Machine learning for the prediction of delirium in elderly intensive care unit patients.

PURPOSE: This study aims to develop and validate a prediction model for delirium in elderly ICU patients and help clinicians identify high-risk patients at the early stage. METHODS: Patients admitted to ICU for at least 24 h and using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (76,943 ICU stays from 2008 to 2019) were considered. Patients with a positive delirium test in the first 24 h and under 65 years of age were excluded. Two prediction models, machine learning extreme gradient boosting (XGBoost) and logistic regression (LR) model, were developed and validated to predict the onset of delirium. RESULTS: Of the 18,760 patients included in the analysis, 3463(18.5%) were delirium positive. A total of 22 significant predictors were selected by LASSO regression. The XGBoost model demonstrated superior performance over the LR model, with the Area Under the Receiver Operating Characteristic (AUC) values of 0.853 (95% confidence interval [CI] 0.846-0.861) and 0.831 (95% CI 0.815-0.847) in the training and testing datasets, respectively. Moreover, the XGBoost model outperformed the LR model in both calibration and clinical utility. The top five predictors associated with the onset of delirium were sequential organ failure assessment (SOFA), infection, minimum platelets, maximum systolic blood pressure (SBP), and maximum temperature. CONCLUSION: The XGBoost model demonstrated good predictive performance for delirium among elderly ICU patients, thus assisting clinicians in identifying high-risk patients at the early stage and implementing targeted interventions to improve outcome.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy.

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

A comprehensive study on carbon emissions flows and key drivers within China's domestic and global value chains.

Numerous studies have examined the transfer of carbon emissions in China's trade. However, few papers have established a link between China's domestic value chains (DVCs) and the global value chains (GVCs) to comprehensively trace the flows of carbon emissions within a unified framework. To address this research gap, our paper aims to connect China's DVCs with the GVCs and map the carbon emissions flows of China's eight regions in both domestic and international trade. Using structural decomposition analysis (SDA), it studies the driving factors behind change in carbon emissions transfer (CET). Our findings are as follows: Firstly, in 2018, the total carbon emissions transfer of China's eight regions amounted to 5122.0mt, a significant increase of 31.1 % compared to 2012. Notably, the carbon emissions transfer through intermediate product trade is more than four times that of the final product trade. Secondly, significant variations exist in the sources and destinations under different trade patterns, which have been largely overlooked in the existing literature. Over 70.0 % of carbon emissions resulting from final product trade are directed towards regions outside of Chinese mainland, while approximately two-thirds of carbon emissions resulting from intermediate product trade are allocated to Chinese mainland's internal regions. Thirdly, the reduction of carbon emissions transfer increment is primarily driven by the carbon intensity, while the indirect demand scale effect of Chinese mainland's internal regions emerges as the most significant driving factor, playing a substantial role in the increase of carbon emissions transfer. Additionally, the unreasonable input-output structure between regions within Chinese mainland has contributed to the rise in carbon emissions transfer. The research findings offer valuable insights and policy recommendations for the formulation of regional carbon reduction policies in China.

The protective mechanism of SIRT3 and potential therapy in acute kidney injury.

Acute kidney injury (AKI) is a complex clinical syndrome with a poor short-term prognosis, which increases the risk of the development of chronic kidney diseases and end-stage kidney disease. However, the underlying mechanism of AKI remains to be fully elucidated, and effective prevention and therapeutic strategies are still lacking. Given the enormous energy requirements for filtration and absorption, the kidneys are rich in mitochondria, which are unsurprisingly involved in the onset or progression of AKI. Accumulating evidence has recently documented that Sirtuin 3 (SIRT3), one of the most prominent deacetylases highly expressed in the mitochondria, exerts a protective effect on AKI. SIRT3 protects against AKI by regulating energy metabolism, inhibiting oxidative stress, suppressing inflammation, ameliorating apoptosis, inhibiting early-stage fibrosis and maintaining mitochondrial homeostasis. Besides, a number of SIRT3 activators have exhibited renoprotective properties both in animal models and in vitro experiments, but have not yet been applied to clinical practice, indicating a promising therapeutic approach. In this review, we unravel and summarize the recent advances in SIRT3 research and the potential therapy of SIRT3 activators in AKI.

Alterations of the gut microbiota in the lupus nephritis: a systematic review.

BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.

Copper/TEMPO-Promoted Denitrogenation/Oxidation Reaction for Synthesis of Primary α-Ketoamides Using α-Azido Ketones.

A copper(II)-promoted denitrogenation/oxidation reaction for the preparation of primary α-ketoamides was developed using α-azido ketones as a substrate and TEMPO as an oxidant. α-Azido ketones were denitrogenated in situ to form an imino ketone intermediate, which underwent a radical addition process and radical migration to form α-ketoamides. It is worth noting that the imino ketone intermediate is the key to this reaction.

Rh(III)-Catalyzed Tandem Reaction Access to (Quinazolin-2-yl)methanone Derivatives from 2,1-Benzisoxazoles and α-Azido Ketones.

A Rh(III)-catalyzed tandem reaction for the synthesis of (quinazolin-2-yl)methanone derivatives has been explored from 2,1-benzisoxazoles and α-azido ketones. The transformation involves Rh(III)-catalyzed denitrogenation of α-azido ketones, aza-[4 + 2] cycloaddition, ring opening, and dehydration aromatization processes. Notably, the aza-[4 + 2] cycloaddition of an imine rhodium complex intermediate with 2,1-benzisoxazoles is the key to this reaction.

Tentacle-type poly(hydroxamic acid)-modified macroporous cellulose beads: Synthesis, characterization, and application for heavy metal ions adsorption.

Herein, a facile yet efficient template method to fabricate macroporous cellulose beads (MCBs) is reported. In this method, micro-size CaCO3 is utilized to create macroporous structure for fast mass transfer, and tentacle-type poly(hydroxamic acid) as adsorption ligand is immobilized on the MCBs to improve adsorption capacity. The obtained tentacle-type poly(hydroxamic acid)-modified MCMs (TP-CMCBs) show uniform spherical shape (about 80 µm), bimodal pore system (macropores≈3.0 µm; diffusional pores≈14.5 nm), and high specific surface area (52.7 m2/g). The adsorption performance of TP-CMCBs is evaluated by heavy metal ions adsorption. TP-CMCBs exhibit not only high adsorption capacities (342.5, 261.5 and 243.2 mg/g for Cu2+, Mn2+ and Ni2+, respectively.), but also fast adsorption rate (>70% of its equilibrium uptake within 30 min). Additionally, TP-CMCBs have excellent reusability, as evidenced by that the adsorption capacities have no obvious change even after five-time consecutive adsorption-desorption cycles. All results demonstrate that the proposed TP-CMCBs have great potential in removal of heavy metal ions.

The impact of awareness diffusion on the spread of COVID-19 based on a two-layer SEIR/V-UA epidemic model.

In this paper, we propose a new susceptible-vaccinated-exposed-infected-recovered with unaware-aware (SEIR/V-UA) model to study the mutual effect between the epidemic spreading and information diffusion. We investigate the dynamic processes of the model with a Kinetic equation and derive the expression for epidemic stability by the eigenvalues of the Jacobian matrix. Then, we validate the model by the Monte Carlo method and numerical simulation on a two-layer scale-free network. With the outbreak of COVID-19, the spread of the epidemic in China prompted drastic measures for transmission containment. We examine the effects of these interventions based on modeling of the information-epidemic and the data of the COVID-19 epidemic case. The results further demonstrate that the epidemic spread can be affected by the effective transmission rate of awareness.

Metal-Free Cascade [4 + 1] Cyclization Access to 4-Aryl-NH-1,2,3-triazoles from N-Tosylhydrazones and Sodium Azide.

A molecular iodine-mediated coupling cyclization reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles has been developed from N-tosylhydrazones and sodium azide. This metal-free cascade [4 + 1] cyclization reaction could rapidly synthesize valuable compounds via a sequential C-N and N-N bond formation. Mechanistic studies demostrate that the nitrogen atoms of the 1,2,3-triazoles are not entirely from sodium azide.

[TGF-beta1 in allograft and long-term renal function].

OBJECTIVE: To determine the relation between transforming growth factor beta1 (TGF-beta1) in allograft and long-term renal function. METHODS: Urine TGF-beta1 relative concentration (divided by urine creatinine) was tested in 168 recipients whose renal function was normal between August 1, 2000 and March 31, 2001. Twenty patients with higher urine TGF-beta1 relative concentrations formed Group A, and another 20 patients with lower urine TGF-beta1 formed Group B. In both groups biopsies were carried out in 15 cases and 12 cases respectively, and TGF-beta1 in the biopsis was tested by immunofluorescence. Blood TGF-beta1 concentrations in the 2 groups were also tested. Three years later, the renal function was compared between the 2 groups. Biopsies were carried out in renal recipients whose creatinine was higher than that of the normal. RESULTS: Blood TGF-beta1 concentrations in the 2 groups were not different significantly; 3 years after the transplantation, there was more loss of renal function and more chronic allograft nephropathy (CAN) cases in Group A than in Group B. Expression of TGF-beta1 in the allografts was higher in Group A than in Group B. The differences in the 2 groups were significant. CONCLUSION: The findings suggest that the higher expression of TGF-beta1 in the allografts is associated with the lower long-term survival rate of kidney graft. The level of urine TGF-beta1 after the renal transplantation can predict the long-term renal function.