The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with ...non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of circulating tumor DNA (ctDNA) in plasma, known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a protocol for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC. Paired plasma and tumor tissue samples were used to evaluate mutation profiles detected by ultra-deep MPS, which showed 87.5% concordance. Cross-platform comparison with droplet digital PCR demonstrated comparable detection performance (91.4% concordance, Cohen's kappa coefficient of 0.85 with 95% CI = 0.72-0.97) and great reliability in quantification of mutation allele frequency (Intraclass correlation coefficient of 0.96 with 95% CI = 0.90-0.98). Our results highlight the potential application of liquid biopsy using ultra-deep MPS as a routine assay in clinical practice for both detection and quantification of actionable mutation landscape in NSCLC patients.
It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that ...cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection.
49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts.
Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired.
Triboelectric nanogenerator (TENG) as a novel energy harvester has raised wide research interests recently, although the environmental effect on its performance is still lacking. This paper attempted ...to experimentally quantify the effect of the relative humidity (RH) as well as the pressure on the charge generated from a TENG. It was found that under the same mechanical excitation, the generated charge of the TENG increased more than 20% when RH decreased from 90% to 10% at the ambient pressure. However, the generated charge decreased as the air pressure decreased from atmospheric pressure to 50Torr at RH close to 0%, while the optimal pressure shifted to a lower level when the relative humidity was higher. This study can contribute not only to the design and packaging of triboelectric devices to operate in varying environments and extreme conditions, but also to the fundamental understanding of the mechanism of triboelectric effect.
Effect of humidity and pressure on the triboelectric nanogenerator. Display omitted
•Triboelectric nanogenerator was fabricated with micro patterns to enhance charge.•Charge increases more than 20% as RH decreases from 90% to 10%.•Charge decreases with increasing rate as pressure decreases to 50Torr.•Optimal condition is 0% RH and ambient pressure.•Optimal pressure would be lower if RH is higher.
•This paper forecasts the crack propagation based on long short-term memory and hidden Markov model.•The present approach reduces significantly a large amount of computational cost when predicting ...crack propagation without any analysis tools.•A novel data-driven model has the ability to learn with less information.•Numerical results show high efficiency of the present approach.
We present in this paper a combined technique of long short-term memory and hidden Markov model to prediction problems of crack propagation in engineering. The primary advantage of the hidden Markov model is that the ability to learn with less information, in other words, its future states do not depend on past ones, based only on the present state. We use long short-term memory to train data, and output consequences improved by adding predicted different changes that are computed by hidden Markov model. Applying this combined method to numerical examples of forecasting crack propagation of singled-edge-notched beam forced by 4-point shear, crack-height growth in Marcellus shale under the hydraulic fracturing and deformations of dam structures made from fiber reinforced concrete material is addressed. The tests were carried out with many different sizes of experimental data. It was found that a combined long short-term memory - hidden Markov model results in more accurate solution than only using long short-term memory, especially in the case of the dataset that is lack of information.
Peptides have attracted considerable attention due to their biocompatibility, functional molecular recognition and unique biological and electronic properties. The strong piezoelectricity in ...diphenylalanine peptide expands its technological potential as a smart material. However, its random and unswitchable polarization has been the roadblock to fulfilling its potential and hence the demonstration of a piezoelectric device remains lacking. Here we show the control of polarization with an electric field applied during the peptide self-assembly process. Uniform polarization is obtained in two opposite directions with an effective piezoelectric constant d
reaching 17.9 pm V
. We demonstrate the power generation with a peptide-based power generator that produces an open-circuit voltage of 1.4 V and a power density of 3.3 nW cm
. Devices enabled by peptides with controlled piezoelectricity provide a renewable and biocompatible energy source for biomedical applications and open up a portal to the next generation of multi-functional electronics compatible with human tissue.
Various strategies for active learning have been proposed in the machine learning literature. In uncertainty sampling, which is among the most popular approaches, the active learner sequentially ...queries the label of those instances for which its current prediction is maximally uncertain. The predictions as well as the measures used to quantify the degree of uncertainty, such as entropy, are traditionally of a probabilistic nature. Yet, alternative approaches to capturing uncertainty in machine learning, alongside with corresponding uncertainty measures, have been proposed in recent years. In particular, some of these measures seek to distinguish different sources and to separate different types of uncertainty, such as the reducible (epistemic) and the irreducible (aleatoric) part of the total uncertainty in a prediction. The goal of this paper is to elaborate on the usefulness of such measures for uncertainty sampling, and to compare their performance in active learning. To this end, we instantiate uncertainty sampling with different measures, analyze the properties of the sampling strategies thus obtained, and compare them in an experimental study.
•Mechanical properties of plasticized starch blend (CSMB) films were non-additive.•The non-additive effect was more pronounced in the glycerol-plasticized system.•CSMB films had most of thermal ...properties close to one of individual (MB) films.•Plasticized CSMB and MB films had a similar crystallinity type.•M¯w of amylose of CSMB films was similar to that of MB films but not the content.
The main objective of the study was to gain insight into structural and mechanical starch behaviors of the plasticized starch blend films. Mechanical properties and starch behaviors of cassava (CS)/and mungbean (MB) (50/50, w/w) starch blend films containing glycerol (Gly) or sorbitol (Sor) at 33% weight content were investigated. It was found that tensile strength TS and %E of the Gly-CSMB films were similar to those of MB films; but%E of all Sor-films was identical. TS of plasticized films increased when AM content and crystallinity increased. When Sor was substituted for Gly, crystallinity of starch films and their TS increased. The CSMB and MB films had somewhat a similar molecular profile and comparable mechanical properties. Therefore, it was proposed the starch molecular profile containing amylopectin with high M¯w, low M¯w of amylose, and the small size of intermediates may impart the high TS and%E of starch films.
Bio‐sourced epoxy resins from resorcinol diglycidyl ether (RDGE) have been obtained by using cationic photopolymerization under UV‐light exposure. The photoinduced bulk resin samples were ...characterized by three‐point bending tests, dynamic mechanical analysis, as well as differential scanning calorimetry analysis, and thermogravimetric analysis. The influence of processing parameters, that is, reactant contents, UV irradiation time, and postcuring conditions on the thermomechanical behavior has been pointed out. For instance, the flexural modulus of the most performing materials reaches 4.1 GPa with the flexural strength and the glass‐transition temperature of around 105 MPa and 99°C, respectively. Interestingly, our optimized protocol has led to the synthesis of new bio‐based materials with more valuable thermal and mechanical properties than those of thermocured materials obtained from petroleum‐based commercial epoxy resins. Focus has been given on processing parameters to optimize the final properties of the material and to open an interesting alternative for sustainable building materials.
Background This study aimed to measure the preferences for mental health support among health professionals, their willingness to support the mental health of colleagues and associated factors. ...Method A descriptive cross-sectional study was performed from August to October 2022 within five hospitals located in Hanoi, Vietnam. A total of 244 health professionals participated in the study. Data on socio-economic status, health and COVID-19-related characteristics, Depression Anxiety Stress Scale (DASS-21); and preferences for mental health support services were collected by using a structured self-reported questionnaire. Multivariate logistic regression models were utilized to identify associated factors with the demand for mental support services. Results 13.9%, 17.1% and 8.6% reported having at least mild depression, anxiety and stress, respectively. There 13.9% did not seek any mental health support during the COVID-19 pandemic. The most common support included talking with friends (52.9%), family (50.8%), colleagues (47.6%) and using social networks/Internet (43.5%). There 31.1% had been aware of mental health services, but only 18.0% used this service at least once. Regarding preferences, 47.3% had a demand for mental support services, and the most preferred service was providing coping skills (25.9%), followed by skills to support others against mental problems (22.2%). Major sources of support included psychiatrists (34.4%), colleagues (29.1%) and family (27.9%). The main preferred channels for support included telephone/mobile phone (35.7%) and Internet (20.9%). Only 12.3% were willing to provide mental support for colleagues during the pandemic. Age, education, perceived mental health status, ever seeking any mental service, and DASS-21 depression score were associated with demand for mental support services. Conclusion This study found a lack of awareness of mental health services for health professionals, as well as moderate levels of demand for this service in this population. Raising awareness and developing tailored mental health support services are important to enhancing the mental well-being of health professionals in Vietnam to prepare for the next pandemic.
Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops ...after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.
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