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Prognostic significance of residual functional SYNTAX score II in acute myocardial infarction
Background The residual functional SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (rFSS) predicts patient prognosis post-percutaneous coronary intervention (PCI). We aimed to integrate rFSS with clinical risk factors (rFSS-II) to comprehensively assess patient prognosis, guided by the quantitative flow ratio (QFR), and compare its predictive efficacy with other scoring systems. Methods We enrolled 175 acute myocardial infarction (AMI) patients undergoing post-PCI physiological measurements. Three distinct models were established based on different calculation methods of rFSS-II, and their respective abilities to predict major adverse cardiac events (MACE) were evaluated. Patients were categorized into high rFSS-II (n = 70) and low rFSS-II (n = 105) groups. The MACE incidence was compared between these groups over a 3-year follow-up period, using multivariable Cox regression analysis to identify MACE predictors. Results High rFSS-II patients had more MACE than low rFSS-II patients (55.7% vs. 18.1%; p < 0.001). The rFSS-II model had higher accuracy than other traditional risk scores, except for rSS-II. In a multivariable-adjusted model, rFSS-II emerged as an independent predictor of MACE (adjusted hazard ratio: 1.08 per 1 unit increase, 95% confidence interval [CI]: 1.05–1.11, p < 0.001). Conclusions QFR-guided rFSS-II proved to have good predictive value among AMI patients 3 years post-PCI. Calculating the total score of all vascular segments with QFR ≤ 0.80 may provide enhanced predictive capability.
De novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders
Abstract SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neurodevelopmental disorders, harbouring SF3B1 constitutional heterozygous variants that appeared mostly de novo. Patients present with a global developmental delay, associated with variable neurological and facial dysmorphic traits. A dichotomy may emerge between patients harbouring predicted loss of function ( n = 9) and missense variants ( n = 17), the latter being associated with a more severe and syndromic phenotype, including heart and gastrointestinal anomalies. We focused on de novo SF3B1 missense variants, which were largely distinct from those reported in cancer. Functional complementation assays show that de novo SF3B1 missense variants did not cause a loss of function of the protein. Targeted and genome-wide analysis of RNA splicing reveal that they affect canonical and alternative splicing more moderately than somatic variants, and subtly modify the splicing of many transcripts. These findings place SF3B1 among the rare U2 snRNP components implicated in both cancer and neurodevelopmental disorders, highlighting its critical and multifaceted role in human disease.
Dynamic response of bi-directional gradient sandwich circular plates under multiple explosive loading
Partial privatization and intellectual capital: The moderating role of firm internationalization and regional development
This study examines the impact of partial privatization on intellectual capital and investigates how corporate internationalization and regional development moderate this relationship. Using a sample of Chinese listed firms over the years of 2010–2023, this study employed Ordinary Least Squares (OLS) as the baseline regression. This study finds that partial privatization positively affects intellectual capital, thereby introducing opportunities about value creation within firms. Further investigations reveal that internationalization weakens the positive impact of partial privatization on intellectual capital, suggesting that exposure to international markets may heighten agency risks associated with a firm’s global expansion. Our findings also show that regional development strengthens this positive relationship, since firms located in developed regions are better positioned to capitalize on the benefits of partial privatization. To ensure the robustness of these findings, we also use two Generalized Method of Moments (GMM) and Propensity Score Matching (PSM) methods to ensure the consistency of the findings. Overall, the results carry significant policy implications, especially concerning the corporate efficiency outcomes of privatization in emerging markets such as China.
Dynamic thermal management under variable operating conditions through magnetic field control
Latent profiles of compassion fatigue among clinical nurse preceptors and their associations with work alienation
Abstract This study aimed to investigate the latent profiles of clinical nurse preceptors (CNPs)’ compassion fatigue (CF), identify the influencing factors, and examine their association with work alienation. Between July and August 2025, 340 nurse preceptors from a tertiary grade A general hospital in Zhejiang Province were recruited as participants using convenience sampling. The Chinese version of the Professional Quality of Life Scale Version 5 (ProQOL-5) and the Work Alienation Scale (WAS) were used to assess compassion fatigue and work alienation, respectively. Demographic information was also collected from the participants. Latent Profile Analysis (LPA) was employed to identify potential profiles of compassion fatigue. After screening variables through univariate analysis and multicollinearity tests, multinomial logistic regression was used to assess the influencing factors. Furthermore, a one-way ANOVA was conducted to examine differences in work alienation among different potential profiles, and the results were interpreted based on the job demands-resources (JD-R) model theoretical framework. A total of 320 CNPs were included in the final analysis. The findings of the latent profile analysis indicated that three latent profiles of CNPs’ compassion fatigue were identified: high-satisfaction-low-exhaustion group ( n = 56, 17.5%), moderate compassion fatigue group ( n = 160, 50%), and severe exhaustion group ( n = 104, 32.5%). Multinomial logistic regression analysis showed that age, marital status, education, years of preceptorship, experience, employment type, and professional title were significant predictors of compassion fatigue among CNPs. There were statistically significant differences in the work alienation scores among the three latent profiles ( P < 0.001). CNPs’ compassion fatigue can be categorised into three types, with significant heterogeneity observed among them. Notable differences exist in work alienation among CNPs with different compassion fatigue types. These findings suggest that clinical managers and educators should develop targeted interventions and support systems based on these circumstances. Therefore, formulating such management strategies is crucial for alleviating work alienation among CNPs and will help improve nurse retention rates and the quality of clinical education.
Investigation into EHR data coverage in the All of Us Research Program via linkage to health insurance claims
In 2020, the All of Us (AoU) Research Program Data Completeness Task Force identified several challenges in the state of program health data, including the high likelihood that Electronic Health Record (EHR) data from recruitment institutions is missing a significant portion of care received by participants. To improve data availability, the AoU Data Completeness Task Force recommended efforts to work with industry partners to better understand the degree of missingness within AoU EHR data, with an initial focus on claims data. In this study we describe efforts from AoU’s collaboration with Swoop, a commercial analytics company holding health insurance claims data for over 80% of Americans, to assess the degree to which health insurance claims data can fill out the complete picture of care received by AoU participants. Using record linkage to link between individual participant AoU EHR data and their respective insurance claims, we quantitatively assess the amount of missing health data in both Swoop claims data and AoU EHR data over a decade long sample, identifying trends in data missingness based on participant characteristics. Our analysis demonstrates that AoU would greatly benefit from ingestion of claims data, gaining an estimated 16 million (90 per person) unique diagnosis codes, 17.8 million (99 per person) unique procedure codes, and 9.4 million (53 per person) unique drug codes through linkage to claims data.
Author Correction: SOX2 drives esophageal squamous carcinoma by reprogramming lipid metabolism and histone acetylation landscape
Synergistic therapeutic impact of dichloroacetate nanoparticles and doxorubicin in modulating pyruvate dehydrogenase kinase in breast carcinoma model
Abstract Breast cancer is treated with chemotherapies causing severe organ side effects. Increased pyruvate dehydrogenase kinase (PDK) enzymes in cancer cell metabolism lead to tumor resistance. This study examined dichloroacetate nanoparticles (DCA-PNPs)/doxorubicin (Dox) impact on PDK enzymes in Ehrlich ascites carcinoma (EAC) cells. DCA-PNPs were synthesized using poly D, L-lactic-co-glycolide, polyvinyl alcohol, and characterized by encapsulation efficiency, drug-loading capacity, spectroscopy, and microscopy. Molecular docking and ADMET analysis were conducted. Seventy female CD1 mice were divided into 10 groups (n = 7). (Gp1) was normal negative control. Gp2 to Gp4 received DCA (50 mg/kg), DCA-PNPs (50 mg/kg), and Dox (0.2 mg/kg), intraperitoneal (i.p.) injection. Gp5 to Gp10 were inoculated with EAC cells 0.5 × 10 6 /mouse. GP5 were untreated group, served as a positive control (EAC-untreated mice or EAC-bearing mice group). GP6 to GP10 were treated with Dox, DCA, DCA-PNPs, Dox/DCA, and Dox/DCA-PNPs (i.p.). On day 14, tumor profile, molecular analysis, and hepatorenal alterations were assessed. Results showed DCA-PNPs size was 22.5 ± 1.72 nm, and (ζ) was − 9.5 mV. Dox exhibited strongest binding affinity across PDKs (− 7.7 to − 8.3 kcal/mol), while DCA showed modest affinities (− 3.7 to − 4.0 kcal/mol). Dox/DCA-PNPs treatment decreased tumor profile and hepatorenal alterations with PDKs gene suppression, increased cancer cell apoptosis and cycle arrest at G0/G1 phase (76.1 and 64.8%). Dox/DCA-PNPs demonstrated anti-tumor activity via inhibiting PDK enzyme.
A study on the refined population spatialization method integrating multi-source data: A case study of Yuxi city
The precise assessment of earthquake disasters requires high accuracy in population spatialization data. With the rapid development of technologies such as remote sensing and social sensing (social perception), and the growing availability of large-scale geographic data, high-resolution remote sensing data and vast geographical spatial data provide new opportunities for inferring more accurate population data. This paper proposes a method that integrates social perception big data, building attribute data, and multi-source remote sensing data. Using Random Forest, XGBoost, LGBM, Gradient Boosting, AdaBoost, and CatBoost models as base learners, and RidgeCV regression as the secondary learner, a higher-performing Stacking ensemble learning prediction model is constructed. The method system is employed to spatialize the population data of Yuxi City for the year 2020 at a 50m resolution using the Partition Density Mapping technique. The results show that: (1) The population estimation model proposed in this paper outperforms the WorldPop dataset and LandScan dataset by more than 40% in terms of accuracy at the administrative village scale, providing higher simulation accuracy for regions with different population densities. This result highlights the refined spatial features of the population depicted in satellite remote sensing images, offering richer and more realistic population distribution information. (2) By measuring the SHAP feature contributions and importance of the variables, it is found that residential building area, POI, and nighttime light intensity are the most significant indicators of population distribution in Yuxi City, suggesting a higher correlation of social factors in population spatial redistribution.
Structural basis of CSN-mediated SCF deneddylation
Abstract Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated deneddylation not only deactivates CRLs but also enables substrate receptor exchange. Although CSN is a promising drug target, the structural basis underlying its catalytic mechanism remains unclear. Here, we use cryo-electron microscopy (cryo-EM) to uncover distinct functional states of CSN-CRL (SCF) complexes, capturing key intermediates of the deneddylation cycle. We visualise an autoinhibited docking state and a catalytic intermediate in which CSN5 Ins-1 loop, RBX1 RING and neddylated Cullin WHB domains are repositioned for isopeptide cleavage. We further resolve four dissociation intermediates that define the stepwise release of CSN from its product, with RBX1 RING stabilising key interactions. Additionally, our structures locate CSNAP within a CSN3-CSN8 groove. Together, our study provides a mechanistic model for CSN function and informs the rational design of CSN-targeted therapeutics.
Development of a paediatric model of diffuse traumatic brain injury in ferrets
Abstract Traumatic brain injury (TBI) is a leading cause of death and disability in children, especially those under five, with younger children more vulnerable to persistent cognitive and neuropsychological effects due to disrupted brain development. Paediatric brains are biomechanically more susceptible to diffuse axonal injury due to anatomical differences, with axonal injury observed in up to 80% of hospitalized children. Despite this, many preclinical TBI models focus on focal injuries, whereas to better model the evolution of axonal injury in the paediatric brain, clinically-relevant diffuse pre-clinical models are required. In this study gyrencephalic paediatric ferrets (2–3 months) equivalent to a 3–5-year-old child were injured with the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA), and the axonal injury response and resultant motor and cognitive deficits examined to 72 h post-injury. Injury was associated with extensive axonal injury, as detected via both the amyloid precursor protein (APP) for transport disruption and neurofilament light (NFL) for neurofilament integrity, in key structures including the corpus callosum, fornix and cortical white matter. Serum GFAP was increased within 30 min of injury, returning to baseline by 72 h, with NFL elevated from 24 h to 72 h post-injury. Injured ferrets had deficits in balance, working memory and spatial memory. The adaptation of the CHIMERA model to paediatric ferrets provides the opportunity to investigate factors driving axonal pathology post-injury and how these interact with neurodevelopment.
Correction: Personalized versus fixed tactile cueing in Parkinson’s disease: Protocol for a randomized controlled trial on gait automaticity
Self-oscillating synchronematic colloids
Construction of multi-state chaotic systems and applications to image encryption
Correction: The relationship between screen time, screen content for children aged 1–3, and the risk of ADHD in preschools
Structural basis of co-translational N-myristoylation in humans
Abstract Modifications of proteins occurring during translation are critical for protein localization, stability and function. N-myristoylation is an essential N-terminal lipid modification catalyzed co-translationally by N-myristoyltransferases (NMTs) which have been identified as promising drug targets. However, its molecular basis in the context of the translating ribosome is not known. Here, we reveal the structural basis for co-translational N-myristoylation by NMT1 on the human ribosome by cryo-electron microscopy (cryo-EM). We show that NMT1 binds near the peptide tunnel exit and interacts with the nascent polypeptide-associated complex (NAC). Unlike other multi-enzyme complexes that act simultaneously, we find that methionine excision by methionine aminopeptidases and N-myristoylation occur sequentially via consecutive binding to the ribosome. Furthermore, our data suggest that NMT1 remains associated with elongating nascent chains, indicating a co-translational chaperone-like function in partnership with NAC. These insights provide a molecular foundation for the understanding of the co-translational N-myristoylation mechanism in humans.
Lactobacillus plantarum and Lactobacillus acidophilus enhance growth performance, immunity, cecal microbiota, and vital organs histomorphology in rabbits
Abstract This study aimed to examine how adding two levels of probiotics, Lactobacillus plantarum and Lactobacillus acidophilus , to the growing V-line rabbits’ basal diet affects growth performance, carcass parameters, hematology, serum biochemistry, digestibility, cecal microbiota, economic evaluation of the diet, and histological and immunohistochemical features of the intestine, kidneys, liver, and heart. Sixty healthy five-week-old male rabbits were allocated at random to three groups, each with four replicates of five rabbits. The standard basal diet was provided to the three groups, with probiotics added to the second and third groups at 0.25 g/kg and 0.50 g/kg, respectively, for the 56-day experimental period. Probiotic supplementation significantly ( P < 0.05) improved growth parameters and the weights of internal organs, while reducing the percentage of abdominal fat. White blood cell counts and other hematological parameters increased significantly ( P < 0.05). Rabbits supplemented with 0.25 and 0.50 g/kg of probiotics showed significantly ( P < 0.05) higher serum total protein, globulin, albumin, T3, T4, IgM, IgG, IgA and levels, and significantly ( P < 0.05) lower triglycerides, ALT, and AST levels compared with the control one. Probiotic supplementation increased ( P < 0.05) the digestibility of dry matter, organic matter, crude fiber, nitrogen-free extract, crude protein, and ether extract. It positively influenced beneficial cecal microbiota. Histological data showed increased villus length, crypt depth (CD), and epithelial thickness in the intestines. The kidney’s renal corpuscle and glomeruli diameter, along with CMFs diameter, increased. Liver PAS staining showed a dose-dependent increase. TNF-α expression rose significantly in both the small and large intestines, while synaptophysin increased in the large intestine (LI). Therefore, adding probiotics to the rabbit diet could improve performance, hematology, serum biochemistry, nutrient digestibility, cecal microbiota, and the economic evaluation of the diet, as well as the histological features of the intestine, kidneys, liver, and heart.
The hidden/ hard to reach men who have sex with men (MSM)—Results from the qualitative study in India
Background To ensure a substantial impact and prevent the resurgence of the epidemic, the HIV programmes should effectively reach hidden key populations (KPs). A qualitative study was conducted to understand hidden men who have sex with men (MSM), and their needs and identify outreach strategies for those who were still unreached. Methods Between 17 March 2019 and 26 July 2019, 42 In-depth Interviews (IDIs), 40 Key Informant Interviews (KIIs), and 16 Focus Group Discussions (FGDs) were conducted covering 170 participants across four states of India. Data were audio recorded, transcribed, translated and analyzed using NVivo software employing a grounded theory approach. Results A diverse spectrum of unreached men were reportedly practicing same-sex behaviors and new hidden MSM categories have been identified. These hidden MSM demonstrated denial, lack of awareness, and a history of forced sexual experiences. Being elusive, hence no access to healthcare services and education resulted in condom-less sex. The very young adolescent MSM were unaware of the risks and perceived risky practices as the norm. Both at urban and rural settings, MSM respondents shared about sexual abuse by a male while studying in 2 nd standard to 6 th standard. The ‘sugar daddies/ older MSM’ who were >50 years old get disengage from the programme, preferentially practice high-risk behaviors, abusing young boys and men who fall prey for money or easy fun. Peers were the most acceptable persons to reach ‘hidden’ MSM. Conclusion A peer-driven approach based on the inbuilt trust of the community and leveraging networks might be a vital outreach strategy to engage this elusive, vulnerable hidden MSM. The vulnerability of young boys and men calls for an urgent need for fostering safer environment for minor male children in the context of this study and strong integration of POCSO Act in the programme. Additionally, there is an urgent need to revisit strategies for engaging middle-aged MSM, the ‘sugar daddies’ or ‘uncles’ in preventing spread of HIV. Policymakers and educational institutions may prioritize comprehensive sex and sexuality education to challenge and transform prevailing social norms affecting young boys in India. It is important for parents and carers to be alert about how these abuse happen, and how to help prevent it.