Browse Articles
Discover research articles across all indexed journals
Bayesian inference of haematopoietic stem/progenitor cell differentiation phenotypic manifolds and their bifurcation points using Gaussian processes and Gibbs sampling
Maynard Smith’s analogy, realized: Common ancestry constrains evolutionary percolation through protein space
Editorial Note: Novel randomization and iterative based algorithms for the transactions assignment in blockchain problem
NuConf: a rotamer library for DNA and RNA and its implementation in the protein design software MUMBO
Abstract Current AI tools for designing macromolecules have been struggling with DNA and RNA structure prediction and design as significantly less experimental training data are available for nucleic acids than for proteins. Therefore, developing alternative approaches remains of interest. MUMBO, a program for designing protein–protein interactions and protein–ligand-binding pockets, uses side-chain-packing algorithms to select from alternative amino acids and conformers generated on a fixed backbone with the help of rotamer libraries. MUMBO identifies the most favourable combinations based on the lowest overall energy. In order to extend the program’s capabilities to designing nucleic acids, we developed NuConf, a discrete pseudorotational angle-dependent nucleoside-specific rotamer library. We derived NuConf by statistically analysing pseudorotational and dihedral angles of more than 175,000 nucleotides from experimental structures and validated it by rebuilding more than 20,000 nucleotides in a custom dataset. Strikingly, our approach predicts nucleotides at least as accurately as amino acids. We show that the implementation of the NuConf library in MUMBO enables modelling and designing DNA and RNA sequences on a fixed backbone together with protein-nucleic acid interaction interfaces. Because its approach and format are program agnostic, NuConf can be used by other molecular design frameworks as well.
ECgo: All-optical induction of single endothelial cell injury and capillary occlusion in the brain
The ability to induce endothelial cell (EC) damage in the mouse brain with high spatial precision is invaluable for mechanistic studies of brain capillary injury and repair. Here, we introduce an optical method, termed Endothelial Cell guided obliteration (ECgo), that utilizes a two-photon-excitable porphyrin-based photosensitizer ( Ps2P ) to selectively obliterate single ECs within the brain microvascular network. Using the developed approach, we were able to induce occlusions of single capillaries with high spatiotemporal control, while preserving the surrounding tissue. Combined with longitudinal two-photon imaging, ECgo enables studies of morphological and functional consequences of targeted single capillary EC injury in vivo under healthy and diseased conditions.
Development and evaluation of AI model with deep learning for segmentation of extraocular muscles in thyroid eye disease
Purpose To develop and evaluate an AI model for the segmentation of extraocular muscles (EOMs) using Magnetic Resonance Imaging (MRI). Design Single-center study with retrospective study. Methods The study included 52 patients with thyroid eye disease (TED) who underwent MRI examination of the orbital region at the Department of Ophthalmology, Osaka Metropolitan University, between October 2020 and June 2023. Manual labelling of all EOMs was performed on all slices. An AI model was created and compared with the manually labelled data using 5-fold cross validation on data sets of 12, 32, and 52 cases. The average signal intensity ratio (SIR) within the EOMs was measured. The primary outcome was the comparison of DICE similarity coefficients (DSC) as the agreement rate between AI’s result and manual labelling amongst the three data sets (52 cases vs 32 cases vs 12 cases). The secondary outcome was the correlation of SIR between the AI and manual labelling. Results A significant difference in DSC was observed between the 12-, 32-, and 52-case data sets for the inferior rectus muscle and medial rectus muscle. A significant correlation was observed between the AI and manual labelling for SIR in all EOMs. Conclusions An AI model was successfully developed for the automatic segmentation of EOMs. There was little measurement error between AI and manual labelling, and the AI model using 52 cases had improved measurement accuracy compared to the AI models using 32 and 12 cases.
Pilot-scale remediation, resource utilization, and long-term stabilization of cadmium, lead and arsenic co-contaminated soil
Reality shock and its associated factors among newly graduated nurses in China: A cross-sectional study
Background Newly graduated nurses often experience a transition period marked by reality shock, which can adversely affect their professional retention and career development. However, the associated factors remain incompletely understood, and there is a notable gap in evidence regarding the role of the impostor phenomenon in this context. Objectives To investigate the reality shock among newly graduated nurses and identify its associated factors, with a specific focus on the impostor phenomenon. Methods A cross-sectional design was implemented, and the high-quality reporting of the study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. From July 2024 to January 2025, a total of 381 newly graduated nurses were recruited from 3 tertiary grade-A hospitals in China by convenience sampling. The inclusion criteria required nurses to hold a valid nurse qualification certificate, be registered at the hospital, have a clinical working time of ＜ 1 year, and provide informed consent while cooperating with investigators. Exclusion criteria applied to hospital trainees, standardized training personnel, and personnel not on duty for various reasons. The Demographic Characteristics Questionnaire, Reality Shock Scale for Newly Graduated Nurses, and Clance Impostor Phenomenon Scale were used. The data was analyzed using descriptive statistics, univariate analyses, correlation, and multiple linear regression analysis. Results The total scores for reality shock and impostor phenomenon were 93.66 ± 38.94 and 44.19 ± 16.94, respectively. Reality shock was positively correlated with the impostor phenomenon ( r = 0.635, p < 0.01). Multiple linear regression analysis showed that educational level, monthly income, number of night shifts per month, and impostor phenomenon were the main factors affecting the reality shock among newly graduated nurses (all p < 0.01), accounting for 51.80% of the total variance. Conclusion This study identified a moderately high level of reality shock among newly graduated nurses. Key determinants associated with this shock included educational level, monthly income, number of night shifts per month, and impostor phenomenon. Nursing management should develop targeted interventions addressing these modifiable factors, particularly impostor phenomenon, which may help mitigate reality shock and facilitate successful career adaptation among newly graduated nurses.
A causal discovery framework for analyzing the impact mechanism of generative AI on digital literacy: an LLM-based behavioral analysis approach
Regulation of Pfh1 helicase activity by nucleic acid interactions and mitochondrial SSB
Pif1-family helicases are essential for proper nuclear and mitochondrial genome maintenance, yet the regulation of their activities remains incompletely understood. Here, we use single-molecule manipulation and visualization techniques to dissect the real-time mechanochemical behavior of Pfh1, the sole Pif1-family helicase in Schizosaccharomyces pombe. We systematically varied force, ATP concentration, fork composition, and the single-stranded DNA–binding protein spRim1, to quantify the unwinding and single-stranded DNA translocation properties of Pfh1. We find that Pfh1 operates through unwinding-rewinding cycles during which coordinated interactions with both DNA strands at the fork optimize ATP utilization. Contacts with the translocating strand modulate ATP affinity, while interactions with the displaced strand control maximum unwinding velocity. Binding of spRim1 to the displaced strand disrupts the latter interactions, increasing the unwinding velocity. Stable interactions of the helicase with both strands at the fork may limit unwinding processivity to ~20 bp, eventually triggering transition to rewinding. Rewinding proceeds through an ATP-dependent process that is incompatible with strand switching, in which ATP turnover modulates DNA contacts and rewinding rate. Binding of spRim1 to the displaced strand further accelerates rewinding, possibly by competing with helicase–DNA interactions, and facilitates recovery of the active unwinding conformation once the fork has rewound. Together, these findings suggest that Pfh1 balances unwinding and rewinding through coordinated ATP-dependent strand interactions, providing insight into how Pif1-family helicases are controlled at replication forks.
Trends in pulmonary exercise testing utilization after the COVID-19 pandemic in Ontario: A population-cohort study
Introduction Pulmonary exercise testing, including six-minute walk tests, exercise oximetry, and independent exercise assessments, are critical tools for managing chronic respiratory and cardiac conditions, evaluating treatment response, and determining long-term oxygen therapy needs. During the COVID-19 pandemic, testing was reduced to limit viral spread. This study aimed to evaluate post-pandemic trends of pulmonary exercise testing utilization in Ontario overall and across demographic groups. Methods We conducted a population-based cohort study using Ontario administrative data between April 2015 and December 2023 to evaluate pulmonary exercise testing before, during, and after the COVID-19 pandemic. We used an Auto-Regressive Integrated Moving Average Model (ARIMA) model and incidence rate ratios to evaluate recovery trends. Subgroup analysis examined if trends were similar in different groups. Results During the study period, 505,902 tests were performed for 362,888 individuals. As of December 2023, testing rates were still 21% below pre-pandemic levels (IRR 0.79, 95%CI 0.70–0.89). Recovery was lower in males (IRR 0.76, 95%CI 0.66–0.86) and individuals living in lower socioeconomic status neighborhoods (IRR 0.71, 95%CI 0.58–0.86). Northern Ontario saw the most pronounced shortfall compared to other regions, with testing rates one-third of pre-pandemic levels (IRR 0.33, 95% CI 0.26–0.43). Conclusion More than three years after the pandemic began, pulmonary exercise testing rates have yet to return to pre-pandemic levels, with certain groups disproportionately affected. This highlights a significant and ongoing disruption in diagnostic capacity and quality of care for people with respiratory and cardiac diseases.
Weekend effect in emergency hospitalizations of older adults in Hong Kong
Abstract The impact of the weekend effect on hospitalization outcomes remains debated. This study evaluated the “weekend effect” by defining two distinct patterns based on admission–discharge timing: “weekend-admission/discharge” (either admission or discharge occurring on weekends) and “weekday-admission-discharge” (both admission and discharge occurring on weekdays). Utilizing 3,447,877 emergency hospitalization spells among older patients in Hong Kong from 2012 to 2021, multivariable logistic regression with a random effect of hospital revealed that the weekend-admission/discharge pattern accounted for 42.5% of hospitalizations and was associated with significantly higher in-hospital mortality (5.0% vs. 3.8%; adjusted odds ratio [aOR] = 1.359, 95% CI: 1.344–1.373). Paradoxically, this pattern demonstrated minimally protective effects for post-discharge outcomes, with lower 30-day mortality (aOR = 0.963, 95% CI: 0.948–0.978) and reduced 30-day emergency readmission risk (aOR = 0.986, 95% CI: 0.979–0.992). Subgroup analyses confirmed consistent elevation of in-hospital mortality risk across all spell groups, while revealing substantial variations by length of stay, clinical specialty, and principal diagnosis. The protective post-discharge effects were predominantly observed among those with longer hospitalizations. These findings demonstrate a complex duality in weekend care outcomes and suggest that the weekend effect reflects systemic care integration challenges and selective discharge patterns rather than simple temporal variations in care quality. Future quality improvement initiatives should focus on enhancing care continuity and developing targeted approaches for high-risk clinical contexts. Meanwhile, more research is needed to elucidate the underlying mechanisms driving these paradoxical outcomes.
Systemic electioneering from the evangelical pulpit: Evidence from a computational analysis
Religious institutions’ engagement in prohibited electoral advocacy is a growing concern for democratic governance. In the United States, such mobilization has been especially visible within the evangelical movement. We examine this phenomenon using a corpus of 88,546 sermons from predominantly evangelical churches, transcribed from 63,683 h of Sunday services spanning the 2020, 2022, and 2024 election cycles and a nonelection control period. Analysis of this corpus reveals that direct political advocacy and endorsements are widespread: 14.7% of churches engaged in this speech during the three months surrounding the 2024 election. This behavior follows a clear electoral rhythm, peaking on the Sunday before Election Day, when 3.5% of churches mobilized. Geographic analysis indicates that advocacy correlates with county partisan composition but lacks strategic targeting; rates in swing states are indistinguishable from those in safe states. Our results provide large-scale quantification of political speech from American pulpits that constitutes prohibited electioneering under current Internal Revenue Service (IRS) guidelines, revealing a pattern of base mobilization driven by local partisan context rather than national electoral strategy.
Correction: Catalytic activity evaluation of phyto synthesized SrO and chitosan encapsulated SrO nanomaterials
Research on the adaptation path of corporate strategy based on the differences in AI governance visions between the Atlantic and China
Correction for Corell-Escuin et al., Dermcidin has antiviral activity and protects against influenza
Unraveling the complexity of nurses’ quality of life: A Fuzzy-Set Qualitative Comparative Analysis (fsQCA) approach to the interplay of psychological, occupational, and social factors
Aim This study aimed to explore the interplay among occupational stress, psychological distress, social support, burnout, and work-family conflict in relation to the quality of life (QOL) of nurses. Methods A total of 503 nurses from two tertiary-level hospitals participated in an online survey. Data were collected on psychological distress, occupational stress, social support, burnout, work-family conflict, and quality of life. Fuzzy-set Qualitative Comparative Analysis (fsQCA) was conducted to identify configuration pathways associated with high and low QOL, thereby providing a nuanced understanding of the causal complexity underlying these outcomes. Results Four configuration pathways were identified as conducive to high QOL: (H1) low burnout, low occupational stress, and high social support; (H2) low work-family conflict, low burnout, low occupational stress, and low psychological distress; (H3) high social support, low work-family conflict, low occupational stress, and low psychological distress; and (H4) high social support, low work-family conflict, low burnout, and low psychological distress. Conversely, two pathways were associated with low QOL: (L1) high occupational stress, high psychological distress, high work-family conflict, and low social support; and (L2) high occupational stress, high psychological distress, high work-family conflict, and high burnout. Conclusion Nurses’ QOL is critically influenced by occupational and psychological stressors, work-family conflict, and social support. Addressing these factors through targeted interventions may reduce burnout and psychological distress while enhancing well-being and job satisfaction.
Large and regional-scale processes influencing Heat Waves: Insights from Qatar
Decisional reference point pathology: A cognitive mechanism for and a correlate of major depressive disorder in humans
The decisional reference point, the central mechanism underlying behavioral economics, conditions our evaluations of all reinforcers. Whether a given event is experienced as positive or negative depends on this reference point. A pathological elevation of the reference point would lead a person to experience once pleasurable activities as negative reinforcers. Thus, it has been hypothesized that a reference point pathology may play a critical role in the symptomology of major depressive disorder (MDD). Here, we test the hypothesis that the reference point is pathologically elevated and dynamically inflexible in patients suffering with MDD compared to healthy controls. We find that depression is associated with a significant elevation of the reference point, and the magnitude of this elevation correlates with disease severity. The ability of patients with MDD to dynamically adjust their reference point to the environment is also dysfunctional. Our findings link the previously demonstrated treatment of depression by deep brain stimulation to modulation of the reference point in the anterior cingulate cortex and identify pathology in the dynamics of reference point setting as a potential cognitive mechanism in the disorder. Finally, these results reveal that a three-minute video game-like task measuring the reference point strongly correlates with depression severity. After further testing for clinical validity, this rapid assay may serve as a potential tool for assessing and monitoring depression.