Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide ...an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity.
Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC.
Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%.
Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.
The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against the transmission of medically important arboviruses. Here we compare Ae. ...aegypti mosquitoes infected with wMelCS or wAlbB to the widely used wMel Wolbachia strain on an Australian nuclear genetic background for their susceptibility to infection by dengue virus (DENV) genotypes spanning all four serotypes. All Wolbachia-infected mosquitoes were more resistant to intrathoracic DENV challenge than their wildtype counterparts. Blocking of DENV replication was greatest by wMelCS. Conversely, wAlbB-infected mosquitoes were more susceptible to whole body infection than wMel and wMelCS. We extended these findings via mosquito oral feeding experiments, using viremic blood from 36 acute, hospitalised dengue cases in Vietnam, additionally including wMel and wildtype mosquitoes on a Vietnamese nuclear genetic background. As above, wAlbB was less effective at blocking DENV replication in the abdomen compared to wMel and wMelCS. The transmission potential of all Wolbachia-infected mosquito lines (measured by the presence/absence of infectious DENV in mosquito saliva) after 14 days, was significantly reduced compared to their wildtype counterparts, and lowest for wMelCS and wAlbB. These data support the use of wAlbB and wMelCS strains for introgression field trials and the biocontrol of DENV transmission. Furthermore, despite observing significant differences in transmission potential between wildtype mosquitoes from Australia and Vietnam, no difference was observed between wMel-infected mosquitoes from each background suggesting that Wolbachia may override any underlying variation in DENV transmission potential.
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.
Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence ...and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.
Photocatalytic degradation using TiO
2
is one of the most effective techniques for treating residual emerging compounds present in water. However, practical applications are limited since it only ...absorbs ultraviolet irradiation. Nitrogen and sulfur (N, S) co-doped TiO
2
nanomaterials (N,S-TiO
2
) were prepared by a controlled sol–gel method; the characterization and photocatalytic activity have been studied for the removal of ciprofloxacin antibiotic under UV–Visible light. The interstitial doping of nitrogen and sulfur substitute oxygen and titanium into the TiO
2
lattice, which increases the valence band and decreases the conduction band, respectively. The lowest value band-gap of 2.5 eV and the crystallite size of 5.13 nm compared to other available synthesis methods was observed on N,S-TiO
2
which allowed to broaden the light absorption to the visible region. The low level electron and hole recombination was related by the N, S doping. The optimal ciprofloxacin removal was obtained at pH 5.5, a dosage of 0.05 g, initial concentration of 30 mg L
−1
with a removal efficiency of 78.7%. A comparison of the effectiveness of antibiotic treatment of N,S-TiO
2
with synthetic TiO
2
and commercial TiO
2
was also made, taking the potential for regeneration into account. The photocatalytic degradation of ciprofloxacin catalyzed by N,S-TiO
2
was described by pseudo-first-order kinetics.
The present work investigates the primary adsorption mechanisms of lead (II) and cadmium (II) cations onto pomelo fruit peel (PFP) from aqueous solution. pH, adsorption time, ion strength, and ...initial metal cation concentrations, which are factors affecting the uptake of these cations, are investigated. Results show that pH and ion strengths strongly affect the removal of these cations from aqueous solution. Different isotherm adsorption models, such as Langmuir, Freundlich, and Sips, are utilized to fit the experimental data in order to determine the adsorption in nature. The Langmuir monolayer adsorption capacities are found to be 47.18 mg/g for lead (II) and 13.35 mg/g for cadmium (II). Kinetic and thermodynamic studies based on a combination of FT-IR and TG-DSC spectroscopies demonstrate that electrostatic attraction plays a primary adsorption mechanism of lead (II) and cadmium (II) cations onto pomelo fruit peel.
Abstract
There are growing concerns on stress among nurses in low- and middle-income countries (LMICs) in South-East Asia. It is important to improve mental health among nurses in these countries. ...The objective of this study was to examine the efficacy of two types of newly developed smartphone-based stress management programs in improving depressive and anxiety symptoms among hospital nurses in Vietnam. This study was a three-arm (including two intervention groups and one control group) randomized trial. Participants were recruited from nurses in a large general hospital in Hanoi, Vietnam. Two types (free-choice and fixed sequential order) of smartphone-based stress management programs were developed. Participants were randomly allocated to Program A (a free-choice, multimodule stress management), Program B (a fixed-order, internet cognitive behavioral therapy, iCBT), or a control group (treatment as usual). The depressive and anxiety symptoms were measured by using the Depression Anxiety and Stress Scales at baseline, 3-, and 7-month follow-up surveys. 951 participants were randomly allocated to each of the three groups. Program B showed a statistically significant effect on improving depressive symptoms at 3-month (p = 0.048), but not at 7-month (p = 0.92); Cohen’s d was − 0.18 (95% CI − 0.34 to − 0.02) and 0.03 (95% CI − 1.00 to 1.05), respectively. Program A failed to show a significant intervention effect on any of the outcomes at 3- or 7-month follow-up (p > 0.05). Despite the small effect size, the present fixed-order iCBT program seems effective in improving depression of hospital nurses in Vietnam. A public health impact of the intervention can be scalable, when considering its accessibility and minimal cost.
Trial registration number: The study protocol is registered at the UMIN Clinical Trials Registry (UMINCTR; ID = UMIN000033139). Registered date of the protocol is 1st Jul. 2018.
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037796
Fucoidans from brown macroalgae (brown seaweeds) have different structures and many interesting bioactivities. Fucoidans are classically extracted from brown seaweeds by hot acidic extraction. Here, ...we report a new targeted enzyme-assisted methodology for fucoidan extraction from brown seaweeds. This enzyme-assisted extraction protocol involves a one-step combined use of a commercial cellulase preparation (Cellic
CTec2) and an alginate lyase from
sp. (SALy), reaction at pH 6.0, 40 °C, removal of non-fucoidan polysaccharides by Ca
precipitation, and ethanol-precipitation of crude fucoidan. The workability of this method is demonstrated for fucoidan extraction from
subsp.
(basionym
) and
as compared with mild acidic extraction. The crude fucoidans resulting directly from the enzyme-assisted method contained considerable amounts of low molecular weight alginate, but this residual alginate was effectively removed by an additional ion-exchange chromatographic step to yield pure fucoidans (as confirmed by
H NMR). The fucoidan yields that were obtained by the enzymatic method were comparable to the chemically extracted yields for both
and
, but the molecular sizes of the fucoidans were significantly larger with enzyme-assisted extraction. The molecular weight distribution of the fucoidan fractions was 400 to 800 kDa for
and 300 to 800 kDa for
, whereas the molecular weights of the corresponding chemically extracted fucoidans from these seaweeds were 10-100 kDa and 50-100 kDa, respectively. Enzyme-assisted extraction represents a new gentle strategy for fucoidan extraction and it provides new opportunities for obtaining high yields of native fucoidan structures from brown macroalgae.
The present study investigated the adsorption of molecular oxytetracycline (OTC) from aqueous solution onto surfactant-modified alumina (SMA). An anionic surfactant, sodium dodecyl sulfate (SDS), ...which was used to modify the alumina surface at high ionic strength induced a significant increase in the removal efficiency of OTC. Some conditions that were effective for the removal of OTC using SMA such as contact time, pH, adsorbent dosage, and ionic strength were systematically studied. The optimum contact time was 180 min, while the pH of the solution, adsorbent dosage and ionic strength were found to be 4, 25 mg/mL and 1 mM NaCl, respectively. The highest removal efficiency for OTC using SMA was >97%. Under the optimal adsorption conditions, OTC removal from an actual water sample collected from shrimp aquaculture achieved a very high removal efficiency of 90%. After the adsorbent was regenerated four times, the removal efficiency of OTC using SMA was still higher than 83%. A two-step adsorption model was successfully applied to fit the experimental results of OTC adsorption isotherms onto SMA at different ionic strengths, while the adsorption kinetics of OTC onto SMA followed a pseudo-second order model. The maximum adsorption capacity of OTC onto SMA was found to be 143 mg/g. The adsorption of OTC onto SMA decreased with the increasing NaCl concentration and pH because the SDS desorption out of the alumina surface was enhanced with an increase in salt concentration and pH. The adsorption mechanisms of OTC onto SMA were discussed in detail based on Fourier transform infrared (FT-IR) spectroscopy, zeta potential measurements, adsorption isotherms of OTC and SDS desorption upon OTC adsorption. Our results demonstrate that the surface modification of alumina with SDS is important to form a novel adsorbent for the removal of tetracycline antibiotics from aqueous solution.
Adsorption of oxytetracycline (OTC) onto surfactant-modified alumina (SMA). The change in surface charge by ζ potential, adsorption isotherms at two ionic strength and the treatment with a real aquaculture water sample. Display omitted
•SMA is a novel adsorbent for OTC removal.•A maximum adsorption capacity of OTC onto SMA is found to be 143 mg/g.•The adsorption agrees with the two-step and pseudo-second-order kinetic models.•Adsorption of OTC onto SMA was mainly controlled by electrostatic attractions.•The removal of OTC is >83% after four recycles.
A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New ...compounds (1 and 2) were obtained and identified by spectroscopic methods (HRESIMS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 µM) toward TNF-α production, respectively.
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