Spatial heterogeneity in the nonlinear impact of built environment on commuting time of active users: A gradient boosting regression tree approach

Many studies provided evidence regarding the influence of built environment (BE) on commuting time. However, few studies have considered the spatial heterogeneity of such impacts. Using data from Nanjing, China, this study employs two-step clustering and gradient boosted regression trees (GBRT) to segment the neighborhoods into different types and investigate the effects of BE characteristics on the commuting time of active users. The results show a strong effect of BE characteristics on commuting time, involving active modes. The importance of BE characteristics varies among neighborhood types. For active commuters in the internal region of Nanjing, commuting time is affected mostly by the land use mix at the work end. The lowest impact of BE in internal regions is associated with metro station density. For active commuters in external region of the city, the relative importance of intersection density at the home end is the largest (as high as 5.76%). Moreover, other significant differences are found in the associations between BE characteristics and active commuting time in the two regions.</p

Local Diffusion Homogeneity Provides Supplementary Information in T2DM-Related WM Microstructural Abnormality Detection

Objectives: We aimed to investigate whether an inter-voxel diffusivity metric (local diffusion homogeneity, LDH), can provide supplementary information to traditional intra-voxel metrics (i.e., fractional anisotropy, FA) in white matter (WM) abnormality detection for type 2 diabetes mellitus (T2DM).Methods: Diffusion tensor imaging was acquired from 34 T2DM patients and 32 healthy controls. Voxel-based group-difference comparisons based on LDH and FA, as well as the association between the diffusion metrics and T2DM risk factors [i.e., body mass index (BMI) and systolic blood pressure (SBP)], were conducted, with age, gender and education level controlled.Results: Compared to the controls, T2DM patients had higher LDH in the pons and left temporal pole, as well as lower FA in the left superior corona radiation (p &lt; 0.05, corrected). In T2DM, there were several overlapping WM areas associated with BMI as revealed by both LDH and FA, including right temporal lobe and left inferior parietal lobe; but the unique areas revealed only by using LDH included left inferior temporal lobe, right supramarginal gyrus, left pre- and post-central gyrus (at the semiovale center), and right superior radiation. Overlapping WM areas that associated with SBP were found with both LDH and FA, including right temporal pole, bilateral orbitofrontal area (rectus gyrus), the media cingulum bundle, and the right cerebellum crus I. However, the unique areas revealed only by LDH included right inferior temporal lobe, right inferior occipital lobe, and splenium of corpus callosum.Conclusion: Inter- and intra-voxel diffusivity metrics may have different sensitivity in the detection of T2DM-related WM abnormality. We suggested that LDH could provide supplementary information and reveal additional underlying brain changes due to diabetes

Peiminine Inhibits Glioblastoma in Vitro and in Vivo Through Cell Cycle Arrest and Autophagic Flux Blocking

Background/Aims: Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumour in adults, with poor survival rate and high mortality rates. Existing treatments do not provide substantial benefits to patients; therefore, novel treatment strategies are required. Peiminine, a natural bioactive compound extracted from the traditional Chinese medicine Fritillaria thunbergii, has many pharmacological effects, especially anticancer activities. However, its anticancer effects on GBM and the underlying mechanism have not been demonstrated. This study was conducted to investigate the potential antitumour effects of peiminine in human GBM cells and to explore the related molecular signalling mechanisms in vitro and in vivo Methods: Cell viability and proliferation were detected with MTT and colony formation assays. Morphological changes associated with autophagy were assessed by transmission electron microscopy (TEM). The cell cycle rate was measured by flow cytometry. To detect changes in related genes and signalling pathways in vitro and in vivo, RNA-seq, Western blotting and immunohistochemical analyses were employed. Results: Peiminine significantly inhibited the proliferation and colony formation of GBM cells and resulted in changes in many tumour-related genes and transcriptional products. The potential anti-GBM role of peiminine might involve cell cycle arrest and autophagic flux blocking via changes in expression of the cyclin D1/CDK network, p62 and LC3. Changes in Changes in flow cytometry results and TEM findings were also observed. Molecular alterations included downregulation of the expression of not only phospho-Akt and phospho-GSK3β but also phospho-AMPK and phospho-ULK1. Furthermore, overexpression of AKT and inhibition of AKT reversed and augmented peiminine-induced cell cycle arrest in GBM cells, respectively. The cellular activation of AMPK reversed the changes in the levels of protein markers of autophagic flux. These results demonstrated that peiminine mediates cell cycle arrest by suppressing AktGSk3β signalling and blocks autophagic flux by depressing AMPK-ULK1 signalling in GBM cells. Finally, peiminine inhibited the growth of U251 gliomas in vivo. Conclusion: Peiminine inhibits glioblastoma in vitro and in vivo via arresting the cell cycle and blocking autophagic flux, suggesting new avenues for GBM therapy

Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review

Abstract Background Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. Case description Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. Conclusions This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy

Optimization of Key Parameters of Energy Management Strategy for Hybrid Electric Vehicle Using DIRECT Algorithm

The rule-based logic threshold control strategy has been frequently used in energy management strategies for hybrid electric vehicles (HEVs) owing to its convenience in adjusting parameters, real-time performance, stability, and robustness. However, the logic threshold control parameters cannot usually ensure the best vehicle performance at different driving cycles and conditions. For this reason, the optimization of key parameters is important to improve the fuel economy, dynamic performance, and drivability. In principle, this is a multiparameter nonlinear optimization problem. The logic threshold energy management strategy for an all-wheel-drive HEV is comprehensively analyzed and developed in this study. Seven key parameters to be optimized are extracted. The optimization model of key parameters is proposed from the perspective of fuel economy. The global optimization method, DIRECT algorithm, which has good real-time performance, low computational burden, rapid convergence, is selected to optimize the extracted key parameters globally. The results show that with the optimized parameters, the engine operates more at the high efficiency range resulting into a fuel savings of 7% compared with non-optimized parameters. The proposed method can provide guidance for calibrating the parameters of the vehicle energy management strategy from the perspective of fuel economy

Tuning nanoscale heterogeneity by non-affine thermal strain to modulate defect activation and maximize magnetocaloric effect of metallic glass

The effects of non-affine thermal strain on the structure, defect activation and magnetocaloric effect (MCE) have been investigated in Gd55Co20Al24.5Si0.5 metallic glass (MG). Maxwell-Voigt models are utilized to analyze the impact of cryogenic thermal cycling (CTC) on the evolution of heterogeneous structure in term of the activated defects during creep deformation. Two kinds of flow defects with different relaxation times are observed from the relaxation spectrum, which show different responses to CTC. A power law between the maximum magnetic entropy change and its peak temperature is uncovered for Gd-based MGs above 85 K, which breaks down below 85 K for the low Gd content MGs including the high-entropy MGs. Through adjusting the CTC number, the maximum magnetic entropy of the present MG is improved to 10.7 JKg-1K−1 under 5 T, which is the largest among the Gd-based MGs with Curie temperature above 85 K. The enhancement of MCE is related to the increased fraction of solid-like zones in the amorphous matrix and nanocrystallization rendered by CTC treatment. This work sheds new insights into the correlation of MCE and nanoscale creep deformation with structural heterogeneity of MGs

Tuning the Defects of Two-Dimensional Layered Carbon/TiO2 Superlattice Composite for a Fast Lithium-Ion Storage

Defect engineering is one of the effective ways to improve the electrochemical property of electrode materials for lithium-ion batteries (LIB). Herein, an organic functional molecule of p-phenylenediamine is embedded into two-dimensional (2D) layered TiO2 as the electrode for LIB. Then, the 2D carbon/TiO2 composites with the tuning defects are prepared by precise control of the polymerization and carbothermal atmospheres. Low valence titanium in metal oxide and nitrogen-doped carbon nanosheets can be obtained in the carbon/TiO2 composite under a carbonization treatment atmosphere of N2/H2 gas, which can not only increase the electronic conductivity of the material but also provide sufficient electrochemical active sites, thus producing an excellent rate capability and long-term cycle stability. The prepared composite can provide a high capacity of 396.0 mAh g&minus;1 at a current density of 0.1 A g&minus;1 with a high capacitive capacity ratio. Moreover, a high specific capacity of 80.0 mAh g&minus;1 with retention rate of 85% remains after 10,000 cycles at 3.0 A g&minus;1 as well as the Coulomb efficiency close to 100%. The good rate-capability and cycle-sustainability of the layered materials are ascribed to the increase of conductivity, the lithium-ion transport channel, and interfacial capacitance due to the multi-defect sites in the layered composite

Rapid detection of carbapenemase activity of Enterobacteriaceae isolated from positive blood cultures by MALDI-TOF MS

Abstract Background Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been proved to be a useful tool for identification of pathogens directly isolated from blood cultures in clinical microbiology laboratories. β-Lactam antibiotics are commonly used for treatment of bloodstream infections caused by Enterobacteriaceae strains, and carbapenem is the superlative class of β-lactam antibiotics. Since the carbapenem resistance rate of Enterobacteriaceae strains raised year by year, efficient detection of carbapenemase activity and timely delivery of carbapenem susceptibility reports of Enterobacteriaceae strains isolated from blood cultures is important for clinicians. Methods We used 64 simulated blood cultures to establish the method of MALDI-TOF MS based ertapenem hydrolysis assay. The cutoff value of logRQ calculated from the peaks intensity of ertapenem and its hydrolysate was first set to identify the strains with carbapenemase activity. Then, we detected and calculated the logRQ values of 385 Enterobacteriaceae strains from positive clinical blood cultures to distinguish the carbapenemase producers and noncarbapenemase producers. Results The mean logRQ value of 32 noncarbapenemase producers was − 0.85 ± 0.14 in simulated blood cultures, while the logRQ value of 32 carbapenemase producers was 0.87 ± 0.55. Thus, the cutoff value of logRQ was set at − 0.45 with sensitivity of 100% and specificity of 100%. In 385 clinical positive blood cultures, the logRQ values of all carbapenem-susceptible Enterobacteriaceae strains (81.3%, 313/385) were < − 0.45. Comparing with the detection of carbapenemase genes, carbapenem-resistant Enterobacteriaceae strains (18.7%, 72/385) were well distinguished by MALDI-TOF MS based ertapenem hydrolysis assay with a sensitivity of 92.5% and specificity of 100%. Conclusions Our data show that MALDI-TOF MS based ertapenem hydrolysis assay is a rapid and accurate method to detect carbapenemase activity of Enterobacteriaceae strains from positive blood cultures, and can be routinely performed in clinical microbiology laboratories