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BACKGROUND: Short-term exposure to particulate matter air pollution has been associated with the exacerbations of COPD, but its association with COPD mortality was not fully elucidated. We aimed to assess the association between short-term particulate matter exposure and the risk of COPD mortality in China using individual-level data. METHODS: We derived 2.26 million COPD deaths from a national death registry database in Chinese mainland between 2013 and 2019. Exposures to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) were assessed by satellite-based models of a 1 × 1 km resolution and assigned to each individual based on residential address. The associations of PM2.5 and PM2.5-10 with COPD mortality were examined using a time-stratified case-crossover design and conditional logistic regressions with distributed lag models. We further conducted stratified analyses by age, sex, education level, and season. FINDINGS: Short-term exposures to both PM2.5 and PM2.5-10 were associated with increased risks of COPD mortality. These associations appeared and peaked on the concurrent day, attenuated and became nonsignificant after 5 or 7 days, respectively. The exposure-response curves were approximately linear without discernible thresholds. An interquartile range increase in PM2.5 and PM2.5-10 concentrations was associated with 4.23% (95% CI: 3.75%, 4.72%) and 2.67% (95% CI: 2.18%, 3.16%) higher risks of COPD mortality over lag 0-7 d, respectively. The associations of PM2.5 and PM2.5-10 attenuated slightly but were still significant in the mutual-adjustment models. A larger association of PM2.5-10 was observed in the warm season. INTERPRETATION: This individual-level, nationwide, case-crossover study suggests that short-term exposure to PM2.5 and PM2.5-10 might act as one of the environmental risk factors for COPD mortality. FUNDING: This study is supported by the National Key Research and Development Program of China (2023YFC3708304 and 2022YFC3702701), the National Natural Science Foundation of China (82304090 and 82030103), the 3-year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.2-YQ31), and the Science and Technology Commission of Shanghai Municipality (21TQ015).
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This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1ß, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1ß in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.
Subject(s)
Anxiety Disorders , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Proto-Oncogene Proteins c-akt , Animals , Rats , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Male , Anxiety Disorders/drug therapy , Anxiety Disorders/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Rats, Sprague-Dawley , Signal Transduction/drug effects , Interleukin-6/genetics , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Protein Interaction Maps , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , HumansABSTRACT
OBJECTIVE: We aimed to assess the performance of common pneumonia severity scores, such as pneumonia severity index (PSI), CURB-65, CRB-65, A-DROP, and SMART-COP, in predicting adverse outcomes in elderly community-acquired pneumonia cohort and to determine the optimal scoring system for specific outcomes of interest. METHODS: A total of 822 elderly inpatients were included in the retrospective cohort study. Clinical and laboratory results on admission were used to calculate the above scores. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital mortality, need for mechanical ventilation (MV) and ICU admission. Model discrimination was evaluated by the area under receiver operating characteristic curves (AUCs). RESULTS: The 30-day and in-hospital mortality rates were 6.8% (56/822) and 8.6% (71/822), respectively. One hundred and ninety-eight (24.0%) received MV and 111 (13.5%) were admitted to the ICU. All five scoring systems showed the same trend of increasing rates of each adverse outcome with increasing risk groups (all p < 0.001). PSI had the highest AUC, sensitivity, and negative predictive value (NPV) in predicting 30-day mortality and in-hospital mortality. SMART-COP had the highest AUC for predicting the need for MV and ICU admission, but PSI had the highest sensitivity and NPV for these two outcomes. DISCUSSION: PSI performed well in identifying elderly patients at risk for 30-day mortality and its high NPV is helpful in excluding patients who are not at risk. Considering their effectiveness and simplicity, SMART-COP and CURB-65 are easier to perform in clinical practice than PSI.
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Even though lead halide perovskite has been demonstrated as a promising optoelectronic material for next-generation display applications, achieving high-efficiency and stable pure-red (620~635 nm) emission to cover the full visible wavelength is still challenging. Here, we report perovskite light-emitting diodes emitting pure-red light at 628 nm achieving high external quantum efficiencies of 26.04%. The performance is attributed to successful synthesizing strongly confined CsPbI3 quantum dots with good stability. The strong binding 2-naphthalene sulfonic acid ligands are introduced after nucleation to suppress Ostwald ripening, meanwhile, ammonium hexafluorophosphate exchanges long chain ligands and avoids regrowth by strong binding during the purification process. Both ligands enhance the charge transport ability of CsPbI3 quantum dots. The state-of-the-art synthesis of pure red CsPbI3 quantum dots achieves 94% high quantum efficiency, which can maintain over 80% after 50 days, providing a method for synthesizing stable strong confined perovskite quantum dots.
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Chronic obstructive pulmonary disease (COPD) has been associated with alterations in the brain cortical structure. Nonetheless, the causality between COPD and brain cortical structure has not been determined. In the present study, we used Mendelian randomization (MR) analysis to explore the causal effects of genetic predicated COPD on brain cortical structure, namely cortical surface area (SA) and cortical thickness (TH). Genetic association summary data for COPD were obtained from the FinnGen consortium (N = 358,369; Ncase = 20,066). PRISm summary genetic data were retrieved from a case-control GWAS conducted in the UK Biobank (N = 296,282). Lung function indices, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were extracted from a meta-analysis of the UK Biobank and SpiroMeta consortium (N = 400,102). Brain cortical structure data were obtained from the ENIGMA consortium (N = 51,665). Inverse-variance weighted (IVW) method was used as the primary analysis, and a series of sensitivity tests were exploited to evaluate the heterogeneity and pleiotropy of our results. The results identified potential causal effects of COPD on several brain cortical specifications, including pars orbitalis, cuneus and inferior parietal gyrus. Furthermore, genetic predicated lung function index (FEV1, FVC and FEV1/FVC), as well as PRISm, also has causal effects on brain cortical structure. According to our results, a total of 15 functional specifications were influenced by lung function index and PRISm. These findings contribute to understanding the causal effects of COPD and lung function to brain cortical structure.
Subject(s)
Mendelian Randomization Analysis , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/physiopathology , Forced Expiratory Volume , Vital Capacity , Genome-Wide Association Study , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiopathology , Cerebral Cortex/pathology , Male , Polymorphism, Single Nucleotide , Case-Control Studies , Lung/physiopathologyABSTRACT
RATIONALE: The phenomenon of hypercoagulability has not been previously documented in individuals with Morvan's syndrome, especially in those associated with contactin-associated protein-like receptor 2 (CASPR2). PATIENT CONCERNS: A previously healthy 32-year-old Chinese male was admitted to the hospital with central and peripheral neurologic symptoms. The patient was tested positive for anti-CASPR2 antibodies, and also presented with an activated coagulation state on admission, characterized by a low activated partial thromboplastin time and a high platelet count. With gradual improvement of clinical symptoms, activated partial thromboplastin time, and platelet count returned to normal. Simultaneously, anti-CASPR2 antibody titers significantly decreased and eventually became undetectable. DIAGNOSES: The patient was diagnosed as Morvan's syndrome with positive anti-CASPAR2 antibodies accompanied with hypercoagulable state. INTERVENTIONS: Plasmapheresis was administered to improve the symptoms combined with prednisolone acetate therapy. OUTCOMES: The patient experienced complete resolution of all symptoms during hospitalization and generally recovery after 2 months of discharge. LESSONS: Emphasis should be directed towards hypercoagulability in individuals diagnosed with Morvan's syndrome, particularly those presenting with positive anti-CASPR2 antibodies. Anticoagulant therapy may represent a novel therapeutic approach for individuals afflicted with Morvan's syndrome and exhibiting positivity for anti-CASPR2 antibodies.
Subject(s)
Autoantibodies , Membrane Proteins , Nerve Tissue Proteins , Thrombophilia , Humans , Male , Adult , Thrombophilia/immunology , Thrombophilia/drug therapy , Autoantibodies/blood , Autoantibodies/immunology , Membrane Proteins/immunology , Nerve Tissue Proteins/immunology , PlasmapheresisABSTRACT
Purpose: Determine if there is a difference in adverse events (AE) between right or left hepatic percutaneous biliary drain placement (PTBD) in patients with biliary strictures. Materials & methods: This retrospective study included patients with benign or malignant biliary stricture treated with PTBD at a single institution from 7/28/2004-3/30/2021. 357 patients met inclusion criteria, 77 (21.6 %) had PTBD on the left and 280 (78.4 %) on the right. AEs associated with the initial drain placement or during subsequent intervention were collected and categorized. AEs that were grouped as periprocedural included: surgery, infection, hemorrhage, and drain failure. AEs in the postprocedural group included: chills, catheter displacement, cholangitis, biliary stones, drain malfunction, fever resolving without treatment, and pericatheter leakage. Surgery was considered a major AE and the remaining AEs were categorized as minor. Statistical analyses were performed using Logistic Regression Analysis and p-values less than 0.05 were considered statistically significant. Results: Overall, there was no statistically significant difference in AEs between right and left drains in the periprocedural and postprocedural period (p = 0.832, OR = 0.95 and p = 0.808, OR = 0.93 respectively). When analyzing minor AEs individually, only cholangitis occurred at a higher rate on the right side (p = 0.033, OR = 0.43). There was no statistical difference in the rate of major AEs in the periprocedural period between left and right drains (p = 0.311, OR = 1.37). Conclusion: Current literature is equivocal when comparing right versus left percutaneous biliary drains. This analysis describes no statistically significant difference in AEs between right and left hepatobiliary drains aside from slightly higher incidence of cholangitis for right sided drains.
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Background: Targeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC. Methods: Three mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs. Results: The analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time-response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects. Conclusion: This study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.
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HYPOTHESIS: In the interfacial wetting boundary, the superhydrophobic surface is often damaged, and the anisotropic wettability of its surface has attracted many researchers' attention. The "petal effect" surface has typical anisotropic wettability. We predict that under the dual conditions of structural defects and high impact velocity, the "petal effect" becomes more adhesive on the surface. EXPERIMENTS: This study refers to the droplet state on rose petals, structural defects were constructed on the superhydrophobic surface. This paper studies the influence of macro-structural defects on the wettability change from natural to bionic "lotus effect" to "petal effect" in both static and dynamic angles. FINDINGS: Macro defects significantly change the static contact angle of the superhydrophobic surface. The higher the impact velocity of the droplet, the higher the energy dissipation of the "petal effect" surface (DSHS), which improves the adhesion of the surface to the droplet and prolongs the contact time. It is found that the defect structure and high impact velocity will directly affect the deposition and desorption of droplets on the superhydrophobic surface, and they are both essential. This wetting dynamic law is very likely to be helpful in the quantitative design of defect structure scale for dynamic desorption of droplets on superhydrophobic surfaces.
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PURPOSE: To determine the safety and efficacy associated with drainage volumes greater than 1,500 mL in a single, unilateral thoracentesis without pleural manometry measurements. MATERIALS AND METHODS: This retrospective, single-institution study included 872 patients (18 years and older) who underwent ultrasound-guided thoracentesis. Patient and procedures data were collected including demographics, number of and laterality of thoracenteses, volume and consistency of fluid removed, and whether clinical or radiologic evidence of re-expansion pulmonary edema (REPE) developed within 24 h of thoracentesis. Fisher's exact test was used to test the significance of the relationship between volume of fluid removed and evidence of REPE. RESULTS: A total of 1376 thoracenteses were performed among the patients included in the study. The mean volume of fluid removed among all procedures was 901.1 mL (SD = 641.7 mL), with 194 (14.1%) procedures involving the removal of ≥ 1,500 mL of fluid. In total, six (0.7%) patients developed signs of REPE following thoracentesis, five of which were a first-time thoracentesis. No statistically significant difference in incidence of REPE was observed between those with ≥ 1,500 mL of fluid removed compared to those with < 1,500 mL of fluid removed (p-value = 0.599). CONCLUSIONS: Large-volume thoracentesis may safely improve patients' symptoms while preventing the need for repeat procedures.
Subject(s)
Pulmonary Edema , Thoracentesis , Ultrasonography, Interventional , Humans , Thoracentesis/methods , Retrospective Studies , Pulmonary Edema/epidemiology , Pulmonary Edema/diagnostic imaging , Pulmonary Edema/etiology , Female , Male , Aged , Middle Aged , Incidence , Aged, 80 and over , Drainage/methods , Adult , Pleural Effusion/epidemiology , Pleural Effusion/diagnostic imagingABSTRACT
The utilization of agricultural and forestry residues for the development and preparation of green binderless fiberboard (BF) is an effective way to realize high-value utilization of lignocellulose biomass resources. This study focuses on the fabrication of BF with excellent mechanical and waterproof properties, utilizing poplar wood residue (PWR) as raw material and Trametes hirsuta as a pretreatment method. During the fermentation process, lignin-degrading enzymes and biological factors, such as sugars, were produced by T. hirsuta, which activated lignin by depolymerizing lignin bonds and modifying structural functional groups, and forming new covalent bonds between poplar fibers, ultimately enhancing adhesion. Additionally, the activated lignin molecules and sugar molecules coalesce under high temperatures and pressures, forming a dense carbonization layer that bolsters the mechanical properties of the fiberboard and effectively shields it from rapid water infiltration. The bio-pretreated BF for 10 days shows a MOR and MOE of up to 36.1 Mpa and 3704.3 Mpa, respectively, which is 261% and 247.8% higher than that of the bio-untreated fiberboard, and the water swelling ratio (WSR) rate is only 5.6%. Chemical composition analysis revealed that repolymerization occurred among lignin, cellulose, and hemicellulose, especially the molecular weight of lignin changed significantly, with the Mw of lignin increasing from 312066 g/mol to 892362 g/mol, and then decreasing to 825021 g/mol. Mn increased from 277790 g/mol to 316987.5 g/mol and then decreased to 283299.5 g/mol at 21 days. Compared to other artificial fiberboards prepared through microbial pretreatment, the BF prepared by microorganisms in this study exhibited the highest mechanical properties among the poplar wood biobased panels.
Subject(s)
Lignin , Populus , Trametes , Wood , Wood/chemistry , Populus/chemistry , Lignin/chemistry , Fermentation , Cellulose/chemistry , Biomass , Construction MaterialsABSTRACT
BACKGROUND: Esophageal cancer brings emotional changes, especially anxiety to patients. Co-existing anxiety makes the surgery difficult and may cause complications. This study aims to evaluate effects of anxiety in postoperative complications of esophageal cancer patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with esophageal cancer and co-existing COPD underwent tumor excision. Anxiety was measured using Hospital Anxiety and Depression Scale (HAD) before surgery. Clavien-Dindo criteria were used to grade surgical complications. A multiple regression model was used to analyze the relationship between anxiety and postoperative complications. The chi-square test was used to compare the differences in various types of complications between the anxiety group and the non-anxiety group. A multinomial logistic regression model was used to analyze the influencing factors of mild and severe complications. RESULTS: This study included a total of 270 eligible patients, of which 20.7% had anxiety symptoms and 56.6% experienced postoperative complications. After evaluation by univariate analysis and multivariate logistic regression models, the risk of developing complications in anxious patients was 4.1 times than non-anxious patients. Anxious patients were more likely to develop pneumonia, pyloric obstruction, and arrhythmia. The presence of anxiety, surgical method, higher body mass index (BMI), and lower preoperative oxygen pressure may increase the incidence of minor complications. The use of surgical methods, higher COPD assessment test (CAT) scores, and higher BMI may increase the incidence of major complications, while anxiety does not affect the occurrence of major complications (P = 0.054). CONCLUSION: Preoperative anxiety is associated with postoperative complications in esophageal cancer patients with co-existing COPD. Anxiety may increase the incidence of postoperative complications, especially minor complications in patient with COPD and esophageal cancer.
Subject(s)
Anxiety , Esophageal Neoplasms , Postoperative Complications , Pulmonary Disease, Chronic Obstructive , Humans , Male , Esophageal Neoplasms/surgery , Esophageal Neoplasms/psychology , Esophageal Neoplasms/complications , Female , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/psychology , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Postoperative Complications/psychology , Anxiety/etiology , Anxiety/epidemiology , Middle Aged , Retrospective Studies , Aged , Preoperative Period , Risk Factors , Esophagectomy/adverse effectsABSTRACT
The tertiary mutation C797S in the structural domain of the EGFR kinase is a common cause of resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs). In this study, we used a potent, selective and irreversible inhibitor, BDTX-189, to target EGFR C797S triple mutant cells for cell activity. The study constructed the H1975-C797S (EGFR L858R/T790 M/C797S) cell line using the CRISPR/Cas9 method and investigated its potential as a fourth-generation tyrosine kinase inhibitor via chemosensitivity approach. The results demonstrated its ability to induce cytotoxic effects, and inhibit EGFR L858R/T790 M/C797S cell growth and proliferation in a dose-dependent manner. Meanwhile, BDTX-189 reduces the protein phosphorylation levels of EGFR, ERK, and AKT, promoting apoptosis. Furthermore, BDTX-189 not only inhibits common EGFR triple mutations but also effectively inhibits EGFR L858R mutation and EGFR L858R/T790 M mutation. These findings support the cytotoxic effect of BDTX-189 and its inhibitory effect on cell division and proliferation with the EGFR C797S triple mutation.
Subject(s)
Apoptosis , Cell Proliferation , ErbB Receptors , Mutation , Protein Kinase Inhibitors , Proto-Oncogene Proteins c-akt , ErbB Receptors/metabolism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Humans , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation/drug effects , Cell Line, Tumor , Apoptosis/drug effects , Phosphorylation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , MAP Kinase Signaling System/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistryABSTRACT
BACKGROUND: The connections between fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) and daily mortality of viral pneumonia and bacterial pneumonia were unclear. OBJECTIVES: To distinguish the connections between PM2.5 and PM2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia. METHODS: Using a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models. RESULTS: We included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM2.5 (lag 0-2 d, 37.6 µg/m3) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM2.5-10 (lag 0-2 d, 28.4 µg/m3) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM2.5 remained, and those of PM2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season. CONCLUSION: This nationwide study presents compelling evidence that both PM2.5 and PM2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM2.5 and somewhat higher sensitivity of viral pneumonia.
Subject(s)
Air Pollutants , Air Pollution , Cross-Over Studies , Particulate Matter , Particulate Matter/analysis , Particulate Matter/adverse effects , Humans , China/epidemiology , Male , Female , Aged , Middle Aged , Air Pollution/adverse effects , Air Pollution/analysis , Air Pollutants/analysis , Air Pollutants/adverse effects , Pneumonia, Bacterial/mortality , Pneumonia/mortality , Pneumonia/chemically induced , Environmental Exposure/adverse effects , Aged, 80 and over , Particle Size , Pneumonia, Viral/mortality , AdultABSTRACT
Omics data sets often pose a computational challenge due to their high dimensionality, large size, and non-linear structures. Analyzing these data sets becomes especially daunting in the presence of rare events. Machine learning (ML) methods have gained traction for analyzing rare events, yet there has been limited exploration of bioinformatics tools that integrate ML techniques to comprehend the underlying biology. Expanding upon our previously developed computational framework of an integrative machine learning approach, we introduce PerSEveML, an interactive web-based tool that uses crowd-sourced intelligence to predict rare events and determine feature selection structures. PerSEveML provides a comprehensive overview of the integrative approach through evaluation metrics that help users understand the contribution of individual ML methods to the prediction process. Additionally, PerSEveML calculates entropy and rank scores, which visually organize input features into a persistent structure of selected, unselected, and fluctuating categories that help researchers uncover meaningful hypotheses regarding the underlying biology. We have evaluated PerSEveML on three diverse biologically complex data sets with extremely rare events from small to large scale and have demonstrated its ability to generate valid hypotheses. PerSEveML is available at https://biostats-shinyr.kumc.edu/PerSEveML/ and https://github.com/sreejatadutta/PerSEveML.
Subject(s)
Biomarkers , Computational Biology , Internet , Machine Learning , Software , Humans , Computational Biology/methods , AlgorithmsABSTRACT
BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .
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The harmless and high-value conversion of organic waste are the core problems to be solved by composting technology. This study introduced an innovative method of promoting targeted humification and nitrogen retention in composting by adding p-benzoquinone (PBQ), the composting without any additives was set as control group (CK). The results indicated that the addition of exogenous quinones led to a 30.1% increase in humic acid (HA) content during the heating and thermophilic phases of composting. Spectroscopic analyses confirmed that exogenous quinones form the core skeleton structure of amino-quinones in HA through composting biochemical reactions. This accelerated the transformation of quinones into recalcitrant HA in the early stages of composting, and reduced CO2 and NH3 by 8% and 78%, respectively. Redundancy analysis (RDA) revealed that the decrease in carbon and nitrogen losses primarily correlated with quinones enhancing HA formation and greater nitrogen incorporation into HA (P < 0.05). Furthermore, the compost treated with quinones demonstrated a decrease in phytotoxicity and earthworm mortality, alongside a significant increase in the relative abundance of actinobacteria, which are associated with the humification process. This research establishes and proposes that co-composting with quinones-containing waste is an effective approach for the sustainable recycling of hazardous solid waste.
Subject(s)
Composting , Humic Substances , Nitrogen , Quinones , Composting/methods , Quinones/metabolism , Quinones/chemistry , Animals , Soil/chemistry , Oligochaeta/metabolism , Food , Refuse Disposal/methods , Food Loss and WasteABSTRACT
Mature compost can promote the transformation of organic matter (OM) and reduce the emission of polluting gases during composting, which provides a viable approach to reduce the environmental impacts of biodegradable plastics (BPs). This study investigated the impact of mature compost on polybutylene adipate terephthalate (PBAT) degradation, greenhouse gas (GHG) emission, and microbial community structure during composting under two treatments with mature compost (MC) and without (CK). Under MC, visible plastic rupture was advanced from day 14 to day 10, and a more pronounced rupture was observed at the end of composting. Compared with CK, the degradation rate of PBAT in MC was increased by 4.44 % during 21 days of composting. Thermobifida, Ureibacillus, and Bacillus, as indicator species under MC treatment, played an important role in PBAT decomposition. Mature compost reduced the total global warming potential (GWP) by 25.91 % via inhibiting the activity of bacteria related to the production of CH4 and N2O. Functional Annotation of Prokaryotic Taxa (FAPROTAX) further revealed that mature compost addition increased relative abundance of bacteria related to multiple carbon (C) cycle functions such as methylotrophy, hydrocarbon degradation and cellulolysis, inhibited nitrite denitrification and denitrification, thus alleviating the emission of GHGs. Overall, mature compost, as an effective additive, exhibits great potential to simultaneously mitigate BP and GHG secondary pollution in co-composting of food waste and PBAT.
Subject(s)
Biodegradable Plastics , Composting , Greenhouse Gases , Refuse Disposal , Greenhouse Gases/analysis , Food Loss and Waste , Food , Soil/chemistry , Methane/analysis , ManureABSTRACT
BACKGROUND: Vancomycin-associated acute kidney injury (VA-AKI) is the most clinically relevant side effect of vancomycin. The objective of this study was to investigate the association between VTC and VA-AKI as well as 30-day mortality in critically ill elderly adults. METHOD: Elderly patients with trough serum vancomycin concentration records(VTC) in the Medical Information Mart-IV (MIMIC-IV) and eICU databases were retrospectively studied. RESULTS: A total of 3,146 critically ill elderly adults were finally enrolled. The incidence of VA-AKI in the elderly population was 76.5%. Logistic regression analysis revealed significant relationships between VA-AKI and various factors, including VTC, comorbidities, and laboratory indicators, and SOFA, and GCS score. For each mg/L increase, the OR for VA-AKI increased by 2.5%. The association between VTC and 30-day mortality was found to be statistically significant (odds ratio (OR): 1.021, 95% CI: 1.010-1.031), P < 0.001). The Restricted cubic splines (RCS) curves revealed that VTC ranged of 19.67 to 35.72 mg/l for AKI and 19.17 to 42.86 mg/l for 30-day mortality exhibit OR with 95% CI above 1, indicating statistically significant associations with an increased risk of AKI and 30-day mortality, respectively. In the subgroup analysis, VTC was identified as a risk factor for VA-AKI in specific patient groups, including white individuals, female patients, those with shock, patients with SOFA > 6, patients with baseline creatinine > 1.2 mg/dl and patients with or without exposed to other nephrotoxic medications. CONCLUSION: This study found the significant association between VTC and the incidence of VA-AKI and 30-day mortality in critically ill elderly adults. The RCS curves indicated concentration ranges for AKI (19.67-35.72 mg/L) and 30-day mortality (19.17-42.86 mg/L), signifying increased risk.