Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as one of the most sensitive and specific biomarkers for predicting cardiac surgery-associated acute kidney injury (CSA-AKI); ...however, variable performance characteristics have been reported. We therefore performed a diagnostic meta-analysis to investigate the diagnostic accuracy of NGAL in early (within 12 h postoperatively) diagnosis of CSA-AKI using established guidelines. The search was carried out electronically with Medline (through PubMed interface), Embase, Cochrane library, ISI Web of Science, Scopus and ClinicalTrials.gov (up to 5 September 2014), and hand-searching was also done. Two reviewers conducted study inclusion, data extractions and quality assessment of the studies independently. The diagnostic capacity of NGAL for CSA-AKI was assessed using pooled sensitivity and specificity, diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUC). Meta-Disc 1.4 and STATA 12.0 were used to investigate the source of heterogeneity and to perform the meta-analysis. Twenty-four studies (33 data sets of 4066 patients) were considered, which were all of good methodological quality. The overall pooled sensitivity of NGAL for the diagnosis of AKI was 0.68 95% confidence interval (CI), 0.65–0.70, and specificity was 0.79 (95% CI, 0.77–0.80). The overall pooled positive likelihood ratio and negative likelihood ratio were 3.98 (95% CI, 3.05–5.20) and 0.33 (95% CI, 0.24–0.45), respectively, with a DOR of 13.05 (95% CI, 7.85–21.70). The receiver operating characteristic analysis showed an AUC standard error (SE) of 0.86 (0.02) and with a Q*-value (SE) of 0.79 (0.02). Subgroup analysis showed that NGAL had better predictive ability in neonates/children compared with adults (DOR, 19.37; AUC, 0.89 vs DOR, 8.98; AUC, 0.83), and adults without pre-existing renal insufficiency (PRI) had higher diagnostic value than adults without PRI to predict CSA-AKI (DOR, 15.43; AUC, 0.87 vs DOR, 6.56; AUC, 0.81). Both plasma/serum and urine NGAL had the highly predictive nature for early diagnosis of CSA-AKI (DOR, 13.09; AUC, 0.85 vs DOR, 13.20; AUC, 0.88), while lower DOR and AUC values were shown (DOR, 8.31; AUC, 0.81) when measured using standardized clinical platforms, compared with research-based assays (DOR, 19.22; AUC, 0.89). I
2-values showed substantial heterogeneity, which mainly stems from characteristics of patient population (P = 0.037). NGAL diagnostic accuracy in early detection of CSA-AKI is high, especially in neonates/children or adults with normal baseline renal function.
Two completely green and facile strategies have been developed to decorate Pd nanoparticles onto carbon nanotubes (CNT) sidewalls vianon-covalent interactions assisted with newly synthesized ...hyperbranched polymers (PiHPs). The resultant CNT/PiHP/Pd heterogeneous catalysts exhibit ultrahigh catalytic reactivity towards the reduction of 4-nitrophenol.
Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML) that is used for prognostic, predictive, monitoring, and efficacy-response assessments. The European ...LeukemiaNet (ELN) MRD Working Party evaluated standardization and harmonization of MRD in an ongoing manner and has updated the 2018 ELN MRD recommendations based on significant developments in the field. New and revised recommendations were established during in-person and online meetings, and a 2-stage Delphi poll was conducted to optimize consensus. All recommendations are graded by levels of evidence and agreement. Major changes include technical specifications for next-generation sequencing-based MRD testing and integrative assessments of MRD irrespective of technology. Other topics include use of MRD as a prognostic and surrogate end point for drug testing; selection of the technique, material, and appropriate time points for MRD assessment; and clinical implications of MRD assessment. In addition to technical recommendations for flow- and molecular-MRD analysis, we provide MRD thresholds and define MRD response, and detail how MRD results should be reported and combined if several techniques are used. MRD assessment in AML is complex and clinically relevant, and standardized approaches to application, interpretation, technical conduct, and reporting are of critical importance.
Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of ...glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors.
Ammonia (NH3) emission inventories are an essential input in chemical transport models and are helpful for policy-makers to refine mitigation strategies. However, current estimates of Chinese NH3 ...emissions still have large uncertainties. In this study, an improved inversion estimation of NH3 emissions in China has been made using an ensemble Kalman filter and the Nested Air Quality Prediction Modeling System. By first assimilating the surface NH3 observations from the Ammonia Monitoring Network in China at a high resolution of 15 km, our inversion results have provided new insights into the spatial and temporal patterns of Chinese NH3 emissions. More enhanced NH3 emission hotspots, likely associated with industrial or agricultural sources, were captured in northwest China, where the a posteriori NH3 emissions were more than twice the a priori emissions. Monthly variations of NH3 emissions were optimized in different regions of China and exhibited a more distinct seasonality, with the emissions in summer being twice those in winter. The inversion results were well-validated by several independent datasets that traced gaseous NH3 and related atmospheric processes. These findings highlighted that the improved inversion estimation can be used to advance our understanding of NH3 emissions in China and their environmental impacts.
Economic uncertainty will result in consumers' unstable environment expectations, thus affecting household consumption decisions. The paper established a consumption model though using the ...cointegration theory and ECM model, and used the annual data from 2002 to 2021 to examine the influence of uncertain expectations on the consumption behavior of rural residents in China. The research results show that consumers' income, consumption, consumption habits liquidity constraints and precautionary savings jointly produce the feelings of uncertainty, which will lead to rural consumers' uncertain expectations. Uncertain expectations will not only lead to rural residents the prudent consumption behavior of residents, but also lead to the lack of confidence of residents, forming phased consumption characteristics. Combining the results of the empirical analysis, this paper gives suggestions to promote rural consumption from the perspective of increasing rural residents' income, reforming the income distribution system, improving the rural financial system, and reinforcing the construction of rural consumption infrastructure.
In the past decade, deep learning models have been applied to bio-sensors used in a body sensor network for prediction. Given recent innovations in this field, the prediction accuracy of novel models ...needs to be evaluated for bio-signals. In this paper, we evaluate the performance of deep learning models for respiratory rate prediction. We consider three datasets from bio-sensors which include electrocardiogram (ECG), photoplethysmogram (PPG) data, and surface electromyogram (sEMG) data. The deep learning models include Long short-term memory (LSTM) networks, Bidirectional LSTM (Bi-LSTM), attention-based variants of LSTM, CNN-LSTM and Convolutional-LSTM networks. The deep learning models are evaluated for two separate windows which are 32 s and 64 s window. The models’ performance is evaluated using mean absolute error (MAE). The 64 s window has more accurate prediction compared to the 32 s window. Our results indicate Bi-LSTM with Bahdanu Attention has the best performance for the bio-signals. LSTM performs best with one of the datasets, yielding an MAE of 0.70 ± 0.02. Bi-LSTM with Bahdanau attention showed best results with two of the three datasets with MAE of 0.51 ± 0.03 for sEMG based data and MAE of 0.24 ± 0.03 with PPG and ECG based data.
•Deep learning methods have a good estimate of breathing rate and breathing patterns.•Surface electromyography can be used in respiratory pattern evaluation.•Long-short term memory method has comparatively great performance.•Attention mechanism improves the performance of algorithm.•Respiratory rate is important measure in health care.
A series of carboxyl-group-functionalized imidazolium-based ionic liquids (CILs) were synthesized and grafted onto silica gel. The catalytic activity of the resulting heterogeneous catalysts toward ...the synthesis of cyclic carbonate via cycloaddition reactions of epoxide and CO2 was studied. The effect on the reaction of the grafted ILs' structures and the reaction conditions such as reaction temperature, time, pressure, and the amount of catalyst used, were systematically investigated. For comparison, silica-grafted imidazolium-based ILs with and without hydroxyl groups were also used to catalyze cycloaddition reactions. The carboxylic acid group in the catalyst was demonstrated to have a synergistic effect with halide anions. A high yield of cyclic carbonates and excellent selectivity could be obtained under optimized conditions.
B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. ...Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on-target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML.
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