bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat shock protein 70 enhances viral replication by stabilizing Senecavirus A nonstructural proteins L and 3D
Authors: Hou Lei , Zeng Penghui , Wu Zhi , Yang Xiaoyu , Guo Jinshuo , Shi Yongyan , Song Jiangwei , Zhou Jianwei , Liu Jue 
Published: December 2024

AbstractSenecavirus A (SVA) is an emerging pathogen that causes idiopathic vesicular infections in pig herds, posing a potential threat to their production performance. Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in host homeostasis under both physiological and stress conditions. However, the effects of Hsp70 on SVA infection and its underlying regulatory mechanisms remain unclear. Here, we confirmed that Hsp70 expression promotes SVA infection, as evidenced by the expression of viral proteins, viral titers, and the number of rSVA-eGFP-infected cells. This positive regulatory role of Hsp70 is mainly involved in post-entry stages of SVA. Viral proteins that interacted with Hsp70 were screened, and co-immunoprecipitation (co-IP) shows an interaction between Hsp70 and SVA L and 3D proteins. Subsequently, we determined that the expression of Hsp70 is beneficial for the stability of the SVA L and 3D proteins. Additionally, the substrate-binding domain (SBD) of Hsp70 plays an important role in the interaction between Hsp70 and SVA L or 3D proteins; and the deletion of this domain results in the loss of the stabilizing effect of Hsp70 on SVA L and 3D proteins and the positive regulatory effect of Hsp70 on SVA replication. These results reveal that Hsp70 promotes SVA infection by stabilizing viral L and 3D proteins and provides a strategy for preventing and controlling SVA infection.
Revealing novel CD8+ T-cell epitopes from the H5N1 avian influenza virus in HBW/B1 haplotype ducks
Authors: Jiao Wanlin , Chen Yingyi , Xie Zimin , Zhao Li , Du Shanyao , Ma Mulin , Liao Ming , Dai Manman 
Published: December 2024

AbstractThe duck CD8+ T-cell response effectively defends against H5N1 highly pathogenic avian influenza virus (HPAIV) infection, but the recognized peptide is rarely identified. Here, we found that the ratio of CD8+ T cells and the expression of IFN-γ and cytotoxicity-associated genes, including granzyme A/K, perforin and IL2, at 7 days post-infection in peripheral blood mononuclear cells (PBMCs) from B1 haplotype ducks significantly increased in the context of defending against H5N1 AIV infection in vivo. Moreover, similar results were observed in cultured and sorted H5N1 AIV-stimulated duck CD8+ T cells in vitro. Next, we selected 109 epitopes as candidate epitopes on the basis of the MHC-I restriction binding peptide prediction website database and further identified twelve CD8+ T-cell epitopes that significantly increased IFN-γ gene expression after stimulating B1 haplotype duck memory PBMCs. In particular, NP338−346, NP473−481, M2−10, PB1540−548 and PA80−88 were highly conserved in H5N1, H5N6, H5N8, H7N9, and H9N2 AIVs. These findings provide directions for the development of universal T-cell epitope vaccines for AIV in ducks.
A spatially-heterogeneous impact of fencing on the African swine fever wavefront in the Korean wild boar population
Authors: Lim Jun-Sik , Vergne Timothée , Kim Eutteum , Guinat Claire , Dellicour Simon , Andraud Mathieu 
Published: December 2024

AbstractIn October 2019, South Korea’s first case of African swine fever (ASF) was reported in wild boar in the north of the country. Despite the implementation of a 2300 km-long fencing strategy, the ASF wavefront continued to invade southward. Our study aimed to investigate the ASF wavefront dynamics in different regions of South Korea, as well as to assess the effectiveness of the fencing measures on ASF dispersal and wavefront velocity. From the nationwide wild boar surveillance system, we extracted 2661 cases, starting from 2 October 2019 (first detection) to 15 September 2022. The cases were categorised into four main spatiotemporal clusters. The average wavefront velocity over the four clusters was estimated at 0.52 km/week, with the cluster in the eastern part of the Korean peninsula exhibiting the fastest velocity (0.99 km/week) compared to the other clusters (0.44, 0.31, and 0.15 km/week). We hypothesise that these differences are related to different wild boar densities due to heterogeneous habitat suitability. We also found that fencing significantly impacted ASF dispersal in only two of the four main clusters, with no evidence that fencing slowed down the spread of the wavefront in any of the clusters. We argue that this heterogeneity might result from fencing locations being misaligned with the true (and unobserved) wavefront.
Establishment of minigenomes for infectious bursal disease virus
Authors: Yang Hui , Zhang Mingrui , Wang Sanying , Peng Daxin , Martinez-Sobrido Luis , Ye Chengjin 
Published: December 2024

AbstractMinigenomes (MGs) have greatly advanced research on the viral life cycle, including viral replication and transcription, virus‒host interactions, and the discovery of antivirals against RNA viruses. However, an MG for infectious bursal disease virus (IBDV) has not been well established. Here, we describe the development of IBDV MG, in which the entire coding sequences of viral genomic segments A and B are replaced with Renilla luciferase (Rluc) or enhanced green fluorescent protein (EGFP) reporter genes. Under the control of the RNA polymerase I promoter, the translation of IBDV MG is controlled by the viral proteins VP1 and VP3. Interestingly, IBDV B MG shows greater activity than does IBDV A MG. Moreover, the sense IBDV B MG was expressed at a higher level than the antisense IBDV B MG. In agreement with our previous findings, the translation of IBDV B MG controlled by VP1 and VP3 is independent of the cellular translation machinery components eukaryotic initiation factor (eIF)4E and eIF4G, but intact VP1 polymerase activity, VP3 dsRNA-binding activity, and the interaction between VP1 and VP3 are indispensable for both sense and antisense IBDV B MG activity. In addition, ribavirin, which inhibits IBDV replication, inhibits IBDV B MG activity in a dose-dependent manner. Collectively, the IBDV MG established in this study provides a powerful tool to investigate IBDV intracellular replication and transcription and virus‒host interactions and facilitates high-throughput screening for the identification of IBDV antivirals.
When animal viruses meet N6-methyladenosine (m6A) modifications: for better or worse?
Authors: Wang Wenjing , Jin Yufei , Xie Ziyun , He Mei , Li Jing , Wang Zihan , Ma Saiya , Zhang Wuchao , Tong Jie 
Published: December 2024

AbstractN6-methyladenosine (m6A) is a prevalent and dynamic RNA modification, critical in regulating gene expression. Recent research has shed light on its significance in the life cycle of viruses, especially animal viruses. Depending on the context, these modifications can either enhance or inhibit the replication of viruses. However, research on m6A modifications in animal virus genomes and the impact of viral infection on the host cell m6A landscape has been hindered due to the difficulty of detecting m6A sites at a single-nucleotide level. This article summarises the methods for detecting m6A in RNA. It then discusses the progress of research into m6A modification within animal viruses’ infections, such as influenza A virus, porcine epidemic diarrhoea virus, porcine reproductive, and respiratory syndrome virus. Finally, the review explores how m6A modification affects the following three aspects of the replication of animal RNA viruses: the regulation of viral genomic RNA function, the alteration of the m6A landscape in cells after viral infection, and the modulation of antiviral immunity through m6A modification. Research on m6A modifications in viral RNA sheds light on virus-host interactions at a molecular level. Understanding the impact of m6A on viral replication can help identify new targets for antiviral drug development and may uncover novel regulatory pathways that could potentially enhance antiviral immune responses.
Development of a reporter feline herpesvirus-1 for antiviral screening assays
Authors: Yang Jia , Li Li , Xu Fuqiang , Jia Fan 
Published: December 2024

AbstractFeline herpesvirus type 1 (FHV-1), a member of the Herpesviridae family, is one of the most important pathogens that causes upper respiratory tract disease in felines. Following infection, FHV-1 can spread retrogradely to the trigeminal ganglia, establishing a life-long latency. Although vaccines are available for routine feline vaccination, FHV-1 is still an agent that poses a serious threat to feline health. There are currently no specific drugs for the treatment of FHV-1. To facilitate the screening of antiviral drugs, we constructed a reporter FHV-1 virus, which expresses a secreted Gaussia luciferase (GLuc) and a bright green fluorescent protein, mNeonGreen. The reporter virus shows slower growth than does the wild-type FHV-1. The expression of the two reporter genes, Gluc and mNeonGreen, was consistent with viral propagation and remained stable during continuous passage in CRFK cells, even after twenty rounds. In addition, the known inhibitor ganciclovir was used to confirm the characteristics of the reporter virus for drug screening. We found that the reporter FHV-1 is suitable for antiviral screening assays. Overall, our work provides a useful tool for screening drugs to combat FHV-1.
The F204S mutation in adrenodoxin oxidoreductase drives salinomycin resistance in Eimeria tenella
Authors: Sun Pei , Wang Chaoyue , Xie Fujie , Chen Linlin , Zhang Yuanyuan , Tang Xinming , Hu Dandan , Gao Yang , Zhang Ning , Hao Zhenkai , Yu Yonglan , Suo Jingxia , Suo Xun , Liu Xianyong 
Published: December 2024

AbstractSalinomycin is a polyether ionophore widely used for the treatment of coccidiosis in poultry. However, the emergence of coccidia strains resistant to salinomycin presents challenges for control efforts, and the mechanisms underlying this resistance in Eimeria remain inadequately understood. In this study, 78 stable salinomycin-resistant strains were generated through experimental evolution approaches. Whole-genome sequencing of salinomycin-resistant Eimeria tenella isolates revealed single nucleotide polymorphisms (SNPs), with 12 candidate genes harboring nonsynonymous mutations identified. To confirm the candidate gene responsible for conferring salinomycin resistance, we leveraged reverse genetic strategies and identified a key amino acid substitution (F204S) in adrenodoxin oxidoreductase (EtADR), which markedly reduced susceptibility to salinomycin. Our results elucidate the complex interactions among salinomycin resistance, parasite fitness, point mutations, and the structure of EtADR, laying the foundation for future studies on drug resistance in Eimeria and contributing to the development of targeted control strategies.
Expanding foresight methodology to better understand the unknown future and identify hard-to-predict events
Authors: Sytnik Veronica M. , Proskuryakova Liliana N. 
Published: December 2024

AbstractThis study focuses on the integration of methods from different theories and research concepts into futures studies in order to better understand the obscure future through the identification of unpredictable and hard-to-predict rare events and factors. Particular emphasis in this study is placed on systems theory, cybernetics, synergetics, theory of chaos, bifurcation theory, catastrophe theory, thermodynamics, and the theory of self-organized criticality that could elucidate the unknown and offer new insights to futures studies. White, black and grey swans, dragon kings, wild cards, and weak signals are rare and high-impact events commonly referred to in the risk management literature, synergetics, and futures studies. The academic literature does not always accurately identify commonalities and differences between them, as well as relevant research tools. This study clarifies the categories of unknown and types of uncertainty associated with these events, their characteristics, and the related existing foresight methods. It is also suggested to enrich foresight methodology by adding instruments from other disciplines.
Relationship between client laughter and session outcomes in metaverse counseling
Authors: Kang Jieun , Baek Woo Hyun , Jeong Yeon Bin , Yang Hyerin , Lee Seongchan , Lee Sang Min 
Published: December 2024

AbstractConsidering the growing interest in VR psychotherapy, this study investigated the relationship between client laughter and session outcomes in metaverse counseling. To investigate the relationships between types of client laughter and session outcomes in metaverse counseling, we employed a multilevel analysis by separating the variables into two levels: session-level (between-sessions) and client-level (between-clients). The dataset included 159 sessions nested among 26 clients. This study found that clients’ cheerful and nervous laughter positively impacted session outcomes at the session level (within individual clients). However, when considering client-level laughter events (between-client), nervous laughter at the session level was not significantly related to session outcomes. Polite, reflective, and contemptuous laughter showed no significant relationship with the session outcomes. None of the laughter events were related to session outcomes at the client level (between clients). However, there was a significant within-level interaction effect between session and cheerful laughter on session outcomes. The implications of the effects of client laughter are discussed in metaverse counseling by comparing them with those of in-person counseling.
BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences
Authors: El-Khatib Sanad M. , Vagadia Arya R. , Le Anh C. D. , Baulch Janet E. , Ng Ding Quan , Du Mingyu , Johnston Kevin G. , Tan Zhiqun , Xu Xiangmin , Chan Alexandre , Acharya Munjal M. 
Published: December 2024

AbstractCranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors. Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline. RZ is an FDA-approved medication for ALS known to increase BDNF in vivo. In an effort to mitigate the detrimental effects of RT-induced BDNF decline in RICD, we tested the efficacy of RZ in a cranially irradiated (9 Gy) adult mouse model. Notably, RT-exposed mice exhibited significantly reduced hippocampal BDNF, accompanied by increased neuroinflammation, loss of neuronal plasticity-related immediate early gene product, cFos, and synaptic density. Spatial transcriptomic profiling comparing the RT + Vehicle with the RT + RZ group showed gene expression signatures of neuroprotection of hippocampal excitatory neurons post-RZ. RT-exposed mice performed poorly on learning and memory, and memory consolidation tasks. However, irradiated mice receiving RZ (13 mg/kg, drinking water) for 6–7 weeks showed a significant improvement in cognitive function compared to RT-exposed mice receiving vehicle. Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and mature neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.
Antioxidant, anti-acetylcholinesterase, and anti-amyloid-β peptide aggregations of hispolon and its analogs in vitro and improved learning and memory functions in scopolamine-induced ICR mice
Authors: Yang Chang-Hang , Li Cai-Wei , Sie Yi-Yan , Chen Liang-Chieh , Yuan Yu-Hsiang , Hou Wen-Chi 
Published: December 2024

Abstract
Background
Hispolon, one of bioactive phenolic compounds from a medicinal mushroom of sang-huang (Phellinus linteus) has been reported to exhibit anticancer and anti-inflammatory activities. The Alzheimer’s disease (AD) is ranked one of the top ten leading causes of death worldwide. Little is known about the effects of hispolon on delaying AD progression.

Results
The hispolon (No.1) and its six structural analogs (No.2 to No.7) were assayed by antioxidant, anti-acetylcholinesterase activities and anti-amyloid-β1-42-peptide aggregations. The No.1, No.6, and No.7 were selected for further molecular docking with acetylcholinesterase and core fragments of amyloid-β-peptide, and also showed capacities to recover cell viabilities in methylglyoxal-treated SH-SY5Y cells and also to enhance neurite outgrowths in PC12 cells. The daily pre-treatments of No.1, No.6, and No.7 for 10-days (40 mg/kg/day) showed to improve learning dysfunctions in scopolamine-induced ICR mice by passive avoidance tests.

Conclusion
The hispolon in the fungus sang-huang might be beneficial to develop functional foods or as lead compounds for treating degenerative disorders.
Long-term prevalence of PTSD symptom in family members of severe COVID-19 patients: a serial follow-up study extending to 18 months after ICU discharge
Authors: Nosaka Nobuyuki , Noguchi Ayako , Takeuchi Takashi , Wakabayashi Kenji 
Published: December 2024

Abstract
Background
Experiencing a loved one's stay in the intensive care unit (ICU) can profoundly affect families, often leading to post-intensive care syndrome-family (PICS-F), a condition particularly exacerbated during the COVID-19 pandemic. While PICS-F significantly impacts the mental health of families of ICU patients, especially in the context of COVID-19, the long-term effects beyond 12 months remain understudied. This study aims to explore the prevalence of PTSD-related symptoms and health-related quality of life (HRQOL) in family members up to 18 months after ICU discharge.

Methods
This prospective study, conducted in a tertiary university hospital in Tokyo, enrolled family members of severe COVID-19 ICU patients (July 2020 to June 2022 with final follow-up ending in December 2023). The primary outcome was family member symptoms of PTSD at 6, 12 and 18 months after ICU discharge, measured by the Impact of Events Scale-Revised (presence of PTSD symptoms defined by score > 24). Secondary outcomes were family member symptoms of anxiety and depression, sleep disorders, and health-related quality of life (HRQOL) at the same timepoint.

Results
Among 97 enrolled family members, 68 participated. At least one PTSD-related symptom was reported by 26% of family members, persisting over 18 months post-discharge (16% at 6 months, 23% at 12 months, and 25% at 18 months). A subgroup (15%) exhibited delayed-onset PTSD symptoms. Family members with PTSD-related symptoms reported lower HRQOL, especially in mental and social components.

Conclusions
The study underscores the importance of long-term support for family members post-ICU discharge, given the sustained prevalence of PTSD-related symptoms among family members of severe COVID-19 patients.
Evolution of the risk of death and hospitalisation in drivers involved in road crashes in spain, 1993–2020: an age-period-cohort analysis
Authors: Martín-delosReyes Luis Miguel , Martínez-Ruiz Virginia , Rivera-Izquierdo Mario , Jiménez-Mejías Eladio , Fernández Martínez Nicolás Francisco , Lardelli-Claret Pablo 
Published: December 2024

Abstract
Background
A prerequisite for understanding temporal changes in road crash severity is an unbiased description of this phenomenon. The aim of this study was to estimate the independent association trends of age, period and cohort with severity, encompassing the risk of death (RD) and the risk of death or hospitalisation (RDH) within 24 h, for drivers of passenger cars involved in road crashes with casualties in Spain from 1993 to 2020.

Methods
The study population comprised 2,453,911 drivers of passenger cars aged 18 to 98 years involved in road crashes included in the registers of the General Directorate of Traffic. Crash- and driver-related variables with sufficient continuity over time were included, establishing RD and RDH as study outcomes. Temporal trends of both outcomes were analysed using multivariable Poisson regression and multivariable age-period-cohort intrinsic estimator models. An additional sensitivity analysis was performed for the subset of single crashes.

Results
Severity estimates showed some variation across strategies. The APC model identified: (1) a J-shaped pattern for the effect of age on severity, (2) a decline in severity between 2001 and 2004 and 2013–2016, and (3) a birth cohort effect for both RD and RDH. In particular, the 1952–1958 cohort had the highest risk (RD = 1.17; 95%CI = 1.11–1.24 and RDH = 1.16; 95%CI = 1.13–1.19), followed by a decreasing trend in subsequent cohorts. Restricting the analysis to single crashes yielded similar results, with the exception of the age effect (severity increased with age). Furthermore, sex differences were observed–female sex was inversely associated with severity, especially for RD.

Conclusions
RD and RDH decreased during the first decade of the 21st century, but seemed to stabilise from 2013 onwards. Evidence from this study support that birth cohort is associated with road crash severity, independent of age and period. This cohort effect might be due, at least partially, to improvements in general and road safety education. Further studies are needed to elucidate the causes of our findings and to identify factors accounting for sex differences.
β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model
Authors: Hagimont Eugénie , Lourenco-Rodrigues Marc-Damien , Chousterman Benjamin-Glenn , Yen-Potin Frances , Durand Manon , Kimmoun Antoine 
Published: December 2024

Abstract
Background
Recent findings suggest that β3-adrenergic receptors (β3-AR) could play a role in the hemodynamic regulation, but their function in septic shock remains unclear. This study investigates the modulation of β3-AR in an experimental murine model of resuscitated septic shock on in vivo hemodynamic, ex vivo vasoreactivity, inflammation and survival.

Method
Wild-type mice were used, undergoing cecal ligation and puncture (CLP) to induce septic shock, with SHAM as controls. Mice were treated with β3-AR agonist or antagonist three hours post-CLP, followed by resuscitation with fluids and antibiotics. Hemodynamic parameters were measured at 18 h following the surgery, and the expression of β-ARs in heart and aorta was assessed via immunostaining and western blot. Vascular reactivity was studied using myography, and inflammatory markers were analyzed through PCR and western blots. A 5-day survival study was conducted, documenting clinical severity scores and survival rates.

Results
β3-AR was expressed in both endothelial and myocardial cells in healthy and septic mice. During septic shock model, β3-AR density on endothelial cells increased post-CLP, while β1- and β2-AR decreased or remained constant. β3-AR antagonist treatment improved hemodynamic parameters, increasing mean arterial pressure and cardiac index, unlike the agonist. Vascular reactivity to phenylephrine was enhanced in aortic rings from both β3-AR agonist and antagonist-treated mice. However, no significant differences in inducible NO synthase expression were observed among treated groups. Despite improved hemodynamic parameters with β3-AR antagonist treatment, survival rates in treated groups remained similar to CLP group.

Conclusions
In an experimental murine model of resuscitated septic shock, β3-AR is resistant to desensitization and its inhibition improves cardiac and vascular function without affecting the short-term survival.