of all the age groups. The present study intends to examine the feasibility of a wearable gadget to remind users to break sitting time (by standing up and moving more), coupled with a brief health coaching session, pamphlet and reminder messages to decrease SB and improve PA.Methods and analysisThis study will employ a multi-methods approach that generates quantitative data from questionnaires and qualitative data from semi-structured interviews following OAs’ involvement in the study. This intervention will be informed by the socio-ecological model (SEM) and the habit formation model. The quantitative and qualitative data will be analysed separately and then integrated for interpretation and reporting, which will assist our knowledge of the feasibility of the programme.Ethics and disseminationEthical approval for this study has been obtained from Swansea University (NM_ 2023 6667 6123). Informed consent will be obtained from participants. The findings of the study will be disseminated to the scientific community through conference presentations and scientific publications. The findings of the current study will determine the suitability of a future effectiveness trial.Trial registration numberNCT06407557.
Barriers and facilitators to implement Assertive Community Treatment (ACT) in Japan: a qualitative study protocol using Consolidated Framework for Implementation Research (CFIR)
Authors: Honyashiki Mina , Yamashita Masafumi , Iwatani Jun , Saito-Yaguchi Akiko 
Published: November 2024

IntroductionAssertive Community Treatment (ACT), which was developed in the 1970s in the USA, is a programme that supports people with severe mental illness living in the community through a multidisciplinary team, individual care and outreach approach. It is widely known that ACT effectively decreases hospital stays and improves Global Assessment of Functioning scores. In Japan, empirical studies on ACT were conducted in the late 2000s. Through the introduction of the standardised programme and domestic network, its implementation nationwide was anticipated. However, to date, the implementation of ACT is limited. There has been no comprehensive research in Japan on what inhibits and promotes the implementation of ACT in community mental health settings. Therefore, in this study, we aimed to systematically and comprehensively investigate the factors influencing the implementation of ACT in Japan using implementation research.Methods and analysisA qualitative study will be conducted using semistructured interviews with key stakeholders in the ACT team. Interviews will be conducted face-to-face or online, using an interview guide. The inclusion criteria are present and past ACT teams. Recruitment will be in two steps. A preinterview questionnaire will be sent to the members of the Community Mental Health Outreach Association regarding their basic characteristics and fidelity to the ACT model, and purposive sampling will be performed based on it. The Consolidated Framework for Implementation Research will be used to collect and analyse the interview data according to the qualitative content analysis, with reference to the fidelity category, because this will help to find influencing factors by identifying constructs that appear to distinguish between high-fidelity and low-fidelity teams.Ethics and disseminationThis study has been approved by the Tokyo Medical University Ethics Approval Committee (approval number: T2022-0175). The findings will be shared via peer-reviewed journal publications and presentations to policymakers and service users.
Online training to improve evidence-based leadership competencies among nurse leaders in China: a feasibility randomised controlled trial
Authors: Hu Shuang , Chen Wenjun , Satamo Maija , Löyttyniemi Eliisa , Yang Min , Liu Gaoming , Chen Jiarui , Tang Yao , Varpula Jaakko , Li Xianhong , Välimäki Maritta 
Published: November 2024

ObjectiveTo evaluate the feasibility of an online evidence-based leadership training programme for nurse leaders and its potential effectiveness in improving nurse leaders’ evidence-based leadership competencies.DesignThis is a two-arm, parallel, feasibility randomised controlled trial.MethodsWe screened all 160 nurse leaders from two Chinese hospitals. Eligible participants who gave their informed consent were randomly assigned to either an evidence-based leadership training group or a conventional online training group at each site and received a 7-month intervention. Pre-test and post-test assessments gauged feasibility and potential effectiveness. Descriptive and inferential statistics were employed for data analysis.ResultsOf the 160 screened participants, 119 (74%) were assigned to the intervention group (n=59, 50%) or active control group (n=60, 50%). In the intervention group, the number of participant logins in the modules ranged from 21 (36%) to 58 (98%), while in the control group, it ranged from 20 (33%) to 57 (95%). Participants in the intervention group (n=59) completed 42% of the 531 assigned tasks, while the control group (n=60) completed 41% of their 540 assigned tasks. Regarding course task adherence, participants in the intervention group returned 3.8 (SD=3.2) tasks (out of 9 tasks), while the control group returned 3.7 (SD=3.5) tasks (out of 9 tasks). A total of 22 (18%) out of 119 participants dropped out of the study, with 9 (15%) out of 59 from the intervention group and 13 (22%) out of 60 from the control group.ConclusionsWhile the intervention demonstrated a degree of feasibility, measures can still be taken to improve intervention acceptability, course adherence and course task adherence. A full and powered randomised controlled trial is needed to test the intervention’s effectiveness and to ensure the feasibility of the study in clinical settings.Trail registration numberClinicalTrials.gov, numbersNCT05244499.
Clinical risk factors for pancreatic cancer: protocol for an umbrella review
Authors: Moore Sarah , Price Sarah , Dongo Gianni , Walter Fiona M , Neal Richard , Abel Gary A 
Published: November 2024

IntroductionIdentifying cancer earlier can help save lives. An increasingly popular approach to diagnosing cancer earlier is in the development of risk prediction models to be applied to the electronic healthcare record of patients. Development of these models requires systematic and thorough identification of the risk factors that might increase an individual’s propensity to develop the disease. This protocol sets out the methods for an umbrella review to identify risk factors that might be included in these models. The example used is pancreatic cancer, a disease with a high percentage of late-stage diagnoses and consequent high mortality.Methods and analysisRelevant systematic reviews will be identified through searching of MEDLINE and EMBASE via Ovid and the Science Citation Index Expanded of the Web of Science Core Collection. Screening will be performed by two independent reviewers using Covidence software and the results reported as a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Data from eligible studies will be extracted independently by two reviewers and each systematic review will be graded using defined credibility assessment criteria and the ROBIS (Risk of Bias in Systematic Reviews) tool. Results will be presented in detail for each paper. Summary results for each risk factor will be discussed in the narrative and summarised using a table, graphical summary and an infographic.Ethics and disseminationEthical approval is not required for this review. Results of the review will be disseminated by publication in a peer-reviewed journal and presented at conferences.PROSPERO registration numberCRD42024526338.