Combined early palliative care for non-small-cell lung cancer patients: a randomized controlled trial in Chongqing, China

PurposeMore effective approaches are needed to improve the prognosis of non-small-cell lung cancer (NSCLC) patients. Thus, we used the E-warm model to assess how early integration of interdisciplinary palliative care was related to the quality of life (QoL), psychological functioning, pain management, and nutrition factors of NSCLC patients.MethodsThis randomized controlled trial enrolled 280 newly diagnosed NSCLC patients, which were randomly divided (1:1) into combined early palliative care (CEPC) and standard oncological care (SC) groups. At baseline and after 24 weeks, the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale, Hospital Anxiety and Depression Scale (HADS), and the Patient Health Questionnaire-9 (PHQ-9) were used to assess QoL and psychological function, respectively. The Numerical Rating Scale (NRS) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess cancer patients’ pain and nutrition levels. The primary outcome was overall survival (OS). Secondary outcomes comprised changes in the QoL, psychological functioning, pain, and nutrition state. The intention-to-treat method was applied for analysis. This study was registered at www.chictr.org.cn (ChiCTR2200062617).ResultsOf the 140 patients enrolled in the CEPC and SC groups, 102 and 82 completed the research. The CEPC group presented higher QoL than the SC group (p < 0.05). Additionally, fewer patients presented depressive symptoms in the CEPC group than in the SC group (p < 0.05), as well as better nutritional status (p = 0.007) and pain management (p = 0.003). Compared to the SC group, CEPC patients had significantly longer OS (20.4 vs. 24.6 months, p = 0.042; HR: 0.19; 95% CI: 0.04-0.85, p = 0.029).ConclusionWith combined early palliative care, NSCLC patients lived longer, had better QoL, were psychologically stable, were in less pain, and were more nutritionally satisfied

Evaluation of pharmacokinetics and toxicology of biosimilar APZ001 antibody in Macaca cynomolgus

Purpose: To compare the pharmacokinetics of APZ001 antibody with those of cetuximab (Erbitux®) and to evaluate the toxicology of the former.Methods: To evaluate cetuximab’s biosimilar APZ001, Crl:CD1(ICR) (CD-1) mice and Macaca fascicularis (cynomolgus monkey) were chosen for the studies on acute toxicity, chronic toxicity, pharmacokinetics in chronic toxicity and immunogenicity toxicity. The study also compared the pharmacokinetic parameters of APZ001 with those of cetuximab upon single and multiple drug administrations in cynomolgus monkeys.Results: Pharmacokinetic parameters including maximum concentration (Cmax) and time to attain maximum drug concentration (Tmax), clearance rate and apparent volume of distribution of APZ001 were compared with those of cetuximab in both single and multiple administration studies. Difference of pharmacokinetics from weekly administration of APZ001 and cetuximab in cynomolgus monkeys was insignificant (p > 0.05), with relative bioavailability of 116.9 %. Both APZ001-treated and cetuximabtreated CD-1 mice showed the same level of food intake and body weight. Hematological and serological data were similar from APZ001 antibody and cetuximab treatments, so were the acute and chronic toxicity. Weekly transfusion of APZ001 did not alter its pharmacokinetic parameters. The administered drug was hardly detected in the serum in the 31st and 37th week of recovery; no accumulation of drug was observed upon withdrawal.Conclusion: APZ001 has extremely similar characteristics as cetuximab in terms of pharmacokinetics and toxicity.Keywords: Cetuximab, Pharmacokinetics, Acute toxicity, Chronic toxicity, Immunogenicity, Biosimila

A novel data-driven robust framework based on machine learning and knowledge graph for disease classification

Abstract(#br)As Noncommunicable Diseases (NCDs) are affected or controlled by diverse factors such as age, regionalism, timeliness or seasonality, they are always challenging to be treated accurately, which has impacted on daily life and work of patients. Unfortunately, although a number of researchers have already made some achievements (including clinical or even computer-based) on certain diseases, current situation is eager to be improved via computer technologies such as data mining and Deep Learning. In addition, the progress of NCD research has been hampered by privacy of health and medical data. In this paper, a hierarchical idea has been proposed to study the effects of various factors on diseases, and a data-driven framework named d-DC with good extensibility is presented. d-DC is able to classify the disease according to the occupation on the premise where the disease is occurring in a certain region. During collecting data, we used a combination of personal or family medical records and traditional methods to build a data acquisition model. Not only can it realize automatic collection and replenishment of data, but it can also effectively tackle the cold start problem of the model with relatively few data effectively. The diversity of information gathering includes structured data and unstructured data (such as plain texts, images or videos), which contributes to improve the classification accuracy and new knowledge acquisition. Apart from adopting machine learning methods, d-DC has employed knowledge graph (KG) to classify diseases for the first time. The vectorization of medical texts by using knowledge embedding is a novel consideration in the classification of diseases. When results are singular, the medical expert system was proposed to address inconsistencies through knowledge bases or online experts. The results of d-DC are displayed by using a combination of KG and traditional methods, which intuitively provides a reasonable interpretation to the results (highly descriptive). Experiments show that d-DC achieved the improved accuracy than the other previous methods. Especially, a fusion method called RKRE based on both ResNet and the expert system attained an average correct proportion of 86.95%, which is a good feasibility study in the field of disease classification

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

Investigation of MnO2-doped (Ba, Ca)TiO3 lead-free ceramics for high power piezoelectric applications

x% mol MnO2-doped Ba0.925Ca0.075TiO3 ceramics (abbreviated as BCT-Mnx, x=0-1.5) were synthesized by conventional solid-state reaction method. The effects of MnO2 addition and (Ba+Ca)/Ti mole ratio (A/B ratio) on the microstructure and electrical properties of the ceramics were investigated. The internal bias filed Ei was determined from the asymmetrical polarization hysteresis loops and found to increase with the doping concentration of MnO2. High mechanical quality factors (Qm\u3e1200) and low dielectric loss (tanδ3 kV/cm, meanwhile, the piezoelectric and electromechanical properties were found to decrease compared with the pure BCT, exhibiting a typical characteristic of hard behavior. Of particular interest is that the microstructure of BCT-Mn0.75 ceramics could be controlled by changing the A/B ratio, where enhanced piezoelectric coefficient d33 on the order of 190 pC/N was obtained in the BCT-Mn0.75 ceramics with A/B=1.01 due to its fine-grained microstructure, with yet high Qm, being on the order of 1000. The high d33 and Qm in MnO2-doped BCT ceramics make it a promising candidate for high power piezoelectric applications

A Comparison Study of the LMAPS Method and the LDQ Method For Time-Dependent Problems

This paper compares numerical solutions of spatial-temporal partial differential equations based on two RBF-based meshless methods: the local method of approximate particular solutions (LMAPS) and the local RBFs-based DQ method (LDQ). To avoid the ill-conditioned problems of the global version, the weighting coefficients at the supporting points are determined by solving low-order linear systems instead of large dense linear systems. The Runge-Kutta method is adopted for time stepping schemes. The numerical experiments have shown that the LMPAS method and the LDQ method are capable of solving the initial boundary value problem for spatial-temporal partial differential equations with high accuracy and efficiency. © 2013 Elsevier Ltd

Dc-bias-field-induced Dielectric Relaxation and AC Conduction in CaCu3Ti4O12 Ceramics

International audienceThe dielectric relaxation and ac conduction of CaCu3Ti4O12 (CCTO) ceramics were investigated at different temperatures under a dc bias. The dc biases give rise to the space charges accumulating, namely electrode response, resulting in the significant increase of dielectric permittivity and dielectric loss tangent. Two Debey-like relaxations, arising from both electrode and grain boundary response, present in low frequency with the increase of the dc biases. The electrode relaxation and grain boundary relaxation are distinguished according to the impedance spectroscopy and the frequency dependent ac conductivity. The relaxation time of electrode and grain boundary is 0.955 ms and 0.026 ms with a dc bias of 10 V at 328 K, respectively

Enhancing E. coli isobutanol tolerance through engineering its global transcription factor cAMP receptor protein (CRP)

The limited isobutanol tolerance of Escherichia coli is a major drawback during fermentative isobutanol production. Different from classical strain engineering approaches, this work was initiated to improve E. coli isobutanol tolerance from its transcriptional level by engineering its global transcription factor cAMP receptor protein (CRP). Random mutagenesis libraries were generated by error-prone PCR of crp, and the libraries were subjected to isobutanol stress for selection. Variant IB2 (S179P, H199R) was isolated and exhibited much better growth (0.18 h−1) than the control (0.05 h−1) in 1.2% (v/v) isobutanol (9.6 g/L). Genome-wide DNA microarray analysis revealed that 58 and 308 genes in IB2 had differential expression (>2-fold, p < 0.05) in the absence and presence of 1% (v/v) isobutanol, respectively. When challenged with isobutanol, genes related to acid resistance (gadABCE, hdeABD), nitrate reduction (narUZYWV), flagella and fimbrial activity (lfhA, yehB, ycgR, fimCDF), and sulfate reduction and transportation (cysIJH, cysC, cysN) were the major functional groups that were up-regulated, whereas most of the down-regulated genes were enzyme (tnaA) and transporters (proVWX, manXYZ). As demonstrated by single-gene knockout experiments, gadX, nirB, rhaS, hdeB, and ybaS were found associated with strain isobutanol resistance. The intracellular reactive oxygen species (ROS) level in IB2 was only half of that of the control when facing stress, indicating that IB2 can withstand toxic isobutanol much better than the control. Biotechnol. Biotechnol