Prediction of sepsis within 24 hours at the triage stage in emergency departments using machine learning.

BACKGROUND: Sepsis is one of the main causes of mortality in intensive care units (ICUs). Early prediction is critical for reducing injury. As approximately 36% of sepsis occur within 24 h after emergency department (ED) admission in Medical Information Mart for Intensive Care (MIMIC-IV), a prediction system for the ED triage stage would be helpful. Previous methods such as the quick Sequential Organ Failure Assessment (qSOFA) are more suitable for screening than for prediction in the ED, and we aimed to find a light-weight, convenient prediction method through machine learning. METHODS: We accessed the MIMIC-IV for sepsis patient data in the EDs. Our dataset comprised demographic information, vital signs, and synthetic features. Extreme Gradient Boosting (XGBoost) was used to predict the risk of developing sepsis within 24 h after ED admission. Additionally, SHapley Additive exPlanations (SHAP) was employed to provide a comprehensive interpretation of the model's results. Ten percent of the patients were randomly selected as the testing set, while the remaining patients were used for training with 10-fold cross-validation. RESULTS: For 10-fold cross-validation on 14,957 samples, we reached an accuracy of 84.1%±0.3% and an area under the receiver operating characteristic (ROC) curve of 0.92±0.02. The model achieved similar performance on the testing set of 1,662 patients. SHAP values showed that the five most important features were acuity, arrival transportation, age, shock index, and respiratory rate. CONCLUSION: Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage. This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

Simultaneously Flame Retarding and Toughening of Epoxy Resin Composites Based on Two-Dimensional Polyhedral Oligomeric Silsesquioxane/Polyoxometalate Supramolecular Nanocrystals with Ultralow Loading.

For industrial practical applications, it is difficult to simultaneously endow epoxy resin (EP) composites with superior flame retardancy, smoke suppression, toughness, and low-dielectric constants. Herein, unique polyhedral oligomeric silsesquioxane/polyoxometalate (POM(Mo)-POSS(ibu-Li)) nanosheets were synthesized via a simple one-pot method using laboratory-made lithium-containing hepta-isobutyl-POSS (ibu-Li-POSS) and the low-cost industrial chromogenic agent H3PMo12O40 as raw materials. The incorporation of 2 wt % POM(Mo)-POSS(ibu-Li) nanoflakes into EP significantly enhanced the compatibility between nanoadditives and the EP matrix. Compared with EP, the flexural and impact strengths increased by 36.2 and 78.2%, respectively. Therefore, POM(Mo)-POSS(ibu-Li) has significant advantages in enhancing the toughness of EP compared with existing flame retardants. The dielectric constant and loss were apparently reduced to meet the increasing requirements of EP-type electronic packaging materials and components. Notably, the synthesized POM(Mo)-POSS(ibu-Li) contained various flame-retardant and smoke-suppression elements such as P, Mo, and Si. The ultralow loading (2 wt %) of POM(Mo)-POSS(ibu-Li) significantly reduced the peak heat release rate, peak of smoke production rate, and CO production rate by 43.9, 40.6, and 65.8%, respectively. Meanwhile, the value of LOI increased directly from 24.0% for EP to 30.2% and passed the V-0 rating in the UL-94 test. However, incorporating 5 wt % POSS derivatives into EP alone to ensure that the prepared composites pass the V-0 rating of the UL-94 test has always been an extraordinarily difficult problem. Therefore, the dilemmas of poor dielectric properties, inherent flammability, and brittleness of EP were completely overcome through the successful application of POM(Mo)-POSS(ibu-Li) supramolecular nanosheets.

Cellulose nanofibers-based composite film with broadening MXene layer spacing and rapid moisture separation for humidity sensing and humidity actuators.

Based on the basic idea of expanding the interlayer spacing of MXene, utilizing the effect of gallic acid-modified cellulose nanofibers for rapid moisture separation, the flexible sensing and driving composite film with a perfect balance among humidity signal response and mechanical properties was prepared. Inspired by the stacking of autumn fallen leaves, the cellulose nanofibers-based composite films were formed by self-assembly under vacuum filtration of blending gallic acid-modified cellulose nanofibers with MXene. The enhanced mechanical properties (tensile strength 131.1 MPa, puncture load 0.88 N, tearing strength 165.55 N/mm, and elongation at break 16.14 %), humidity sensing (the stable induced voltage 63.7 mV and response/recovery time 3.2/5.1 s), and humidity driving (154.7° bending angle) properties were observed. The synergistic effect of hydrogen bonds, the "pinning effect" arising from the side chains, and the hierarchical layered microstructure contributed to the enhanced performance. This work exemplifies the application of green natural product for preparing intelligent sensing, wearable devices, and biomimetic robots.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma.

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

Constructing a 3D Ion Transport Channel-Based CNF Composite Film with an Intercalated Structure for Superior Performance Flexible Supercapacitors.

The weak stiffness, huge thickness, and low specific capacitance of commonly utilized flexible supercapacitors hinder their great electrochemical performance. Learning from a biomimetic interface strategy, we design flexible film electrodes based on functional intercalated structures with excellent electrochemical properties and mechanical flexibility. A composite film with high strength and flexibility is created using graphene (reduced graphene oxide (rGO)) as the plane layer, layered double metal hydroxide (LDH) as the support layer, and cellulose nanofiber (CNF) as the connection agent and flexible agent. The interlayer height can be adjusted by the ion concentration. The highly interconnected network enables excellent electron and ion transport channels, facilitating rapid ion diffusion and redox reactions. Moreover, the high flexibility and mechanical properties of the film achieve multiple folding and bending. The CNF-rGO-NiCoLDH film electrode exhibits high capacitance performance (3620.5 mF cm-2 at 2 mA cm-2), excellent mechanical properties, and high flexibility. Notably, flexible all-solid assembled CNF-rGO-NiCoLDH//rGO has an extremely high area energy density of 53.5 mWh cm-2 at a power density of 1071.2 mW cm-2, along with cycling stability of 89.8% retention after 10 000 charge-discharge cycles. This work provides a perspective for designing high-performance energy storage materials for flexible electronics and wearable devices.

Construction and validation of classification models for predicting the response to concurrent chemo-radiotherapy of patients with esophageal squamous cell carcinoma based on multi-omics data.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. METHODS: A total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package "rms" v6.2-0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. RESULTS: Seven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158-0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). CONCLUSION: We developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.

Hydrophobic modification of cellulose nanofibers by gallic acid and the application in pressure sensing.

Via rational molecular structure design and using gallic acid (GA) for hydrophobic modification of cellulose nanofibers (CNF), the "polymer dipole" CNF-GA with hydrophilic main chains and hydrophobic side chains was prepared, which improved the poor piezoelectric properties of CNF used for preparing pressure sensors. Due to the appearance of the side chains, the elongation at break of the CNF-GA-2, compared with CNF, was enhanced by 186 %, and the excellent tensile strength, puncture load, and tearing strength were displayed. Moreover, the significant glass transition temperature (Tg) near the human body temperature was exhibited for CNF-GA, making it possible to be applied in temperature sensing. Most importantly, the CNF-GA-2 showed the maximum hydrophobicity, with a contact angle of 76.77°. Finally, the CNF-GA-2/MXene nanocomposite film was prepared by the CNF-GA-2 with MXene through vacuum filtration. The results indicated that the film had excellent piezoelectric properties (d33 = 63.283), the generated stable induced voltage (125.6 mV), the preferable piezoresistive performance (ΔR/R0 = 2.15), the fast response/recovery time (48/61 ms), which could achieve dynamic and static responses. Moreover, this film could be used for real-time detection of limb movements (such as wrists).

Acetyl-CoA Acetyltransferase 2 Confers Radioresistance by Inhibiting Ferroptosis in Esophageal Squamous Cell Carcinoma.

PURPOSE: The overall survival of patients with esophageal squamous cell carcinoma (ESCC) is not high due to the lack of markers to evaluate concurrent chemoradiation therapy (CCRT) resistance. The aim of this study is to use proteomics to identify a protein related to radiation therapy resistance and explore its molecular mechanisms. METHODS AND MATERIALS: Proteomic data for pretreatment biopsy tissues from 18 patients with ESCC who underwent CCRT (complete response [CR] group, n = 8; incomplete response [

Clinical differences between small and large pheochromocytomas and paragangliomas.

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors, most of which are characterized by the release of catecholamine, and range in diameters from less than 1 cm to 10 cm or more. However, knowledge of the differences in clinical features between small and large PPGLs is insufficient. Methods: A retrospective analysis of patients with PPGLs treated at our institution between January 2018 and June 2020 was performed. The clinical characteristics of patients were investigated, and comparisons were made between patients with large and small PPGLs. The logistic regression analysis was used to confirm the risk factors, and the receiver operating characteristic curve was used to evaluate the diagnostic performance of the variables. Results: Totally 263 patients were included, including 110 patients in small tumor group and 153 patients in large tumor group. There were more male patients in the large tumor group (p=0.009). More patients had hypertension (p<0.001) and diabetes (p=0.002) in the large tumor group. The 24-h urinary epinephrine (24hU-E) (p < 0.001) and 24-h urinary norepinephrine (24hU-NE) (p=0.002) concentrations were higher in the large tumor group. In terms of tumor location, adrenal-PPGLs were more frequent in the large tumor group (p<0.001). Multivariate logistic regression analysis showed that male sex [odds ratio (OR): 2.871, 95% confidence interval (CI): 1.444-5.711, p=0.003], 24hU-E concentrations (OR: 1.025, 95% CI:1.004-1.047, p=0.020), 24hU-NE concentrations (OR: 1.002, 95%CI: 1.001-1.004, p=0.045), and adrenal-PPGLs (OR: 2.510, 95% CI:1.256-5.018, p=0.009) were positive risk factors for large tumors. Taking above variables into the same model, the area under the receiver operating characteristic curve of the model for predicting the large tumor was 0.772 (95% CI: 0.706-0.834). After the short-term follow-up, there was no significant difference in tumor recurrence between the two groups (p=0.681). Conclusions: Significant differences in numerous clinical characteristics exist between large and small PPGLs. The male patients were more likely to be with large tumors, and such tumors were more likely to reside on the adrenal glands. Catecholamine measurements also help predict tumor size of PPGLs. Clinical decision-making will benefit from this information.

Development and Validation of a New Staging System for Esophageal Squamous Cell Carcinoma Patients Based on Combined Pathological TNM, Radiomics, and Proteomics.

OBJECTIVE: This study aimed to construct a new staging system for patients with esophageal squamous cell carcinoma (ESCC) based on combined pathological TNM (pTNM) stage, radiomics, and proteomics. METHODS: This study collected patients with radiomics and pTNM stage (Cohort 1, n = 786), among whom 103 patients also had proteomic data (Cohort 2, n = 103). The Cox regression model with the least absolute shrinkage and selection operator, and the Cox proportional hazards model were used to construct a nomogram and predictive models. Concordance index (C-index) and the integrated area under the time-dependent receiver operating characteristic (ROC) curve (IAUC) were used to evaluate the predictive models. The corresponding staging systems were further assessed using Kaplan-Meier survival curves. RESULTS: For Cohort 1, the RadpTNM4c staging systems, constructed based on combined pTNM stage and radiomic features, outperformed the pTNM4c stage in both the training dataset 1 (Train1; IAUC 0.711 vs. 0.706, p < 0.001) and the validation dataset 1 (Valid1; IAUC 0.695 vs. 0.659, p < 0.001; C-index 0.703 vs. 0.674, p = 0.029). For Cohort 2, the ProtRadpTNM2c staging system, constructed based on combined pTNM stage, radiomics, and proteomics, outperformed the pTNM2c stage in both the Train2 (IAUC 0.777 vs. 0.610, p < 0.001; C-index 0.898 vs. 0.608, p < 0.001) and Valid2 (IAUC 0.746 vs. 0.608, p < 0.001; C-index 0.889 vs. 0.641, p = 0.009) datasets. CONCLUSIONS: The ProtRadpTNM2c staging system, based on combined pTNM stage, radiomic, and proteomic features, improves the predictive performance of the classical pTNM staging system.

Targeting USP10 induces degradation of oncogenic ANLN in esophageal squamous cell carcinoma.

Anillin (ANLN) is a mitosis-related protein that promotes contractile ring formation and cytokinesis, but its cell cycle-dependent degradation mechanisms in cancer cells remain unclear. Here, we show that high expression of ANLN promotes cytokinesis and proliferation in esophageal squamous cell carcinoma (ESCC) cells and is associated with poor prognosis in ESCC patients. Furthermore, the findings of the study showed that the deubiquitinating enzyme USP10 interacts with ANLN and positively regulates ANLN protein levels. USP10 removes the K11- and K63-linked ubiquitin chains of ANLN through its deubiquitinase activity and prevents ANLN ubiquitin-mediated degradation. Importantly, USP10 promotes contractile ring assembly at the cytokinetic furrow as well as cytokinesis by stabilizing ANLN. Interestingly, USP10 and the E3 ubiquitin ligase APC/C co-activator Cdh1 formed a functional complex with ANLN in a non-competitive manner to balance ANLN protein levels. In addition, the macrolide compound FW-04-806 (F806), a natural compound with potential for treating ESCC, inhibited the mitosis of ESCC cells by targeting USP10 and promoting ANLN degradation. F806 selectively targeted USP10 and inhibited its catalytic activity but did not affect the binding of Cdh1 to ANLN and alters the balance of the USP10-Cdh1-ANLN complex. Additionally, USP10 expression was positively correlated with ANLN level and poor prognosis of ESCC patients. Overall, targeting the USP10-ANLN axis can effectively inhibit ESCC cell-cycle progression.

Cisplatin-induced pyroptosis is mediated via the CAPN1/CAPN2-BAK/BAX-caspase-9-caspase-3-GSDME axis in esophageal cancer.

Esophageal cancer is the seventh most common cancer globally. Chemotherapy resistance remains a significant challenge in the treatment of esophageal cancer patients. Cisplatin can damage tumor cells by inducing pyroptosis. However, the underlying molecular mechanisms remain unclear. In this work, we aim to investigate pyroptosis-dependent molecular mechanisms underlying cisplatin sensitivity and find potential biomarkers to predict response to cisplatin-based chemotherapy for esophageal cancer patients. Pyroptosis-associated proteins were screened via proteomics for esophageal cancer (n = 124) and bioinformatics analysis. We observed that high calpain-1 (CAPN1) and calpain-2 (CAPN2) expression were associated with favorable clinical outcomes and prolonged survival in esophageal cancer patients. We employed immunohistochemistry to evaluate the expression of CAPN1 and CAPN2 in pretreatment tumor biopsies from 108 patients with esophageal cancer who received concurrent chemoradiotherapy (CCRT). These results suggested that esophageal cancer patients with high expression of both CAPN1 and CAPN2 are likely to experience a complete response to CCRT and have significantly better survival. Western blotting, LDH release, calpain activity and cell viability assays indicated that cisplatin could activate calpain activity, while calpain inhibition or knockout suppressed cisplatin-induced pyroptosis. Mechanistically, we uncovered a novel mechanism whereby cisplatin induced pyroptosis via activation of a CAPN1/CAPN2-BAK/BAX-caspase-9-caspase-3-GSDME signaling axis in esophageal cancer cells. Collectively, this study is the first to explore the effects of calpain on cisplatin-induced pyroptosis in esophageal cancer cells. Further, our findings also imply that the combination of CAPN1 and CAPN2 could be considered as a promising biomarker of cisplatin sensitivity and prognosis in patients with esophageal cancer, providing a possibility to guide individualized treatment.

P300/CBP-associated factor (PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer.

BACKGROUND: Fascin is crucial for cancer cell filopodium formation and tumor metastasis, and is functionally regulated by post-translational modifications. However, whether and how Fascin is regulated by acetylation remains unclear. This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis. METHODS: Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor (PCAF), and immunofluorescence was used to investigate their colocalization. An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry. A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma (ESCC) cells using Western blotting by overexpressing and knocking down PCAF expression. An in vitro cell migration assay was performed, and a xenograft model was established to study in vivo tumor metastasis. Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation. The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry. RESULTS: Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471 (K471) by PCAF. Using the specific anti-AcK471-Fascin antibody, Fascin was found to be acetylated in ESCC cells, and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown. Functionally, Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis, whereas Fascin-K471 deacetylation exhibited a potent oncogenic function. Moreover, Fascin-K471 acetylation reduced filopodial length and density, and lifespan of ESCC cells, while its deacetylation produced the opposite effect. In the filipodium shaft, K471-acetylated Fascin displayed rapid dynamic exchange, suggesting that it remained in its monomeric form owing to its weakened actin-bundling activity. Clinically, high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients. CONCLUSIONS: Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells. Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.

Simple and rapid nicotine analysis using a disposable silica nanochannel-assisted electrochemiluminescence sensor.

Nicotine analysis is essential to medicine, toxicology and the tobacco industry. However, no simple, portable and disposable method was developed to meet their demands. Here, we report a simple, rapid and disposable silica nanochannel (SAN)-based electrochemiluminescence (ECL) sensor for nicotine analysis by simply assembling a SAN electrode with a paper cover. The sensing principle of the disposable sensor is based on the size exclusion effect and charge selectivity, which obviously prolong the sensor service time. We find that the sensor exhibits good specificity to nicotine, and most of the complex matrices are unlikely to impact the detection. The performance of the disposable sensor in cigarettes, e-cigarettes, nicotine gums, and lozenges is fully validated, showing satisfactory linearity, sensitivity (a limit of detection of 27.82 nM), and accuracy (a recovery between 96.00% and 106.51%). The disposable sensor can be potentially applied for on-site nicotine analysis.