Chemotherapy has been reported to induce epithelial-mesenchymal transition (EMT) in tumor cells, which is a critical step in the process of metastasis leading to cancer spreading and treatment ...failure. However, the underlying mechanisms of chemotherapy-induced EMT remain unclear, and the involvement of microRNAs (miRNA) in this process is poorly understood. To address these questions, we established stable chemotherapy-resistant tongue squamous cell carcinoma (TSCC) cell lines CAL27-res and SCC25-res by exposing the parental CAL27 and SCC25 lines to escalating concentrations of cisplatin for 6 months. CAL27-res and SCC25-res cells displayed mesenchymal features with enhanced invasiveness and motility. MiRNA microarray illustrated that miR-200b and miR-15b were the most significantly downregulated microRNAs in CAL27-res cells. Ectopic expression of miR-200b and miR-15b with miRNA mimics effectively reversed the phenotype of EMT in CAL27-res and SCC25-res cells, and sensitized them to chemotherapy, but inhibition of miR-200b and miR-15b in the sensitive lines with anti-sense oligonucleotides induced EMT and conferred chemoresistance. Retrieving the expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a target for miR-200b and miR-15b, in the presence of the miRNA mimics by transfecting CAL27-res cells with pcDNA3.1-BMI1-carrying mutated seed sequences of miR-200b or miR-15b at its 3'-UTR recapitulated chemotherapy-induced EMT. In vivo, enforced miR-200b or miR-15b expression suppressed metastasis of TSCC xenografts established by CAL27-res cells. Clinically, reduced miR-200b or miR-15b expression was associated with chemotherapeutic resistance in TSCCs and poor patient survival. Our data suggest that reduced expression of miR-200b and miR-15b underscores the mechanisms of chemotherapy-induced EMT in TSCC, and may serve as therapeutic targets to reverse chemotherapy resistance in tongue cancers.
Summary
Background
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease in the US. Understanding the epidemiology of NAFLD, with specific focus on individuals with ...hepatic fibrosis is important to guide healthcare resource planning.
Aim
To evaluate prevalence and predictors of hepatic fibrosis among US adults with NAFLD.
Methods
We performed a cross‐sectional study using data from the updated 2011‐2014 National Health and Nutrition Examination Survey, a national, stratified, multistage sampling survey of non‐institutionalised US adults age ≥ 20. METAVIR F2 or greater fibrosis among individuals with NAFLD was assessed using AST to Platelet Ratio Index (APRI) score > 0.7. METAVIR F3 or greater fibrosis was assessed using NAFLD fibrosis score (NFS) > 0.676 and FIB‐4 score > 3.25. Multivariate logistic regression models evaluated for predictors of fibrosis among individuals with NAFLD.
Results
Overall prevalence of NAFLD among US adults was 21.9% (95% CI 20.6‐23.3), representing 51.6 million adults. Among individuals with NAFLD, we observed a 23.8% prevalence of ≥F2 fibrosis, representing 12.2 million individuals, and we observed a 2.3%‐9.7% prevalence of ≥F3 fibrosis, representing as many as 5.0 million adults. On multivariate regression analyses, increasing age, obesity and concurrent diabetes mellitus were associated with increased risk of ≥F3 fibrosis.
Conclusions
NAFLD represents a major healthcare burden among US adults with as many as 5 million adults estimated to have NAFLD with ≥F3 fibrosis. Age and the components of the metabolic syndrome are independently associated with higher risk of fibrosis.
Linked ContentThis article is linked to Brennan and Dillon et al and Wong papers. To view these articles visit https://doi.org/10.1111/apt.14396, https://doi.org/10.1111/apt.14850 and https://doi.org/10.1111/apt.14909.
Dissipative particle dynamics (DPD) is a mesoscale particle method that bridges the gap between microscopic and macroscopic simulations. It can be regarded as a coarse-grained molecular dynamics ...method suitable for larger time and length scales. It has been successfully applied to different areas of interests, especially in modeling the hydrodynamic behavior of complex fluids in mesoscale. This paper presents an overview on DPD including the methodology, formulation, implementation procedure and some related numerical aspects. The paper also reviews the major applications of the DPD method, especially in modeling (1) micro drop dynamics, (2) multiphase flows in micro-channels and fracture networks, (3) movement and suspension of macromolecules in micro channels and (4) movement and deformation of single cells. The paper ends with some concluding remarks summarizing the major features and future possible development of this unique mesoscale modeling technique.
The Nottingham histological grade (NHG) is a well-established prognostic factor for breast cancer that is broadly used in clinical decision making. However, ∼50% of patients are classified as grade ...2, an intermediate risk group with low clinical value. To improve risk stratification of NHG 2 breast cancer patients, we developed and validated a novel histological grade model (DeepGrade) based on digital whole-slide histopathology images (WSIs) and deep learning.
In this observational retrospective study, routine WSIs stained with haematoxylin and eosin from 1567 patients were utilised for model optimisation and validation. Model generalisability was further evaluated in an external test set with 1262 patients. NHG 2 cases were stratified into two groups, DG2-high and DG2-low, and the prognostic value was assessed. The main outcome was recurrence-free survival.
DeepGrade provides independent prognostic information for stratification of NHG 2 cases in the internal test set, where DG2-high showed an increased risk for recurrence (hazard ratio HR 2.94, 95% confidence interval CI 1.24-6.97, P = 0.015) compared with the DG2-low group after adjusting for established risk factors (independent test data). DG2-low also shared phenotypic similarities with NHG 1, and DG2-high with NHG 3, suggesting that the model identifies morphological patterns in NHG 2 that are associated with more aggressive tumours. The prognostic value of DeepGrade was further assessed in the external test set, confirming an increased risk for recurrence in DG2-high (HR 1.91, 95% CI 1.11-3.29, P = 0.019).
The proposed model-based stratification of patients with NHG 2 tumours is prognostic and adds clinically relevant information over routine histological grading. The methodology offers a cost-effective alternative to molecular profiling to extract information relevant for clinical decisions.
•A novel deep learning model was developed and validated for improved breast cancer histological grading.•The model uses routine histopathology images and provides independent prognostic value for stratification of the NHG 2 group.•Model-based histological grading offers a cost-effective alternative to molecular profiling for improved risk stratification.
Background
Acupuncture is used to treat chronic functional constipation (CFC) in China, despite limited evidence. We aim to assess the effectiveness and safety of acupuncture in managing CFC.
Methods
...A multicenter randomized controlled trial was performed involving 684 patients with CFC; the patients were randomly allocated to receive He acupuncture (n = 172), Shu‐mu acupuncture (n = 171), He‐shu‐mu acupuncture (n = 171), or oral administration of mosapride (n = 170). Sixteen sessions of acupuncture were given in the treatment duration of 4 weeks. The primary outcome was the change in spontaneous bowel movements (SBMs) at week 4 (at the end of treatment) compared to baseline. The secondary outcomes included stool consistency (Bristol scale), the degree of straining during defecation, and adverse events.
Key Results
The SBMs increased in all the four groups at week 4, and the magnitude of increase was equivalent in the four groups (He acupuncture, 2.7 95% CI, 2.3‐3.1; Shu‐mu acupuncture, 2.7 95% CI, 2.3‐3.0; He‐shu‐mu acupuncture, 2.2 95% CI, 1.9‐2.5; and mosapride, 2.4 95% CI, 2.0‐2.9; P = .226). However, the change in SBMs at week 8 was significantly smaller in mosapride group (1.4 95% CI, 1.0‐1.8) than the three acupuncture groups (2.4 95% CI, 2.1‐2.7, 2.3 95% CI, 1.9‐2.7, 2.1 95% CI, 1.7‐2.5 in He, Shu‐mu, and He‐shu‐mu group, respectively, P = .005).
Conclusions & Interferences
The three acupuncture treatments were as effective as mosapride in improving stool frequency and stool consistency in CFC, but the magnitude of the treatment effect is unknown due to the lack of sham acupuncture control.
The effectiveness of acupuncture in the treatment of chronic functional constipation is unknown. Our study result showed that acupuncture treatments are as effective as mosapride in improving stool frequency and stool consistency.
•Thermal buckling and free vibration of viscoelastic sandwich shell is studied.•The sandwich shell is composed of two FGM skins and an auxetic honeycomb core.•Poisson's ratio of the auxetic honeycomb ...core is tunable.•Negative Poisson's ratio for the core of the sandwich shell is considered.
In this paper, thermal buckling and free vibration of viscoelastic functionally graded sandwich shell with tunable auxetic honeycomb core is investigated. The sandwich shell has functionally graded material (FGM) skins at top and bottom and tunable auxetic honeycomb core at the middle. The viscoelastic behavior of the skins and core are modeled according to complex modulus approach in combination with the elastic–viscoelastic correspondence principle. Poisson's ratio of the auxetic honeycomb core is tunable. It has positive or negative value, which depends on an angle parameter of the unit cell of the auxetic honeycomb core. The equations of motion for the viscoelastic FGM sandwich shell with tunable auxetic honeycomb core are derived using Hamilton's principle. Analytical solution for simply supported shell is obtained using Navier's solution procedure. The effects of the geometry parameters, temperature rise, parameters of the tunable auxetic honeycomb core are studied.
In this article, an accurate and robust numerical formulation is presented for the simulation of the fluid-structure interaction in incompressible fluid flow. The incompressible Navier-Stokes ...equation is discretized with a stabilized finite element framework on the fixed Eulerian grid. Both symmetric and non-symmetric Nitsche's methods are accessed and employed to weakly impose Dirichlet boundary condition along the interface embedded in the element together with the ghost penalty method stabilizing the solution jump across the element edges. An easy-to-implement and robust numerical integration scheme based on a projection approach is proposed. To the author's knowledge, so far, there is no application of a projection-based approach in the field of numerical integration to deal with discontinuities. Therefore, the results presented in this article is considered as a pioneered and novel projection-based approach in the field of numerical integration to deal with embedded discontinuous function. A second-order staggered-partitioned scheme is employed to weakly couple the fluid and structure solvers. A second-order accurate and unconditionally stable time integration scheme is implemented for simulations. Accurate numerical results are obtained in the numerical examples and validation cases, including vortex-induced vibration (VIV), rotation, freely fall and rigid-body contact.
Since the 1980s, vacuum hot rolling has been developed to fabricate the stainless steel clad plates by the Iron and Steel Institute of Japan. Herein, hot rolling is a widely used solid-state bonding ...process to join the carbon steel substrate and stainless steel cladding. In this paper, we provide a brief overview of the vacuum hot rolling process and effective parameters on the interface characteristics and shear strength of stainless steel clad plate. The effects of surface preparation condition, atmosphere condition, vacuum degree, rolling temperature, rolling reduction ratio, interlayer, heat treatment on the microstructure, interface characteristics and mechanical properties of stainless steel clad plate have been analyzed in detail. It is shown that the interface transition zone is formed due to the carbon diffusion, and the strong interface bonding is attributed to the sufficient alloy elements diffusion of Fe, Cr and Ni. Moreover, the interface shear strength and toughness are also affected by interfacial precipitation phase and multiple oxides. Finally, the present work concluded the bonding mechanism of hot-rolled stainless steel clad based on the oxide film theory, diffusion theory, recrystallization theory and three stage theory.
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