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Exploring discrepancies between in vivo and simulated correction in 3D-planned distal radius osteotomies: the influence of biological factors
Three-dimensional virtual surgical planning (3D VSP) with patient-specific surgical guides (PSSGs) can improve the accuracy of corrective distal radius osteotomy. Simulation on 3D-printed bone models allows controlled evaluation of planned corrections, but such models do not reproduce biological factors, including bone quality and soft-tissue tension. The extent to which simulated corrections reflect in vivo surgical results remains unclear. This exploratory study included 13 patients who underwent corrective distal radius osteotomy using 3D VSP and PSSGs. Simulated osteotomies were performed on patient-specific 3D-printed bone models. Residual correction errors in volar tilt (VT), radial inclination (RI), and radial length (RL) were calculated relative to the 3D VSP for both in vivo and simulated corrections. Discrepancies between in vivo and simulated corrections were assessed, and their associations with age, bone mineral density estimated from Hounsfield units, and planned maximum distraction were explored using Spearman’s rank correlation. Residual correction errors in simulated osteotomies were generally comparable to those observed in vivo. The largest differences between simulated and in vivo corrections were observed for VT (3.2), although the mean difference remained within clinically acceptable limits. A positive correlation was found between RL discrepancy and planned maximum distraction (rₛ = 0.71, 95% CI: 0.27–0.91, p = 0.01), and a negative correlation was found between RL discrepancy and bone mineral density (rₛ = −0.64, 95% CI: −0.88 – −0.13, p = 0.02). No correlations were identified for VT or RI. Simulated distal radius osteotomies on 3D-printed bone models produced correction errors broadly comparable to those achieved in vivo. However, small but systematic discrepancies in VT and RL suggest that biological factors may influence the relation between simulated and clinical outcomes. These findings support the use of simulation models for comparative studies while highlighting the need for cautious interpretation of simulation-based results.
Fascicle lengthening during a large torque reduction subsequently decreases dorsiflexion torque steadiness
Abstract Here we assessed the effect of different rates and amplitudes of active torque reduction on the subsequent steady-state EMG amplitude, torque steadiness, and fascicle length during submaximal voluntary fixed-end (isometric) dorsiflexion contractions. Based on previous findings following active muscle-tendon unit lengthening, we expected a reduced steady-state EMG amplitude and torque steadiness relative to torque-matched reference contractions. In Experiment 1, thirteen participants performed reference contractions to 40% of maximum voluntary torque (MVT) and test contractions to 60 then 40% MVT over durations of 0.25, 0.5, 1 or 2 s. In Experiment 2, fourteen different participants performed reference contractions to 15, 30, and 45% MVT and test contractions to 85 then 15, 30, or 45% MVT at a fixed rate. Increasing the rate or amplitude of active torque reduction respectively increased tibialis anterior’s fascicle lengthening rate (1.6 to 6.9 mm·s − 1 , p ≤.041) or amplitude (3.6 to 7.5 mm; p <.001). However, fascicle lengthening did not subsequently change EMG amplitudes relative to the reference conditions (−1.5 to 2.7% MVC, p ≥.102) at similar steady-state torques. Fascicle lengthening amplitudes of ≥ 8 ± 3% (5.2 ± 1.7 mm) reduced torque steadiness (0.7 to 1.5%, p ≤.005) relative to reference conditions though, but the contributing mechanisms remain unclear and are worthy of further investigation.
Multivalent mRNA vaccine platform with compatible antigens conferred broad-spectrum protection against orthoebolaviruses’ exposure
Several orthoebolaviruses have been established, including Orthoebolavirus zairense [for Ebola virus (EBOV)], Orthoebolavirus sudanense [for Sudan virus (SUDV)], and Orthoebolavirus bundibugyoense [for Bundibugyo virus (BDBV)]. Orthoebolaviruses are highly virulent pathogens that cause severe disease in humans. However, most existing vaccines primarily target EBOV, and fail to provide robust cross-protection against other lethal orthoebolaviruses. The development of a broad-spectrum vaccine has the potential to efficiently mitigate outbreaks caused by multiple orthoebolaviruses. In this study, we developed and evaluated a broad-spectrum mRNA vaccine, designated [GPs+NP]@LNP, formulated with a single lipid nanoparticle (LNP) platform to encapsulate a mixed mRNA payload encoding the glycoproteins (GPs) of EBOV, BDBV, and SUDV, along with the nucleoprotein (NP) of EBOV. This rational antigenic combination was designed to engage both humoral and cellular arms of the immune system. Consistent with this design, the compatibility of humoral immunity-driving GPs and cellular immune-dominating NPs supports complementary immune responses, which together are associated with broad and durable protection against EBOV, BDBV, and SUDV in animal models. Antigenic coordination within a single LNP formulation may therefore represent an effective strategy to optimize vaccine immunogenicity, protective effect, durability, and safety. Collectively, these findings highlight [GPs+NP]@LNP as a promising approach for the development of next-generation vaccines targeting multiple pathogenic orthoebolaviruses.
Knowledge gaps and positive attitudes toward adult vaccination among nursing students: A Cross-sectional study
Background Vaccination is one of the most effective public-health measures, yet adult coverage in Spain remains suboptimal due to misinformation and hesitancy. Nursing students, as future immunization promoters, play a pivotal role in vaccine recommendations. This study explored knowledge, attitudes, and recommendation practices regarding adult vaccination among undergraduate nursing students. Methods An observational, descriptive, cross-sectional study was conducted in the province of Alicante, Spain, between April and May 2025. An ad hoc electronic survey with 19 closed-ended items was distributed to students from the three universities offering the Nursing degree in this province; 562 students participated. Differences across academic years were analyzed using Pearson’s χ² test for categorical variables and the Kruskal-Wallis test for the continuous variable age (non-normally distributed). Results Overall, 39.1% of nursing students were unaware of the Spanish adult vaccination schedule with significant differences across academic years (55.7% in first-year vs. 27.2% in fourth-year students; p < 0.001). Only 44.1% reported sufficient training on vaccines. Attitudes toward adult vaccination were predominantly positive: 61.4% highly favorable, 62.5% highly effective, 66.7% supporting mandatory vaccination. Additionally, 65.5% would recommend all scheduled adult vaccines. However, 47.9% perceived resistance from other healthcare professionals when recommending vaccines (p < 0.001 for the increase across academic years). Conclusions Nursing students in Alicante exhibit positive attitudes toward adult vaccination, yet significant knowledge gaps regarding the Spanish adult vaccination schedule persist even in the final year. Targeted curricular reinforcement from the first academic year is warranted within these three institutions to strengthen their role as immunization promoters.
Investigating the effects of reaction time on scaling dynamics in produced water and its implications for enhanced re-injection practices
HIV-1 Vif–dependent SUMOylation regulates viral RNA splicing
Global burden-integrated analysis of osteoarthritis research-to-translation dynamics, 1999–2023
Background Osteoarthritis (OA) is a leading cause of global disability, yet the temporal relationship between disease burden and research and translational activity has not been systematically examined using an integrated, system-level framework. Methods We conducted a retrospective, system-level analysis of osteoarthritis (OA) research and disease burden from 1999 to 2023. Annual global OA burden estimates (prevalence, YLDs, and DALYs) were obtained from the Global Burden of Disease framework and harmonized with year-wise data on OA publications, experimental model use, interventional clinical trials, and funding acknowledgements derived from PubMed and ClinicalTrials.gov. Publication domains were classified using predefined, rule-based queries applied to metadata fields. Temporal trends, proportional composition, and burden–research scaling relationships were evaluated using descriptive regression and proportion-based analyses. Results Between 1999 and 2023, global osteoarthritis (OA) disability-adjusted life years (DALYs) approximately doubled, while annual OA publication volume increased more than fourfold. Log–log regression indicated elastic scaling of research output relative to DALYs (β > 1), reflecting disproportionate growth in publication activity. In contrast, interventional clinical trial initiation peaked in the late 2000s and declined in recent years, with trial activity representing a consistently small fraction of total OA publications. Human-relevant experimental approaches constituted a modest and relatively stable proportion of OA research over time. Lag-association analyses demonstrated strong temporal co-trending between DALYs and total publications, moderate alignment for human-relevant research, and weaker associations for clinical trial activity. Conclusion Over 1999–2023, osteoarthritis research activity expanded substantially relative to disease burden, while downstream clinical translation and adoption of human-relevant approaches remained comparatively limited.
Comparative efficacy of intermittent hypoxic training modalities on athletes’ performance: a systematic review with pairwise and network meta-analyses
Effects of bulevirtide on atherosclerosis in an ApoE-deficient mouse model
Objective Bile acids are known to have a positive impact on atherosclerosis. The study investigates the impact of sodium taurocholate co-transporting polypeptide (NTCP) inhibition with bulevirtide, organic anion transporting polypeptide (OATP) inhibition with rifampicin, and their combination on bile acid levels and atherosclerosis in apolipoprotein E–deficient (ApoE⁻/⁻) mice. Methods Fifty-six female ApoE⁻/⁻ mice on a Western type diet were treated daily for four weeks with bulevirtide (5 mg/kg), rifampicin (20 mg/kg), a combination of both, or vehicle. Plasma bile acids and lipids were measured at sacrifice. Atherosclerotic lesion size was quantified in the aortic sinus, and macrophage content was analyzed by Mac-2 immunohistochemistry. Results Plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels remained unchanged across all groups, being accompanied with no changes of atherosclerotic lesion size (p = 0.896). However, treatment with bulevirtide (p = 0.017), rifampicin (p = 0.003), but mostly their combination (p < 0.001) significantly increased plasma bile acid concentrations and altered the macrophage-to-lesion area ratio, at least for the combination therapy group (p = 0.020). The combined treatment exhibited the highest bile acid levels, indicating additive effects of dual transporter inhibition. Conclusions While lesion sizes remained unaffected, the combined NTCP and OATP inhibition significantly enhanced bile acid levels and reduced macrophage content in early atherosclerotic lesions of ApoE⁻/⁻ mice. These results highlight the association of bile acid with the modulation of plaque composition as a potential therapeutic mode of action.
Integrated network pharmacology and experimental validation to elucidate the mechanism of Lysimachia paridiformis var. stenophylla Franch. in rheumatoid arthritis
Reversing the great degradation of nature by reducing factors related to cropland expansion
As one of the main causes of habitat loss, agricultural cropland expansion is a major threat to biodiversity. We analyze past and anticipated future trends in population, per capita crop demand, and crop yield to estimate agricultural cropland requirements globally by 2050 and 2100, assuming moderate levels of climate change. According to a model of “business as usual,” higher-income countries would be expected to show little or no net growth in cropland by the end of the century whereas cropland area could nearly double in lower-income countries. We consider two strategies to reduce global cropland expansion: decreasing per capita crop demand in higher-income countries by eating healthier diets, reducing food waste, and reducing biofuel production, and accelerating economic development in lower-income countries. Economic development in lower-income countries could reduce future cropland requirements via slower population growth, improved crop yield, and higher volumes of global crop trade, which could more than offset rising per capita crop demand. These impacts would far exceed reductions in cropland requirements from decreased crop demand in higher-income countries. Further, by combining accelerated economic development in lower-income countries with reduced crop demand in higher-income countries in tandem with reduced trade friction, global cropland requirements could shrink dramatically by the year 2100. Although economic growth is often considered to work in opposition to environmental conservation, accelerating economic development in lower-income countries would not only help alleviate poverty but could also confer benefits for biodiversity and global climate change.
Is early childhood exposure a key predictor of adulthood problematic gaming?
Internet Gaming Disorder (IGD) is a proposed condition wherein a preoccupation with video games causes distress and functional impairment. However, the extent to which IGD resembles substance use disorders is controversial. In substance-related disorders, the timing of first exposure correlates with adult symptom severity; however, it is unclear whether IGD symptoms share a similar pattern. The present study used growth mixture modelling to identify how the onset of frequent gaming during early life relates to problematic gaming in adults. A four-class model that differentially predicted current IGD symptoms was identified. The ‘Consistently High Group’ (high levels of gaming during childhood and adolescence) displayed higher IGD symptoms than the ‘Low Escalating Group” (low gaming during these stages) and ‘Rapidly Escalating Group’ (low gaming during preschool followed by high gaming). However, the ‘Consistently High Group’ did not show greater IGD symptoms than the ‘Moderate Group,’ which was the only other group with substantial preschool gaming. Regression analyses confirmed that gaming during preschool and high school predicted current IGD symptoms, with preschool gaming being the strongest predictor. This study highlights additional parallels between substance-related disorders and IGD, specifically identifying an early age of onset as a predictor of adult symptom severity. These results may inform caregivers and paediatric guidelines concerning when and how video game play is introduced and motivate further research clarifying how problematic gaming may emerge through interactions between developmental exposure, mental health, environmental factors, and individual traits.
A modified HIV model with Beddington–DeAngelis incidence and cure rate
Abstract This study presents a refined within-host human immunodeficiency virus (HIV) dynamics model that integrates several biologically relevant mechanisms often treated in isolation. The model incorporates a Beddington–DeAngelis functional response to describe the infection incidence, accounting for saturation effects in both target cells and free virus particles. It further includes a cure rate for infected cells, representing the efficacy of antiretroviral therapy or intrinsic immune clearance, and logistic growth for CD4 $$^+$$ T-cell populations. A novel contribution is the explicit inclusion of both cellular (cytotoxic T-lymphocytes, CTLs) and humoral (antibody) immune responses. We perform a complete dynamical analysis of the continuous-time system, deriving the basic reproduction number $$\mathcal {R}_0$$ as a sharp threshold. We establish the existence and uniqueness of the disease-free and endemic equilibria and analyze their local stability. Furthermore, we prove the global asymptotic stability of the endemic equilibrium when $$\mathcal {R}_0> 1$$ using a Lyapunov function. To facilitate numerical investigation, we construct a dynamically consistent nonstandard finite difference (NSFD) discretization that preserves the positivity and stability properties of the continuous model. Numerical simulations validate the theoretical findings and illustrate the distinct roles of the saturation parameters $$m_1$$ and $$m_2$$ , as well as the immune response, in modulating infection outcomes. The results highlight how the interplay between viral kinetics and immune effectors can determine disease progression or clearance, providing theoretical insights that could inform therapeutic strategies.
Predictions from deep learning propose substantial protein–carbohydrate interplay
Noncovalent interaction between proteins and carbohydrates (sugars, glycans) is the basis for biological functions from metabolic regulation to intercellular recognition. It is a grand challenge to identify the protein–carbohydrate interactomes in organisms. Direct experiments would require extensive libraries of glycans to distinguish binding from nonbinding proteins. Computational screening of proteins for carbohydrate binding potential provides an attractive alternative. Current estimates propose that <5% of proteins bind carbohydrates, a number that is not well established. We therefore developed a neural network, “Protein interaction of Carbohydrates Predictor” (PiCAP), to predict whether a protein noncovalently binds to a carbohydrate. We trained PiCAP on a manually curated dataset of known carbohydrate binders and proteins that we identified as likely not to bind carbohydrates (transcription factors, cytoskeletal components, and small-molecule-binding proteins). PiCAP achieves 90% balanced accuracy on protein-level predictions of carbohydrate binding/nonbinding. Using the same datasets, we developed Carbohydrate Protein Site Identifier 2 (CAPSIF2) to predict protein residues that interact noncovalently with carbohydrates. CAPSIF2 achieves a Dice coefficient of 0.57 on residue-level predictions on our independent test dataset, outperforming previous models. To demonstrate the models’ biological applicability, we investigated human cell surface proteins and further predicted the likelihood of carbohydrate binding in six proteomes ( Escherichia coli , Mus musculus, Homo sapiens, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster ). PiCAP predicts that ~35 to 40% of proteins in these proteomes bind carbohydrates, with 75% of extracellular and cell surface proteins predicted to bind. The PiCAP predicted binders are enriched for functions including growth factor receptor binding, inflammation, and cell–cell adhesion.
How does rural population aging affect agricultural green development in China?
Rapid population aging significantly impacts socioeconomic development and poses substantial challenges for agricultural green development (AGD), which have so far not been well understood. This study uses data from the China Family Panel Studies conducted in 2018, 2020, and 2022 and adopts the instrumental variable two-stage least squares (IV-2SLS) method to analyze the impact and mechanisms of rural population aging on AGD from a micro-level perspective of farmers. The benchmark regression results show that rural population aging significantly hinders AGD: an increase in the proportion of older adults in the household reduces AGD by 0.346. The impact in the western region is greater than that in the central and eastern regions, primarily by restricting improvements in economic benefits (agricultural output). In contrast, its effect on environmental benefits (agricultural chemical inputs) is not statistically significant. The adoption of agricultural socialized services by older adults increases agricultural output while reducing chemical inputs, thereby mitigating the adverse effects of rural population aging on AGD. However, surging service prices discourage utilization, prompting farmers to transfer or abandon part of their farmland and continue traditional resource-intensive practices. Our analysis indicates that it is crucial to establish mechanisms to curb farmland abandonment and enhance the accessibility of agricultural socialized services for older adults in the context of rapid population aging.
Determinants of medical crowdfunding information sharing attitudes through integrated source credibility and technology acceptance models
Correction for Zhang et al., Conserved use of tetraspanin CD9 as an entry receptor by rhabdoviruses spanning multiple genera
A novel approach for the EEG-driven assessment of divided attention through mutual information theory: A case study at the wheel
Monitoring how attention is distributed across concurrent task demands is fundamental in daily life contexts such as mobility, education and industrial control. However, existing neurophysiological measures, typically based on univariate EEG markers, are sensitive to generic cognitive load, visual complexity, or motor activity, and therefore lack specificity for attentional splitting. Here, we introduce the Attentional Split Index (ASI), a novel EEG-based metric that employ Mutual Information (MI) theory, designed to quantify the coordinated modulation of multiple neurometrics that emerges when attention is divided across tasks. Twenty-five participants completed a realistic driving protocol combining a main driving task in two different environments (Urban, Highway) with four types of attentional-split demands, i.e., Focused, Auditory Continuous Performance Test (ACPT), Matrix, Surrogate Reference Task (SURT). Traditional neurometrics (parietal alpha, inverse frontal beta, frontal theta/beta ratio) exhibited partial sensitivity to task demands but failed to selectively reflect attentional splitting. In contrast, the ASI showed a robust and systematic increase across conditions, distinguishing not only explicit multitasking segments but also subtler differences between Urban and Highway focused driving. Eye-tracking and subjective distraction rating showed a strong and significant correlation with the ASI (Urban: r ET = 0.515 and r SUB = 0.744; Highway: r ET = 0.357 and r SUB = 0.673; all p < 10 −2 ), confirming high behavioural and phenomenological coherence. Surrogate analyses demonstrated that ASI effects were absent when temporal coordination across neurometrics was artificially disrupted, and that real ASI exceeded surrogate values in the vast majority of participants during multitasking but not during eyes-open baseline. Together, these findings establish the ASI as a specific, robust, and ecologically coherent neural marker of attentional splitting, with promising implications for neuroergonomics and next-generation adaptive human–machine systems.
Investigation of adaptive interception systems for concentrate in spiral concentrators
Emergence of cooperation due to opponent-specific responses in Prisoner’s Dilemma
Complex life would be impossible without cooperation at all levels of biological organization. However, Darwinian selection is commonly believed to favor selfish behavior, making societies of cooperators vulnerable to cheaters. A quintessential model of this behavior is the game of Prisoner’s Dilemma in which cheaters always win, even though being cooperative results in greater rewards. Numerous scenarios have been proposed that allow for the evolution of cooperation in restrictive settings that postulate altruism between genetic relatives, explore mechanisms of direct and indirect reciprocity, focus on competition between groups, or impose spatial structure on the population. It is difficult to imagine how these scenarios would account for the evolution of cooperation in populations of organisms that lack sophisticated assessment mechanisms and have no spatial constraints. Here we demonstrate that it is possible to achieve high levels of cooperativity in the game of Prisoner’s Dilemma without introducing any additional assumptions about genetic relatedness, population structure, or explicit reciprocal arrangements. The only requirement is that the willingness to cooperate varies depending on the opponent, for example in response to the opponent’s physical appearance and patterns of behavior. This mechanism requires consistent opponent recognition during multiple encounters. Evolution of cooperativity due to opponent-specific responses may be the only available mechanism in many biological settings and may serve as a starting point for more sophisticated modes of cooperation observed in animal and human societies.