Predictors of Shunt Dysfunction and Overall Survival in Patients with Variceal Bleeding Treated with Transjugular Portosystemic Shunt Creation Using the Fluency Stent Graft

Publication date: Available online 17 January 2018
Source:Academic Radiology
Author(s): Yue-Meng Wan, Yu-Hua Li, Ying Xu, Hua-Mei Wu, Ying-Chun Li, Xi-Nan Wu, Jin-Hui Yang
Rationale and ObjectivesTransjugular intrahepatic portosystemic shunt (TIPS) is an established method for portal hypertension. This study was to investigate the long-term safety, technical success, and patency of TIPS, and to determine the risk factors and clinical impacts of shunt dysfunction.Materials and MethodsA total of 154 consecutive patients undergoing embolotherapy of gastric coronary vein and/or short gastric vein and TIPS creation were prospectively studied. Follow-up data included technical success, patency and revision of TIPS, and overall survival of patients.ResultsDuring the study, the primary and secondary technical success rates were 98.7% and 100%, respectively. Sixty-three patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt occlusion. The cumulative 60-month primary, primary assisted, and secondary patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month overall survival rates were similar between the TIPS dysfunction group and the TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein thrombosis (P < .001), use of bare stents (P = .018), and portal pressure gradient (PPG) (P = .020) were independent predictors for shunt dysfunction, hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival. The accuracy of PPG for shunt dysfunction was statistically significant (P < .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity.ConclusionsThe long-term safety, technical success, and patency of TIPS were good; baseline portal vein thrombosis, use of bare stents, and PPG were significantly associated with shunt dysfunction; shunt dysfunction has little impact on patients' long-term survival because of high secondary patency rates.



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Can You Do Health Disparities Research with Publicly Available Datasets?

Publication date: Available online 17 January 2018
Source:Academic Radiology
Author(s): Danny R. Hughes
Rationale and ObjectivesGiven the growing importance of identifying and reducing health disparities, it is important for radiologist researchers to engage in this space to promote evidence-based imaging disparities policy. However, researchers are often hindered by access to appropriate data to perform quality research.Materials and MethodsThis paper reviews existing publicly available data sets that may be useful for performing imaging disparities research.ResultsMultiple data sources are publicly available and have been used by previous researchers to examine imaging disparities.ConclusionsThis paper provides an overview of publicly available data sources that radiologists can use for imaging disparities research. Appropriate use of these data sources will require researchers to carefully consider the overall research question and level of analysis.



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Effect of Matrix Size on the Image Quality of Ultra-high-resolution CT of the Lung

Publication date: Available online 17 January 2018
Source:Academic Radiology
Author(s): Akinori Hata, Masahiro Yanagawa, Osamu Honda, Noriko Kikuchi, Tomo Miyata, Shinsuke Tsukagoshi, Ayumi Uranishi, Noriyuki Tomiyama
Rationale and ObjectivesThis study aimed to assess the effect of matrix size on the spatial resolution and image quality of ultra-high-resolution computed tomography (U-HRCT).Materials and MethodsSlit phantoms and 11 cadaveric lungs were scanned on U-HRCT. Slit phantom scans were reconstructed using a 20-mm field of view (FOV) with 1024 matrix size and a 320-mm FOV with 512, 1024, and 2048 matrix sizes. Cadaveric lung scans were reconstructed using 512, 1024, and 2048 matrix sizes. Three observers subjectively scored the images on a three-point scale (1 = worst, 3 = best), in terms of overall image quality, noise, streak artifact, vessel, bronchi, and image findings. The median score of the three observers was evaluated by Wilcoxon signed-rank test with Bonferroni correction. Noise was measured quantitatively and evaluated with the Tukey test. A P value of <.05 was considered significant.ResultsThe maximum spatial resolution was 0.14 mm; among the 320-mm FOV images, the 2048 matrix had the highest resolution and was significantly better than the 1024 matrix in terms of overall quality, solid nodule, ground-glass opacity, emphysema, intralobular reticulation, honeycombing, and clarity of vessels (P < .05). Both the 2048 and 1024 matrices performed significantly better than the 512 matrix (P < .001), except for noise and streak artifact. The visual and quantitative noise decreased significantly in the order of 512, 1024, and 2048 (P < .001).ConclusionIn U-HRCT scans, a large matrix size maintained the spatial resolution and improved the image quality and assessment of lung diseases, despite an increase in image noise, when compared to a 512 matrix size.



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Evaluation of trabecular pattern of mandible using fractal dimension, bone area fraction, and gray scale value: comparison of cone-beam computed tomography and panoramic radiography

Abstract

Objective

This study was performed to compare the fractal dimension (FD), bone area fraction (BAF), and gray scale value (GSV) on digital panoramic radiography (DPR) and cross-sectional cone-beam computed tomography (CBCT) using image analysis and to determine whether a relationship exists among parameters associated with bone quality.

Methods

Thirty edentulous human hemimandibles were scanned by DPR and CBCT. Ninety regions of interest (ROIs) were evaluated on DPR and CBCT images to calculate the FD and BAF. The GSV of the ROI on CBCT was also calculated.

Results

Statistically significant differences were observed in the FD values of the ROIs between DPR and CBCT (p = 0.002) and in the BAF values of ROIs between DPR and CBCT (p = 0.017). The Spearman's correlation test revealed a statistically significant high correlation between the FD and BAF values of the ROIs on DPR and between the FD and BAF values of the ROIs on CBCT (p < 0.01). No significant correlations were observed between the GSVs of ROIs on CBCT and the FD values of ROIs on DPR, the BAF values of ROIs on DPR, the FD values of ROIs on CBCT, and the BAF values of ROIs on CBCT (p > 0.05).

Conclusions

The GSV did not support the FD and BAF. Additionally, DPR and CBCT did not have similar image quality for assessing the FD, BAF, and GSV. In evaluating the trabecular structure, the use of panoramic radiographs should be continued because the image resolution of CBCT is lower and its generalized dose is higher than that of panoramic radiography. These results may serve as a reference for clinical practitioners using dental CBCT to analyze the trabecular structures of alveolar bones.

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Frequency and Severity of Acute Allergic-Like Reactions to Intravenously Administered Gadolinium-Based Contrast Media in Children

Objectives The purpose of this study is to determine the frequency and severity of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in children before, during, and after the transition from gadopentetate dimeglumine to gadoterate meglumine as our primary clinical GBCM. Materials and Methods Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act–compliant retrospective investigation. Allergic-like reactions to GBCM in pediatric patients were retrospectively assessed from January 2009 to January 2017, which included a departmental change of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like reactions were identified from departmental and hospital databases. The number of doses of GBCM was obtained from billing data. Allergic-like reaction frequencies for each GBCM were calculated and compared using the chi-squared test. Results A total of 32,365 administrations of GBCM occurred during the study period (327 for gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions occurred after 21 (0.06%) administrations. Reaction frequencies were not significantly different among the GBCM (0.3% gadofosveset trisodium; 0% gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine; P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1 (4.8%) was severe. The overall reaction frequency peaked during the 6-month transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%), compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P = 0.0095). Conclusion Allergic-like reactions to GBCM in children are rare. Gadoterate meglumine has a reaction frequency that does not significantly differ from other GBCMs. During the transition from gadopentetate dimeglumine to gadoterate meglumine, an increase in the frequency of reported allergic-like reactions was observed, likely reflective of the Weber effect. Received for publication October 10, 2017; and accepted for publication, after revision, November 18, 2017. Conflicts of interest and sources of funding: none declared. Correspondence to: Monica M. Forbes-Amrhein, MD, PhD, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 5031 Cincinnati, OH 45229-3026. E-mail: mforbesa@gmail.com. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Frequency and Severity of Acute Allergic-Like Reactions to Intravenously Administered Gadolinium-Based Contrast Media in Children

Objectives The purpose of this study is to determine the frequency and severity of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in children before, during, and after the transition from gadopentetate dimeglumine to gadoterate meglumine as our primary clinical GBCM. Materials and Methods Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act–compliant retrospective investigation. Allergic-like reactions to GBCM in pediatric patients were retrospectively assessed from January 2009 to January 2017, which included a departmental change of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like reactions were identified from departmental and hospital databases. The number of doses of GBCM was obtained from billing data. Allergic-like reaction frequencies for each GBCM were calculated and compared using the chi-squared test. Results A total of 32,365 administrations of GBCM occurred during the study period (327 for gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions occurred after 21 (0.06%) administrations. Reaction frequencies were not significantly different among the GBCM (0.3% gadofosveset trisodium; 0% gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine; P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1 (4.8%) was severe. The overall reaction frequency peaked during the 6-month transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%), compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P = 0.0095). Conclusion Allergic-like reactions to GBCM in children are rare. Gadoterate meglumine has a reaction frequency that does not significantly differ from other GBCMs. During the transition from gadopentetate dimeglumine to gadoterate meglumine, an increase in the frequency of reported allergic-like reactions was observed, likely reflective of the Weber effect. Received for publication October 10, 2017; and accepted for publication, after revision, November 18, 2017. Conflicts of interest and sources of funding: none declared. Correspondence to: Monica M. Forbes-Amrhein, MD, PhD, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 5031 Cincinnati, OH 45229-3026. E-mail: mforbesa@gmail.com. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Evaluation of permanent and primary enamel and dentin mineral density using micro-computed tomography

Abstract

Objectives

The present study was performed to investigate the mineral density distribution in enamel and dentin for both permanent and primary teeth and to establish the standard density per tooth type using micro-computed tomography (CT).

Methods

Fifty-seven extracted human teeth (37 permanent, 20 primary) were evaluated in the present study. The enamel and dentin mineral densities in the extracted teeth were measured using micro-CT. Cubic regression curves were used to determine the mineral density distribution in the enamel and dentin for each tooth type.

Results

The mean values, distributions, and regression equations of the mineral densities were obtained. The mean mineral density values for permanent enamel and dentin were significantly higher than those for their primary counterparts for each tooth type.

Conclusions

In the present study, we demonstrated the distribution of mineral density in sound enamel and dentin and attempted to determine the standard mineral density for each tooth type using micro-CT. The mineral density distributions found in this study contribute to our understanding of the mechanical properties of enamel and dentin. A positive correlation suggests that the systemic bone mineral density could be predicted based on the analysis of exfoliated teeth, such as in patients with hypophosphatasia. The present results may be useful in establishing a numerical standard for the mechanism involved in root fracture and for early detection of root fracture risk.

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Biological residues define the ice nucleation properties of soil dust

Soil dust is a major driver of ice nucleation in clouds leading to precipitation. It consists largely of mineral particles with a small fraction of organic matter constituted mainly of remains of micro-organisms that participated in degrading plant debris before their own decay. Some micro-organisms have been shown to be much better ice nuclei than the most efficient soil mineral. Yet, current aerosol schemes in global climate models do not consider a difference between soil dust and mineral dust in terms of ice nucleation activity. Here, we show that particles from the clay and silt size fraction of four different soils naturally associated with 0.7 to 11.8 % organic carbon (w/w) can have up to four orders of magnitude more ice nucleation sites per unit mass active in the immersion freezing mode at −12 °C than montmorillonite, the nucleation properties of which are often used to represent those of mineral dusts in modelling studies. Most of this activity was lost after heat treatment. Removal of biological residues reduced ice nucleation activity to, or below that of montmorillonite. Desert soils, inherently low in organic content, are a large natural source of dust in the atmosphere. In contrast, agricultural land use is concentrated on fertile soils with much larger organic matter contents than found in deserts. It is currently estimated that the contribution of agricultural soils to the global dust burden is less than 20 %. Yet, these disturbed soils can contribute ice nuclei to the atmosphere of a very different and much more potent kind than mineral dusts.

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Health and medical research is the most impactful research on the internet, so why is more of it not open?… https://t.co/t29bnpajfM

Health and medical research is the most impactful research on the internet, so why is more of it not open?… https://t.co/t29bnpajfM

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All drugs should be held to the same rigorous standards - but does the oncology community have a rejection bias whe… https://t.co/ZiVpdM62n6

All drugs should be held to the same rigorous standards - but does the oncology community have a rejection bias whe… https://t.co/ZiVpdM62n6

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RT @Cheryl_Cruwys : #UKIBCS Breast Density & Impacts on Health @ecancer https://t.co/X558tzbwNB

RT @Cheryl_Cruwys : #UKIBCS Breast Density & Impacts on Health @ecancer https://t.co/X558tzbwNB

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Correction: Interventions that improve maternity care for immigrant women in the UK: protocol for a narrative synthesis systematic review

Higginbottom GMA, Evans C, Morgan M, et al. Interventions that improve maternity care for immigrant women in the UK: protocol for a narrative synthesis systematic review. BMJ Open 2017;7:e016988. doi: 10.1136/bmjopen-2017-016988

The following Disclaimer statement should have been included in the article:

Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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GMC’s push for erasure of paediatrician is questionable

The General Medical Council’s High Court appeal for the erasure of Hadiza Bawa-Garba,1 is not aimed at improving patient care if it discourages duty of candour. It may also deter trainees from...

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Oral Immunotherapy in Japanese Children with Anaphylactic Peanut Allergy

Background: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic patients. Methods: We enrolled 22 peanut anaphylactic patients who underwent OIT between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline double-blind, placebo-controlled food challenge. After starting in-hospital OIT, participants gradually increased ingestion to 795 mg of peanut protein per day at home and then took a maintenance dose (795 mg) daily. After 3 asymptomatic months, participants underwent an oral food challenge (OFC) of 795 mg after 2 weeks of peanut avoidance to confirm sustained unresponsiveness. The historical control group consisted of 11 patients with anaphylaxis by OFC and underwent the second OFC after 2 years. Results: All patients (22/22) achieved desensitization by 8 months after starting OIT and completed the protocol within 2 years. Two years later, 15/22 patients (68.1%) in the OIT group achieved sustained unresponsiveness, whereas only 2 (18.1%) in the control group passed the second OFC. After 2 years, the median peanut-specific IgE had significantly decreased (from 38.5 to 12.4 kUA/L) in the OIT group, but not in the control group. Median peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased from baseline after 1 month. The adverse reaction rate per ingestion was 43% in hospital and 5% at home. Three patients received adrenaline at the hospital and 2 at home. Conclusions: These data suggest that for patients with peanut anaphylaxis, OIT can increase the threshold and support achieving sustained unresponsiveness with relative safety.
Int Arch Allergy Immunol

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Application of gamma irradiation knowledge in tissue sterilisation: inactivation of malaria parasite

Abstract

Malaria is one of the exclusion criteria used in selecting tissue donors and the absence of this information can lead to rejection of tissues for transplant. The studies on the malaria parasite have been confined to low dose attenuation of parasites in blood for transfusion purposes. There is no published information relating to the inactivation of malaria parasites with irradiation for the sterilisation of tissues. A dose-surviving parasite population following radiation was replotted using D₀ value from a published paper whereby D₁₀ value of 41 Gy was obtained. Calculation of sterilisation dose for achieving SAL 10⁻⁶ of malaria parasites demonstrated the effectiveness of the sterilisation dose of 25 kGy being used in tissue banking.

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Influence of ultrasound pretreatment on enzymolysis kinetics and thermodynamics of sodium hydroxide extracted proteins from tea residue

Abstract

The effect of ultrasound pretreatment using Single Frequency Counter Current Ultrasound (SFCCU) on the enzymolysis of tea residue protein (TRP) extracted with sodium hydroxide was investigated. The concentration of TRP hydrolysate, enzymolysis kinetics and thermodynamic parameters after SFCCU pretreatment were determined and compared with traditional enzymolysis. The results indicated that both ultrasound assisted and traditional enzymolysis conformed to first-order kinetics within the limits of the studied parameters. Temperature and sonication had affirmative effect on the enzymolysis of TRP with temperature yielding greater impact. Michaelis constant (K_M ) in ultrasonic pretreated enzymolysis decreased by 32.7% over the traditional enzymolysis. The highest polypeptide concentration of 24.12 mg ml⁻¹ was obtained with the lowest energy requirement at improved conditions of 50 g L⁻¹ of TRP, alcalase concentration of 2000 U g⁻¹, time of 10 min and temperature of 50 °C for the ultrasonic treated enzymolysis. The values of reaction rate constant (k) for TRP enzymolysis increased by 78, 40, 82 and 60% at 20, 30, 40 and 50 °C, respectively. The thermodynamic properties comprising activation energy (Ea), change in enthalpy (∆H) and entropy (∆S) were reduced by ultrasound pretreatment whereas Gibbs free energy (∆G) was increased.

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Isolation and identification of antimicrobial substances from Korean Lettuce ( Youngia sonchifolia M.)

Abstract

The aim of this study was to identify of antimicrobial substances from Korean Lettuce (Youngia sonchifolia M.). Water and ethanol extracts of Youngia sonchifolia M. exhibited antimicrobial activities against the microorganisms tested. Ethanol extract showed strong antimicrobial activities against most Gram positive and Gram negative microorganisms, whereas no lactic acid bacteria and yeasts were not affected. The antimicrobial compound G-6 was isolated from the ethyl acetate fraction obtained by silica gel column chromatography and HPLC and was confirmed as stable against heat treatment. Molecular weight of G-6 was calculated as 154 kDa based on information in the MS spectrum. G-6 was identified as 2-nonynoic acid (C₉H₁₄O₂) by UV, LC-EI/MS, and LC-CI/MS. In support of this, the chromatogram of G-6 was consistent with that of the 2-nonynoic acid standard. Antimicrobial activity of 2-nonynoic acid was identified in all samples, with a significant difference based on concentratio.

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Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated be...

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Optimizing highly noncoplanar VMAT trajectories: the NoVo method

We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar trajectories. While the use of noncoplanar beam arrangements for intensity modulated radiation therapy (IMRT), and in particular high fraction stereotactic radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less common as the availability of treatment machines handling these is limited. For both IMRT and VMAT, the beam angle selection problem is highly nonconvex in nature, which is why automated beam angle selection procedures have not entered mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the simultaneous trajectories of the gantry and the couch) by first computing a ##IMG## [http://ift.tt/2DBfdkz] {$4\pi$} solution (beams from every possible direction, suitably discretized) and then eliminating beams by ex...

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Measurement of effective detective quantum efficiency for a photon counting scanning mammography system and comparison with two flat panel full-field digital mammography systems

Effective detective quantum efficiency (eDQE) describes the resolution and noise properties of an imaging system along with scatter and primary transmission, all measured under clinically appropriate conditions. Effective dose efficiency (eDE) is the eDQE normalised to mean glandular dose and has been proposed as a useful metric for the optimisation of clinical imaging systems. The aim of this study was to develop a methodology for measuring eDQE and eDE on a Philips microdose mammography (MDM) L30 photon counting scanning system, and to compare performance with two conventional flat panel systems. A custom made lead-blocker was manufactured to enable the accurate determination of dose measurements, and modulation transfer functions were determined free-in-air at heights of 2, 4 and 6 cm above the breast support platform. eDQE were calculated for a Philips MDM L30, Hologic Dimensions and Siemens Inspiration digital mammography system for 2, 4 and 6 cm thick poly(methyl me...

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Quantification of fat fraction in lumbar vertebrae: correlation with age and implications for bone marrow dosimetry in molecular radiotherapy

Absorbed dose to active bone marrow is a predictor of hematological toxicity in molecular radiotherapy. Due to the complex composition of bone marrow tissue, the necessity to improve the personalized dosimetry has led to the application of non-conventional imaging methods in nuclear medicine. The aim of this study is to apply magnetic resonance imaging (MRI) for quantification of the fat fraction in lumbar vertebrae and to analyze its implications for bone marrow dosimetry. First, a highly accelerated two-point Dixon MRI sequence for fat-water separation was validated in a 3T system against the magnetic resonance spectroscopy (MRS) gold standard. The validation was performed in a fat-water phantom composed of 11 vials with different fat fractions between 0% and 100%, and subsequently repeated in the lumbar vertebrae of three healthy volunteers. Finally, a retrospective study was performed by analyzing the fat fraction in five lumbar vertebrae of 44 patients scanned with t...

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Objective image characterization of a spectral CT scanner with dual-layer detector

This work evaluated the performance of a detector-based spectral CT system by obtaining objective reference data, evaluating attenuation response of iodine and accuracy of iodine quantification, and comparing conventional CT and virtual monoenergetic images in three common phantoms. Scanning was performed using the hospital’s clinical adult body protocol. Modulation transfer function (MTF) was calculated for a tungsten wire and visual line pair targets were evaluated. Image noise power spectrum (NPS) and pixel standard deviation were calculated. MTF for monoenergetic images agreed with conventional images within 0.05 lp cm −1 . NPS curves indicated that noise texture of 70 keV monoenergetic images is similar to conventional images. Standard deviation measurements showed monoenergetic images have lower noise except at 40 keV. Mean CT number and CNR agreed with conventional images at 75 keV. Measured iodine concentration agreed with true concentration within 6% for insert...

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An analytical poroelastic model for ultrasound elastography imaging of tumors

The mechanical behavior of biological tissues has been studied using a number of mechanical models. Due to the relatively high fluid content and mobility, many biological tissues have been modeled as poroelastic materials. Diseases such as cancers are known to alter the poroelastic response of a tissue. Tissue poroelastic properties such as compressibility, interstitial permeability and fluid pressure also play a key role for the assessment of cancer treatments and for improved therapies. At the present time, however, a limited number of poroelastic models for soft tissues are retrievable in the literature, and the ones available are not directly applicable to tumors as they typically refer to uniform tissues. In this paper, we report the analytical poroelastic model for a non-uniform tissue under stress relaxation. Displacement, strain and fluid pressure fields in a cylindrical poroelastic sample containing a cylindrical inclusion during stress relaxation are computed. Finite e...

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A variational approach to liver segmentation using statistics from multiple sources

Medical image segmentation plays an important role in digital medical research, and therapy planning and delivery. However, the presence of noise and low contrast renders automatic liver segmentation an extremely challenging task. In this study, we focus on a variational approach to liver segmentation in computed tomography scan volumes in a semiautomatic and slice-by-slice manner. In this method, one slice is selected and its connected component liver region is determined manually to initialize the subsequent automatic segmentation process. From this guiding slice, we execute the proposed method downward to the last one and upward to the first one, respectively. A segmentation energy function is proposed by combining the statistical shape prior, global Gaussian intensity analysis, and enforced local statistical feature under the level set framework. During segmentation, the shape of the liver shape is estimated by minimization of this function. The improved Chan–Vese model is u...

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3D-printed adaptive acoustic lens as a disruptive technology for transcranial ultrasound therapy using single-element transducers

The development of multi-element arrays for better control of the shape of ultrasonic beams has opened the way for focusing through highly aberrating media, such as the human skull. As a result, the use of brain therapy with transcranial-focused ultrasound has rapidly grown. Although effective, such technology is expensive. We propose a disruptive, low-cost approach that consists of focusing a 1 MHz ultrasound beam through a human skull with a single-element transducer coupled with a tailored silicone acoustic lens cast in a 3D-printed mold and designed using computed tomography-based numerical acoustic simulation. We demonstrate on N   =  3 human skulls that adding lens-based aberration correction to a single-element transducer increases the deposited energy on the target 10 fold.

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A line fiducial method for geometric calibration of cone-beam CT systems with diverse scan trajectories

Modern cone-beam CT systems, especially C-arms, are capable of diverse source-detector orbits. However, geometric calibration of these systems using conventional configurations of spherical fiducials (BBs) may be challenged for novel source-detector orbits and system geometries. In part, this is because the BB configurations are designed with careful forethought regarding the intended orbit so that BB marker projections do not overlap in projection views. Examples include helical arrangements of BBs (Rougee et al 1993 Proc. SPIE 1897 161–9) such that markers do not overlap in projections acquired from a circular orbit and circular arrangements of BBs (Cho et al 2005 Med. Phys . 32 968–83). As a more general alternative, this work proposes a calibration method based on an array of line-shaped, radio-opaque wire segments. With this method, geometric parameter estimation is accomplished by relating the 3D line equations representing the wire...

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Effects of Human Connection through Social Drones and Perceived Safety

This study investigates whether people perceive social drones differently depending on pilot type and perceived safety. A “drone campus tour guide” social drone service was examined to explore these values. This study involves a between-subjects experiment using two drone control types (human-driven and algorithm-driven) and two levels of perceived safety (low and high). The results demonstrate that the drone pilot type changes the service experience when the drone is flying in an unsafe manner. In the group where the drones were flown in an unsafe manner, participants exhibited higher levels of satisfaction with the algorithm-driven drone guide, while both types of drones received the same level of satisfaction when they were flown safely. The results have implications for understanding how expectations influence service evaluations in relation to human connection.

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Random Attractor of Reaction-Diffusion Hopfield Neural Networks Driven by Wiener Processes

This paper studies the global existence and uniqueness of the mild solution for reaction-diffusion Hopfield neural networks (RDHNNs) driven by Wiener processes by applying a Schauder fixed point theorem and a priori estimate; then the random attractor for this system is also studied by constructing proper random dynamical system.

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Complex Dynamics in an Evolutionary General Equilibrium Model

We propose an exchange economy evolutionary model with discrete time, in which there are two utility-maximizing groups of agents which differ in the preference structure. Assuming an evolutionary mechanism based on the relative utility values realized by the two kinds of agents, we analytically and numerically investigate the existence of equilibria, their stability, and possible phenomena of coexistence between groups, mainly in terms of the heterogeneity degree in the preference structure. We find that our system has two trivial equilibria, at which just one of the two groups is present, and possibly a nontrivial equilibrium, characterized by the coexistence of the two groups of agents. Such nontrivial equilibrium may be stable, attracting all trajectories, or unstable. In the latter case, interesting, periodic, or chaotic, dynamics arise. We prove that the nontrivial equilibrium emerges via a transcritical bifurcation and loses stability via a flip bifurcation, after which the coexistence between groups is oscillatory in nature, presenting a regular or irregular behavior. In order to better investigate the role of the heterogeneity degree parameter, we perform a bifurcation analysis considering different scenarios, characterized by a balanced or unbalanced endowment distribution of the two goods.

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QVOA Techniques for Estimation of Fracture Directions

Some new computational techniques are suggested for estimating symmetry axis azimuth of fractures in the viscoelastic anisotropic target layer in the framework of QVOA analysis (Quality factor Versus Offset and Azimuth). The different QVOA techniques are compared using synthetic viscoelastic surface reflected data with and without noise. I calculated errors for these techniques which depend on different sets of azimuths and intervals of offsets. Superiority of the high-order “enhanced general” and “cubic” techniques is shown. The high-quality QVOA techniques are compared with one of the high-quality AVOA techniques (Amplitude Versus Offset and Azimuth) in the synthetic data with noise and attenuation. Results are comparable.

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A Privacy-Preserving Incentive Mechanism for Participatory Sensing Systems

The proliferation of mobile devices has facilitated the prevalence of participatory sensing applications in which participants collect and share information in their environments. The design of a participatory sensing application confronts two challenges: “privacy” and “incentive” which are two conflicting objectives and deserve deeper attention. Inspired by physical currency circulation system, this paper introduces the notion of E-cent, an exchangeable unit bearer currency. Participants can use the E-cent to take part in tasks anonymously. By employing E-cent, we propose an E-cent-based privacy-preserving incentive mechanism, called EPPI. As a dynamic balance regulatory mechanism, EPPI can not only protect the privacy of participant, but also adjust the whole system to the ideal situation, under which the rated tasks can be finished at minimal cost. To the best of our knowledge, EPPI is the first attempt to build an incentive mechanism while maintaining the desired privacy in participatory sensing systems. Extensive simulation and analysis results show that EPPI can achieve high anonymity level and remarkable incentive effects.

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Study on Fluid-Rock Interaction and Reuse of Flowback Fluid for Gel Fracturing in Desert Area

Hydraulic fracturing requires a large volume of fresh water, which is difficult and expensive to obtain in the desert area such as Tarim Basin. Currently, flowback fluid is typically transported to the sewage treatment plant and then discharged after reaching environmental requirements; however, this is not only costly, but also a waste of water resource. Therefore, it is imperative to understand the potential interactions between fracturing fluid and reservoir rock, and then find solutions to reuse the flowback water for subsequent fracturing. In this study, once flowback fluid was directly collected from the field, its chemical compositions were analyzed; then, filtering, decoloring, and chelating methods were chosen to effectively remove or shield the unfavorable reintroduced components. Moreover, pH value was further tuned during different stages of the recycling process to ensure good gelation and cross-linking properties of guar. Cross-linked guar synthesized with the flowback fluid was evaluated in the lab through shear resistance tests and coreflood tests under the reservoir conditions; results indicated the recycled gel behaved similarly as the original gel, or even better. From this work, a cheap and effective treatment process was proposed to reuse the flowback fluid in the desert area.

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Effects of Huanglian Jiedu Decoration in Rat Gingivitis

Gingivitis is an inflammatory disease that affects gingival tissues through a microbe-immune interaction. Huanglian Jiedu decoction (HLJD) is used traditionally for clearing and detoxifying in China, which had been reported to possess many pharmacological effects. Rat gingival inflammation model was established by lipopolysaccharide (LPS) injection for 3 consecutive days, and HLJD was given by gavage before LPS injection. After 3 days rats were sacrificed and tissue samples were evaluated. Serum cytokine levels such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoabsorbent assay (ELISA). Oxidative stress related molecules such as total antioxidant capacity (T-AOC), malondialdehyde (MDA), and reactive oxygen species (ROS) were determined. Expression of AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway were inspected by western blotting. Histological changes of gingival tissues were tested with hematoxylin-eosin (HE) staining. HLJD significantly decreased serum levels of IL-6 and TNF-α, suppressed generation of MDA and ROS, and enhanced T-AOC creation. Moreover, HLJD inhibited expressions of AMPK and ERK1/2. The inflammation severity of gingival tissue by HE staining was severe in model group but relieved in HLJD group obviously. HLJD exhibited protective effects against gingival damage through suppressing inflammation reaction and elevating antioxidation power.

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Evidence for Nearly Complete Decoupling of Very Stable Nocturnal Boundary Layer Overland

Concentrations of 222Rn at 0.1 m and 6.5 m height above ground level and 222Rn flux density were measured during nights characterized by strong cooling, light winds and clear sky conditions in the Carpathian Basin in Hungary. A very stable boundary layer (vSBL) formed on 14 nights between 15 August and 3 September 2009. On 12 nights, an estimated 72% (s.d. 20%) of 222Rn emitted from the surface since sunset was retained within the lowest 6.5 m above the ground until sunrise the following morning. On two nights an intermittent increase in wind speed at 9.4 m height was followed by a rise in temperature at 2.0 m height, indicating a larger atmospheric motion that resulted in 222Rn at 0.1 m around sunrise being the same as around the preceding sunset. It does not seem to be rare in a large continental basin for a vSBL to be nearly completely decoupled from the atmosphere above for the entire period from sunset to sunrise.

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Inter-comparison of different direct and indirect methods to determine radon flux from soil

The physical and chemical characteristics of radon gas make it a good tracer for use in the application of atmospheric transport models. For this purpose the radon source needs to be known on a global scale and this is difficult to achieve by only direct experimental methods. However, indirect methods can provide radon flux maps on larger scales, but their reliability has to be carefully checked. It is the aim of this work to compare radon flux values obtained by direct and indirect methods in a measurement campaign performed in the summer of 2008. Different systems to directly measure radon flux from the soil surface and to measure the related parameters terrestrial γ dose and 226Ra activity in soil, for indirect estimation of radon flux, were tested. Four eastern Spanish sites with different geological and soil characteristics were selected: Teruel, Los Pedrones, Quintanar de la Orden and Madrid. The study shows the usefulness of both direct and indirect methods for obtaining radon flux data. Direct radon flux measurements by continuous and integrated monitors showed a coefficient of variation between 10% and 23%. At the same time, indirect methods based on correlations between 222Rn and terrestrial γ dose rate, or 226Ra activity in soil, provided results similar to the direct measurements, when these proxies were directly measured at the site. Larger discrepancies were found when proxy values were extracted from existing data bases. The participating members involved in the campaign study were the Institute of Energy Technology (INTE) of the Technical University of Catalonia (UPC), Huelva University (UHU), and Basel University (BASEL).

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EUROCarbDB: An open-access platform for glycoinformatics

The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://ift.tt/2ranXM3.

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Erfassung der Psychopathologie mit dem AMDP-System

Das AMDP-System wurde unter anderem basierend auf Konzepten der Schizophrenie in den 1960er- und 1970er-Jahren im europäischen Sprachbereich entwickelt. Entsprechend der damaligen Klassifikation wurden Symptome zusammengestellt und in einem Glossar definiert. In der Folgezeit fand das AMDP-System, besonders in Studien zu schizophrenen Patienten, aber auch in der klinischen Praxis, große Anwendung. Die im AMDP-System enthaltenen Symptome und Syndrome erlauben eine differenzierte Abbildung der schizophrenen Symptomatik.

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Time and moral judgment

Do moral judgments hinge on the time available to render them? According to a recent dual-process model of moral judgment, moral dilemmas that engage emotional processes are likely to result in fast deontological gut reactions. In contrast, consequentialist responses that tot up lives saved and lost in response to such dilemmas would require cognitive control to override the initial response. Cognitive control, however, takes time. In two experiments, we manipulated the time available to arrive at moral judgments in two ways: by allotting a fixed short or large amount of time, and by nudging people to answer swiftly or to deliberate thoroughly. We found that faster responses indeed lead to more deontological responses among those moral dilemmas in which the killing of one to save many necessitates manhandling an innocent person and in which this action is depicted as a means to an end. Thus, our results are the first demonstration that inhibiting cognitive control through manipulations of time alters moral judgments.

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Stable carbon isotopes as indicators for micro-geomorphic changes in palsa peats

Palsa peats are unique northern ecosystems formed under an arctic climate and characterized by a high biodiversity and sensitive ecology. The stability of the palsas are seriously threatened by climate warming which will change the permafrost dynamic and induce a degradation of the mires. We used stable carbon isotope depth profiles in two palsa mires of Northern Sweden to track environmental change during the formation of the mires. Soils dominated by aerobic degradation can be expected to have a clear increase of carbon isotopes (δ13C) with depth, due to preferential release of 12C during aerobic mineralization. In soils with suppressed degradation due to anoxic conditions, stable carbon isotope depth profiles are either more or less uniform indicating no or very low degradation or depth profiles turn to lighter values due to an enrichment of recalcitrant organic substances during anaerobic mineralisation which are depleted in 13C. The isotope depth profile of the peat in the water saturated depressions (hollows) at the yet undisturbed mire Storflaket indicated very low to no degradation but increased rates of anaerobic degradation at the Stordalen site. The latter might be induced by degradation of the permafrost cores in the uplifted areas (hummocks) and subsequent breaking and submerging of the hummock peat into the hollows due to climate warming. Carbon isotope depth profiles of hummocks indicated a turn from aerobic mineralisation to anaerobic degradation at a peat depth between 4 and 25 cm. The age of these turning points was 14C dated between 150 and 670 yr and could thus not be caused by anthropogenically induced climate change. We found the uplifting of the hummocks due to permafrost heave the most likely explanation for our findings. We thus concluded that differences in carbon isotope profiles of the hollows might point to the disturbance of the mires due to climate warming or due to differences in hydrology. The characteristic profiles of the hummocks are indicators for micro-geomorphic change during permafrost up heaving.

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Finite Element Heterogeneous Multiscale Method for the Wave Equation

A finite element heterogeneous multiscale method is proposed for the wave equation with highly oscillatory coefficients. It is based on a finite element discretization of an effective wave equation at the macro scale, whose a priori unknown effective coefficients are computed on sampling domains at the micro scale within each macro finite element. Hence the computational work involved is independent of the highly heterogeneous nature of the medium at the smallest scale. Optimal error estimates in the energy norm and the L2 norm and convergence to the homogenized solution are proved, when both the macro and the micro scales are refined simultaneously. Numerical experiments corroborate the theoretical convergence rates and illustrate the behavior of the numerical method for periodic and heterogeneous media.

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Local nonreflecting boundary condition for time-dependent multiple scattering

Starting from a high-order local nonreflecting boundary condition (NBC) for single scattering [25], we derive a local NBC for time-dependent multiple scattering problems in three space dimensions, which is completely local both in space and time. To do so, we first develop an exterior evaluation formula for a purely outgoing wave field, given its values and those of certain auxiliary functions needed for the local NBC at the artificial boundary. By combining that evaluation formula with the decomposition of the total scattered field into purely outgoing contributions, we obtain a completely local NBC for time-dependent multiple scattering problems. The accuracy and stability of this new local NBC are evaluated by coupling it to a standard finite difference method.

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Meta-analysis of zooarchaeological data from SW Asia and SE Europe provides insight into the origins and spread of animal husbandry

Identifying spatial and temporal variation in animal exploitation patterns is essential for building our understanding of the transition from hunting to stock-keeping. Quantitative analysis of the published records of over 400,000 animal bones recovered from 114 archaeological sites from SW Asia and SE Europe from c12 ka to c7.5 ka cal BP (thousands of calibrated radiocarbon years before present) demonstrates significant spatiotemporal variability in faunal exploitation patterns. Sites in the Euphrates region show adoption of domestic taxa by c10.5 ka cal BP, although on average these taxa contribute less than 10% to total assemblage size. This rises to a median of about 40% by c9.5 ka cal BP, and then to about 45% of total NISP by c8.5 ka cal BP. By c10.5 ka in the Tigris and Zagros region domesticates contribute less than 5% to faunal assemblages, but then rise to a median of about 20% by c9.5 ka and 40% by c8.4 ka cal BP. In contrast, Levantine sites have low numbers of domestic taxa (<1%) until c8.8 ka cal BP, when the proportion dramatically increases to a median of about 35%. This apparent delayed-adoption pattern also holds true for the southern Levant, which shows, on average, low levels (<1%) of domestic taxa until 8.8 ka cal BP, at which point domesticates contribute a median of about 10% to assemblages. In the northern parts of SW Asia, the mid- to late-10th millennium cal BP is pivotal, as proportions of domestic taxa show a dramatic increase in frequency during this time, and the ‘package’ of domestic sheep, goat, cattle and pig becomes more firmly established. This sets the trend for sites of the 9th millennium and the appearance of Neolithic communities in SE Europe from the 8th millennium cal BP onwards, from which point domestic animals are ubiquitous in faunal assemblages. Research highlights ► The problem we are addressing is how, when and where animals were domesticated in Southwest Asia during the Early Holocene. More specifically, we question the widely held view of a single trajectory towards domestication and show that there was great regional variation in faunal exploitation patterns before, during, and after the period in which animal domesticates were first brought under human control; variations which have not previously been properly recognized or defined and which have major implications for our understanding of the domestication process. ► The evidence we provide to support our conclusion is based on a meta-analysis of published zooarchaeological reports describing over 400,000 animal remains from 114 sites in SW Asia and SE Europe from the 12th to the 8th millennium cal BP. This is the most comprehensive account of published zooarchaeological data from the area of interest ever attempted. The data drawn from the exercise is subject to quantitative assessment to document regional variation in exploitation patterns. These analyses are fully documented and include a complete list of the sources used to compile the data. ► We believe the subject matter and our results are of wide enough interest for publication in JAS.

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Spectacular light pillars rise up in frozen North America

The same cold weather that has caused frozen sharks to wash up on the US East Coast has given us a light show more often seen in polar regions

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Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study

Abstract

Purpose

The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis.

Methods

We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016.

Results

The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate.

Conclusion

The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.

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In vivo therapeutic efficacy of TNFα silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic mice

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Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

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Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

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JCDD, Vol. 5, Pages 2: Function of Adenylyl Cyclase in Heart: the AKAP Connection

JCDD, Vol. 5, Pages 2: Function of Adenylyl Cyclase in Heart: the AKAP Connection

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd5010002

Authors: Tanya Baldwin Carmen Dessauer

Cyclic adenosine monophosphate (cAMP), synthesized by adenylyl cyclase (AC), is a universal second messenger that regulates various aspects of cardiac physiology from contraction rate to the initiation of cardioprotective stress response pathways. Local pools of cAMP are maintained by macromolecular complexes formed by A-kinase anchoring proteins (AKAPs). AKAPs facilitate control by bringing together regulators of the cAMP pathway including G-protein-coupled receptors, ACs, and downstream effectors of cAMP to finely tune signaling. This review will summarize the distinct roles of AC isoforms in cardiac function and how interactions with AKAPs facilitate AC function, highlighting newly appreciated roles for lesser abundant AC isoforms.

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Convergence analysis of trigonometric methods for stiff second-order stochastic differential equations

We study a class of numerical methods for a system of second-order SDE driven by a linear fast force generating high frequency oscillatory solutions. The proposed schemes permit the use of large step sizes, have uniform global error bounds in the position (i.e. independent of the large frequencies present in the SDE) and offer various additional properties. This new family of numerical integrators for SDE can be viewed as a stochastic generalisation of the trigonometric integrators for highly oscillatory deterministic problems.

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Book Review: Die Aufhebung des Politischen: Lü Zuqian (1137-1181) und der Aufstieg des Neukonfuzianismus

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On Wang Hui's Re-Imagination of Asia and Europe

For roughly two decades now, WANG HUI has been a prominent voice within academic, cultural and political discourses in China, but increasingly also in Europe and the United States. WANG's still developing oeuvre might be understood as an attempt to 'provincialize Europe' (DIPESH CHAKRABARTY) from a political perspective and by drawing on historical and present-day China. In this article, the main focus is on one specifi c aspect in this attempt, namely WANG's view of Europe, and I shall investigate that aspect on the basis of an article by WANG on the concept of Asia: "The Politics of Imagining Asia" (2007). I fi rst discuss WANG's genealogical analysis of Asia as a “European concept” before attending to what he perceives as derivations of it in Asia itself. I then engage with WANG's proposal to go beyond the framework of nation-state/ empire, and argue that he fails to offer an attractive re-imagination of the concept of Asia. When fi nally turning to his view of Europe, I shall issue a criticism of some misplaced anti-Eurocentrism in his work on the conceptual level. Seit nunmehr fast zwei Jahrzehnten ist Wang HUI in den wissenschaftlichen, kulturellen und politischen Diskussionen in China, zunehmend aber auch in Europa und in den Vereinigten Staaten, eine prominente Stimme. Die von WANG entwickelte Vorstellung könnte als ein Versuch der "Provinzialisierung Europas" (Dipesh CHAKRABARTY) in politischer Hinsicht und in Bezug auf das historische und heutige China verstanden werden. Der Schwerpunkt dieses Artikels liegt auf einem spezifi schen Aspekt dieses Versuchs, und zwar auf WANGS Sichtweise von Europa. Diesen Aspekt untersucht der Autor auf der Grundlage eines Artikels von WANG über den Begriff Asien: "The Politics of Imagining Asia" (Die Politik der Imagination Asiens) (2007). Zunächst diskutiert der Autor WANGS genealogische Analyse Asiens als "Europäischen Begriff", bevor er auf Abweichungen von diesem Begriff in Asien selbst eingeht. Danach setzt sich der Autor mit WANGS Vorschlag auseinander, über den Rahmen des Nationalstaates/Reiches hinauszugehen, und weist darauf hin, dass WANG keine attraktive Re-Imagination des Begriffs von Asien anbietet. Wenn der Autor abschließend auf WANGS Sicht von Europa eingeht, kritisiert er einen gewissen deplazierten Anti-Eurozentrismus in dessen Arbeit auf begriffl icher Ebene.

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Vaccines, Vol. 6, Pages 6: Interaction between Hepatitis B Virus and Toll-Like Receptors: Current Status and Potential Therapeutic Use for Chronic Hepatitis B

Vaccines, Vol. 6, Pages 6: Interaction between Hepatitis B Virus and Toll-Like Receptors: Current Status and Potential Therapeutic Use for Chronic Hepatitis B

Vaccines doi: 10.3390/vaccines6010006

Authors: Zhiyong Ma Qian Cao Yong Xiong Ejuan Zhang Mengji Lu

Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV infection. However, the contribution of innate immunity to removing HBV has been explored in recent years. Toll-like receptors (TLRs) are recognized as the first line of antiviral immunity because they initiate intracellular signaling pathways to induce antiviral mediators such as interferons (IFNs) and other cytokines. Recent studies show that the activation of TLR-mediated signaling pathways results in a suppression of HBV replication in vitro and in vivo. However, HBV has also evolved strategies to counter TLR responses including the suppression of TLR expression and the blockage of downstream signaling pathways. Antiviral treatment in chronic HBV-infected patients leads to an upregulation of TLR expression and the restoration of its innate antiviral functions. Thus, TLR activation may serve as an additional immunotherapeutic option for treating chronic HBV infection in combination with antiviral treatment.

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On the One-Dimensional Modeling of Vertical Upward Bubbly Flow

The one-dimensional two-fluid model approach has been traditionally used in thermal-hydraulics codes for the analysis of transients and accidents in water–cooled nuclear power plants. This paper investigates the performance of RELAP5/MOD3 predicting vertical upward bubbly flow at low velocity conditions. For bubbly flow and vertical pipes, this code applies the drift-velocity approach, showing important discrepancies with the experiments compared. Then, we use a classical formulation of the drag coefficient approach to evaluate the performance of both approaches. This is based on the critical Weber criteria and includes several assumptions for the calculation of the interfacial area and bubble size that are evaluated in this work. A more accurate drag coefficient approach is proposed and implemented in RELAP5/MOD3. Instead of using the Weber criteria, the bubble size distribution is directly considered. This allows the calculation of the interfacial area directly from the definition of Sauter mean diameter of a distribution. The results show that only the proposed approach was able to predict all the flow characteristics, in particular the bubble size and interfacial area concentration. Finally, the computational results are analyzed and validated with cross-section area average measurements of void fraction, dispersed phase velocity, bubble size, and interfacial area concentration.

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The Controls of Pore-Throat Structure on Fluid Performance in Tight Clastic Rock Reservoir: A Case from the Upper Triassic of Chang 7 Member, Ordos Basin, China

The characteristics of porosity and permeability in tight clastic rock reservoir have significant difference from those in conventional reservoir. The increased exploitation of tight gas and oil requests further understanding of fluid performance in the nanoscale pore-throat network of the tight reservoir. Typical tight sandstone and siltstone samples from Ordos Basin were investigated, and rate-controlled mercury injection capillary pressure (RMICP) and nuclear magnetic resonance (NMR) were employed in this paper, combined with helium porosity and air permeability data, to analyze the impact of pore-throat structure on the storage and seepage capacity of these tight oil reservoirs, revealing the control factors of economic petroleum production. The researches indicate that, in the tight clastic rock reservoir, largest throat is the key control on the permeability and potentially dominates the movable water saturation in the reservoir. The storage capacity of the reservoir consists of effective throat and pore space. Although it has a relatively steady and significant proportion that resulted from the throats, its variation is still dominated by the effective pores. A combination parameter (ε) that was established to be as an integrated characteristic of pore-throat structure shows effectively prediction of physical capability for hydrocarbon resource of the tight clastic rock reservoir.

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The Association of Gut Microbiota with Nonalcoholic Steatohepatitis in Thais

Objectives. Nonalcoholic steatohepatitis (NASH) can progress to advanced fibrosis; the link between intestinal bacterial overgrowth and NASH has been proposed. Gut microbiota may promote inflammation and provoke disease progression. We evaluated gut microbiota pattern in NASH and its influencing factors. Methods. A case-controlled study with sixteen NASH and eight control subjects was done. We performed DNA extraction from stool samples and bacterial 16S rRNA sequencing using MiSeq™. The sequences were clustered into operational taxonomic units using Quantitative Insights Into Microbial Ecology software. We calculated relative abundances, determined alpha diversity, obtained beta diversity by principal coordinate analysis, and conducted the partial least-squares regression model. Results. The relative abundance of Bacteroidetes tended to be higher in NASH group. The Bacteroidetes/Firmicutes (B/F) ratio was significantly elevated in NASH patients. The pattern of gut microbiota in NASH was clearly separated from that of control subjects. Factors influencing the separation of NASH from control subjects were age, diabetes, body mass index, Bacteroidetes phylum, metformin, Actinobacteria, Verrucomicrobia, Thermotogae, and Caldithrix and Bacteroidetes/Firmicutes ratio. Conclusions. Bacteroidetes phylum (Bacteroides and Prevotella genus) is abundant in NASH subjects, who exhibited an elevated B/F ratio. NASH patients showed a specific pattern of gut microbiota independent of diabetes or metformin use.

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A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients’ survival independent of clinicopathological variables. Five networks were significantly associated with patients’ survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients’ survival in two test sets and training set (, and for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients’ prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction.

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An Experimental Investigation of Unbonded Laminated Elastomeric Bearings and the Seismic Evaluations of Highway Bridges with Tested Bearing Components

This paper presents an experimental program performed to investigate the behavioral characteristics of unbonded steel-reinforced laminated elastomeric bearings (U-SLEBs), which have been widely used for highway bridges in China. The influences on the friction behaviors, stiffness, and energy dissipations of the different parameters, such as compressive stresses, loading rates, and rubber material, were discussed. The responses of the U-SLEBs were compared with those of the bonded steel-reinforced laminated elastomeric bearings (B-SLEBs). Then, effective analytical models were developed, which considered the mechanical degradation of the U-SLEBs and simulated the realistic behaviors of the B-SLEBs. The seismic responses of a multispan continuous bridge with tested bearing components were also evaluated. The results showed that the mechanical properties of the U-SLEBs tended to degrade due to friction sliding. However, the degrees of the decrease were found to be dependent on the influencing parameters. Meanwhile, the B-SLEBs exhibited stiffening behaviors that led to tearing under large displacement demands. The bridges using U-SLEBs were found to suffer less damage due to the reliable sliding behavior of U-SLEBs. It is recommended that shear keys, which are reasonably designed in the transverse direction, be constructed in order to achieve better seismic performance.

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The Cytoreductive Effect of Radiotherapy for Small Cell Ovarian Carcinoma of the Pulmonary Type: A Case Report and Review of the Literature

Small cell ovarian carcinoma of the pulmonary type is a rare and highly aggressive tumor for which a suitable treatment strategy has not been established. A 45-year-old woman presented with abdominal swelling, and primary ovarian carcinoma was suspected. The postoperative pathological diagnosis was small cell ovarian carcinoma of the pulmonary type. She also had complicated grade 1 endometrioid carcinoma of the uterine corpus. Three courses of cisplatin and etoposide therapy were administered as adjuvant chemotherapy. Because the tumor was chemotherapy resistant, she underwent palliative abdominal irradiation at a dose of 26 Gy in 13 fractions, which induced cytoreduction and provided symptomatic relief. She died 4 months after surgery. Lactate dehydrogenase was a useful tumor marker during treatment. Here, we present an extremely rare case of a patient with small cell ovarian carcinoma of the pulmonary type treated with radiotherapy after surgery and chemotherapy.

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Modification of Potato Starch by Acetylmalic Acid Chloroanhydride and Physicochemical Research of the New Product

The article presents the research results of the product’s properties of potato starch modification by acetylmalic acid chloroanhydride. Modification of potato starch has been carried out and has been confirmed by elemental analysis. In the infrared spectra, changes in the frequency oscillations of native starch in the noncharacteristic region have occurred: the frequency of oscillations at 981.81 cm−1 has increased and in the spectrum of modified starch has been at 1024.82 cm−1; the band with frequency of oscillations of 923.07 cm−1 has shifted to 866.66 cm−1, and the band with frequency of oscillations of 609.79 cm−1 has shifted to 672.22 cm−1, indicating the change in noncharacteristic region of the native starch sample after acylation. The properties of obtained modified product have been studied and this modification has appeared to change the shape of moisture and starch bonds, along with decreasing appearance of grains and reduced degree of crystallinity from 12 to 4%.

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Modeling Air Traffic Situation Complexity with a Dynamic Weighted Network Approach

In order to address the flight delays and risks associated with the forecasted increase in air traffic, there is a need to increase the capacity of air traffic management systems. This should be based on objective measurements of traffic situation complexity. In current air traffic complexity research, no simple means is available to integrate airspace and traffic flow characteristics. In this paper, we propose a new approach for the measurement of air traffic situation complexity. This approach considers the effects of both airspace and traffic flow and objectively quantifies air traffic situation complexity. Considering the aircraft, waypoints, and airways as nodes, and the complexity relationships among these nodes as edges, a dynamic weighted network is constructed. Air traffic situation complexity is defined as the sum of the weights of all edges in the network, and the relationships of complexity with some commonly used indices are statistically analyzed. The results indicate that the new complexity index is more accurate than traffic count and reflects the number of trajectory changes as well as the high-risk situations. Additionally, analysis of potential applications reveals that this new index contributes to achieving complexity-based management, which represents an efficient method for increasing airspace system capacity.

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Atmospheric Dynamics Leading to West European Summer Hot Temperatures Since 1851

Summer hot temperatures have many impacts on health, economy (agriculture, energy, and transports), and ecosystems. In Western Europe, the recent summers of 2003 and 2015 were exceptionally warm. Many studies have shown that the genesis of the major heat events of the last decades was linked to anticyclonic atmospheric circulation and to spring precipitation deficit in Southern Europe. Such results were obtained for the second part of the 20th century and projections into the 21st century. In this paper, we challenge this vision by investigating the earlier part of the 20th century from an ensemble of 20CR reanalyses. We propose an innovative description of Western-European heat events applying the dynamical system theory. We argue that the atmospheric circulation patterns leading to the most intense heat events have changed during the last century. We also show that the increasing temperature trend during major heatwaves is encountered during episodes of Scandinavian Blocking, while other circulation patterns do not yield temperature trends during extremes.

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Different Setting Conditions Affect Surface Characteristics and Microhardness of Calcium Silicate-Based Sealers

Objective. To investigate the effect of different setting conditions on surface microhardness and setting properties of calcium silicate-based sealers. Methods. Three sealers, EndoSequence Bioceramic (BC; Brasseler USA, Savannah, GA, USA), Endoseal MTA (ES; Maruchi, Wonju, Korea), and Well-Root ST (WR; Vericom, Chuncheon, Korea), were compared. Specimens were exposed to either butyric acid (pH 5.4) or phosphate-buffered saline (PBS [pH 7.4]) for 48 h and stored at 100% humidity for 12 days. The control specimens were stored at 100% humidity for 14 days. Surface microhardness was measured, topographic changes were observed, and phase analysis was performed using X-ray diffraction. Microhardness according to storage conditions was compared using one-way analysis of variance and Tukey’s multiple comparison tests (). Results. The BC and ES sealers exhibited decreased microhardness when stored in acid or PBS compared with control (). In the WR group, acid exposure lowered microhardness of the specimens compared with control (). Scanning electron microscopy revealed different topographies in specimens from all tested sealers exposed to acid or PBS. Conclusion. The surface microhardness of calcium silicate-based sealers was reduced by exposure to either acid or PBS. Acid solutions, however, had a more detrimental effect than PBS.

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Apocynum venetum Leaf Extract Exerts Antidepressant-Like Effects and Inhibits Hippocampal and Cortical Apoptosis of Rats Exposed to Chronic Unpredictable Mild Stress

We investigated the effects of Apocynum venetum leaf extract (AVLE) on depressive behaviors and neuronal apoptosis in a chronic unpredictable mild stress (CUMS) rat model of depression. Rats were randomly divided into six groups: control, chronic unpredictable mild stress, fluoxetine, AVLE30, AVLE60, and AVLE120. Except for the control group, all rats were submitted to chronic unpredictable mild stress paradigms for four weeks to induce depressive behavior. Neuronal apoptosis was assessed by the terminal deoxynucleotidyl transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) method. The expression levels of apoptosis-related proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X Protein (Bax), cysteine-aspartic acid protease-3 and protease-9 (caspase-3 and caspase-9), cytochrome c (cyt-C), brain-derived neurotrophic factor (BDNF), and cAMP-response element binding (CREB) protein, were evaluated by western blot. Treatment with AVLE (60 or 120 mg/kg/day) significantly improved depressive behavior. Increased apoptosis of hippocampus and cortical neurons were observed in CUMS rats, while 120 mg/kg/day of AVLE significantly reversed these changes and achieved the best antidepressant-like effects among the doses tested. Moreover, AVLE (120 mg/kg) significantly increased Bcl-2, BDNF, and CREB protein expression and decreased Bax, cyt-C, and caspase family protein expression. Our results indicate that AVLE has potent antidepressant activity, likely due to its ability to suppress neuronal apoptosis.

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Enteroparasites in Riverside Settlements in the Pantanal Wetlands Ecosystem

Background. Intestinal parasites are a major source of health problems in developing countries, where socioeconomic, cultural, and environmental conditions contribute in maintaining the biological cycles of various parasites and facilitating their spread. The objective of this study, conducted in Corumbá, Mato Grosso do Sul state, Brazil, was to investigate the occurrence of intestinal parasites in riverside communities in the South Pantanal wetlands and conduct educational interventions focused on health and environmental preservation. Method. In total, 196 stool samples were tested for parasites using the merthiolate-iodine-formaldehyde concentration (MIFC) technique and spontaneous sedimentation and educational activities were carried out. Results. Enteroparasite prevalence was 72% (65.6–78.2%; 95% CI). Of the 141 positive cases, monoparasitism was found in 34.7%, biparasitism in 23%, and polyparasitism in 14.3%. Entamoeba coli was the most frequent protozoan (70.2%). Among helminths, hookworms were the most prevalent. Enteroparasitosis prevalence did not differ for sex or place of abode but proved higher in individuals older than 10 years. Conclusion. The high positivity rate for enteroparasites found for the communities stems from lack of sanitation and poor personal and environmental hygiene habits, indicating that effective health policies and educational interventions are needed to reduce the current risk levels.

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Accurate Rapid Lifetime Determination on Time-Gated FLIM Microscopy with Optical Sectioning

Time-gated fluorescence lifetime imaging microscopy (FLIM) is a powerful technique to assess the biochemistry of cells and tissues. When applied to living thick samples, it is hampered by the lack of optical sectioning and the need of acquiring many images for an accurate measurement of fluorescence lifetimes. Here, we report on the use of processing techniques to overcome these limitations, minimizing the acquisition time, while providing optical sectioning. We evaluated the application of the HiLo and the rapid lifetime determination (RLD) techniques for accurate measurement of fluorescence lifetimes with optical sectioning. HiLo provides optical sectioning by combining the high-frequency content from a standard image, obtained with uniform illumination, with the low-frequency content of a second image, acquired using structured illumination. Our results show that HiLo produces optical sectioning on thick samples without degrading the accuracy of the measured lifetimes. We also show that instrument response function (IRF) deconvolution can be applied with the RLD technique on HiLo images, improving greatly the accuracy of the measured lifetimes. These results open the possibility of using the RLD technique with pulsed diode laser sources to determine accurately fluorescence lifetimes in the subnanosecond range on thick multilayer samples, providing that offline processing is allowed.

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Clinical Characteristics and Survival Outcomes for Non-Small-Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Double Mutations

Multiple randomized clinical trials have demonstrated that epidermal growth factor receptor (EGFR) exon 19 deletion (19Del) and exon 21 L858R mutation (L858R) are highly correlated with sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC). A mutation in exon 20 (T790M) is reportedly associated with resistance to EGFR-TKIs. However, few studies have focused on patients harboring double mutations in these 3 mutation sites. In this retrospective study, forty-five patients (45/2546, 1.7%) harbored double mutations of 19Del, L858R, and T790M. Twenty-four patients with EGFR double mutations received EGFR-TKI therapy. Clinical characteristics of these patients, including the response to EGFR-TKIs and progression-free survival outcome for EGFR-TKI treatment (PFS-TKI), were analyzed. Patients with EGFR double mutations were more likely to be nonsmokers, have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1, have adenocarcinoma, and be at stage III-IV. The ORR, DCR, and median PFS-TKI in patients harboring EGFR double mutations were lower than in patients with a single EGFR-activating mutation. The differences in ORR and DCR were statistically insignificant between the 3 groups. Patients with double mutations of 19Del and T790M had longer PFS-TKIs than patients in the other 2 groups.

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IJMS, Vol. 19, Pages 256: Aquaporin Expression and Water Transport Pathways inside Leaves Are Affected by Nitrogen Supply through Transpiration in Rice Plants

IJMS, Vol. 19, Pages 256: Aquaporin Expression and Water Transport Pathways inside Leaves Are Affected by Nitrogen Supply through Transpiration in Rice Plants

International Journal of Molecular Sciences doi: 10.3390/ijms19010256

Authors: Lei Ding Yingrui Li Limin Gao Zhifeng Lu Min Wang Ning Ling Qirong Shen Shiwei Guo

The photosynthetic rate increases under high-N supply, resulting in a large CO2 transport conductance in mesophyll cells. It is less known that water movement is affected by nitrogen supply in leaves. This study investigated whether the expression of aquaporin and water transport were affected by low-N (0.7 mM) and high-N (7 mM) concentrations in the hydroponic culture of four rice varieties: (1) Shanyou 63 (SY63), a hybrid variant of the indica species; (2) Yangdao 6 (YD6), a variant of indica species; (3) Zhendao 11 (ZD11), a hybrid variant of japonica species; and (4) Jiuyou 418 (JY418), another hybrid of the japonica species. Both the photosynthetic and transpiration rate were increased by the high-N supply in the four varieties. The expressions of aquaporins, plasma membrane intrinsic proteins (PIPs), and tonoplast membrane intrinsic protein (TIP) were higher in high-N than low-N leaves, except in SY63. Leaf hydraulic conductance (Kleaf) was lower in high-N than low-N leaves in SY63, while Kleaf increased under high-N supply in the YD6 variant. Negative correlations were observed between the expression of aquaporin and the transpiration rate in different varieties. Moreover, there was a significant negative correlation between transpiration rate and intercellular air space. In conclusion, the change in expression of aquaporins could affect Kleaf and transpiration. A feedback effect of transpiration would regulate aquaporin expression. The present results imply a coordination of gas exchange with leaf hydraulic conductance.

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IJMS, Vol. 19, Pages 259: Aux/IAA Gene Family in Plants: Molecular Structure, Regulation, and Function

IJMS, Vol. 19, Pages 259: Aux/IAA Gene Family in Plants: Molecular Structure, Regulation, and Function

International Journal of Molecular Sciences doi: 10.3390/ijms19010259

Authors: Jie Luo Jing-Jing Zhou Jin-Zhi Zhang

Auxin plays a crucial role in the diverse cellular and developmental responses of plants across their lifespan. Plants can quickly sense and respond to changes in auxin levels, and these responses involve several major classes of auxin-responsive genes, including the Auxin/Indole-3-Acetic Acid (Aux/IAA) family, the auxin response factor (ARF) family, small auxin upregulated RNA (SAUR), and the auxin-responsive Gretchen Hagen3 (GH3) family. Aux/IAA proteins are short-lived nuclear proteins comprising several highly conserved domains that are encoded by the auxin early response gene family. These proteins have specific domains that interact with ARFs and inhibit the transcription of genes activated by ARFs. Molecular studies have revealed that Aux/IAA family members can form diverse dimers with ARFs to regulate genes in various ways. Functional analyses of Aux/IAA family members have indicated that they have various roles in plant development, such as root development, shoot growth, and fruit ripening. In this review, recently discovered details regarding the molecular characteristics, regulation, and protein–protein interactions of the Aux/IAA proteins are discussed. These details provide new insights into the molecular basis of the Aux/IAA protein functions in plant developmental processes.

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IJMS, Vol. 19, Pages 262: Mutation Analysis in Cultured Cells of Transgenic Rodents

IJMS, Vol. 19, Pages 262: Mutation Analysis in Cultured Cells of Transgenic Rodents

International Journal of Molecular Sciences doi: 10.3390/ijms19010262

Authors: Ahmad Besaratinia Albert Zheng Steven Bates Stella Tommasi

To comply with guiding principles for the ethical use of animals for experimental research, the field of mutation research has witnessed a shift of interest from large-scale in vivo animal experiments to small-sized in vitro studies. Mutation assays in cultured cells of transgenic rodents constitute, in many ways, viable alternatives to in vivo mutagenicity experiments in the corresponding animals. A variety of transgenic rodent cell culture models and mutation detection systems have been developed for mutagenicity testing of carcinogens. Of these, transgenic Big Blue® (Stratagene Corp., La Jolla, CA, USA, acquired by Agilent Technologies Inc., Santa Clara, CA, USA, BioReliance/Sigma-Aldrich Corp., Darmstadt, Germany) mouse embryonic fibroblasts and the λ Select cII Mutation Detection System have been used by many research groups to investigate the mutagenic effects of a wide range of chemical and/or physical carcinogens. Here, we review techniques and principles involved in preparation and culturing of Big Blue® mouse embryonic fibroblasts, treatment in vitro with chemical/physical agent(s) of interest, determination of the cII mutant frequency by the λ Select cII assay and establishment of the mutation spectrum by DNA sequencing. We describe various approaches for data analysis and interpretation of the results. Furthermore, we highlight representative studies in which the Big Blue® mouse cell culture model and the λ Select cII assay have been used for mutagenicity testing of diverse carcinogens. We delineate the advantages of this approach and discuss its limitations, while underscoring auxiliary methods, where applicable.

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IJMS, Vol. 19, Pages 258: Microenvironment Stimuli HGF and Hypoxia Differently Affected miR-125b and Ets-1 Function with Opposite Effects on the Invasiveness of Bone Metastatic Cells: A Comparison with Breast Carcinoma Cells

IJMS, Vol. 19, Pages 258: Microenvironment Stimuli HGF and Hypoxia Differently Affected miR-125b and Ets-1 Function with Opposite Effects on the Invasiveness of Bone Metastatic Cells: A Comparison with Breast Carcinoma Cells

International Journal of Molecular Sciences doi: 10.3390/ijms19010258

Authors: Emanuela Matteucci Paola Maroni Francesco Nicassio Francesco Ghini Paola Bendinelli Maria Desiderio

We examined the influence of microenvironment stimuli on molecular events relevant to the biological functions of 1833-bone metastatic clone and the parental MDA-MB231 cells. (i) In both the cell lines, hepatocyte growth factor (HGF) and the osteoblasts’ biological products down regulated nuclear Ets-1-protein level in concomitance with endogenous miR-125b accumulation. In contrast, under hypoxia nuclear Ets-1 was unchanged, notwithstanding the miR-125b increase. (ii) Also, the 1833-cell invasiveness and the expression of Endothelin-1, the target gene of Ets-1/HIF-1, showed opposite patterns under HGF and hypoxia. We clarified the molecular mechanism(s) reproducing the high miR-125b levels with the mimic in 1833 cells. Under hypoxia, the miR-125b mimic maintained a basal level and functional Ets-1 protein, as testified by the elevated cell invasiveness. However, under HGF ectopic miR-125b downregulated Ets-1 protein and cell motility, likely involving an Ets-1-dominant negative form sensible to serum conditions; Ets-1-activity inhibition by HGF implicated HIF-1α accumulation, which drugged Ets-1 in the complex bound to the Endothelin-1 promoter. Altogether, 1833-cell exposure to HGF would decrease Endothelin-1 transactivation and protein expression, with the possible impairment of Endothelin-1-dependent induction of E-cadherin, and the reversion towards an invasive phenotype: this was favoured by Ets-1 overexpression, which inhibited HIF-1α expression and HIF-1 activity. (iii) In MDA-MB231 cells, HGF strongly and rapidly decreased Ets-1, hampering invasiveness and reducing Ets-1-binding to Endothelin-1 promoter; HIF-1α did not form a complex with Ets-1 and Endothelin-1-luciferase activity was unchanged. Overall, depending on the microenvironment conditions and endogenous miR-125b levels, bone-metastatic cells might switch from Ets-1-dependent motility towards colonization/growth, regulated by the balance between Ets-1 and HIF-1.

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Brain Sciences, Vol. 8, Pages 15: Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

Brain Sciences, Vol. 8, Pages 15: Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

Brain Sciences doi: 10.3390/brainsci8010015

Authors: Mayra Paolillo Cinzia Boselli Sergio Schinelli

Glioblastoma is known to be one of the most lethal and untreatable human tumors. Surgery and radiotherapy in combination with classical alkylating agents such as temozolomide offer little hope to escape a poor prognosis. For these reasons, enormous efforts are currently devoted to refine in vivo and in vitro models with the specific goal of finding new molecular aberrant pathways, suitable to be targeted by a variety of therapeutic approaches, including novel pharmaceutical formulations and immunotherapy strategies. In this review, we will first discuss current molecular classification based on genomic and transcriptomic criteria. Also, the state of the art in current clinical practice for glioblastoma therapy in the light of the recent molecular classification, together with ongoing phases II and III clinical trials, will be described. Finally, new pharmaceutical formulations such as nanoparticles and viral vectors, together with new strategies entailing the use of monoclonal antibodies, vaccines and immunotherapy agents, such as checkpoint inhibitors, will also be discussed.

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Dissecting the mechanisms and molecules underlying the potential carcinogenicity of red and processed meat in colorectal cancer (CRC): an overview on the current state of knowledge

Meat is a crucial nutrient for human health since it represents a giant supply of proteins, minerals, and vitamins. On the opposite hand, the intake of red and processed meat is taken into account dangerous du...

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Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer

Summary

The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil domain, in the fusion partner that induce abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation. ALK gene rearrangement have been observed in 3%–5% of non-small cell lung cancers (NSCLCs), and multiple ALK inhibitors have been developed for the treatment of ALK-positive lung cancer. Among those inhibitors, in Japan, three (four in the US) ALK tyrosine kinase inhibitors (TKIs) have been approved and are currently used in clinics. All of the currently approved ALK-TKIs have been shown to induce marked tumor regression in ALK-rearranged NSCLC; however, tumors inevitably relapse because of acquired resistance within a few years. This review focuses on ALK-TKIs, their resistance mechanisms, and the potential therapeutic strategies to overcome resistance.

This article is protected by copyright. All rights reserved.

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Wet cupping therapy improves local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis

Abstract

Objective

To observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS).

Methods

Fifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment effificacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flflowmetry, and its variations before and after treatment in both groups were compared as well.

Results

In both groups, the VAS scores signifificantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints signifificantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05).

Conclusions

WCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

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