•Grain refinement increased the corrosion resistance of AZ61 alloy.•Proper annealing further increased the corrosion resistance.•Nanoscale particles decreased their susceptibility to microgalvanic ...corrosion.
Ultrafine-grained (1.1–1.5μm) AZ61 alloys containing nanoscaled β-Mg17Al12 phase particles (70–140nm) were prepared using high-ratio differential speed rolling (HRDSR) and their corrosion behaviours were studied in a 0.1M NaCl solution. The grain size reduction by HRDSR improved the corrosion resistance by enhancing passivity of the surface film. Post-annealing further increased the corrosion resistance by decreasing dislocation density in matrix. When significant grain growth took place, however, the corrosion resistance was decreased because of the pronounced negative effect of the increase in grain size. Refinement of β phase to nanoscale size decreased the susceptibility to microgalvanic corrosion.
The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated ...the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection.
This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant
, volume of extravascular extracellular space
and blood plasma volume
) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival.
Baseline median
, baseline first quartile
, and posttreatment median
were significant independent variables, as determined by univariate analysis (
< .05). By multivariate Cox regression analysis including methylation status of O
-methylguanine-DNA methyltransferase, baseline median
was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48,
= .003).
Baseline median
from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.
Reactor experiment for neutrino oscillation (RENO) began data-taking from August 2011. It successfully observed reactor antineutrino disappearance in April 2012 to measure the smallest mixing angle ...of θ13. Two identical detectors, one at near location and the other at far location, are constructed at the Yonggwang nuclear power plant in South Korea, to compare the observed reactor neutrino fluxes. Each RENO detector is filled with 16 mass tons of Gadolinium loaded liquid scintillator (GdLS) in the neutrino target region, and with 28 mass tons of unloaded liquid scintillator (LS) in the γ-catcher region surrounding the target. LS was developed to satisfy chemical, physical, optical properties, and safety requirements. Linear alkyl benzene (LAB) was chosen as a solvent because of its high flash-point, sufficient light yield, and being environmentally friendly. GdLS is carefully developed to keep a long attenuation length and high light yield for a long time period. In this paper, we report the characteristics and mass production of the RENO LS and GdLS.
•Exosomes have been identified to hold exceptional value in clinical diagnostics and tumor therapy.•A short overview of conventional methods of exosome isolation is summarized.•The recent ...advancements of microfluidic strategy for exosomes isolation and detection are overviewed.•A brief overview of exosome-based drug delivery for tumor therapy is provided.•The current challenges and outlook of these fields are assessed.
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Exosomes are a class of cell-secreted, nano-sized extracellular vesicles with a bilayer membrane structure of 30–150 nm in diameter. Their discovery and application have brought breakthroughs in numerous areas, such as liquid biopsies, cancer biology, drug delivery, immunotherapy, tissue repair, and cardiovascular diseases. Isolation of exosomes is the first step in exosome-related research and its applications. Standard benchtop exosome separation and sensing techniques are tedious and challenging, as they require large sample volumes, multi-step operations that are complex and time-consuming, requiring cumbersome and expensive instruments. In contrast, microfluidic platforms have the potential to overcome some of these limitations, owing to their high-precision processing, ability to handle liquids at a microscale, and integrability with various functional units, such as mixers, actuators, reactors, separators, and sensors. These platforms can optimize the detection process on a single device, representing a robust and versatile technique for exosome separation and sensing to attain high purity and high recovery rates with a short processing time. Herein, we overview microfluidic strategies for exosome isolation based on their hydrodynamic properties, size filtration, acoustic fields, immunoaffinity, and dielectrophoretic properties. We focus especially on advances in label-free isolation of exosomes with active biological properties and intact morphological structures. Further, we introduce microfluidic techniques for the detection of exosomal proteins and RNAs with high sensitivity, high specificity, and low detection limits. We summarize the biomedical applications of exosome-mediated therapeutic delivery targeting cancer cells. To highlight the advantages of microfluidic platforms, conventional techniques are included for comparison. Future challenges and prospects of microfluidics towards exosome isolation applications are also discussed. Although the use of exosomes in clinical applications still faces biological, technical, regulatory, and market challenges, in the foreseeable future, recent developments in microfluidic technologies are expected to pave the way for tailoring exosome-related applications in precision medicine.
Summary
What is known and objective
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) such as erlotinib or gefitinib are indicated for the treatment of non‐small cell lung ...cancer (NSCLC). EGFR tyrosine kinase domain mutations have been reported to be associated with EGFR‐TKI response in patients with NSCLC. Certain patient subgroups in which EGFR somatic mutations are more frequently observed are thought to derive more clinical benefit from EGFR‐TKI therapy. We performed a systematic review and meta‐analysis to summarize the evidence regarding the association of smoking status with overall survival (OS) and progression‐free survival (PFS) in patients with NSCLC receiving EGFR‐TKI therapy with erlotinib or gefitinib.
Methods
Eligible studies were selected by two independent reviewers using the inclusion and exclusion criteria predefined in the protocol. Eligible studies included those evaluating the association of smoking status with OS and PFS in patients with NSCLC receiving erlotinib or gefitinib. Non‐clinical studies, case reports, non‐peer‐reviewed s and non‐relevant studies were excluded.
Results and discussion
Data on OS and PFS in patients with NSCLC treated with EGFR‐TKIs were available in nine and ten trials, respectively. The OS and PFS from both the treatment and control groups were not significantly different between never smokers and former or current smokers (OS: odds ratio OR, 0·80; 95% confidence interval CI, 0·63–1·09; PFS: OR, 0·75; 95% CI, 0·49–1·14), respectively. However, in comparison within each smoking group, EGFR‐TKI treatment led to more favourable OS and PFS in never smokers (OS: OR, 0·55; 95% CI, 0·42−0·73; PFS: OR, 0·43; 95% CI, 0·33−0·54), compared with former or current smokers (OS: OR, 0·89; 95% CI, 0·80−0·97; PFS: OR, 0·73; 95% CI, 0·62−0·85).
What is new and conclusion
Among patients with NSCLC receiving EGFR‐TKI therapy with erlotinib or gefitinib, never smokers appear to show longer OS and PFS as compared to former or current smokers. However, this is based on indirect comparisons and more robust larger head‐to‐head trials are required for more robust inferences.
This meta‐analysis suggests never smokers appear to show longer OS and PFS as compared to former or current smokers among patients with NSCLC receiving EGFR‐TKI therapy with erlotinib or gefitinib.
Background
Acquired bilateral telangiectatic macules (ABTM) are a newly recognized disease entity, which manifest as multiple telangiectatic pigmented macules confined mostly to the upper arms.
...Objectives
To evaluate clinical and dermoscopic features in a group of 50 patients with ABTM and to determine the diagnostic usefulness of dermoscopy in ABTM.
Methods
Patients were selected from two tertiary teaching hospitals in Korea Pusan National University Hospitals (Busan and Yangsan). Fifty patients (41 males and 9 females; mean age 48.1 years; range 26–78 years) with ABTM were included in the study. The dermoscopic findings were graded using a 4‐point scale: none (0), mild (1), moderate (2) and severe (3). In addition, the results of 23 patients with and 27 patients without chronic liver disease (CLD) were compared to determine whether the presence of CLD affects dermoscopic findings.
Results
Three distinct dermoscopic patterns were observed; brown pigmentations, telangiectasia (linear‐irregular vessels) and an angioid streak pattern. Brown pigmentation in the group without CLD had higher severity score than those in CLD group (mean score: 2.00 vs. 1.48, P = 0.033). However, mean telangiectasia severity score was higher in the CLD group (2.14 vs. 1.39, P < 0.001). The angioid streak pattern was more severe and more common in patients with CLD than in those without 1.37 vs. 0.35 (P < 0.001) and 63.0% vs. 26.1%, respectively.
Conclusions
Detailed observations with dermoscopy can provide first clues of the presence of ABTM and underlying chronic liver disease.
To assess the diagnostic performance of ultrasound (US) for calcium pyrophosphate deposition (CPPD) at the level of menisci, hyaline cartilage (HC), tendons, and synovial fluid (SF) of the knee, and ...to examine inter- and intra-observer reliability.
We consecutively included patients with knee effusion over a 2-year period (43 patients with CPPD and 131 controls). All patients underwent SF analysis, conventional radiography (CR), and US examination using the Outcome Measures in Rheumatology (OMERACT) definition of the US characteristics of CPPD. Two independent operators performed the US, and inter-observer agreement was calculated. Intra-observer agreement was examined with static images obtained for all enrolled patients.
US revealed calcium pyrophosphate (CPP) deposits in menisci, HC, and tendon more frequently in patients with CPPD than in control patients. The presence of US CPP deposits in SF was not significantly different between the two groups. Combined US evaluation of the three components (menisci, HC, and tendon) showed the best diagnostic performance. The sensitivity and specificity for US evaluation of the three components were 74.4% and 77.1%, respectively, while for CR evaluation, the sensitivity and specificity were 44.2% and 96.9%, respectively. Inter- and intra-observer agreement were excellent for medial (κ = 0.930, 0.972) and lateral menisci (κ = 0.905, 0.942), HC (κ = 0.844, 0.957), and SF (κ = 0.817, 0.925). Tendon showed fair inter-observer (κ = 0.532) and good intra-observer reliability (κ = 0.788).
Based on the OMERACT definition, US demonstrated better diagnostic capacity than CR to diagnose CPPD, with excellent reliability. Combined evaluation of menisci, HC, and tendon showed the best diagnostic accuracy.
Collagen-derived gelatin/hydroxyapatite (HA) nanocomposites were biomimetically synthesized for hard tissue engineering scaffold. In vitro osteoblastic cellular responses to the nanocomposites were ...assessed in comparison with those conventionally mixed gelatin–HA composites. A three-dimensional culture method involving floating cells in a culture medium was introduced to assist in the initial attachment of the cells to the scaffolds, and the proliferation and differentiation behaviors of the cells were examined. The osteoblastic MG63 cells attached to the nanocomposites to a significantly higher degree and subsequently proliferated more. The alkaline phosphatase (ALP) activity and osteocalcin produced by the cells were significantly higher on the nanocomposite scaffolds than on the conventional composite scaffolds. These improved cellular responses on the nanocomposites are considered to result from the increased ionic release and serum protein adsorption on the nanocomposites, which was derived from the different structural and morphological characteristics, i.e., the nanocomposite scaffolds retained less-crystallized and smaller-sized apatite crystals and a more well-developed pore configuration than the conventional ones. Based on these findings, the biomimetically synthesized nanocomposite scaffolds are believed to be potentially useful in hard tissue regeneration and tissue engineering fields.
Circulating tumor DNA (ctDNA) has emerged as a tumor-specific biomarker for the early detection of various cancers. To date, several techniques have been devised to enrich the extremely small amounts ...of ctDNA present in plasma, but they are still insufficient for cancer diagnosis, especially at the early stage. Here, we developed a novel method, CUT (CRISPR-mediated, Ultrasensitive detection of Target DNA)-PCR, which uses CRISPR endonucleases to enrich and detect the extremely small amounts of tumor DNA fragments among the much more abundant wild-type DNA fragments by specifically eliminating the wild-type sequences. We computed that by using various orthologonal CRISPR endonucleases such as SpCas9 and FnCpf1, the CUT-PCR method would be applicable to 80% of known cancer-linked substitution mutations registered in the COSMIC database. We further verified that CUT-PCR together with targeted deep sequencing enables detection of a broad range of oncogenes with high sensitivity (<0.01%) and accuracy, which is superior to conventional targeted deep sequencing. In the end, we successfully applied CUT-PCR to detect sequences with oncogenic mutations in the ctDNA of colorectal cancer patients' blood, suggesting that our technique could be adopted for diagnosing various types of cancer at early stages.
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