Accurate grading for prostatic carcinoma in pathological images is important to prognosis and treatment planning. Since human grading is always time-consuming and subjective, this paper presents a ...computer-aided system to automatically grade pathological images according to Gleason grading system which is the most widespread method for histological grading of prostate tissues. We proposed two feature extraction methods based on fractal dimension to analyze variations of intensity and texture complexity in regions of interest. Each image can be classified into an appropriate grade by using Bayesian, k -NN, and support vector machine (SVM) classifiers, respectively. Leave-one-out and k -fold cross-validation procedures were used to estimate the correct classification rates (CCR). Experimental results show that 91.2%, 93.7%, and 93.7% CCR can be achieved by Bayesian, k -NN, and SVM classifiers, respectively, for a set of 205 pathological prostate images. If our fractal-based feature set is optimized by the sequential floating forward selection method, the CCR can be promoted up to 94.6%, 94.2%, and 94.6%, respectively, using each of the above three classifiers. Experimental results also show that our feature set is better than the feature sets extracted from multiwavelets, Gabor filters, and gray-level co-occurrence matrix methods because it has a much smaller size and still keeps the most powerful discriminating capability in grading prostate images.
The study of circulating tumor cells (CTCs) offers pathways to develop new diagnostic and prognostic biomarkers that benefit cancer treatments. In order to fully exploit and interpret the information ...provided by CTCs, the development of a platform is reported that integrates acoustics and microfluidics to isolate rare CTCs from peripheral blood in high throughput while preserving their structural, biological, and functional integrity. Cancer cells are first isolated from leukocytes with a throughput of 7.5 mL h−1, achieving a recovery rate of at least 86% while maintaining the cells' ability to proliferate. High‐throughput acoustic separation enables statistical analysis of isolated CTCs from prostate cancer patients to be performed to determine their size distribution and phenotypic heterogeneity for a range of biomarkers, including the visualization of CTCs with a loss of expression for the prostate specific membrane antigen. The method also enables the isolation of even rarer, but clinically important, CTC clusters.
A platform that integrates acoustics and microfluidics to isolate rare circulating tumor cells from peripheral blood in high throughput while preserving their structural, biological, and functional integrity is developed. The platform utilizes divider design to modify fluid velocity profile thus improving separation accuracy, and a hybrid poly(dimethylsiloxane)–glass resonator design to form an acoustic resonator, thus improving separation throughput.
Real-time reverse transcription-PCR (RT-PCR) is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 ...(COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs and two sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log
genome copies/ml sample for detecting the
,
, and
genes, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and nonstructural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.
Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus ...2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.
Background and Aims
Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer‐specific survival in various BTC subtypes, including gallbladder ...cancer, ampulla of Vater cancer, and cholangiocarcinoma.
Approach and Results
Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose–response relationship. Cox’s proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow‐up of 1.59 years, the 5‐year survival rate was 27.4%. The multivariate‐adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC‐specific death. Adjusted HRs for BTC‐specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose–response trend (P < 0.001; nonusers as a reference). Cancer‐specific mortality was lower with postdiagnosis aspirin use in patients with all major BTC subtypes.
Conclusions
The nationwide study revealed that postdiagnosis aspirin use was associated with improved BTC‐specific mortality of various subtypes. The findings suggest that additional randomized trials are required to investigate aspirin’s efficacy in BTC.
Abstract
The standard size of bougie for laparoscopic sleeve gastrectomy (LSG) is not yet established. Therefore, a systematic review and network meta-analysis were conducted to assess the weight ...loss effects and associated complications of LSG for patients with morbid obesity, based on different bougie sizes. A total of 15 studies were reviewed in this systemic review and network meta-analysis (2,848 participants), including RCTs and retrospective studies in PubMed, and Embase until September 1, 2020. The effectiveness of different bougie calibration sizes was assessed based on excess weight loss (EWL), total complications, and staple line leak. Within this network meta-analysis, S-sized (≤ 32 Fr.) and M-sized (33–36 Fr.) bougies had similar effects and were associated with the highest EWL improvement among all different bougie sizes (S-sized: standardized mean difference SMD, 10.52; 95% confidence interval CI − 5.59 to − 26.63, surface under the cumulative ranking curve SUCRA, 0.78; and M-sized: SMD, 10.16; 95% CI − 3.04–23.37; SUCRA, 0.75). M-sized bougie was associated with the lowest incidence of total complications (M-sized: odds ratio, 0.43; 95% CI, 0.16–1.11; SUCRA, 0.92). Based on our network meta-analysis, using M-sized bougie (33–36 Fr.) is an optimal choice to balance the effectiveness and perioperative safety of LSG in the clinical practice.
C1GALT1 controls the crucial step of GalNAc-type O-glycosylation and is associated with both physiologic and pathologic conditions, including cancers. EPH receptors comprise the largest family of ...receptor tyrosine kinases (RTKs) and modulate a diverse range of developmental processes and human diseases. However, the role of C1GALT1 in the signaling of EPH receptors remains largely overlooked. Here, we showed that C1GALT1 high expression in gastric adenocarcinomas correlated with adverse clinicopathologic features and is an independent prognostic factor for poor overall survival. Silencing or loss of C1GALT1 inhibited cell viability, migration, invasion, tumor growth and metastasis, as well as increased apoptosis and cytotoxicity of 5-fluorouracil in AGS and MKN45 cells. Phospho-RTK array and western blot analysis showed that C1GALT1 depletion suppressed tyrosine phosphorylation of EPHA2 induced by soluble Ephrin A1-Fc. O-glycans on EPHA2 were modified by C1GALT1 and both S277A and T429A mutants, which are O-glycosites on EPHA2, dramatically enhanced phosphorylation of Y588, suggesting that not only overall O-glycan structures but also site-specific O-glycosylation can regulate EPHA2 activity. Furthermore, depletion of C1GALT1 decreased Ephrin A1-Fc induced migration and reduced Ephrin A1 binding to cell surfaces. The effects of C1GALT1 knockdown or knockout on cell invasiveness in vitro and in vivo were phenocopied by EPHA2 knockdown in gastric cancer cells. These results suggest that C1GALT1 promotes phosphorylation of EPHA2 and enhances soluble Ephrin A1-mediated migration primarily by modifying EPHA2 O-glycosylation. Our study highlights the importance of GalNAc-type O-glycosylation in EPH receptor-regulated diseases and identifies C1GALT1 as a potential therapeutic target for gastric cancer.
Calreticulin (CRT) and vascular endothelial growth factor-A (VEGF-A) are crucial for angiogenesis, and mediate multiple malignant behaviors in gastric cancer. In this study, we report that CRT is ...positively correlated with VEGF-A in gastric cancer patients. Moreover, high expressions of both CRT and VEGF-A are markedly associated with the pathological stage, progression, and poor prognosis in the patients. Therefore, we sought to elucidate the mechanism by which CRT affects VEGF-A in gastric cancer. Firstly, we demonstrate the novel finding that knockdown of CRT reduced VEGF-A mRNA stability in two gastric cancer cell lines, AGS and MKN45. The AU-Rich element (ARE) is believed to play a crucial role in the maintenance of VEGF-A mRNA stability. Luciferase reporter assay shows that knockdown of CRT significantly decreased the activity of renilla luciferase with VEGF-A ARE sequence. Additionally, competition results from RNA-binding/electrophoretic mobility shift assay indicate that CRT forms an RNA-protein complex with the VEGF-A mRNA by binding to the ARE. In addition, the proliferation rate of human umbilical vein endothelial cells (HUVEC) was significantly reduced when treated with conditioned medium from CRT knockdown cells; this was rescued by exogenous VEGF-A recombinant protein. Our results demonstrate that CRT is involved in VEGF-A ARE binding protein complexes to stabilize VEGF-A mRNA, thereby promoting the angiogenesis, and progression of gastric cancer.
The addition of Ag nanoparticles (Ag NPs) with an average size of 30 nm into ZnO increases the electric conductivity up to 1000 times. While a similar increase in the conductivity is observed in a ...mixture of Ag nanoparticles and Al-doped ZnO (AZO) films, a physical mechanism underlying the change in electric conductivity is not the same for Ag NP-added ZnO and Ag NP-added AZO. In Ag NP-added ZnO, an ohmic junction is formed at the ZnO–Ag interface, and electrons are accumulated in ZnO near the ZnO–Ag interface until electron-rich islands are connected. However, in Ag NP-added AZO, electrons in Ag NPs move to the AZO matrix via thermionic emission and travel through the AZO matrix. This change in electron transport at ZnO–Ag and AZO–Ag interfaces is due to the fact that the work function of ZnO (4.62 eV) is larger than those of Ag (4.24 eV) and AZO (4.15 eV). An increase in Ag NP content in the ZnO matrix leads to the overlap of the electron accumulation regions and forms a percolation path for the electron transport without deteriorating the electron mobility. Hence, the electron concentration increases to 2.4 × 1020/cm3 in the 1.4 vol % Ag NP-added ZnO film. In addition, Ag NPs have a negligible effect on the transmittance, and the best Haacke figure of merit (ΦH) values are 2.86 and 5.18 for ZnO:Ag NP and AZO:Ag NP, respectively.
Precise and selective manipulation of colloids and biological cells has long been motivated by applications in materials science, physics and the life sciences. Here we introduce our harmonic ...acoustics for a non-contact, dynamic, selective (HANDS) particle manipulation platform, which enables the reversible assembly of colloidal crystals or cells via the modulation of acoustic trapping positions with subwavelength resolution. We compose Fourier-synthesized harmonic waves to create soft acoustic lattices and colloidal crystals without using surface treatment or modifying their material properties. We have achieved active control of the lattice constant to dynamically modulate the interparticle distance in a high-throughput (>100 pairs), precise, selective and reversible manner. Furthermore, we apply this HANDS platform to quantify the intercellular adhesion forces among various cancer cell lines. Our biocompatible HANDS platform provides a highly versatile particle manipulation method that can handle soft matter and measure the interaction forces between living cells with high sensitivity.
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