bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural insights into hybridoma-derived neutralizing monoclonal antibodies against Omicron BA.5 and XBB.1.16 variants of SARS-CoV-2
Authors: Hu Hengrui , Leng Chao , Shu Yanni , Peng Lu , Wu Fan , Liu Jia , Zhang Xiaolu , Zhou Wei , Xiao Qinghong , Li Yufeng , Wu Bihao , Shen Jiamei , Li Jiang , Gong Rui , Yan Bing , Deng Fei , Hu Zhihong , Cao Sheng , Wang Manli 
Published: January 2025

ABSTRACT

The emergence of novel variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose an ongoing challenge for global public health services, highlighting the urgent need for effective therapeutic interventions. Neutralizing monoclonal antibodies (mAbs) are a major therapeutic strategy for the treatment of COVID-19 and other viral diseases. In this study, we employed hybridoma technology to generate mAbs that target the BA.5 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Through a comprehensive screening process, we identified four mAbs capable of effectively neutralizing BA.5, XBB.1.16, and related variant infections
in vitro
, among which ORB10 was found to neutralize BA.5 variants with a plaque reduction neutralization test (PRNT
50
) of 8.7 ng/mL. Additionally, competitive binding assays, sequencing of heavy and light chain variable regions, and binding kinetics characterization provided insights into the epitopes and binding affinities of the identified mAbs. Moreover,
in vivo
experiments in the K18-hACE2 mouse model demonstrated the protective efficacy of ORB10 against both BA.5 and XBB.1.16 variants. Finally, cryo-electron microscopy structural analysis of the ORB10–RBD complex identified key residues involved in the antibody–antigen interactions, providing insights into the molecular mechanisms of neutralization and immune escape of SARS-CoV-2 Omicron variants from mAbs.

IMPORTANCE

The ongoing evolution of SARS-CoV-2 has led to the emergence of variants capable of evading immune responses elicited by natural infection and vaccination, especially the highly transmissible and immune-evasive Omicron variants. This study generated and characterized a panel of monoclonal antibodies (mAbs) specifically targeting the RBD of the Omicron BA.5 variant, of which the ORB10 showed efficacy against Omicron BA.5 and XBB.1.16 variants both
in vitro
and
in vivo
. Cryo-EM structural analysis further elucidated the binding epitope interactions and neutralization mechanism between ORB10 and the BA.5 RBD protein. This study enhances our understanding of antibody-mediated neutralization of SARS-CoV-2 and provides valuable insights into the development of effective therapeutic strategies to combat ongoing SARS-CoV-2 variant infections.
HCMV infection downregulates GPX4 and stimulates lipid peroxidation but does not induce ferroptosis
Authors: Martin Madison , Kumar Rinki , Buchkovich Nicholas J. , Norbury Christopher C. 
Published: January 2025

ABSTRACT

Human cytomegalovirus (HCMV) modulates numerous cellular pathways to facilitate infection, including key components in cellular iron homeostasis. Iron is essential to many cellular processes but, if present in excess, drives cell death through ferroptosis. Ferroptosis is a process that is dependent upon the accumulation of oxidatively damaged phospholipids (lipid peroxides); when these lipid peroxides accumulate in membranes, this culminates in plasma membrane rupture and eventual cell lysis. Here, we demonstrate that HCMV infection downregulates the expression of a key modulator of lipid peroxidation, glutathione peroxidase 4 (GPX4). HCMV infection also markedly increased levels of lipid peroxides within infected cells. Despite the marked downregulation of GPX4 by HCMV, further inhibition of GPX4 impaired virus replication. Interestingly, overexpression of GPX4 did not reduce the production of lipid peroxides within infected cells. In contrast, lipid peroxide levels were reduced by treatment with ferrostatin-1, a ferrous iron-dependent scavenger of alkoxyl radicals, indicating a role for iron in the production of lipid peroxides. HCMV-infected cells became less sensitive to GPX4 inhibition as infection progressed, requiring substantially higher levels of GPX4 inhibitors to induce ferroptosis compared to uninfected cells. This observed difference in sensitivity to ferroptosis upon infection correlated with a large increase in lipid production by infected cells. Therefore, the marked stimulation of lipid peroxidation by HCMV likely proceeds through a pathway that is independent of GPX4 regulation, but the ability of lipid peroxides to stimulate ferroptosis by modulating plasma membrane rupture is likely blunted by the massive increase in lipid production during HCMV infection.

IMPORTANCE
Human cytomegalovirus (HCMV) infection is intimately linked with countless host cell pathways that are modulated in a coordinated fashion to facilitate infection. Here, we describe HCMV-induced regulation of lipid peroxidation, a precursor of the iron-regulated cell death pathway known as ferroptosis, during human cytomegalovirus infection. These studies reveal hitherto unidentified changes in metabolism mediated by HCMV that decrease sensitivity to ferroptosis, despite increases in lipid peroxidation and transient increases in intracellular iron levels in infected cells.
Complete genome sequence of
Bacillus pumilus
X14-67 with antimicrobial properties isolated from aged
Pericarpium citri reticulatae
“Chachiensis”
Authors: He Qianxian , Xiong Shijie , Chen Gu 
Published: January 2025

ABSTRACT

Bacillus pumilus
X14-67 was isolated from
Pericarpium citri reticulatae
“Chachiensis,” the natural aged pericarps of
Citrus reticulata
Blanco. It had inhibitory activity against
Staphylococcus aureus
,
Escherichia coli
,
Salmonella paratyphi
, and
Candida albicans
. Here, its genome was sequenced and annotated to understand its antimicrobial properties.
System-based insights into parasitological and clinical treatment failure in Chagas disease
Authors: Ernst Luis , Macedo Giovana C. , McCall Laura-Isobel 
Published: January 2025

ABSTRACT

Infectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in mechanisms of clinical and parasitological treatment failure in the context of Chagas disease, a neglected tropical disease causing cardiac and gastrointestinal symptoms. Parasite drug resistance and persistence, drug pharmacokinetics and dynamics, as well as persistently altered host immune responses and tissue damage are the most common reasons for Chagas disease treatment failure. We discuss the therapeutics that failed before regulatory approval, limitations of current therapeutic options and new treatment strategies to overcome persistent parasites, inflammatory responses, and metabolic alterations. Large-scale omics analyses were critical in generating these insights and will continue to play a prominent role in addressing the challenges still facing Chagas disease drug treatment.
Risk factors for brain metastasis in lung cancer: an umbrella review of systematic reviews and meta-analyses
Authors: Wan Xinliang , Mo Handan , Chen Jixin , Zhou Qichun , Qiu Shenghong , Zou Yongchun , Wu Wanyin , Tang Qing , Wang Sumei 
Published: January 2025

ObjectivesTo conduct an umbrella review to extensively evaluate and summarise the evidence regarding the relationship between risk factors and the occurrence of brain metastasis in lung cancer.DesignUmbrella review of systematic reviews and meta-analyses.Data sourcesFour databases (PubMed, EMBASE, Web of Science and Cochrane Library) were searched from inception to 10 November 2024.Eligibility criteriaSystematic reviews and meta-analyses that assessed the relationship between risk factors and brain metastasis in lung cancer were included. Only English language studies were considered.Data extraction and synthesisTwo authors independently extracted data and assessed the methodological quality and risk of bias of the included studies. Certainty of evidence was evaluated and summarised for each identified risk factor.ResultsSix systematic reviews/meta-analyses were included. The quality of these studies varied, with most having low or critically low methodological quality. Epidermal growth factor receptor mutations, female gender, lung adenocarcinoma and advanced tumour stage were associated with an increased risk of brain metastasis. Prophylactic cranial irradiation and older age were associated with reduced risk.ConclusionsThis umbrella review suggests that several risk factors may be associated with brain metastasis in lung cancer, but the overall quality of evidence is low. Future studies with improved methodologies are needed to validate these findings.PROSPERO registration numberCRD42023484563
Prevalence of piriformis syndrome and its associated risk factors among university students in Pakistan: a cross-sectional study
Authors: Batool Nusrat , Azam Naila , Moafa Hassan N , Hafeez Azka , Mehmood Humaira , Imtiaz Nimbal , Shehzad Waqas A , Malik Asaad Saleem , Alhazmi Ajiad , Almalki Manal , Moafa Almutasim B , Moshi Jobran M 
Published: January 2025

ObjectiveTo determine the prevalence of piriformis syndrome (PS) among undergraduate university health sciences students aged 18 to 25 and assess the significant predictors of PS regardless of its type and severe PS in particular.DesignA cross-sectional study.SettingThe study was conducted at a tertiary care hospital of a public university in Pakistan from December 2023 to May 2024.ParticipantsA total of 190 subjects enrolled in the study who met the eligibility criteria, which included being an undergraduate health sciences student (medical and allied health specialities), aged 18 up to 25 years, and willing to participate in the study. Participants were selected using multistage random sampling.Primary and secondary outcome measuresThe prevalence of PS in addition to associated risk factors as a primary outcome measures. Secondary outcome measures included the severity of PS.ResultsOf the total, 119 (62.6%) were female, 114 (60.0%) were between 22 and 25 years old, and 125 (65.8%) had standard body mass index. The prevalence of PS was (61.1%), whereas half suffered from severe PS, and the remaining half had mild and moderate PS. We found that factors such as casual sitting positions, sitting duration and International Physical Activity Questionnaire (IPAQ) score (physical activity) were associated with odds of PS in the crude and adjusted regression analyses. When stratified by severity of PS, factors such as writing positions, casual sitting positions, sitting duration and IPAQ score (physical activity) were associated with odds of severe PS in the crude and adjusted regression analyses.ConclusionsStudents have a high prevalence of PS, with an increased likelihood of buttock pain associated with prolonged sitting, poor posture and physical inactivity. Future research that includes several factors related to students’ social and psychological backgrounds is required.
Effect of early establishment of full enteral feeding with exclusive mother’s own milk in preterm babies: a retrospective cohort study
Authors: Umasekar Urmila , Amboiram Prakash , Balakrishnan Umamaheswari , Sirala Jagadeesh Nalini 
Published: January 2025

BackgroundHuman milk, especially the mother’s own milk (MOM), is highly recommended for preterm babies considering its numerous benefits. Prioritising the use of exclusive MOM in enteral feeding plans is essential for maximising the health and development of preterm babies. This study evaluated the effect of early establishment of full enteral feed (FEF) with exclusive MOM on feeding rate and neonatal nutritional outcomes at discharge among preterm babies.MethodsA retrospective cohort study was conducted using medical records of single preterm babies born between 27 and 33+6weeks of gestational age and admitted to a single tertiary care hospital in South India between June 2019 and May 2022. The primary exposure was the establishment of FEF with exclusive MOM. The outcomes assessed were the exclusive MOM feeding rate and neonatal nutritional outcomes at discharge.ResultsA total of 160 preterm babies met the inclusion criteria. Among these 104 (65%) achieved FEF with exclusive MOM. The exclusive MOM feeding rate at discharge was significantly higher among preterm babies who achieved FEF with exclusive MOM, 91.3% vs 62.5% (RR: 1.46 (95% CI: 1.18 to 1.81)). Preterm babies who achieved FEF with exclusive MOM were five times more likely to continue exclusive MOM feeding at discharge (aOR: 5.37, 95% CI: 2.04 to 14.16). The median time taken to achieve exclusive MOM among the exposure group was 6 days (95% CI: 5.6 to 6.3) compared with 12 days (95% CI: 10.2 to 13.8) for the unexposed group (HR: 0.26 (95% CI: 0.17 to 0.38; p<0.001)). There was no significant difference in growth and neonatal complications between the groups. Availability of MOM within 48 hours was strongly associated with achieving FEF with exclusive MOM, with an adjusted OR of 6.12 (95% CI: 2.81 to 13.30).ConclusionsEarly establishment of FEF with exclusive MOM increases the exclusive MOM feeding rate at discharge. Early access to MOM within 48 hours significantly enhances the likelihood of achieving FEF with exclusive MOM.
Analysis of 19 439 lower limb amputations in children in Brazilian health system over 14 years
Authors: Portela Felipe Soares Oliveira , Louzada Andressa Cristina Sposato , da Silva Marcelo Fiorelli Alexandrino , Portugal Maria Fernanda Cassino , Galvão Fernando Ayroza , Teivelis Marcelo Passos , Junior Edson Amaro , Wolosker Nelson 
Published: January 2025

BackgroundAmputations in children represent significant events. Few studies analyse amputations in this specific population, and most of them are old, regionalised and with small sample sizes. Besides, there are no large studies in low-income and middle-income countries. This study aims to analyse a large sample of amputations (19 439 procedures performed in the Brazilian public health system) in children aged 0–14 over 14 years.MethodsRetrospective cross-sectional population-based analysis of all lower limb amputations performed in the Brazilian public health system between 2008 and 2021 in children up to 14. Using a public database, all types of amputations were selected, defining the number of procedures, their main aetiologies, trends over the years, patient demographics and regional distribution.Results19 439 lower limb amputations were performed in the Brazilian public health system between 2008 and 2021, mainly at the toe level (85%). Amputations occurred predominantly in males (64%) and children aged 0–4 (47%). The global trend is a non-significant decrease in the total number of amputations over the period (p=0.427), but we observe a significant decrease (p<0.001) in amputations in older children (aged 10–14). Amputations are more concentrated in the most populated regions, while the highest mortality is found in the least densely populated areas. Trauma is the main aetiology associated with lower limb amputations in Brazilian children (60%).ConclusionThe epidemiology of amputations in Brazil differs from the rest of the world. Trauma is the main aetiology.
Construction of a ‘civilised smoking environment’: a novel strategy undermining tobacco control efforts in China
Authors: Deng Hui , Fang Ling , Mao Yimeng , Zhao Yuchen , Qian Chenyu , Guo Wenjie , Zhu Weiyun , Yan Xiaotao , Wen Sisi , Zhang Shuai , Wang Fan , Zheng Pinpin 
Published: January 2025

ObjectiveIn 2018, the Chinese tobacco industry initiated the nationwide ‘civilised smoking environment’ campaign via a 5-year action plan. The goal of this study was to analyse content of reports regarding this topic as evidence to policy-makers to prevent interference from the tobacco industry.MethodsA search of WiseNews, a Chinese media information service provider, for reports regarding the ‘civilised smoking environment’ between January 2018 and December 2022. Reports were coded separately by two trained researchers using a codebook developed by the team, including four sections with 19 items.ResultsA total of 1062 reports were included, of which 66.5% were from general media. Key themes include mention of approaches to promote the civilised smoking environment (59.8%), primarily by establishing civilised smoking areas (86.1%). A majority of reports (72.9%) disclosed key promoters of these initiatives, including the Tobacco Monopoly Administration (69.5%), Tobacco Corporation (52.3%) and other government agencies (20.4%). Funders were mentioned in 252 reports (23.7%), primarily the Tobacco Monopoly Administration (60.3%) and Tobacco Corporation (50.8%). Most reports (92.8%) supported these initiatives, while only 45 (4.2%) opposed it.Conclusions‘Civilised smoking environment’ in China was promoted and financed primarily by tobacco industry and widely supported by media. This undermines smoke-free environments and violates the WHO Framework Convention on Tobacco Control. China’s government should cease its involvement in these initiatives, and government agencies should refrain from agreeing, supporting, cooperating or participating in these activities.
Exploring Students’ Perceptions of Cutting‐Edge Nursing Simulation: A Phenomenological Study
Authors: Pasay-An Eddieson , Alqarni Aida Sanad , Sacgaca Lailani , Alsulami Amal , Pangket Petelyne , Gonzales Ferdinand , Gonzales Analita , Benjamin Lizy Sonia , Estadilla Lorraine , Alreshidi Maha Sanat , Mostoles Romeo , Alshammari Salman Amish 
Published: January 2025

Introduction: Gap remains in understanding how students perceive the impact of simulations on their development of critical thinking skills and how their emotional well‐being is affected during high‐fidelity simulations. This gap occurs because little attention is paid to what students think about such specifics in learning activities.Aim: This study aimed to explore the strengths and weaknesses of simulation as perceived by students, with a focus on understanding the associated scenario design, emotional impact, and skills development.Methods: This qualitative study was conducted at a government university in central Saudi Arabia. Twenty nursing students participated in one‐to‐one interviews between November 2023 and January 2024.Results: Five themes and six subthemes emerged from the students’ verbatim accounts: (1) conceptual understanding (subtheme: preparation for real‐world practice), (2) development and refinement of clinical skills (subtheme: identifying weaknesses), (3) trepidation to triumph (subthemes: stepping outside the comfort zone and reframing difficulty), (4) technical and scenario limitations of advanced simulation (subtheme: gap between simulation and reality), and (5) yearning for the cutting edge (subtheme: interest in immersive learning technologies).Conclusion: Participants reported positive experiences, including increased confidence, skill development, and an improved understanding of complex clinical concepts. However, limitations such as unrealistic scenarios and technical difficulties were identified. This study emphasizes the potential of advanced technologies, such as virtual and augmented reality, to overcome these challenges and create more immersive and engaging learning experiences.
Functional magnetic resonance spectroscopy of prolonged motor activation using conventional and spectral GLM analyses
Authors: Morelli Maria , Dudzikowska Katarzyna , Deelchand Dinesh K. , Quinn Andrew J. , Mullins Paul G. , Apps Matthew A. J. , Wilson Martin 
Published: January 2025

Abstract
Functional MRS (fMRS) is a technique used to measure metabolic changes in response to increased neuronal activity, providing unique insights into neurotransmitter dynamics and neuroenergetics. In this study, we investigate the response of lactate and glutamate levels in the motor cortex during a sustained motor task using conventional spectral fitting and explore the use of a novel analysis approach based on the application of linear modelling directly to the spectro-temporal fMRS data. fMRS data were acquired at a field strength of 3 Tesla from 23 healthy participants using a short echo-time (28 ms) semi-LASER sequence. The functional task involved rhythmic hand clenching over a duration of 8 min and standard MRS preprocessing steps, including frequency and phase alignment, were employed. Both conventional spectral fitting and direct linear modelling were applied, and results from participant-averaged spectra and metabolite-averaged individual analyses were compared. We observed a 20% increase in lactate in response to the motor task, from participant-averaged spectral fitting, consistent with findings at higher magnetic field strengths. However, statistical testing showed some variability between the two averaging schemes and fitting algorithms. While lactate changes were supported by the direct spectral modelling approach, smaller increases in glutamate (2%) were inconsistent. Exploratory spectral modelling identified a 4% decrease in aspartate, aligning with conventional fitting and observations from prolonged visual stimulation. We demonstrate that lactate dynamics in response to a prolonged motor task are observed using short-echo time semi-LASER at 3 Tesla, and that direct linear modelling of fMRS data is a useful complement to conventional analysis. Future work includes mitigating spectral confounds, such as scalp lipid contamination and lineshape drift, and further validation of our novel direct linear modelling approach through experimental and simulated datasets.
Machine Learning for Explanation of Subgrid Convective Precipitation: A Case Study over CONUS Using a Convection-Allowing Model and SHAP Analysis
Authors: Kang Hyoungseok , Ebtehaj Ardeshir 
Published: January 2025

Abstract
Understanding the role of dynamic, thermodynamic, and cloud microphysical parameters governing the occurrence and magnitude of convective precipitation at subgrid scales is crucial for reducing uncertainties in extreme precipitation properties projected by global climate models. This study evaluates the efficacy of extreme gradient boosting decision trees in detecting subgrid convective precipitation features (CPFs) and estimating their extent using convection-allowing simulations based on observations across the contiguous United States (CONUS). Our annual analysis reveals that despite the imbalanced nature of detecting subgrid CPFs, the model achieves an 85% F1 score using key CPF predictors at 100-km grids. Performance metrics for CPF detection and extent estimation show significant seasonal variations corresponding to mesoscale environmental conditions influencing their space–time dynamics. Shapley values from the model indicate that cloud liquid and ice water content are primary predictors in CPF detection, while midlevel vorticity induced by convective heating profiles predominantly influences CPF extent estimation.

Significance Statement
Understanding future changes in precipitation extremes requires a grasp of small-scale convective processes, which global circulation models currently cannot explain. This study aims to enhance our understanding of where, when, and to what extent machine learning can characterize the occurrence and extent of convective precipitation features. Learning from convective-enabled simulations and ground-based radar data over the contiguous United States, the findings demonstrate that extreme gradient-boosted decision trees can effectively capture these features and explain the relative importance of cloud microphysics, thermodynamics, and dynamic environmental forces that drive the space–time variability of convective precipitation.