Clinical application of metagenomic next-generation sequencing for the diagnosis of suspected infection in adults: A cross-sectional study.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Effect of adjuvant radiotherapy after breast-conserving surgery in elder women with early-stage breast cancer: a propensity-score matching analysis.

Purpose: The study aimed to explore the role of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elder women with early-stage breast cancer (BC). Methods: BC patients with 70-79 years of age, stage T1-2N0-1M0, undergoing BCS were screened in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015. The clinicopathological characteristics were balanced with propensity-score matching (PSM) method. Kaplan-Meier curves and Cox regression analyses were performed to determine the impact of adjuvant RT on BC patients. Results: Ultimately, 12,310 patients treated with adjuvant RT and 4837 patients treated with no RT, were involved in the analysis. Overall, patients treated with adjuvant RT was associated with a better breast cancer-specific survival (BCSS) (HR: 1.980 [1.596- 2.456], P < 0.001) and overall survival (OS) (HR: 2.214 [1.966- 2.494], P < 0.001) than those who did not undergo RT. After 1:1 PSM, adjuvant RT still performed advantage in both BCSS (HR: 1.918 [1.439- 2.557], P < 0.001) and OS (HR: 2.235 [1.904- 2.624], P < 0.001). In the multivariate COX analysis of BCSS, widowed, divorced and separated patients, tumor grade III, T2 stage, N1 stage, no RT, molecular subtypes with luminal B and triple negative were associated with a shorter BCSS (P < 0.05). In the multivariate COX analysis of OS, age ≥74 years, widowed, divorced and separated patients, tumor grade II/III, T2 stage, no RT, no chemotherapy, molecular subtypes with triple negative were associated with a shorter OS (P < 0.05). Furthermore, the advantages of adjuvant RT were observed in all subgroup analysis. Conclusion: Adjuvant RT after BCS can improve both BCSS and OS in elderly patients with early-stage BC. Additionally, all subgroups analysis-derived BCSS and OS were in support of RT.

Depletion of reactive oxygen species induced by beetroot (Beta vulgaris) extract leads to apoptosis-like death in Cronobacter sakazakii.

This research aimed to disclose the antibacterial activity of beetroot extract (Beta vulgaris) against Cronobacter sakazakii and its possible mechanisms. We evaluated its antibacterial activity by measuring the minimum inhibitory concentration (MIC) and time-kill kinetics. We also evaluated the intracellular ATP levels, bacterial apoptosis-like death (ALD), and reactive oxygen species (ROS) levels to reveal the possible antibacterial mechanisms. Our results showed that the MIC of beetroot extract against C. sakazakii was 25 mg/mL and C. sakazakii (approximately 8 log cfu/mL) was completely inhibited after treatment with 2 MIC of beetroot extract for 3 h. Beetroot extract reduced intracellular ATP levels and facilitated characteristics of ALD in C. sakazakii, such as membrane depolarization, increased intracellular Ca2+ levels, phosphatidylserine externalization, caspase-like protein activation, and DNA fragmentation. Additionally, and different from most bacterial ALD caused by the accumulation of ROS, beetroot extract reduced the intracellular ROS levels in C. sakazakii. Our experimental data provide a rationale for further research of bacterial ALD and demonstrate that beetroot extract can inhibit C. sakazakii in food processing environments.

Artificial Intelligence Enhanced Reliability Assessment Methodology With Small Samples.

Due to the high price of the product and the limitation of laboratory conditions, reliability tests often get a small number of failed samples. If the data are not handled properly, the reliability evaluation results will incur grave errors. In order to solve this problem, this work proposes an artificial intelligence (AI) enhanced reliability assessment methodology by combining Bayesian neural networks (BNNs) and differential evolution (DE) algorithms. First, a single hidden layer BNN model is constructed by fusing small samples and prior information to obtain the 95% confidence interval (CI) of the posterior distribution. Then, the DE algorithm is used to iteratively generate optimal virtual samples based on the 95% CI and small samples trends. A reliability assessment model is reconstructed based on double hidden layers BNN model by combining virtual samples and test samples in the last stage. In order to verify the effectiveness of the proposed method, an accelerated life test (ALT) of the subsurface electronic control unit (S-ECU) was carried out. The verification test results show that the proposed method can accurately evaluate the reliability life of a product. And compared with the two existing methods, the results show that this method can effectively improve the accuracy of the reliability assessment of a test product.

Circ_0008726 promotes malignant progression of ESCC cells through miR-206/HOXA13 pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the gastrointestinal tract. Circular RNAs (circRNAs) are involved in the pathogenesis of cancer. This study aimed to elucidate the role and molecular mechanism of circ_0008726 in ESCC. METHODS: The expression levels of circ_0008726, microRNA (miR)-206 and homeobox A13 (HOXA13) were detected by quantitative real-time PCR (QRT-PCR). Cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays were conducted to detect the proliferative ability of ESCC cells. Apoptosis and invasion of ESCC cells were detected by flow cytometry and transwell assays. Tube formation assay was used to detect the angiogenesis of ESCC cells. The expression of related proteins was detected by western blot analysis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circ_0008726, miR-206 and HOXA13. Xenograft mice model was established to study the in vivo effect of circ_0008726 knockdown. RESULTS: Expression of circ_0008726 was up-regulated in ESCC tissues and cells. Knockdown of circ_0008726 repressed proliferation, invasion, angiogenesis, and promoted apoptosis of ESCC cells. Circ_0008726 acted as a sponge for miR-206, and HOXA13 was a target of miR-206. The suppressive effects of circ_0008726 knockdown on cell proliferation, invasion, and angiogenesis were abated by miR-206 down-regulation. Meanwhile, overexpression of HOXA13 partially reversed the suppressive effects of miR-206 enrichment on ESCC cell malignant behaviors. Knockdown of circ_0008726 inhibited ESCC tumor growth in vivo. CONCLUSION: In short, circ_0008726 exerted the carcinogenic effects to regulate the proliferation, invasion, angiogenesis and apoptosis of ESCC cells by targeting miR-206/HOXA13 axis.

Diagnostic Value of Metagenomic Next-Generation Sequencing for Pneumonia in Immunocompromised Patients.

Introduction: The diagnosis of pulmonary infection and the identification of pathogens are still clinical challenges in immunocompromised patients. Metagenomic next-generation sequencing (mNGS) has emerged as a promising infection diagnostic technique. However, its diagnostic value in immunocompromised patients needs further exploration. Purposes: This study was to evaluate the diagnostic value of mNGS compared with comprehensive conventional pathogen tests (CTs) in the etiology of pneumonia in immunocompromised patients and immunocompetent patients. Methods: We retrospectively reviewed 53 patients who were diagnosed with pneumonia from May 2019 to June 2021. There were 32 immunocompromised patients and 21 immunocompetent patients with pneumonia who received both mNGS and CTs. The diagnostic performance was compared between mNGS and CTs in immunocompromised patients, using the composite diagnosis as the reference standard. And, the diagnostic value of mNGS for mixed infections was further analyzed. Results: Compared to immunocompetent patients, the most commonly pathogens, followed by Cytomegalovirus, Pneumocystis jirovecii and Klebsiella pneumoniae in immunocompromised patients. Furthermore, more mixed infections were diagnosed, and bacterial-fungal-virus coinfection was the most frequent combination (43.8%). mNGS can detect more types of pathogenic microorganisms than CTs in both groups (78.1% vs. 62.5%, P = 0.016and 57.1% vs. 42.9%, P = 0.048). The overall diagnostic positive rate of mNGS for pathogens was higher in immunocompromised patients (P = 0.002). In immunocompromised patients, a comparable diagnostic accuracy of mNGS and CTs was found for bacterial, fungal, and viral infections and coinfection. mNGS had a much higher sensitivity for bacterial infections (92.9% vs. 50%, P < 0.001) and coinfections (68.8% vs. 48.3%, P < 0.05), and it had no significant advantage in the detection of fungal infections, mainly due to the high sensitivity for Pneumocystis jirovecii in both groups. Conclusion: mNGS is more valuable in immunocompromised patients and exhibits apparent advantages in detecting bacterial and mixed infections. It may be an alternative or complementary diagnostic method for the diagnosis of complicated infections in immunocompromised patients.

Rapid, accurate, and novel diagnostic technique for respiratory pathogens: Clinical application of loop-mediated isothermal amplification assay in older patients with pneumonia, a multicenter prospective observational study.

Background: Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method using only one type of enzyme that can amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. Chips for Complicated Infection Detection (CCID) is based on LAMP. This study translate CCID into clinical application and evaluate its diagnostic value for pneumonia. Methods: Eighty one older patients with pneumonia were prospectively enrolled from January 1 to July 23, 2021, and 57 sputum/airway secretion and 35 bronchoalveolar lavage fluid samples were collected and analyzed by CCID and conventional microbiological tests (CMTs). Samples were collected, transported, monitored, and managed by a multidisciplinary team using a sample management information system. Results: CCID turnaround time was 50 min, and the detection limit was 500 copies/reaction. The percentage of positive samples was significantly higher using CCID than CMTs, especially for Klebsiella pneumoniae (odds ratio [OR], 9.0; 95% confidence interval [CI], 1.1-70.5; p < 0.05), Enterococcus faecalis (OR, ∞; p < 0.01), Stenotrophomonas maltophilia (OR, ∞; p < 0.01), fungi (OR, 26.0; 95% CI, 3.6-190.0; p < 0.01), and viruses (CCID only; p < 0.01). In addition, the percentage of positive results was significantly higher using CCID than CMTs in patients who used antibiotics for more than 3 days (91.9% vs. 64.9%; p < 0.01). Analyzing clinical impact, 55 cases (59.8%) benefited from CCID. Conclusion: CCID allows the rapid and accurate detection of pneumonia in older patients. Moreover, this technique is less affected by previous antibiotic treatment and can improve patient care.

A performance degradation evaluation method for a turbocharger in a diesel engine.

As one of the key systems of the marine power plant diesel engine, the turbocharger directly affects whether the diesel engine can continuously and stably provide the power required for the ship. Owing to a number of uncontrollable factors, such as harsh working conditions and complex structures, the turbocharger may have various failures, causing it to lose its intended function. At present, the fault diagnosis of the marine turbocharger has not been paid enough attention yet and in most cases, the method of 'ex post diagnosis' is still adopted. When analysing the nonlinear correspondence between the failure symptoms and failure causes, it is difficult for the existing theories to meet the actual diagnostic requirements. This paper introduces the concept of gas-path diagnosis into the condition monitoring for a marine turbocharger for the first time and proposes the flow capacity index which characterizes the flow capacity of the component and the isentropic efficiency index which characterizes the operating efficiency of the component as two dimensionless evaluation indicators for turbocharger health status. Moreover, the nonlinear mapping relationship between these two health parameters and the gas-path measurable parameters of the turbocharger is studied, and a novel performance degradation evaluation method for a turbocharger is established. The proposed method has been tested in three test cases where the degradation of a model turbocharger has been analysed. These case studies have illustrated that the proposed method can accurately isolate the degraded components and further quantify the degradation of the components.

A case of lung adenocarcinoma with a concurrent EGFR mutation and ALK rearrangement: A case report and literature review.

The echinoderm microtubule associated protein like 4­anaplastic lymphoma kinase (EML4­ALK) fusion is almost mutually exclusive to epidermal growth factor receptor (EGFR) or K­RAS mutation in non­small cell lung cancer (NSCLC), and it is extremely rare for patients to exhibit both mutations. The present study reported the case of a 71-year­old female diagnosed with adenocarcinoma, exhibiting mutations in EGFR and EML4­ALK. The present study treated this patient with EGFR­TK inhibitors, as the first line therapy, and gefitinib therapy revealed a good response until now. In addition, previously reported cases and associated literature were reviewed. The present study provided a greater understanding of the molecular biology and optimal treatment for patients with NSCLC with >1 driver mutation.