Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis

Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.

Different antibiotic susceptibility between antrum and corpus of the stomach,a possible reason for treatment failure of Helicobacter pylori infection

AIM: To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori (H. pylori) therapy-naive or pre-treated.

Echo-enhanced ultrasound with pulse inversion imaging: A new imaging modality for the differentiation of cystic pancreatic tumours

AIM： To describe and discuss echo-enhanced sonography in the differential diagnosis of cystic pancreatic lesions. METHODS： The pulse inversion technique （with intravenous injection of 2.4 mL SonoVue） or the power-Doppler mode under the conditions of the 2^nd harmonic imaging （with intravenous injection of 4 g Levovist） was used for echo-enhanced sonography. RESULTS： Cystadenomas frequently showed many vessels along fibrotic strands. On the other hand, cystadenocarcinomas were poorly and chaotically vascularized. ＂Young pseudocysts＂ were frequently found to have a highly vascularised wall. However, the wall of the ＂old pseudocysts＂ was poorly vascularized. Data from prospective studies demonstrated that based on these imaging criteria the sensitivities and specificities of echoenhanced sonography in the differentiation of cystic pancreatic masses were 〉 90%. CONCLUSION： Cystic pancreatic masses have a different vascularization pattern at echo-enhanced sonography. These characteristics are useful for their differential diagnosis, but histology is still the gold standard.

Long-term antifibrotic action of interferon-γ treatment in patients with chronic hepatitis B virus infection

BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C virus.However,in many liver diseases the cause is either unknown or untreatable.The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma(IFN-γ)treatment in patients chronically infected with hepatitis B virus. METHODS:A total of 42 patients,30 treated with IFN-γand 12 controls,were enrolled from an original clinical trial(Clin Gastroenterol Hepatol 2005;3:819.).Three serial liver biopsies that were obtained at the initiation and end of IFN-γtreatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system. RESULTS:Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However,all controls were excluded from follow-up due to death,loss and elevated virus level within 2 years.Twenty-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further antiviral or anti-fibrotic treatment.Improved inflammatory and fibrotic scores were found after nine months of IFN-γtreatment according to the modified Chevallier scoring system(inflammation:11.8±6.5 at the beginning of IFN-γtreatment vs.9.2±4.1 after 9 months, P<0.05;fibrosis:15.0±7.3 at baseline vs.12.6±6.8 after 9 months, P<0.05).Among them,14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation,and the fibrotic score was increased(14.2±8.3 vs.11.9±7.6 after 9 months, P<0.05). CONCLUSIONS:Nine-month IFN-γtreatment significantly improves the fibrosis score in patients with chronic HBV infection.The majority of patients demonstrate stable serum biochemical indices and quality of life.However,they do not show a long-term benefit according to histological criteria. Given the limited sample size,long-term IFN-γtreatment regimens should be assessed in further clinical trials.

Solid-pseudopapillary tumor of the pancreatic tail

We report a case of the rare solid-pseudopapillary tumor of the pancreas. In contrast to other pancreatic tumors,the solid-pseudopapillary tumor has a favorable prognosis.The 60-year-old female patient we report on here was treated by left pancreatic resection combined with splenectomy for a non-metastasizing tumor of the pancreas. A solid-pseudopapillary tumor was found on histology. The patient had no signs of metastases at present.Since a microscopically invasive tumor growth is assumed,oncologically curative resection should be preferred vs the less radical enucleation. The rare solid-pseudopapillary tumor of the pancreas has a good prognosis after successful oncological resection.

Helicobacter pylori and gastric cancer: current status of the Austrian-Czech-German gastric cancer prevention trial (PRISMA-Study)

AIM To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease.METHODS It is a prospective, randomized,double-blind, placebo-controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacterpylori gastritis are randomized to receive a 7-day course of omeprazole 2 × 20 mg,clarithromycin 2 × 500 mg, and amoxicillin 2 ×lg for 7 days, or omeprazole2 × 20mg plusplacebo. Follow - up endoscopy is scheduled 3months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, anddeath.RESULTS Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus-dominant type of H.pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (n -- 86), H. pylori infection infection was cured in 88.9% of patients. Currently, thecumulative follow-up time is 3046 months (253.8patient-years, median follow-up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three(1.8%) patients reached study endpoints other than gastric cancer.CONCLUSION Among men between 55 and 65years of age, the gastric cancer phenotype of H.pylori gastritis appears to be more common than expected. Further follow- up and continuing recruitment are necessary to fulfil the main aim of the study.

Smoking prevalence in the area of responsibility of the German Ministry of Defense——results of the employee survey in the context of occupational health management

Background:Tobacco use,correlated with reduced physical fitness,is one of the leading causes of avoidable death worldwide.It increases the risk of dementia and can shorten the lifespan by 10 years.For the German Armed Forces(Bundeswehr),figures on smoking behavior have not been comprehensively captured.This study analyzes current data in a large sample from this population.Methods:Based on an employee survey as part of the Occupational Health Management System,data on smoking behavior from 13,326 participants were analyzed in relation to age,gender,professional status,education level and membership in military operational units versus other agencies.Results:Smoking behavior varied significantly(P<0.001)by age group(younger>older),gender,professional status,military agency membership status,and education level(the lower the education level,the higher the smoking rates).With the exception of the downward trend in smoking behavior with increasing age among civilian employees,these results were all significant(P<0.005).Conclusions:This data analysis shows that smoking prevalence among personnel in the area of responsibility of the Federal Ministry of Defense is comparable to the current data from corresponding surveys of the German population.Depending on gender,they generally show values that are slightly above those of the German population.The well-known trend in the general population of decreasing smoking prevalence with increasing age is also seen in this analysis.However,there are considerable differences in the smoking prevalence among individual subgroups(professional status,agency,gender,education level).The data show that particular young soldiers in the armed forces should be the target group for further preventive measures.

Risk factors for musculoskeletal injuries in the military: a qualitative systematic review of the literature from the past two decades and a new prioritizing injury model

Background: Musculoskeletal injuries(MSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. MSkIs affect members of the military during initial training,operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for MSkIs in the military is not available.Methods: A systematic literature search was carried out using the PubMed, Ovid/Medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed(using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was made.Results: In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/nonmodifiable, as well as extrinsic/intrinsic risk factors.Conclusions: This is the qualitative systematic review of studies on risk factors for MSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.

Central plasticity resulting from chronic low back pain in degenerative disorders of the spine

Degenerative disorders of the spine are the most common cause of chronic low back pain（c LBP）;in Western Europe alone,billions of euros are spent each year on both conservative and surgical treatments for c LBP.And though only 5%of all patients with low back pain suffer from lumbar disc herniation（LDH）,

青少年应激引起腹侧海马长时程增强的持续增加：星形细胞谷氨酰胺合成酶的作用

童年期创伤是引发与压力有关的精神病的最重要风险因素之一,例如创伤后压力障碍或抑郁。尽管已证实星形胶质细胞在调节递质释放和突触可塑性中发挥作用,然而目前尚不清楚星形胶质递质代谢在这种应激诱导的精神病理学中所起的作用。在啮齿动物,可以通过青少年应激暴露来模拟童年逆境,从而导致焦虑加剧以及成年后应对压力的能力下降。我们描述了这种幼年应激大鼠,无论成年期是否有其他应激,都会导致腹侧CA1(v CA1)Schaffer侧支的突触效力降低,而高频刺激后突触传递的长时程增强(LTP)增加。我们通过阻断星形胶质谷氨酸降解酶谷氨酰胺合成酶(GS)测试谷氨酸-谷氨酰胺循环是否引起青少年应激后可塑性的持久变化。用蛋氨酸亚砜亚胺对正常大鼠的切片中GS的药理抑制的确模仿青少年应激对vCA1-LTP的影响,而提供谷氨酰胺足以使LTP正常化。评估在青少年、成年期或青少年/成年联合应激后,vCA1辐射层中的稳态mRNA水平揭示了GS、星形细胞谷氨酸和谷氨酰胺转运蛋白表达的明显变化。尽管青少年应激后GS mRNA表达水平持续降低,但GS蛋白水平保持稳定。本研究结果表明,星形胶质细胞和谷氨酸-谷氨酰胺循环在介导青少年应激对vCA1(与焦虑和情绪记忆处理有关的区域)的可塑性的长期影响中起关键作用。

Microstructure and mechanical properties of the pressure die cast magnesium alloy AZ91D after long-term thermal exposure

The thermal resistance of the pressure die cast magnesium alloy AZ91D is yet not investigated sufficiently. Inorder to assess the effect of a thermal exposure on the microstructural stability and the mechanical properties, the alloyAZ91D is subjected to a long-term annealing for 1 000 h at 80 °C, 100 °C, 120 °C, 150 °C, 180 °C and 200 °C. After theannealing, the microstructural appearance of the material is investigated by light and scanning electron microscopy andcompared with the as-cast condition. Furthermore, tensile tests, hardness measurements and fracture toughness tests arecarried out and the measured values are discussed on the basis of the microstructural changes. The results reveal thedistinct correlation between the microstructural changes, especially the precipitation of discontinuous and continuousβ-particles (Mg17 Al12), and the mechanical properties.

Comparing the effectiveness of karate and fitnes training on cognitive functioning in older adults——A randomized controlled trial

Background：Recent studies demonstrate a slowdown in deterioration of cognitive functioning in old age through aerobic training.There is evidence that the combination of aerobic,balance,and coordination exercises leads to an improvement or maintenance of cognitive functions.Such age-related exercises can especially be found in East Asian martial arts.The purpose of the current study is to verify whether karate training for older adults improves cognitive functioning and,if an improvement can be found,which cognitive field are influenced Methods：Eighty-nine older women and men（mean age：70 years） participated in this study.The participants were randomized into 2 intervention groups（karate group and fitnes group,duration of intervention：5 months） and a control group.All participants had to accomplish a cognitive test battery before and after the intervention.In a secondary study the karate group had an additional intervention for another 5 months.Results：The results show that there is a significan improvement in motor reactivity,stress tolerance,and divided attention only after the 5-month karate training period.Additionally,the results of the secondary study indicate further improvements after 10 months.Conclusion：The 5-month karate training can help to enhance attention,resilience,and motor reaction time,but a training period of 10 months is even more efficient

Monitoring the Coldhead of Magnetic Resonance Imaging Systems by Means of Vibration Analysis

Magnetic resonance imaging (MRI) systems require a cooling close to the absolute zero point. This is necessary to avoid thermal losses due to the extremely high currents in the coils of the electromagnet used to generate the static magnetic field. The cooling is usually achieved using helium based refrigerating machine. The coldhead is an important and critical mechanical component in this system. An inefficient or failed coldhead can lead to severe damages to the MRI system or to the loss of helium. Hence, a continuous and reliable monitoring of this system component is necessary but not always available. To tackle this problem, we propose a monitoring system by means of analyzing the structure-borne noises caused by the mechanical activities of the coldhead. For this purpose, a measurement system based on piezoelectric elements was designed and implemented. Vibrations were measured at various locations at the MRI scanner with and without MR imaging. In all positions, the function of the coldhead could be detected. Hence, the developed system is suitable for monitoring an MRI’s coldhead without directly accessing the MR scanner’s hardware or software. For a future long-term monitoring, the aim is to predict a failure of the MRI’s coldhead based on changes in the vibrations signals.

On Improvement of Teaching Quality for a Selected Mathematical Topic Using Artificial Neural Networks Modeling(With a Case Study)

This paper motivated and inspired by an interdisciplinary critical educational issue adopted for a research work approach. It concerned with application of realistic Artificial Neural Networks (ANNs) models integrating reading brain function with multi-sensory cognitive learning theory. Specifically, these models adopted to improve tutoring quality (academic achievement) while teaching children “how to read?” considering the analysis and evaluation of phonics methodology. Herein, quantitative analysis and evaluation of this issue performed by considering two computer aided learning (CAL) packages concerned with a specific selected mathematical topic namely: long division process. Via realistic modeling of packages using (ANNs) based upon associative memory learning paradigm. In more details, at educational field practice; both CAL packages have been applied for teaching children algorithmic steps performing long division processes. Moreover, learning performance evaluation of presented packages considers children outcomes’ achievement after tutoring for suggested Mathematical Topic either with or without associated tutor’s voice. Interestingly, statistical analysis of obtained educational case study results at children classrooms (for both applied packages) versus classical tutoring proved to be in well agreement with obtained after ANNs computer simulation results.

Automatic Arabic Document Classification Based on the HRWiTD Algorithm

The documents contain a large amount of valuable knowledge on various subjects and, more recently, documents on the Internet are available from various sources. Therefore, automatic, rapid and accurate classification of these documents with less human interaction has become necessary. In this paper, we introduce a new algorithm called the highest repetition of words in a text document (HRWiTD) to classify the automatic Arabic text. The corpus is divided into a train set and a test set to be applied to proposed classification technique. The train set is analyzed for learning and the learning data is stored in the Learning Dataset file. The category that contains the highest repetition for each word is assigned as a category for the word in Learning Dataset file. This file includes non-duplicate words with the value of higher repetition and categories and they get from all texts in the train set. For each text in the test set, the category of words is assigned to a specific category by using Learning Dataset file. The category that contains the largest number of words is assigned as the predicted category of the text. To evaluate the classification accuracy of the HRWiTD algorithm, the confusion matrix method is used. The HRWiTD algorithm has been applied to convergent samples from six categories of Arabic news at SPA (Saudi Press Agency). As a result, the accuracy of the HRWiTD algorithm is 86.84%. In addition, we used the same corpus with the most popular machine learning algorithms which are C5.0, KNN, SVM, NB and C4.5, and their results of classification accuracy are 52.86%, 52.38%, 51.90%, 51.90% and 30%, respectively. Thus, the HRWiTD algorithm gives better classification accuracy compared to the most popular machine learning algorithms on the selected domain.

Image-Based Methods for Interaction with Head-Worn Worker-Assistance Systems

In this paper, a mobile assistance-system is described which supports users in performing manual working tasks in the context of assembling complex products. The assistance system contains a head-worn display for the visualization of information relevant for the workflow as well as a video camera to acquire the scene. This paper is focused on the interaction of the user with this system and describes work in progress and initial results from an industrial application scenario. We present image-based methods for robust recognition of static and dynamic hand gestures in realtime. These methods are used for an intuitive interaction with the assistance-system. The segmentation of the hand based on color information builds the basis of feature extraction for static and dynamic gestures. For the static gestures, the activation of particular sensitive regions in the camera image by the user’s hand is used for interaction. An HMM classifier is used to extract dynamic gestures depending on motion parameters determined based on the optical flow in the camera image.

机床结构应用材料(选译)

现代机床结构中使用材料的种类非常广泛,从钢材、铸铁到纤维增强复合材料都有使用,还有采用多种材料组合和混合结构的情况,此外融合了传感器和执行器功能的创新智能材料使得功能集成结构得以实现。因此材料的设计和应用反映了关于复杂布局以及机架和部件优化各个方面的自由度。本文介绍了目前机床结构中应用的技术上最先进的材料,评论了相应的科学文献资料,概述并深入探讨了材料的选择以及高性能、高精度、高效率机床的开发。

Comprehensive Euler/Lagrange modelling including particle erosion for confined gas-solid flows

The present research aims to assess the capability of a comprehensive Euler/Lagrange approach for predicting gas-solid flows and the associated solid particle erosion.The open-source code OpenFOAM®4.1 was used to carry out the numerical simulations,where the standard Lagrangian libraries were substantially extended to account for all necessary models.Particles are tracked considering both translational and rotational motion as well as all relevant forces,such as gravity/buoyancy,drag and transverse lift due to shear and particle rotation.The tracking time step was dynamically adapted ac-cording to the locally relevant time scales,which drastically reduces computational times.Stochastic approaches are adopted to model particle turbulent dispersion,particle collisions with rough walls and particle-particle interactions.Five solid particle erosion models,available in the literature,were considered to estimate pipe bend erosion.Three study cases are provided to validate the adopted nu-merical approach and erosion models extensively.The first case intends to evaluate the ability of the extended CFD code to predict the behaviour of gas-solid flows in pneumatic conveying systems.This goal is achieved by comparing the numerical results with the experimental data obtained by Huber(1997)and Huber and Sommerfeld(1994,1998)in a pneumatic conveying system.Here,the importance of considering inter-particle collisions and surface roughness for predicting particle velocity,mass flux and mean diameter distributions in gas-solid flows is highlighted.The second and third case intend to evaluate the ability of the erosion models in estimating bend erosion in diluted gas-solid flows.The erosion data obtained experimentally by Mazumder et al.(2008)and Solnordal et al.(2015)in very dilut pneumatic conveying systems is used for validating the numerical results,neglecting now inter-particle collisions and two-way coupling.Besides a comprehensive analysis of the different influential properties on erosion,the innovation of the present study is as follows.For the first time also a temporal modifi-cation of the surface roughness due to the erosion was considered in the simulations obtained from previous measurements(Novelletto Ricardo&Sommerfeld,2020).As the surface roughness is increased due to erosion,eventually erosion rate becomes lower.This is the result of diminishing wall collision frequency.Simulations for several degrees of surface roughness showed that larger roughness is coupled with a drastic reduction of erosion.Hence,numerical simulations neglecting wall surface roughness are not realistic.The consideration of a particle size distribution instead of mono-sized computations showed a possible reduction of erosion rate.The detailed analysis of the different single-particle erosion models revealed that the model proposed by Oka et al.(2005)and Oka and Yoshida(2005)yields the best agreement with the measurements,however particle and wall properties are needed.

The effect of side walls on particles mixing in rotating drums

In this paper, we study the effects of the presence and shape of side walls and of the overall length of rotating cylindrical drums on the mixing of particles with differing sizes by application of the discrete element method (DEM). By varying the semi-axis of the spheroidally shaped side walls and the length of the overall drum, we observe the formation of circulation patterns near the side walls. Although there is a vast amount of literature studying mixing regimes in rotating drums, little is known about the effect of the side walls of the drum on particle mixing. The results of our study demonstrate that introducing curved side walls induces a strong circulation pattern near these side walls, but has, paradoxically, a negative impact on mixing and actually promotes segregation. The cause for this segregation is the difference in velocity of differently sized particles near the curved side walls. Large particles accumulate at the curved side walls, whereas small particles move away from the curved side walls. When the length of the drum is increased, the overall effect of the side walls is decreased, although it does remain observable, even in very large drums.

Coding variants of the interleukin-11 receptor with reduced protein maturation show protease-dependent trans-signaling and transduce normal STAT3 signaling

Interleukin-11(IL-11)is a member of the IL-6 family of cytokines.1 IL-11 activates its target cells via binding to the IL-11 receptor(IL-11R),which also exists in soluble forms generated by proteolytic cleavage(sIL-11R,required for trans-signaling).2 Formation of the IL-11/IL-11R complex leads to the recruitment and homodimerization of two molecules of the signal-transducingβ-receptor gp130,which then activates intracellular signaling cascades,including the Jak/STAT,PI3K and ERK pathways.