Synthesis of Quinolinoneylnitrones and Coumarinylnitrones via a Cascade Hydroamination and Aza-MBH-Type Reaction.

Nitrones are quite useful intermediates and have been broadly applied in organic synthesis, drug discovery, and photochemistry research. Many functional nitrones have been successfully prepared using various strategies. In this work, an efficient method for synthesizing novel quinolinoneylnitrone and coumarinylnitrone derivatives was developed. Preliminary mechanistic research suggests that this protocol included a cascade hydroamination and aza-MBH-type reaction.

Enhanced patient-based real-time quality control using the graph-based anomaly detection.

OBJECTIVES: Patient-based real-time quality control (PBRTQC) is an alternative tool for laboratories that has gained increasing attention. Despite the progress made by using various algorithms, the problems of data volume imbalance between in-control and out-of-control results, as well as the issue of variation remain challenges. We propose a novel integrated framework using anomaly detection and graph neural network, combining clinical variables and statistical algorithms, to improve the error detection performance of patient-based quality control. METHODS: The testing results of three representative analytes (sodium, potassium, and calcium) and eight independent variables of patients (test date, time, gender, age, department, patient type, and reference interval limits) were collected. Graph-based anomaly detection network was modeled and used to generate control limits. Proportional and random errors were simulated for performance evaluation. Five mainstream PBRTQC statistical algorithms were chosen for comparison. RESULTS: The framework of a patient-based graph anomaly detection network for real-time quality control (PGADQC) was established and proven feasible for error detection. Compared with classic PBRTQC, the PGADQC showed a more balanced performance for both positive and negative biases. For different analytes, the average number of patient samples until error detection (ANPed) of PGADQC decreased variably, and reductions could reach up to approximately 95 % at a small bias of 0.02 taking calcium as an example. CONCLUSIONS: The PGADQC is an effective framework for patient-based quality control, integrating statistical and artificial intelligence algorithms. It improves error detection in a data-driven fashion and provides a new approach for PBRTQC from the data science perspective.

The usefulness of contrast echocardiography in the evaluation of cardiac masses: a multicenter study.

BACKGROUND: Cardiac masses can encompass a variety of conditions, such as tumors, thrombi, vegetations, calcific lesions, and other rare diseases. Treatment and management of these types of cardiac masses differ considerably. Thus, accurately distinguishing among thrombi, benign tumors, and malignant tumors in the heart is of great importance. Contrast echocardiography (CE) has emerged as a promising technology. Although published guidelines suggest that CE can enhance image quality and assist in differentiating between benign and malignant lesions, most studies on CE diagnosis of cardiac masses are limited to case reports or retrospective/small-sample-sized prospective cohorts. This study aims to evaluate the diagnostic accuracy of CE in patients with suspected cardiac masses and address the insufficient evidence for differential diagnosis using CE. METHODS: Between April 2018 and July 2022, a prospective multicenter study was conducted, which included 145 consecutive patients suspected to have cardiac masses based on transthoracic echocardiography. All patients underwent CE examinations. The echocardiographic diagnosis relied on qualitative factors such as echogenicity, boundary, morphology of the base, mass perfusion, pericardial effusion, and motility as well as quantitative factors such as the area of the masses and the peak intensity ratio of the masses to adjacent myocardium (A1/A2). RESULTS: The final confirmed diagnoses were as follows: 2 patients had no cardiac mass, 4 patients had pseudomass, 43 patients had thrombus, 66 patients had benign tumors, and 30 patients had malignant tumors. The receiver operating characteristic (ROC) analysis indicated that an optimal A1/A2 cutoff value of 0.499 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.977, 97.9%, 90.7%, 95.9%, and 95.1%, respectively. The optimal A1/A2 cutoff value of 1.583 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.950, 93.3%, 93.9%, 87.5%, and 96.9%, respectively. CONCLUSIONS: Combined with qualitative and quantitative analyses, CE has the potential to accurately differentiate among different types of cardiac masses.

Bibenzyl-Phenylpropane Hybrids with Immunosuppressive Activities from Dendrobium Nobile Lindl.

Fifteen bibenyls and four fluorenones, including five new bibenzyl-phenylpropane hybrids, were isolated from the aerial part of Dendrobium nobile Lindl. Their structures were determined by spectroscopic methods. Bioassay on the LPS-induced proliferations of mouse splenic B lymphocytes, and Con A-induced T lymphocytes showed that compounds 1, 2, and 14 showed excellent immunosuppressive activities with IC50 values of 1.23, 1.01, and 3.87 µM, respectively, while compounds 3-4, 7, 10, 13, and 15 exhibited moderate immunosuppressive activities with IC50 values ranging from 6.89 to 14.2 µM.

Bimetallic iron complex constructed clusters and single atoms neighboring structure to enhance oxygen reduction reaction performance.

Electrocatalysts are useful in lowering the energy barrier in oxygen reduction reaction (ORR). In this study, a catalyst with neighboring Fe single-atom and cluster is created by adsorbing a bimetallic Fe complex onto N-doped carbon and then pyrolyzing it. The resulting catalyst has good performance and a half-wave potential of 0.89 V. When used in Zn-air batteries, the voltage drops by only 8.13 % after 145 h of cycling. Theoretical studies show that electrons transfer from neighboring clusters to single atoms and the catalyst has a lower d-band center. These reduce intermediate desorption energy, hence improving ORR performance. This work demonstrates the capacity to adjust the catalytic properties through the interaction of diverse metal structures, which helps to design more efficient catalysts.

Optimum programmed intermittent epidural bolus interval time of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL: a randomized controlled trial.

Background: The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects (EI90), without the use of patient-controlled epidural analgesia (PCEA). Methods: A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI90 (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL was estimated using probit regression. Results: The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5-50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score > 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups. Conclusion: The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5-50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.

Evaluating the Commutability of Reference Materials for α-Fetoprotein: Accurate Value Assignment With Multiple Systems and Trueness Verification.

Background: The accurate measurement of α-fetoprotein (AFP) is critical for clinical diagnosis. However, different AFP immunoassays may yield different results. Appropriate AFP reference materials (RMs) were selected and assigned accurate values for applications with external quality assessment (EQA) programs to standardize AFP measurements. Methods: Forty individual clinical samples and six different concentrations of candidate RMs (Can-RMs, L1-L6) were prepared by the Beijing Center for Clinical Laboratories. The Can-RMs were assigned target values by performing five immunoassays, using WHO International Standard 72/225 as a calibrator, and sent to 45 clinical laboratories in Beijing for AFP measurements. The commutability of all RMs was assessed based on CLSI and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approaches. Analytical performance was assessed for compliance based on accuracy (total error, TE), trueness (bias), and precision (CV). Results: The Can-RMs were commutable for all immunoassays using the CLSI approach and for 6 of 10 assay combinations using the IFCC approach. RMs diluted in WHO RM 72/225 were commutable among all assays with the CLSI approach, except for serum matrix (Autolumo vs. Roche analyzer) and diluted water matrix (Abbott vs. Roche/Mindray analyzer), whereas some inconclusive and non-commutable results were found using the IFCC approach. The average pass rates based on the TE, bias, and CV were 91%, 81%, and 95%, respectively. Conclusions: The commutability of the RMs differed between both evaluation approaches. The Can-RMs exhibited good commutability with the CLSI approach, suggesting their suitability for use with that approach as commutable EQA materials with assigned values and for monitoring the performance of AFP measurements.

Investigation of Hydrocarbon Generation from Jurassic Coal Measures in the Southern Junggar Basin, Northwestern China, Using Closed-System Pyrolysis.

There are several sets of coal-bearing source rocks within the Lower and Middle Jurassic (J1-2) in the southern Junggar sub-basin. To obtain a comprehensive understanding of hydrocarbon generation and the amount of potentially generated natural gas, Rock-Eval analysis was conducted on source rock samples to assess their kerogen types and quality. At the same time, maceral observation and gold-tube pyrolysis were carried out to quantify the different maceral groups and to predict the gas potential, respectively. The Rock-Eval data indicate that the investigated samples are dominated by type III kerogen and occasionally supplemented with type II kerogen. Among the six immature source rocks selected for gold-tube pyrolysis, they are vitrinite-dominated except for a dark mudstone from the Badaowan Formation that is liptinite-dominated. A positive relationship between the maximum gas yield and the liptinite content was observed. However, the accuracy of liptinite content estimation largely depends on the experience level of the organic petrographer. The optimized C1-5 generation activation energies for the six source rocks cover a broad range between 50 and 74 kcal/mol. A relatively larger proportion of higher activation energies (74 kcal/mol) for the carbonaceous mudstone from the Badaowan Formation and also for the dark mudstone from the Sangonghe Formation implies late gas generation. Under geological conditions, the modeled gas conversion from J1-2 source rocks in the central part of the southern Junggar sub-basin ranged from 52 to 74%, indicating good exploration potential. Notably, the computed gas generation from the dark mudstone from the Sangonghe Formation resembles that from the Xishanyao Formation. Gas generation from the Sangonghe Formation should be considered in the future.

Epidural dexmedetomidine or esketamine versus fentanyl to decrease ropivacaine use for labor analgesia: A randomized non-inferiority study.

Background: Epidural nonopioid adjuvants also reduce local anesthetic use. We aimed to test the hypothesis that, compared with the present standard fentanyl, the hourly consumption of local anesthetic was at least as good when dexmedetomidine or esketamine was combined with local anesthetic for patient-controlled epidural analgesia (PCEA). Methods: A total of 120 laboring nulliparous subjects requiring labor analgesia were recruited for the final statistical analysis. Subjects were randomized to receive 0.075 % ropivacaine added with one of three equivalent adjuvants: 0.4 µg/mL fentanyl, 0.4 µg/mL dexmedetomidine, or 1.0 mg/mL esketamine. The primary outcome was hourly ropivacaine consumption. Compared with the fentanyl group, a 20 % difference in hourly local anesthetic consumption between the dexmedetomidine and esketamine groups was considered a clinical difference (non-inferiority margin). Results: The hourly ropivacaine consumption of the fentanyl group was 12.4 (95 % confidence interval CI 11.2 to 13.6) ml/h, so the prespecified non-inferiority limit was 2.5 ml/h. The hourly ropivacaine consumption of the fentanyl group was not inferior to that of the dexmedetomidine group (12.4 ml/h vs. 11.9 ml/h, risk difference, 0.5; 95 % confidence interval CI, -1.0 to 2.0, meeting criteria for non-inferiority). However, the hourly ropivacaine consumption of the esketamine group was 14.3 ml/h, and that of the fentanyl group was 12.4 ml/h (risk difference, 1.9, 95 % CI, 0.2 to 3.6), failing to confirm non-inferiority with a non-inferiority margin of 20 %. The incidence of pruritus was highest in the fentanyl group, whereas the occurrence of mild dizziness was highest in the esketamine group. Conclusions: In setting of the conditions of this study, epidural dexmedetomidine was non-inferior compared with epidural fentanyl in combination with ropivacaine for PCEA during labor. Meanwhile, we failed to establish the non-inferiority of epidural esketamine compared with epidural fentanyl in combination with ropivacaine for labor analgesia.

Comparable analysis of six immunoassays for carcinoembryonic antigen detection.

Objective: This study aimed to assess the current status of carcinoembryonic antigen (CEA) detection. We evaluated the correlation, consistency, and comparability of CEA results among six automated immunoassays, and combined with the results of CEA trueness verification of the Beijing Center for Clinical Laboratories (BCCL) for further analysis. Methods: Abbott Architect i2000, Beckman DxI800, Roche Cobas E601, Diasorin Liaison XL, Maccura IS1200, and Autolumo A2000 were used to detect 40 individual serum CEA samples. Taking the optimal analytical quality specifications calculated from data on biological variation as the evaluation criterion. Passing-Bablok regression and Bland-Altman analysis were performed between each assay and all-assays median values to evaluate the correlation and relative difference. The concordance correlation coefficient (CCC) was used for consistency analysis. Additionally, the trueness verification program used samples at three concentration levels to assess the bias, coefficient of variation (CV), and total error (TE) between the average measured values and the target value. Results: The Spearman's rank correlation coefficient (rs) was ≥0.996 and the CCC ranged between 0.9448 and 0.9990 for each assay vs. all-assays median. Considering the all-assays median value of each sample as a reference, there were proportional and systematic differences according to the Passing-bablok regression analysis. The relative difference of the four assays (Abbott Architect i2000, Autolumo A2000, Diasorin Liaison XL, and Maccura IS1200) met the optimal analytical quality specifications. On the other hand, Beckman DxI800 (13.2 %) and Roche Cobas E601 (-9.0 %) were only able to fulfill the desirable analytical quality specifications. The average pass rates for bias, CV, and TE of the trueness verification program were 80 %, 98 %, and 96 %, respectively. Conclusions: The six automated immunoassays vs. all-assays median have a good correlation in CEA detection. However, there is a lack of comparability of CEA results. Further improvements are needed in harmonization among CEA detections.