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Κυριακή, 12 Μαρτίου 2017

Oncogene addiction in non-small cell lung cancer: focus on ROS1 inhibition


Publication date: Available online 12 March 2017
Source:Cancer Treatment Reviews
Author(s): Francesco Facchinetti, Giulio Rossi, Emilio Bria, Jean-Charles Soria, Benjamin Besse, Roberta Minari, Luc Friboulet, Marcello Tiseo
Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in1-2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e. g. EGFR and KRAS mutations, ALK gene fusions), seeking for ROS1 rearrangements is crucial. Dedicated molecular diagnostics should be standardized, hopefully relying upon practical and efficient algorithms, comprehending immunohistochemistry and fluorescence in situ hybridisation. The major clinical impact exerted by crizotinib represents the main reason for which not even a sole ROS1-positive tumor should be undetected. The recent approval of the inhibitor by both American and European health agencies would hopefully boost the widespread testing for ROS1, eventually increasing the absolute number of positive cases, potential further source of information regarding molecular and clinical resistance. In vitro and clinical evidence have already been generated concerning crizotinib resistance and strategies to maintain patients under specific driver-inhibition are being successfully developed. Gathering data concerning diagnostics, preclinical evidence, clinical practice and ongoing studies, the present review depicts the current scenario of ROS1 inhibition in NSCLC.

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Astaxanthin attenuated pressure overload-induced cardiac dysfunction and myocardial fibrosis: Partially by activating SIRT1

Publication date: Available online 12 March 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Jun Zhang, Quan-zhen Wang, Shao-hua Zhao, Xiang Ji, Jie Qiu, Jian Wang, Yi Zhou, Qian Cai, Jie Zhang, Hai-qing Gao
BackgroundMyocardial fibrosis contributes to cardiac dysfunction. Astaxanthin (AST), a member of the carotenoid family, is a well-known antioxidant, but its effect on and underlying mechanisms in myocardial fibrosis are poorly understood.MethodsIn vivo, myocardial fibrosis and cardiac dysfunction were induced using transverse aortic constriction (TAC). AST was administered to mice for 12 weeks post-surgery. In vitro, transforming growth factor β1 (TGF-β1) was used to stimulate human cardiac fibroblasts (HCFs). EX-527 (6-chloro-2, 3, 4, 9-tetrahydro-1H-carbazole-1-carboxamide) and SIRT1 siRNA were used to inhibit SIRT1 in vivo and in vitro, respectively. The effects of AST on cardiac function and fibrosis were determined. SIRT1 expression and activity were measured to explore the mechanisms underlying its effects.ResultsAST improved cardiac function and attenuated fibrosis. Receptor activated-SMADs (R-SMADs), including SMAD2 and SMAD3, played important roles in these processes. The TAC surgery-induced increases in the expression of phosphorylated and acetylated R-SMADs were attenuated by treatment with AST, the translocation and transcriptional activity of R-SMADs were also restrained. These effects were accompanied by an increase in the expression and activity of SIRT1. Inhibiting SIRT1 attenuated the acetylation and transcriptional activity of R-SMADs, but not their phosphorylation and translocation.ConclusionsOur data demonstrate that AST improves cardiac function and attenuates fibrosis by decreasing phosphorylation and deacetylation of R-SMADs. SIRT1 contributes to AST’s protective function by reducing acetylation of R-SMADs.General SignificanceThese data suggest that AST may be useful as a preventive/therapeutic agent for cardiac dysfunction and myocardial fibrosis.

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Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: There are clear effects of thyroid hormone on the heart. Some clinical studies have shown an increased risk of heart disease and death in patients with hypothyroidism, both mild and overt. Read More….

The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.

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Structural, rheological and nutraceutical potential of β-glucan from barley and oat

Publication date: Available online 12 March 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Asima Shah, Adil Gani, F.A. Masoodi, Shoib M. Wani, Bilal Ahmad Ashwar
β-glucan in oat and barley were characterized by FT-IR spectroscopy, size-exclusion chromatography and purity estimation by Megazyme β-glucan assay kit. Oat and barley β-glucan had average molecular weights of 2.0×103kDa and 1.79 ×103kDa, respectively. Rheological analysis suggested that β-glucan consisted of interchain aggregations and showed shear thinning behavior as revealed from Herschel-Bulkely model and frequency sweep. Antioxidant activity was evaluated by three complementary assays. Oat β- glucan showed increased DPPH scavenging activity, reducing power, and protection against DNA damage than barley β-glucan. Further, the antiproliferative potential of β-glucan was tested against three human cancer cell lines using MTT assay (3- (4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide). β-glucan exhibited dose dependent cancer cell growth inhibition with oat β-glucan being more potent than barley β-glucan. This study demonstrates that barley and oat beta glucans hold nutraceutical potential of importance for functional food development and human health in general.

Graphical abstract


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Anticoagulant: An agent that is used to prevent the formation of blood clots. Anticoagulants have various uses. Some are used for the prevention or treatment of disorders characterized by abnormal blood clots and emboli. Examples of diseases and conditions that require anticoagulant treatment to reduce the risk of blood clots include heart attack, stroke, deep venous thrombosis, pulmonary embolism, and atrial fibrillation. There are different classes of anticoagulant drugs:

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Biophysical basis of cadherin mediated cell-cell adhesion

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Andrew Vae Priest, Omer Shafraz, Sanjeevi Sivasankar
Classical cadherin transmembrane cell-cell adhesion proteins play essential roles in tissue morphogenesis and in mediating tissue integrity. Cadherin ectodomains from opposing cells interact to form load-bearing trans dimers that mechanically couple cells. Cell-cell adhesion is believed to be strengthened by cis clustering of cadherins on the same cell surface. This review summarizes biophysical studies of the structure, interaction kinetics and biomechanics of classical cadherin ectodomains. We first discuss the structure and equilibrium binding kinetics of classical cadherin trans and cis dimers. We then discuss how mechanical stimuli alters the kinetics of cadherin interaction and tunes adhesion. Finally, we highlight open questions on the role of mechanical forces in influencing cadherin structure, function and organization on the cell surface.

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Hypoxia and B cells

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Natalie Burrows, Patrick Henry Maxwell
The ability of cells to sense and adapt to changes in oxygen is mediated by hypoxia-inducible factor (HIF). Immune cells function in physiologically complex and varying environments whereby oxygen, pH, nutrients, metabolites and cytokines are continuously fluctuating. HIF is well known to play an important role in coordinating the adaptation and function of both innate immune cells and T cells in these complex environments. This review summarises recent discoveries concerning how hypoxia and HIF control B cell behaviour, and regulate antibody quality and decisions concerning tolerance. Hypoxia and HIF activation may provide an important context; coordinating metabolism with variable demands for quiescence, rapid proliferation, and differentiation. Understanding when and how HIF is activated during B cell development and response is important as drugs targeting HIF could influence antibody responses, providing novel therapeutic opportunities for vaccine adjuvants and in treating autoimmunity.

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9-cis Retinoic Acid modulates myotrophin expression and its miR in physiological and pathophysiological cell models

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Mariarita Perri, Maria Cristina Caroleo, Nannan Liu, Luca Gallelli, Giovambattista De Sarro, Hiroyuki Kagechika, Erika Cione
Functional studies indicate that essential cellular processes are controlled by Vitamin A derivatives. Among these the retinoic acid isoforms, all-trans- and 9-cis (9cRA), regulate the expression of various genes in both physiological and pathological conditions. Using several in vitro experimental models such as pancreatic β-cells, pre-adipocytes and breast cancer cells with different phenotypes, we demonstrated the capability of 9cRA to modulate myotrophin (Mtpn) and miR-375 expressions. The 9cRA effect in pancreatic β-cells line INS-1 832/13 point out a decreased expression of Mptn at both mRNA and protein levels associated to a concomitant increase of miR-375. We also studied the effect of this molecule on 3T3-L1 pre-adipocytes cells demonstrating a down-regulation of Mtpn and a dramatic increase of miR-375. Moreover, in the in vitro breast cancer model such as MDA-MB-231 and MCF-7 cells, 9cRA showed different effect on both Mtpn and miR-375 expression. In INS-1 832/13, 3T3-L1 pre-adipocytes and MCF-7 but not in MDA-MB-231, the effect of 9cRA on Mptn gene expression and its miR was under the control of RARs and RXRs receptors, as revealed by the exposure of these cell line to LE540 or HX603 receptor antagonists. In our findings 9cRA emerges has a hormone with a regulatory action on miR-375 that in most cases interfere with Mtpn expression.

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Doxycycline protects human intestinal cells from hypoxia/reoxygenation injury: Implications from an in-vitro hypoxia model

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Lars Hummitzsch, Karina Zitta, Rouven Berndt, Matthias Kott, Christin Schildhauer, Kerstin Parczany, Markus Steinfath, Martin Albrecht
Intestinal ischemia/reperfusion (I/R) injury is a grave clinical emergency and associated with high morbidity and mortality rates. Based on the complex underlying mechanisms, a multimodal pharmacological approach seems necessary to prevent intestinal I/R injury. The antibiotic drug doxycycline, which exhibits a wide range of pleiotropic therapeutic properties, might be a promising candidate for also reducing I/R injury in the intestine.To investigate possible protective effects of doxycycline on intestinal I/R injury, human intestinal CaCo-2 cells were exposed to doxycycline at clinically relevant concentrations. In order to mimic I/R injury, CaCo-2 were thereafter subjected to hypoxia/reoxygenation by using our recently described two-enzyme in-vitro hypoxia model. Investigations of cell morphology, cell damage, apoptosis and hydrogen peroxide formation were performed 24hours after the hypoxic insult.Hypoxia/reoxygenation injury resulted in morphological signs of cell damage, elevated LDH concentrations in the respective culture media (P<0.001) and increased protein expression of proapoptotic caspase-3 (P<0.05) in the intestinal cultures. These events were associated with increased levels hydrogen peroxide (P<0.001). Preincubation of CaCo-2 cells with different concentrations of doxycycline (5µM, 10µM, 50µM) reduced the hypoxia induced signs of cell damage and LDH release (P<0.001 for all concentrations). The reduction of cellular damage was associated with a reduced expression of caspase-3 (5µM, P<0.01; 10µM, P<0.01; 50µM, P<0.05), while hydrogen peroxide levels remained unchanged.In summary, doxycycline protects human intestinal cells from hypoxia/reoxygenation injury in-vitro. Further animal and clinical studies are required to prove the protective potential of doxycycline on the intestinal I/R injury under in-vivo conditions.

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The shift in GH3 cell shape and cell motility is dependent on MLCK and ROCK

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Dulce Ávila-Rodríguez, Carmen Solano Agama, Sirenia González-Pozos, Juan Vicente Méndez-Méndez, Alma Ortiz Plata, Laura Arreola-Mendoza, María E Mendoza-Garrido
Cytoskeletal organization, actin-myosin contractility and the cell membrane together regulate cell morphology in response to the cell environment, wherein the extracellular matrix (ECM) is an indispensable component. Plasticity in cell shape enables cells to adapt their migration mode to their surroundings. GH3 endocrine cells respond to different ECM proteins, acquiring different morphologies: a rounded on collagen I-III (C I-III) and an elongated on collagen IV (C IV). However, the identities of the molecules that participate in these responses remain unknown. Considering that actin-myosin contractility is crucial to maintaining cell shape, we analyzed the participation of MLCK and ROCK in the acquisition of cell shape, the generation of cellular tension and the cell motility mode. We found that a rounded shape with high cortical tension depends on MLCK and ROCK, whereas in cells with an elongated shape, MLCK is the primary protein responsible for cell spreading. Further, in cells with a slow and directionally persistent motility, MLCK predominates, while rapid and erratic movement is ROCK-dependent. This behavior also correlates with GTPase activation. Cells on C I-III exhibited higher Rho-GTPase activity than cells on C IV and vice versa with Rac-GTPase activity, showing a plastic response of GH3 cells to their environment, leading to the generation of different cytoskeleton and membrane organizations and resulting in two movement strategies, rounded and fibroblastoid-like.

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Sestrin 2 induces autophagy and attenuates insulin resistance by regulating AMPK signaling in C2C12 myotubes

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Huige Li, Sujuan Liu, Hairui Yuan, Yanmei Niu, Li Fu
Impaired insulin-stimulated glucose uptake in skeletal muscle serves a critical role in the development of insulin resistance (IR), whereas the precise mechanism of the process remains unknown. Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes. Activation of Sesn2 may activate AMP-activated protein kinase (AMPK) accompanied by suppression of mammalian target of rapamycin (mTOR), which may ultimately lead to autophagy induction. In view of the potential protective effects of autophagy on the physiological and the pathological regulatory processes via the regulation of energy homeostasis and metabolism, we investigated the effects of Sesn2 on the components of the insulin signaling pathway and insulin-stimulated glucose uptake in palmitate-induced insulin-resistant C2C12 myotubes. We showed that Sesn2 effectively restored the impaired insulin signaling. Moreover, autophagic activity decreased in response to palmitate, whereas Sesn2 significantly reversed the palmitate-suppressed autophagic signaling in this context. Our findings further revealed that Sesn2-induced autophagy contributed to restore the impaired insulin signaling through the activation of AMPK signal. Even in the presence of palmitate, Sesn2 up-regulation maintained insulin sensitivity and glucose metabolism via AMPK-dependent autophagic activation.

Graphical abstract


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Nucleolin is a nuclear target of heparan sulfate derived from glypican-1

Publication date: Available online 12 March 2017
Source:Experimental Cell Research
Author(s): Fang Cheng, Mattias Belting, Lars-Åke Fransson, Katrin Mani
The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells. In all cells, nuclear HS-anMan targeted a limited number of sites of variable size where it colocalized with DNA and nucleolin, an established marker for nucleoli. HS-anMan also colocalized with ethynyl uridine-tagged nascent RNA and two acetylated forms of histone H3. Acute hypoxia increased the formation of HS-anMan in both Tg2576 and U87 cells. A portion of HS-anMan colocalized with nucleolin at small discrete sites, while most of the nucleolin and nascent RNA was dispersed. In U87 cells, HS-anMan, nucleolin and nascent RNA reassembled after prolonged hypoxia. Nucleolar HS may modulate synthesis and/or release of rRNA.

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Antibodies against monomeric C-reactive protein – A promising biomarker of lupus nephritis?

Publication date: Available online 12 March 2017
Source:Clinical Biochemistry
Author(s): Katarzyna Jakuszko, Magdalena Krajewska, Katarzyna Kościelska-Kasprzak, Marta Myszka, Agata Sebastian, Katarzyna Gniewek, Piotr Wiland, Marian Klinger
Objective and aimA significant incidence of systemic lupus erythematosus (SLE), the severity of lupus nephritis and varying responses to treatment rationalize the search for novel biomarkers of disease activity.The aim of the study was to assess whether antibodies against monomeric C reactive protein (anti-mCRP) are associated with the presence of lupus nephritis, correlate with disease activity, and whether they can serve to evaluate a response to treatment.MethodsThe study involved 74 patients with lupus nephritis, 29 patients with systemic lupus without renal involvement and 31 patients with primary glomerulonephritis; the control group included 31 healthy volunteers. Interleukin-6 and tumor necrosis factor alpha were measured using commercially available ELISA tests. The presence of anti-mCRP in the serum was tested with the use of in-house ELISA.ResultsThe highest prevalence and concentrations of antibodies against monomeric C-reactive protein were observed among patients with lupus nephritis, as compared to other groups. The elevated level of anti-mCRP was associated with standard clinical and laboratory indicators of SLE activity. Moreover, the highest concentrations of both Il-6 and TNF-α were observed for patients with the most severe nephropathy. A significant decrease in anti-mCRP and cytokines' levels in the course of treatment was observed.ConclusionThe study gives further evidence that antibodies against monomeric C-reactive protein may be considered an indicator of renal involvement in patients with SLE. Assessment of anti-mCRP supports monitoring of disease activity and can be used in evaluating the treatment effectiveness.

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Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway.

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Ethyl Acetate Extracts of Semen Impatientis Inhibit Proliferation and Induce Apoptosis of Human Prostate Cancer Cell Lines through AKT/ERK Pathways

Objective. To investigate the inhibitory effect of ethyl acetate extracts of Impatiens balsamina L. on prostate cancer cells. Methods. Impatiens balsamina L. was extracted to get water, ethanol, oil ether, ethyl acetate, and butanol extracts. CCK-8 assay was used to detect the inhibitory effect. Apoptosis rates and cell cycle distribution were detected by flow cytometry. Transwell assay was performed to test the ability of migration. The expressions of Bcl-2, Bax, cleaved-caspase-3, p-ERK, ERK, p-AKT, AKT, cyclin D1, cyclin E, and MMP2 were detected by Western blot. Results. Ethyl acetate extracts had the strongest inhibitory effect. After being treated with different concentrations of ethyl acetate extracts, the percentage of G0/G1 phase increased significantly, cyclin D1 and cyclin E expression decreased, apoptosis rate was significantly higher, and the ability of migration of PC-3 and RV1 was inhibited significantly. Western blot showed that the expressions of Bcl-2, p-ERK, and p-AKT were significantly decreased, but the expressions of Bax and caspase-3 cleavage were increased. Conclusions. Impatiens balsamina L. inhibited the proliferation of human prostate cancer cells; ethyl acetate extracts have the strongest effect. It could inhibit cell proliferation and migration, cause G1 phase arrest, and induce apoptosis probably through inhibition of the AKT and ERK pathways.

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Adaptive Image Compressive Sensing Using Texture Contrast

The traditional image Compressive Sensing (CS) conducts block-wise sampling with the same sampling rate. However, some blocking artifacts often occur due to the varying block sparsity, leading to a low rate-distortion performance. To suppress these blocking artifacts, we propose to adaptively sample each block according to texture features in this paper. With the maximum gradient in 8-connected region of each pixel, we measure the texture variation of each pixel and then compute the texture contrast of each block. According to the distribution of texture contrast, we adaptively set the sampling rate of each block and finally build an image reconstruction model using these block texture contrasts. Experimental results show that our adaptive sampling scheme improves the rate-distortion performance of image CS compared with the existing adaptive schemes and the reconstructed images by our method achieve better visual quality.

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Elastomeric Nanocomposite Based on Exfoliated Graphene Oxide and Its Characteristics without Vulcanization

Rubber nanocomposites have emerged as one of the advanced materials in recent years. The aim of this work was to homogeneously disperse graphene oxide (GO) sheets into Nitrile Butadiene Rubber (NBR) and investigate the characteristics of GO/NBR nanocomposite without vulcanization. A suitable solvent was found to dissolve dry NBR while GO was exfoliated completely in an aqueous base solution using sonication. GO was dispersed into NBR at different loadings by solution mixing to produce unvulcanized GO/NBR nanocomposites. Scanning Electron Microscopy (SEM), Fourier-Transform Infrared Spectroscopy (FTIR), and X-Ray Diffraction (XRD) were used to characterize the samples. Furthermore, mechanical and electrical properties of unvulcanized GO/NBR nanocomposites were carried out to determine the influence of GO on the NBR properties. The results showed that the modulus of GO/NBR nanocomposite at 1 wt% of GO was enhanced by about 238% compared with unfilled NBR. These results provide insight into the properties of unvulcanized GO/NBR nanocomposite for application as coatings or adhesives.

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Systematic Theoretical Analysis of Dual-Parameters Readout by a Novel -Type Passive Sensor

This paper systematically studied the simultaneous measurement of two parameters by a -type passive sensor from the theoretical perspective. Based on the lumped circuit model of the typical -type passive dual-parameter sensor system, the influencing factors of the signal strength of the sensor as well as the influencing factors of signal crosstalk were both analyzed. It is found that the influencing factors of the readout signal strength of the sensor are mainly quality factors ( factors) of the tanks, coupling coefficients, and the resonant frequency interval of the two tanks. And the influencing factors of the signal crosstalk are mainly coupling coefficient between the sensor inductance coils and the resonant frequency interval of the two tanks. The specific influence behavior of corresponding influencing factors on the signal strength and crosstalk is illustrated by a series of curves from numerical results simulated by using MATLAB software. Additionally, a decoupling scheme for solving the crosstalk problem algorithmically was proposed and a corresponding function was derived out. Overall, the theoretical analysis conducted in this work can provide design guidelines for making the dual-parameter -type passive sensor useful in practical applications.

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Effect of Postsowing Compaction on Cold and Frost Tolerance of North China Plain Winter Wheat

Improper postsowing compaction negatively affects soil temperature and thereby cold and frost tolerance, particularly in extreme cold weather. In North China Plain, the temperature falls to 5 degrees below zero, even lower in winter, which is period for winter wheat growing. Thus improving temperature to promote wheat growth is important in this area. A field experiment from 2013 to 2016 was conducted to evaluate effects of postsowing compaction on soil temperature and plant population of wheat at different stages during wintering period. The effect of three postsowing compaction methods—(1) compacting wheel (CW), (2) crosskill roller (CR), and (3) V-shaped compacting roller after crosskill roller (VCRCR)—on winter soil temperatures and relation to wheat shoot growth parameters were measured. Results showed that the highest soil midwinter temperature was in the CW treatment. In the 20 cm and 40 cm soil layer, soil temperatures were ranked in the following order of CW > VCRCR > CR. Shoot numbers under CW, CR, and VCRCR treatments were statistically 12.40% and 8.18% higher under CW treatment compared to CR or VCRCR treatments at the end of wintering period. The higher soil temperature under CW treatment resulted in higher shoot number at the end of wintering period, apparently due to reduced shoot death by cold and frost damage.

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Bilateral Sertoli Cell Tumors in a Patient with Androgen Insensitivity Syndrome

Androgen insensitivity syndrome is the most common cause of male pseudohermaphroditism and the third most common cause of primary amenorrhea. This genetic alteration is a consequence of inherited defects on the X chromosome causing total or partial damage to the intrauterine virilization process due to functional abnormalities in the androgen receptors. The present report describes a 22-year-old patient with a female phenotype and a 46, XY karyotype, presenting with bilateral inguinal tumors. The tumors were surgically removed at the Santa Casa de Misericórdia Hospital in Vitória, Espírito Santo, Brazil. Pathology revealed bilateral testicles with Sertoli cell tumors. According to the international literature, prophylactic gonadectomy following puberty is recommended due to the progressive risk of neoplastic transformation in the residual gonads.

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Changes in the MicroRNA Profile Observed in the Subcutaneous Adipose Tissue of Obese Patients after Laparoscopic Adjustable Gastric Banding

Background. Laparoscopic adjustable gastric banding (LAGB) results in significant lasting weight loss and improved metabolism in obese patients. To evaluate whether epigenetic factors could concur to these benefits, we investigated the subcutaneous adipose tissue (SAT) microRNA (miRNA) profile before (T0) and three years (T1) after LAGB in three morbidly obese women. Case Reports. SAT miRNA profiling, evaluated by TaqMan Array, showed four downexpressed (miR-519d, miR-299-5p, miR-212, and miR-671-3p) and two upexpressed (miR-370 and miR-487a) miRNAs at T1 versus T0. Bioinformatics predicted that these miRNAs regulate genes belonging to pathways associated with the cytoskeleton, inflammation, and metabolism. Western blot analysis showed that PPAR-alpha, which is the target gene of miR-519d, increased after LAGB, thereby suggesting an improvement in SAT lipid metabolism. Accordingly, the number and diameter of adipocytes were significantly higher and lower, respectively, at T1 versus T0. Bioinformatics predicted that the decreased levels of miR-212, miR-299-5p, and miR-671-3p at T1 concur in reducing SAT inflammation. Conclusion. We show that the miRNA profile changes after LAGB. This finding, although obtained in only three cases, suggests that this epigenetic mechanism, by regulating the expression of genes involved in inflammation and lipid metabolism, could concur to improve SAT functionality in postoperative obese patients.

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Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model

No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week ( = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.

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Online Behavior Analysis-Based Student Profile for Intelligent E-Learning

With the development of mobile platform, such as smart cellphone and pad, the E-Learning model has been rapidly developed. However, due to the low completion rate for E-Learning platform, it is very necessary to analyze the behavior characteristics of online learners to intelligently adjust online education strategy and enhance the quality of learning. In this paper, we analyzed the relation indicators of E-Learning to build the student profile and gave countermeasures. Adopting the similarity computation and Jaccard coefficient algorithm, we designed a system model to clean and dig into the educational data and also the students’ learning attitude and the duration of learning behavior to establish student profile. According to the E-Learning resources and learner behaviors, we also present the intelligent guide model to guide both E-Learning platform and learners to improve learning things. The study on student profile can help the E-Learning platform to meet and guide the students’ learning behavior deeply and also to provide personalized learning situation and promote the optimization of the E-Learning.

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The Impact of Ce-Zr Addition on Nickel Dispersion and Catalytic Behavior for CO2 Methanation of Ni/AC Catalyst at Low Temperature

The CO2 methanation was studied over 7 wt.% nickel supported on Ce0.2Zr0.8O2/AC to evaluate the correlation of the structural properties with catalytic performance. The catalysts were investigated in more detail by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). A sample of 7 wt.% nickel loading supported on activated carbon (AC) was also prepared for comparison. The results demonstrated that the ceria-zirconia solid solution phase could disperse and stabilize the nickel species more effectively and resulted in stronger interaction with nickel than the parent activated carbon phase. Therefore, 7% Ni/Ce0.2Zr0.8O2/AC catalyst exhibited higher activity for CO2 reduction than 7% Ni//AC. It can attain 85% CO2 conversion at 350°C and have a CH4 selectivity of 100% at a pressure as low as 1 atm. The high activity of prepared catalysts is attributed to the good interaction between Ni and Ce0.2Zr0.8O2 and the high CO2 adsorption capacity of the activated carbon as well.

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Mode of Delivery according to Leisure Time Physical Activity before and during Pregnancy: A Multicenter Cohort Study of Low-Risk Women

Objectives. To examine the association between maternal leisure time physical activity and mode of delivery. Study Design. Population-based multicentre cohort. From the Danish Dystocia Study, we included 2,435 nulliparous women, who delivered a singleton infant in cephalic presentation at term after spontaneous onset of labor in 2004-2005. We analysed mode of delivery according to self-reported physical activity at four stages, that is, the year before pregnancy and during first, second, and third trimester, in logistic regression models. Further, we combined physical activity measures at all four stages in one variable for a proportional odds model for cumulative logits. Main Outcome Measures. Mode of delivery (emergency caesarean section; vacuum extractor; spontaneous vaginal delivery). Results. The odds of emergency caesarean section decreased with increasing levels of physical activity with statistically significant trends at all four time stages except the third trimester. This tendency was confirmed in the proportional odds model showing 28% higher odds of a more complicated mode of delivery among women with a low activity level compared to moderately active women. Conclusions. We found increasing leisure time physical activity before and during pregnancy associated with a less complicated delivery among low-risk, nulliparous women.

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Mathematical and Computational Modeling in Complex Biological Systems

The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology.

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Retrospective study of rare cutaneous malignant adnexal tumors of the head and neck in a tertiary care cancer hospital: a case series

Adnexal tumors of the skin are a large and diverse group of benign and malignant neoplasms, which exhibit morphological differentiation toward one of the different types of adnexal epithelium present in normal...

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Two alternative binding mechanisms connect the protein translocation Sec71/Sec72 complex with heat shock proteins [Protein Structure and Folding]

The biosynthesis of many eukaryotic proteins requires accurate targeting to and translocation across the endoplasmic reticulum (ER) membrane. Post-translational protein translocation in yeast requires both the Sec61 translocation channel, and a complex of four additional proteins: Sec63, Sec62, Sec71, and Sec72. The structure and function of these proteins are largely unknown. This pathway also requires the cytosolic Hsp70 protein Ssa1, but whether Ssa1 associates with the translocation machinery to target protein substrates to the membrane is unclear. Here, we use a combined structural and biochemical approach to explore the role of Sec71/Sec72 subcomplex in post-translational protein translocation. To this end, we report a crystal structure of the Sec71/Sec72 complex, which revealed that Sec72 contains a tetratricopeptide repeat (TPR) domain that is anchored to the ER membrane by Sec71. We also determined the crystal structure of this TPR domain with a C-terminal peptide derived from Ssa1, which suggests how Sec72 interacts with full-length Ssa1. Surprisingly, Ssb1, a cytoplasmic Hsp70 that binds ribosome- associated nascent polypeptide chains also binds to the TPR domain of Sec72, even though it lacks the TPR-binding C-terminal residues of Ssa1. We demonstrate that Ssb1 binds through its ATPase domain to the TPR domain, an interaction that leads to inhibition of nucleotide exchange. Taken together, our results suggest that translocation substrates can be recruited to the Sec71/72 complex either post-translationally through Ssa1 or co-translationally through Ssb1.

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A vicious partnership between AKT and PHLDA3 to facilitate neuroendocrine tumors


Neuroendocrine tumors (NETs) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of NETs. It has been shown that the mTOR inhibitor everolimus can improve the progression-free survival of pancreatic NET (PanNET) patients, suggesting that inhibition of the PI3K-Akt-mTOR pathway may suppress the progression of PanNETs. PHLDA3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to PIP3. Our analysis of PanNETs revealed frequent loss-of-heterozygosity and DNA methylation at the PHLDA3 locus, resulting in strong suppression of PHLDA3 transcription. Such alterations in the PHLDA3 gene were also frequently found in lung NETs, suggesting the possibility that various types of NETs have in common the functional loss of the PHLDA3 gene.

This article is protected by copyright. All rights reserved.

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STEMS pilot trial: a pilot cluster randomised controlled trial to investigate the addition of patient direct access to physiotherapy to usual GP-led primary care for adults with musculoskeletal pain


Around 17% of general practitioner (GP) consultations are for musculoskeletal conditions, which will rise as the population ages. Patient direct access to physiotherapy provides one solution, yet adoption in the National Health Service (NHS) has been slow.


A pilot, pragmatic, non-inferiority, cluster randomised controlled trial (RCT) in general practice and physiotherapy services in the UK.


Investigate feasibility of a main RCT.


Adult patients registered in participating practices and consulting with a musculoskeletal problem.


4 general practices (clusters) randomised to provide GP-led care as usual or the addition of a patient direct access to physiotherapy pathway.


Process outcomes and exploratory analyses of clinical and cost outcomes.

Data collection

Participant-level data were collected via questionnaires at identification, 2, 6 and 12 months and through medical records.


The study statistician and research nurses were blinded to practice allocation.


Of 2696 patients invited to complete study questionnaires, 978 participated (intervention group n=425, control arm n=553) and were analysed. Participant recruitment was completed in 6 months. Follow-up rates were 78% (6 months) and 71% (12 months). No evidence of selection bias was observed. The direct access pathway was used by 90% of patients in intervention practices needing physiotherapy. Some increase in referrals to physiotherapy occurred from one practice, although waiting times for physiotherapy did not increase (28 days before, 26 days after introduction of direct access). No safety issues were identified. Clinical and cost outcomes were similar in both groups. Exploratory estimates of between group effect (using 36-item Short Form Health Survey (SF-36) Physical Component Summary (PCS)) at 6 months was –0.28 (95% CI –1.35 to 0.79) and at 12 months 0.12 (95% CI –1.27 to 1.51).


A full RCT is feasible and will provide trial evidence about the clinical and cost-effectiveness of patient direct access to physiotherapy.

Trial registration number


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Thyroid High-Impact Articles


FREE ACCESS through March 24, 2017
Read now:

Latest Impact Factor: 3.784
The Official Journal of: American Thyroid Association

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum
Erik K. Alexander, Elizabeth N. Pearce, Gregory A. Brent, Rosalind S. Brown, Herbert Chen, Chrysoula Dosiou, William A. Grobman, Peter Laurberg, John H. Lazarus, Susan J. Mandel, Robin P. Peeters, Scott Sullivan

Consanguinity and the Risk of Hashimoto’s Thyroiditis
Raja Y. Zaghlol, Alireza Haghighi, Motasem M. Alkhayyat, Othman F. Theyab, Amal M. Owaydah, Mu’taz M. Massad, Mohammad A. Atari, Ayman A. Zayed

Response to Therapy Status Is an Excellent Predictor of Pregnancy-Associated Structural Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer
Luba Rakhlin, Stephanie Fish, R. Michael Tuttle

Can an Educational Intervention Improve Iodine Nutrition Status in Pregnant Women? A Randomized Controlled Trial
Parisa Amiri, Najmeh Hamzavi Zarghani, Pantea Nazeri, Fazlollah Ghofranipour, Mehrdad Karimi, Atieh Amouzegar, Parvin Mirmiran, Fereidoun Azizi

Stimulation of Thyroid Function by Human Chorionic Gonadotropin During Pregnancy: A Risk Factor for Thyroid Disease and a Mechanism for Known Risk Factors
Tim I.M. Korevaar, Yolanda B. de Rijke, Layal Chaker, Marco Medici, Vincent W.V. Jaddoe, Eric A. P. Steegers, Theo J. Visser, Robin P. Peeters

Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy
Mitsuru Ito, Akira Miyauchi, Mako Hisakado, Waka Yoshioka, Akane Ide, Takumi Kudo, Eijun Nishihara, Minoru Kihara, Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Shuji Fukata, Mitsushige Nishikawa, Hirotoshi Nakamura, Nobuyuki Amino

The post Thyroid High-Impact Articles appeared first on American Thyroid Association.

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Changes in Circulating Peptide YY and Ghrelin Are Associated With Early Smoking Relapse


Publication date: Available online 12 March 2017
Source:Biological Psychology
Author(s): Andrine M. Lemieux, Mustafa al’Absi
Ghrelin and peptide YY (PYY) during ad libitum smoking have been associated with decreased reported craving (ghrelin) and increased positive affect (PYY), and higher baseline ghrelin levels predicted subsequent increased risk of smoking relapse. The current study assessed PYY and ghrelin during ad libitum smoking and again after the initial 48hours of a smoking cessation attempt. The data compared smokers who abstained for 28days (n=37), smokers who relapsed (n=54), and nonsmokers (n=37). Plasma samples and subjective measures assessing craving and mood were collected at the beginning of each session. Results showed that relapsers experienced greater levels of distress (ps <.01). While nonsmokers and abstainers showed no change in ghrelin across the initial 48h, relapsers declined (p <.01). With PYY relapsers increased (p <.05) across the early abstinent phase. PYY and ghrelin may be useful predictors of relapse, specifically in reference to early withdrawal.

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Staged Venture Capital Investment considering Unexpected Major Events

This paper presents a dynamic model of capital financing, taking into consideration unexpected major events occurring within continuous time model. We are considering a special jump-diffusion model first described by Samuelson (1973) while using traditional geometric Brownian motion. This paper seeks to accurately show the innovative project valuation when unexpected major events occur and get the analytical results of the project option value. Furthermore, we analyzed the impact of multistaged financing; results indicated that both sources of uncertainty positively impact the project option value; particularly, the option price when considering unexpected major events occurrence is larger than the option price without unexpected major events. Based on a comparative-static analysis, new propositions for optimal amount of investment and optimal level of project are derived from simulations.

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Psychological Aspects of Androgen Insensitivity Syndrome: Two Cases Illustrating Therapeutical Challenges

Androgen Insensitivity Syndrome (AIS) and its heterogeneous phenotypes comprise the pieces of a challenging clinical problem. The lack of standardized guidelines results in controversies regarding the proper diagnostic and therapeutic approach, including the time and type of intervention. Due to its variable phenotype, AIS is not diagnosed at the proper age that would allow optimal psychological and medical support to the patient. Therapeutic approaches are not established, mainly due to the rarity of the disease. In addition, various social and ethical consequences may emerge. The aim of this double case report is to outline the difficulties that may rise during diagnostic, therapeutic, and psychological approach of AIS, especially concerning the handling of the relatives’ reaction.

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Prevalence and Complications of Pregestational and Gestational Diabetes in Saudi Women: Analysis from Riyadh Mother and Baby Cohort Study (RAHMA)

The objectives of this study were to estimate the burden of diabetes and to explore the adverse pregnancy outcomes associated with pregestational diabetes mellitus (pre-GDM) and gestational diabetes mellitus (GDM) among the Saudi pregnant population. In this subcohort, we compared the maternal and the neonatal outcomes of diabetic women with pre-GDM and GDM to the outcomes of nondiabetic mothers who delivered during the same period. From the total cohort, 9723 women participated in this study. Of the participants, 24.2% had GDM, 4.3% had pre-GDM, and 6951 were nondiabetic. After adjustment for confounders, women with GDM had increased odds of delivering a macrosomic baby (OR: 1.6; 95% CI: 1.2–2.1). Women with pre-GDM were more likely to deliver by Cesarean section (OR: 1.65; CI: 1.32–2.07) and to have preterm delivery

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A 10-Year Follow-Up of Two-Incision and Modified Watson-Jones Total Hip Arthroplasty in Patients with Osteonecrosis of the Femoral Head

Long-term data and information indicating whether minimally invasive surgery (MIS) approaches are safe and effective with total hip arthroplasty (THA) are lacking. Between 2004 and 2006, 75 patients with alcohol-related osteonecrosis of the femoral head (ONFH) who underwent 75 THAs with the two-incision approach were studied. The medical records, radiographic parameters, and functional outcomes were collected prospectively. All data were compared with those for matched patients who underwent a modified Watson-Jones (WJ) approach. THA using the two-incision approach was associated with longer operation time, more blood loss, more lateral femoral cutaneous nerve injury, and more periprosthetic femoral fractures ( for all four) than the modified WJ approach. The Harris Hip Score (HHS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) increased significantly from the period preoperatively to 6 weeks postoperatively and thereafter up to the last follow-up in both groups. However, there were no significant differences in terms of radiographic parameters and functional outcomes between the two groups throughout the study period. Both the two-incision and the modified WJ approach provided satisfactory results and survival rates at a mean follow-up of 10.8 years. A prospective, randomized, large-scale cohort study is still warranted for evidence-based recommendations.

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Effects of High-Intensity Interval Training on Aerobic Capacity in Cardiac Patients: A Systematic Review with Meta-Analysis

Purpose. The aim of this study was to compare the effects of high-intensity interval training (INTERVAL) and moderate-intensity continuous training (CONTINUOUS) on aerobic capacity in cardiac patients. Methods. A meta-analysis identified by searching the PubMed, Cochrane Library, EMBASE, and Web of Science databases from inception through December 2016 compared the effects of INTERVAL and CONTINUOUS among cardiac patients. Results. Twenty-one studies involving 736 participants with cardiac diseases were included. Compared with CONTINUOUS, INTERVAL was associated with greater improvement in peak VO2 (mean difference 1.76 mL/kg/min, 95% confidence interval 1.06 to 2.46 mL/kg/min, ) and VO2 at AT (mean difference 0.90 mL/kg/min, 95% confidence interval 0.0 to 1.72 mL/kg/min, ). No significant difference between the INTERVAL and CONTINUOUS groups was observed in terms of peak heart rate, peak minute ventilation, VE/VCO2 slope and respiratory exchange ratio, body mass, systolic or diastolic blood pressure, triglyceride or low- or high-density lipoprotein cholesterol level, flow-mediated dilation, or left ventricular ejection fraction. Conclusions. This study showed that INTERVAL improves aerobic capacity more effectively than does CONTINUOUS in cardiac patients. Further studies with larger samples are needed to confirm our observations.

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An Uncommon Cause of a Small-Bowel Obstruction

Sarcoidosis is a systemic granulomatous disease of unknown etiology, characterized by the formation of noncaseating granulomas. Gastrointestinal (GI) system involvement that is clinically recognizable occurs in less than 0.9% of patients with sarcoidosis, with data revealing small intestine involvement in 0.03% of the cases. A high index of suspension is required in patients presenting with small-bowel obstruction and previous history of sarcoidosis. Establishing a definitive diagnosis of GI sarcoidosis depends on biopsy evidence of noncaseating granulomas, exclusion of other causes of granulomatous disease, and evidence of sarcoidosis in at least one other organ system. Treatment of GI sarcoidosis depends on symptomatology and disease activity. Herein, we are presenting a case of 67-year-old female patient who had acute small-bowel obstruction at the level of jejunum with postoperative histopathologic evidence of noncaseating granulomatous inflammation with multinucleated giant cells, consistent with sarcoidosis.

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An Efficient Quality-Related Fault Diagnosis Method for Real-Time Multimode Industrial Process

Focusing on quality-related complex industrial process performance monitoring, a novel multimode process monitoring method is proposed in this paper. Firstly, principal component space clustering is implemented under the guidance of quality variables. Through extraction of model tags, clustering information of original training data can be acquired. Secondly, according to multimode characteristics of process data, the monitoring model integrated Gaussian mixture model with total projection to latent structures is effective after building the covariance description form. The multimode total projection to latent structures (MTPLS) model is the foundation of problem solving about quality-related monitoring for multimode processes. Then, a comprehensive statistics index is defined which is based on the posterior probability of the monitored samples belonging to each Gaussian component in the Bayesian theory. After that, a combined index is constructed for process monitoring. Finally, motivated by the application of traditional contribution plot in fault diagnosis, a gradient contribution rate is applied for analyzing the variation of variable contribution rate along samples. Our method can ensure the implementation of online fault monitoring and diagnosis for multimode processes. Performances of the whole proposed scheme are verified in a real industrial, hot strip mill process (HSMP) compared with some existing methods.

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Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.

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Investigating the Temporal Effect of User Preferences with Application in Movie Recommendation

As the rapid development of mobile Internet and smart devices, more and more online content providers begin to collect the preferences of their customers through various apps on mobile devices. These preferences could be largely reflected by the ratings on the online items with explicit scores. Both of positive and negative ratings are helpful for recommender systems to provide relevant items to a target user. Based on the empirical analysis of three real-world movie-rating data sets, we observe that users’ rating criterions change over time, and past positive and negative ratings have different influences on users’ future preferences. Given this, we propose a recommendation model on a session-based temporal graph, considering the difference of long- and short-term preferences, and the different temporal effect of positive and negative ratings. The extensive experiment results validate the significant accuracy improvement of our proposed model compared with the state-of-the-art methods.

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Study of Chemical Intermediates by Means of ATR-IR Spectroscopy and Hybrid Hard- and Soft-Modelling Multivariate Curve Resolution-Alternating Least Squares

3,5-Diamino-1,2,4-triazole (DAT) became a significant energetic materials intermediate, and the study of its reaction mechanism has fundamental significance in chemistry. The aim of this study is to investigate the ability of online attenuated total reflection infrared (ATR-IR) spectroscopy combined with the novel approach of hybrid hard- and soft-modelling multivariate curve resolution-alternating least squares (HS-MCR) analysis to monitor and detect changes in structural properties of compound during 3,5-diamino-1,2,4-triazole (DAT) synthesis processes. The subspace comparison method (SCM) was used to obtain the principal components number, and then the pure IR spectra of each substance were obtained by independent component analysis (ICA) and HS-MCR. The extent of rotation ambiguity was estimated from the band boundaries of feasible solutions calculated using the MCR-BANDS procedure. There were five principal components including two intermediates in the process in the results. The reaction rate constants of DAT formation reaction were also obtained by HS-MCR. HS-MCR was used to analyze spectroscopy data in chemical synthesis process, which not only increase the information domain but also reduce the ambiguities of the obtained results. This study provides the theoretical basis for the optimization of synthesis process and technology of energetic materials and provides a strong technical support of research and development of energy material with extraordinary damage effects.

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Esthetic Reconstruction of Diastema with Adhesive Tooth-Colored Restorations and Hyaluronic Acid Fillers

Objective. This report presents a comprehensive esthetic treatment with adhesive tooth-colored restorations in a combination with hyaluronic acid (HA) fillers of diastema in an orthodontic patient with relapse. Case Report. A 36-year-old female patient consulted about 1.5–2 mm midline diastema after an orthodontic relapse of replacing missing central incisors with lateral incisors and dark-colored gingival tissue as a result of a metal post and core with porcelain fused to a metal (PFM) crown at the left lateral incisor. Restorative treatments included replacing the PFM with all-ceramic material and placing a ceramic veneer on the right lateral incisor. To close the space, crown forms of both lateral incisors were altered. A direct resin composite was then used to reform right and left canines to a more ideal lateral incisor shape. An HA fillers injection was used to fill the remaining open gingival embrasure. Eighteen months after treatment, the interdental papilla remained stable and the patient was satisfied with the result. Conclusion. Esthetic reconstruction of diastema and open gingival embrasure in this case can be accomplished without orthodontic retreatment. Tooth-colored restorations and HA filler injection appears a promising modality to address this patient’s esthetic concern.

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A Thermostabilized, One-Step PCR Assay for Simultaneous Detection of Klebsiella pneumoniae and Haemophilus influenzae

Klebsiella pneumoniae and Haemophilus influenzae are two common pathogens associated with respiratory tract infections. The identification of these pathogens using conventional molecular diagnostic tests requires trained personnel, cold-chain transportation, and storage-dependance, which does not render them user-friendly. The aim of this study was to develop a thermostabilized, cold-chain-free, one-step multiplex PCR for simultaneous detection of K. pneumoniae and H. influenzae. The multiplex PCR assay was designed to amplify the php gene of K. pneumoniae (202 bp) and p6 gene of H. influenzae (582 bp). In addition, the specific primer to amplify glm gene of Helicobacter pylori (105 bp) was included as an internal amplification control. Subsequently, the designed primers and all PCR reagents were thermostabilized by lyophilization. The stability of the thermostabilized PCR was evaluated using the Q10 method. The sensitivity and specificity of performances for thermostabilized PCR were evaluated using 127 clinical isolates and were found to be 100% sensitive and specific. The thermostabilized PCR mix was found to be stable for 30 days and the Q10 accelerated stability was found to be 3.02 months. A cold-chain-free, PCR assay for easy, rapid, and simultaneous detection of K. pneumoniae and H. influenzae was successfully developed in this study.

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Flexural Strengthening of Damaged T-Joists with Severe Corrosion Using CFRP Sheets

This paper evaluates the residual safety of isolated T-joists with severe corrosion for the two extreme cases of boundary conditions, simply supported and fixed-ended, in order to help in making decisions about the magnitude of the necessary intervention. When the T-joist is part of a complete slab, the boundary conditions will be in an intermediate situation between these two extreme cases, so that it is possible to assess the safety with respect to its degree of embedding. The research is conducted for the cases of healthy T-joist, T-joist with complete corrosion of the lower reinforcement, and repaired T-joists with a variable number of CFRP sheets. This work is based on the ACI 318 load test to maintain a structure in use and proposes a Load Factor (LF), which estimates the safety reserve. The simply supported T-joists specimens with severe corrosion do not meet the Load Factor or ACI 318 criteria, even with a large number of CFRP sheets. On the other hand, fixed-ended cases can be kept in use despite corrosion by applying light CFRP strengthening, and with four sheets the initial safety is restored.

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Combination of Chemotherapy and Cancer Stem Cell Targeting Agents: Preclinical and Clinical Studies

The cancer stem cell model claims that the initiation, maintenance, and growth of a tumor are driven by a small population of cancer cells termed cancer stem cells. Cancer stem cells possess a variety of phenotypes associated with therapeutic resistance and often cause recurrence of the diseases. Several strategies have been investigated to target cancer stem cells in a variety of cancers, such as blocking one or more self-renewal signaling pathways, reducing the expression of drug efflux and ATP-binding cassette efflux transporters, modulating epigenetic aberrations, and promoting cancer stem cell differentiation.

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Oncogene addiction in non-small cell lung cancer: focus on ROS1 inhibition

Detection of genetic alterations mastering lung cancer biology provides suitable targets for personalized anti-cancer therapy. In non-small cell lung cancer (NSCLC), activating mutations of EGFR, HER2, BRAF, MET, as well as gene fusions involving ALK, ROS1, RET, the members of NTRK and FGFR families, govern the oncogenic potential of malignant cells. The detection and targeting of those genetic abnormalities have demonstrated major improvement in clinical outcomes. Altogether, genetic alterations suitable of targeted treatments are currently detected in 30-40% of advanced non-small cell lung cancers (mainly adenocarcinomas) in Western populations [1]; in Asian countries the prevalence is higher, due to the elevated percentage of EGFR-mutated tumors [2].

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Drip Loss Assessment by Different Analytical Methods and Their Relationships with Pork Quality Classification

We analyzed drip loss in pork by comparing the standard bag (DL), filter-paper wetness (FPW), and EZ-DripLoss methods by weighing the meat juice container and dabbed sample after 24 h and 48 h. Samples were classified into quality categories based on pH, color, and drip loss. The relationship between DL and FPW revealed the cut-off of 5% DL as corresponding to FPW of 139 mg; 1.89% when analyzed by weighing meat juice container or dabbed sample after 24 h; and 3.18% and 3.74% for those analyzed by weighing both meat juice container and dabbed sample after 48 h, respectively. Highest correlations were observed between DL and EZ when the meat juice container was weighed after 48 h (). The EZ-DripLoss method in which the meat juice container was weighed after 24 h was able to distinguish drip loss into meat-quality categories in accordance with the bag method. Therefore, this method is recommended for meat categorization because of its greater standardization and ease of application.

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