Development and validation of novel interpretable survival prediction models based on drug exposures for severe heart failure during vulnerable period.

BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.

Short-term usage of proton pump inhibitors during admission was associated with increased risk of rehospitalization in critically ill patients with myocardial infarction: a cohort study.

PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.

Polyamide 6 microplastics as carriers led to changes in the fate of bisphenol A and dibutyl phthalate in drinking water distribution systems: The role of adsorption and interfacial partitioning.

Microplastics (MPs) co-exist with plastic additives and other emerging pollutants in the drinking water distribution systems (DWDSs). Due to their strong adsorption capacity, MPs may influence the occurrence of additives in DWDSs. The article investigated the occurrence of typical additives bisphenol A (BPA) and dibutyl phthalate (DBP) in DWDSs under the influence of polyamide 6 (PA6) MPs and further discussed the partitioning of BPA/DBP on PA6s, filling a research gap regarding the impact of adsorption between contaminants on their occurrence within DWDSs. In this study, adsorption experiments of BPA/DBP with PA6s and pipe scales were conducted and their interaction mechanisms were investigated. Competitive adsorption experiments of BPA/DBP were also carried out with site energy distribution theory (SEDT) calculations. The results demonstrated that PA6s might contribute to the accumulation of BPA/DBP on pipe scales. The adsorption efficiencies of BPA/DBP with both PA6s and pipe scales were 26.47 and 2.61 times higher than those with only pipe scales. It was noteworthy that BPA had a synergistic effect on the adsorption of DBP on PA6s, resulting in a 26.47 % increase in DBP adsorption. The article provides valuable insights for the compounding effect of different types of additives in water quality monitoring and evaluation.

Experiment-free exoskeleton assistance via learning in simulation.

Exoskeletons have enormous potential to improve human locomotive performance1-3. However, their development and broad dissemination are limited by the requirement for lengthy human tests and handcrafted control laws2. Here we show an experiment-free method to learn a versatile control policy in simulation. Our learning-in-simulation framework leverages dynamics-aware musculoskeletal and exoskeleton models and data-driven reinforcement learning to bridge the gap between simulation and reality without human experiments. The learned controller is deployed on a custom hip exoskeleton that automatically generates assistance across different activities with reduced metabolic rates by 24.3%, 13.1% and 15.4% for walking, running and stair climbing, respectively. Our framework may offer a generalizable and scalable strategy for the rapid development and widespread adoption of a variety of assistive robots for both able-bodied and mobility-impaired individuals.

Development and implementation of a high-fidelity simulation training course for medical and nursing collaboration based on the Fink integrated course design model.

Aim: The purpose of this study is to examine the design and implementation of a high-fidelity simulation training course for medical and nursing collaboration, based on the Fink integrated course design model. Additionally, the study aims to validate the teaching effectiveness of the course. Background: Previous empirical studies have highlighted the effectiveness of collaborative healthcare education in institutional teaching and hospital training. However, the development of healthcare collaborative education in China has been slow to develop in China. In recent years, Chinese nursing educators and researchers have shown interest in utilizing high-fidelity simulators for healthcare collaborative education. These simulators help address the limitations of traditional nursing teaching and healthcare separation simulation. Nevertheless, a standardized simulation interprofessional education curriculum is still lacking. Therefore, nursing educators need to develop a standardized high-fidelity simulation training curriculum for healthcare collaboration, guided by established science curriculum development theories. Methods: A high-fidelity simulation training course on healthcare collaboration was designed based on the Fink integrated curriculum design model. The course was taught to 14 nursing students and 8 clinical medicine students from March to July 2022. To comprehensively evaluate the effectiveness of the healthcare collaboration high-fidelity simulation training course, several assessment tools were used. These included course grades, satisfaction and self-confidence scales, simulation teaching practice scales, healthcare collaboration attitude scales, critical thinking skills scales, and semi-structured interviews. Results: After the course was implemented, students demonstrated high overall scores (79.19 ± 5.12) and reported high satisfaction ratings (4.44 ± 0.37). They also exhibited increased self-confidence (4.16 ± 0.33). Additionally, students evaluated all four dimensions of the course teaching practice scale positively. Furthermore, the study demonstrated significant improvements in various aspects, such as attitudes toward medical and nursing collaboration (t = -7.135, P < 0.01), shared education and teamwork (t = -3.247, P = 0.002), job autonomy for nurses (t = -1.782, P = 0.000), and reduced physician dominance (t = -6.768, P = 0.000). The critical thinking skills of the students showed significant improvement, with higher scores in truth-seeking (t = -3.052, P = 0.004), analytical ability (t = -2.561, P = 0.014), systematic ability (t = -3.491, P = 0.001), self-confidence in critical thinking (t = -4.024, P = 0.000), and curiosity (t = -5.318, P = 0.000) compared to their scores before the course (all P < 0.05). The interviews showed that the course's student-centered approach enabled active learning. Students suggested enhancing teaching cases and allocating more time for reflection and summarization. Conclusion: The study successfully designed a high-fidelity simulation training course for healthcare collaboration by utilizing the Fink integrated curriculum design model. The findings provide valuable insights for the development of standardized curricula and healthcare collaboration education in China. Moreover, the course adheres to best practice principles, fostering improved attitudes toward healthcare collaboration and enhancing students' healthcare collaboration and clinical thinking skills.

The effect of polyvinyl chloride (PVC) color on biofilm development and biofilm-heavy metal chemodynamics in the aquatic environment.

Plastic surfaces are colonized by microorganisms and biofilms are formed in the natural aquatic environment. As the biofilm develops, it changes the density and buoyancy of the plastic-biofilm complex, results in plastic sinking, and increases the heavy metals accumulated by biofilm's mobility and availability in aquatic ecosystems. In this experiment, biofilms were cultured on five colors of polyvinyl chloride (PVC; transparent, green, blue, red, black) in an aquatic environment to investigate the effects of plastic color on biofilm formation and development (Phase 1) and to study the effects of being sunk below the photic zone on biofilm (Phase 2). The PVC color significantly affected the biofilm formation rate but had no impact on the final biofilm biomass. After sinking the biofilm-PVC below the photic zone in Phase 2, the layer of diatoms on the biofilm surface began to disintegrate, and the biomass and Chlorophyll-a (Chla) content of the biofilm decreased, except on the red PVC. Below the photic zone, the microbial community of the biofilm changed from primarily autotrophic microbes to mostly heterotrophic microbes. Microbial diversity increased and extracellular polymeric substances (EPS) content decreased. The primary factor leading to microbial diversity and community structure changes was water depth rather than PVC color. The changes induced in the biofilm led to an increase in the concentration of all heavy metals in the biofilm, related to the increase in microbial diversity. This study provides new insights into the biofilm formation process and the effects on a biofilm when it sinks below the photic zone.

Artemisinin Alleviates Cerebral Ischemia/Reperfusion-Induced Oxidative Damage via Regulating PHB2-Mediated Autophagy in the Human Neuroblastoma SH-SY5Y Cell Line.

Oxidative stress plays a key role in cerebral ischemia/reperfusion injury. Artemisinin (ART) has antioxidative stress activity in addition to its powerful antimalarial effects. In this article, we investigated the effect of ART on OGD/R-induced oxidative stress injury and its underlying mechanisms. We used oxygen-glucose deprivation/reoxygenation (OGD/R) to establish an in vitro model of cerebral ischemia/reperfusion (I/R) injury. CCK-8 and lactate dehydrogenase (LDH) release were used to assess cellular damage. Measurement of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and mitochondrial membrane potential (MMP) estimates oxidative stress-induced damage and protection from ART effect. OGD/R treatment aggravated oxidative stress damage, whereas ART reversed the effects of OGD/R. Autophagy is closely related to oxidative stress; in order to confirm whether the antioxidative stress effect of ART is related to PHB2-mediated autophagy, we examined the protein expression of prohibitin 2 (PHB2), TOMM20, p62, and the conversion of microtubule-associated protein light chain 3I (LC3I) to LC3II and found that the protein expression of PHB2, TOMM20, p62, and LC3II/LC3I was significantly correlated with OGD/R treatment. The colocalization of PHB2 and LC3, TOMM20, and LC3 was reduced after OGD/R treatment, and ART reversed this change. After silencing PHB2, the protective effect of ART against OGD/R-induced oxidative stress injury was reduced, the protein expressions of PHB2, TOMM20 and LC3II/LC3I and the colocalization of PHB2 and LC3, TOMM20, and LC3 were decreased. We used chloroquine to block the lysosomal pathway and found that ART increased the conversion of LC3I to LC3II, silencing PHB2 which inhibited the conversion of LC3I to LC3II, and impaired mitophagy. Our findings showed that ART attenuated OGD/R-induced oxidative stress damage through PHB2-mediated mitophagy. To the current knowledge, our study is the first to demonstrate that ART attenuates OGD/R-induced oxidative stress injury through PHB2-mediated autophagy in the human neuroblastoma SH-SY5Y cell line, which provided new insights into the treatment of OGD/R injury.

Nonreceptor Tyrosine Kinase c-Abl-Mediated PHB2 Phosphorylation Aggravates Mitophagy Disorder in Parkinson's Disease Model.

Mitophagy and oxidative stress play important roles in Parkinson's disease (PD). Dysregulated mitophagy exacerbates mitochondrial oxidative damage; however, the regulatory mechanism of mitophagy is unclear. Here, we provide a potential mechanistic link between c-Abl, a nonreceptor tyrosine kinase, and mitophagy in PD progression. We found that c-Abl activation reduces the interaction of prohibitin 2 (PHB2) and microtubule-associated protein 1 light chain 3 (LC3) and decreases the expressive level of antioxidative stress proteins, including nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), and the antioxidant enzyme heme oxygenase-1 (HO-1) in 1-methyl-4-phenylpyridinium- (MPP+-) lesioned SH-SY5Y cells. Importantly, we found that MPP+ can increase the expression of phosphorylated proteins at the tyrosine site of PHB2 and the interaction of c-Abl with PHB2. We showed for the first time that PHB2 by changing tyrosine (Y) to aspartate (D) at site 121 resulted in impaired binding of PHB2 and LC3 in vitro. Moreover, silencing of PHB2 can decrease the interaction of PHB2 and LC3 and exacerbate the loss of dopaminergic neurons. We also found that STI 571, a c-Abl family kinase inhibitor, can decrease dopaminergic neuron damage and ameliorate MPTP-induced behavioral deficits in PD mice. Taken together, our findings highlight a novel molecular mechanism for aberrant PHB2 phosphorylation as an inhibitor of c-Abl activity and suggest that c-Abl and PHB2 are potential therapeutic targets for the treatment of individuals with PD. However, these results need to be further validated in PHB2 Y121D mice.

Melatonin Treatment for Sleep Disorders in Parkinson's Disease: A Meta-Analysis and Systematic Review.

OBJECTIVE: The efficacy of melatonin on sleep disorders in Parkinson's disease (PD) is still unclear. The purpose of this study was to investigate the efficacy of melatonin on sleep disorders in PD by summarizing evidence from randomized clinical trials (RCTs). METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched for studies published before 20 August 2021. Results were analyzed using Review Manager 5.2 software. We used Trial Sequential Analysis (TSA) software to avoid false-positive results caused by random errors. RESULTS: We included 7 studies in this systematic review and meta-analysis. The results of the meta-analysis showed that compared with placebo, the subjective sleep quality of patients with PD significantly improved after melatonin treatment (MD = -2.19, 95% CI: -3.53 to -0.86, P = 0.001). In the systematic review, we qualitatively analyzed the efficacy of melatonin on the objective sleep quality of patients with PD, and the results showed that melatonin exerted a positive effect with good safety and tolerability. However, there was no significant improvement in excessive daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS). CONCLUSION: We found that melatonin can significantly improve the subjective and objective sleep quality of patients with PD with good safety and tolerability. Melatonin could be considered an effective treatment for insomnia in patients with PD.

Idebenone improves motor dysfunction, learning and memory by regulating mitophagy in MPTP-treated mice.

The progression of Parkinson's disease (PD) is often accompanied by the loss of substantia nigra dopaminergic neurons, mitophagy damage, learning, and memory impairment. Idebenone is a therapeutic drug that targets the mitochondria of neurodegenerative diseases, but its role in Parkinson's disease and its pathological mechanism are still unclear. The purpose of this study was to investigate whether idebenone could improve behavioral disorders, especially motor, learning, and memory disorders, in mouse PD models and to explore its molecular mechanism. In the present study, C57BL-6 mice underwent intraperitoneal injection of MPTP (30 mg/kg) once a day for five consecutive days. Then, a 200 mg/kg dose was given as a single daily gavage of idebenone dissolved in water for 21 days after the successful establishment of the subacute MPTP model. Motor, learning, and memory were measured by a water maze and a rotarod test. Our results showed that idebenone could reduce MPTP-induced dopaminergic neuron damage and improve movement disorders, memory, and learning ability, which may be associated with upregulating mitochondrial autophagy-related outer membrane proteins VDAC1 and BNIP3 and activating the Parkin/PINK1 mitochondrial autophagy pathway. To confirm whether idebenone promotes the smooth progression of autophagy, we used eGFP-mCherry-LC3 mice to construct a subacute model of Parkinson's disease and found that idebenone can increase autophagy in dopaminergic neurons in Parkinson's disease. In summary, our results confirm that idebenone can regulate the expression of the mitochondrial outer membrane proteins VDAC1 and BNIP3, activate Parkin/PINK1 mitophagy, promote the degradation of damaged mitochondria, reduce dopaminergic neuron damage, and improve behavioral disorders in Parkinson's disease mice.

Utilizing waste duckweed from phytoremediation to synthesize highly efficient FeNxC catalysts for oxygen reduction reaction electrocatalysis.

Duckweed is a universal aquatic plant to remove nitrogen source pollutants in the field of phytoremediation. Due to the naturally abundant nitrogen, synthesis of carbon materials from duckweed would be a high-value approach. In oxygen reduction reaction (ORR) of metal-air batteries and fuel cells, non-noble metals and heteroatoms co-doped electrocatalysts with excellent catalytic activity and remarkable stability are promising substitutes for Pt-based catalysts. The first-class ORR performance is determined by appropriate pore structure and active sites, which are strongly associated with the feasible synthesis methods. Herein, a facile one-step synthesis strategy for the transition metals- and nitrogen-codoped carbon (MNxC) based catalysts with hierarchically porous structure was developed. The MNxC (M = Fe, Co, Ni, and Mn) active sites were constructed and FeNxC (D-ZB-Fe) was the best electrocatalyst with excellent ORR performance. Results showed that D-ZB-Fe exhibited an obvious honeycomb porous structure with specific surface area of 1342.91 m2·g-1 and total pore volume of 1.085 cm3·g-1. It also possessed considerable active atoms and sites, where the proportion of pyridine N and graphite N was up to 72.9%. The above feature made for a superior ORR electrocatalytic activity. In specific, the onset and half-wave potential were 0.974 V and 0.857 V vs. RHE (Reversible Hydrogen Electrode), respectively. When compared with performances of commercial Pt/C, the four-electron pathway and relatively low peroxide yield, ca. 5%, were almost equivalent. Furthermore, D-ZB-Fe showed an excellent stability and remarkably methanol tolerance by the durability test. In conclusion, this research provides a new synthesis strategy of electrocatalysts with porous structures and active sites.

Neologisms are epidemic: Modeling the life cycle of neologisms in China 2008-2016.

This paper adopts models from epidemiology to account for the development and decline of neologisms based on internet usage. The research design focuses on the issue of whether a host-driven epidemic model is well-suited to explain human behavior regarding neologisms. We extracted the search frequency data from Google Trends that covers the ninety most influential Chinese neologisms from 2008-2016 and found that the majority of them possess a similar rapidly rising-decaying pattern. The epidemic model is utilized to fit the evolution of these internet-based neologisms. The epidemic model not only has good fitting performance to model the pattern of rapid growth, but also is able to predict the peak point in the neologism's life cycle. This result underlines the role of human agents in the life cycle of neologisms and supports the macro-theory that the evolution of human languages mirrors the biological evolution of human beings.

3,3',4,4',5-Pentachlorobiphenyl influences mitochondrial apoptosis pathway in granulosa cells.

3,3',4,4',5-Polychlorinated biphenyl (PCB126) is a persistent organic environmental pollutant which can affect various biological activities of organisms, such as immunity, neurological function, and reproduction. In our study, we aimed to investigate the effects of PCB126 on granulosa cells (GCs). GCs were collected from ovaries in PMSG-treated mice, after 24 hours culture. GCs were then incubated with 10 pg/mL, 100 pg/mL, and 10 ng/mL of PCB126 for another 24 hours. Following these steps, exposed GCs were collected for further experimentation. Our data showed that the number of GCs in the 10 ng/mL PCB126 decreased. Meanwhile, pyknotic nuclei and condensed chromatin increased, while the apoptotic cells in the 10 ng/mL PCB126 group were significantly increased. Furthermore, the expression of the apoptotic executive protein caspase-3 increased after PCB126 treatment. The expression of Bax, Bcl-2, and Bim related to the mitochondrial apoptosis pathway were also influenced to different degrees. Thus, our data suggested that PCB126 affect the GCs apoptosis, and mitochondrial apoptosis pathway was involved in this process.