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Πέμπτη 7 Δεκεμβρίου 2017

Muscle recruitment and coordination during upper-extremity functional tests

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Publication date: Available online 7 December 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Keshia M. Peters, Valerie E. Kelly, Tasha Chang, Madeline C. Weismann, Sarah Westcott-McCoy, Katherine M. Steele
Performance-based tests, such as the Jebsen Taylor Hand Function Test or Chedoke Arm and Hand Activity Inventory, are commonly used to assess functional performance after neurologic injury. However, the muscle activity required to execute these tasks is not well understood, even for unimpaired individuals. The purpose of this study was to evaluate unimpaired muscle recruitment and coordination of the dominant and non-dominant limbs during common clinical tests. Electromyography (EMG) recordings from eight arm muscles were monitored bilaterally for twenty unimpaired participants while completing these tests. Average signal magnitudes, activation times, and cocontraction levels were calculated from the filtered EMG data, normalized by maximum voluntary isometric contractions (MVICs). Overall, performance of these functional tests required low levels of muscle activity, with average EMG magnitudes less than 6.5% MVIC for all tests and muscles, except the extensor digitorum, which had higher activations across all tasks (11.7±2.7% MVIC, dominant arm). When averaged across participants, cocontraction was between 25-62% for all tests and muscle pairs. Tasks evaluated by speed of completion, rather than functional quality of movement demonstrated higher levels of muscle recruitment. These results provide baseline measurements that can be used to evaluate muscle-specific deficits after neurologic injury and track recovery using common clinical tests.



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Alteration of autophagy-related proteins in peripheral blood mononuclear cells of patients with Parkinson's disease

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Publication date: March 2018
Source:Neurobiology of Aging, Volume 63
Author(s): Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6). Reverse transcription–polymerase chain reaction and Western blot analysis confirmed significantly increased protein levels of upstream autophagy (ULK1, Beclin1, and autophagy/beclin1 regulator 1) with negative feedback of mRNA expression for these proteins in PD. These protein levels were correlated with increased levels of α-synuclein in PBMCs. The expression level of the oligomeric form of α-synuclein in PBMCs paralleled the clinical severity of PD and the degeneration of cardiac sympathetic nerves. Basal activity of autophagy can be lower in patients with PD. Alteration of basal autophagy may be a fundamental aspect of PD.



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Striking a chord with healthy aging: memory system cooperation is related to preserved configural response learning in older adults

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Publication date: March 2018
Source:Neurobiology of Aging, Volume 63
Author(s): Michelle W. Voss, Rachel Clark, Michael Freedberg, Timothy Weng, Eliot Hazeltine
Evidence from tasks that primarily tap either hippocampal- or striatal-based memory systems suggests that although these systems often compete for control of behavior, aging is associated with greater cooperation between them. This may stem from altered prefrontal cortex function. Here, we use a configural response task designed to engage both memory systems to test how age affects their interaction with cortical regions including the prefrontal cortex. We found that although older and younger adults learned just as well, older adults showed greater initial activation in cortical networks associated with visuospatial-action mapping and resolving conflict for competing memory representations. Older adults also showed greater functional coupling of the striatum with the left inferior frontal gyrus, in parallel with similar hippocampal coupling to ventral visual regions as young adults. Overall, our results support the proposal that aging is associated with more cooperative memory systems, but we did not find that greater cooperation is associated with less interaction between the prefrontal cortex and core memory system structures during learning.



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Assessment of debris inputs from land into the river in the Three Gorges Reservoir Area, China

Abstract

Riverine debris in the Three Gorges Reservoir Area (TGRA) poses a threat to electricity generation, ship navigation, and water environment. Quantifying riverine debris inputs from land into the river is a foundation for modeling of the transport and accumulation of floating debris on the water surface in the TGRA. However, this has not been researched to date. In this study, debris inputs from land into the river in the TGRA were assessed according to the response relationship between debris inputs and surface runoff. The land-based debris inputs in the TGRA were estimated using simulated surface runoff which was simulated by the Soil and Water Assessment Tool (SWAT) model. Results showed that 15.32 × 106 kg of land-based debris was inputted into the main channel of the TGRA in 2015 which accounted for 9.74% of total debris inputs (the monitoring data of river-sourced and land-sourced debris inputs was 157.27 × 106 kg). Debris inputs varied seasonally and peaked in the summer season (July to September). Compared with monthly measured data, the average relative errors in 2015 were below 30%. In addition, areas with higher debris pollution inputs were mainly located in the upper section of the TGRA, between the Tang River Basin and the Long River Basin. The proposed method was tested and determined to be reliable; thus, it can be used to quickly estimate debris inputs from land into the river by surface runoff of the outlets in a river basin. Moreover, this method provides new insight into the estimation of land-based debris inputs into rivers.



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Time resolution requirements for civilian radioxenon emission data for the CTBT verification regime

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Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Pieter De Meutter, Johan Camps, Andy Delcloo, Benoît Deconninck, Piet Termonia
The capability of the noble gas component of the International Monitoring System as a verification tool for the Comprehensive Nuclear-Test-Ban Treaty is deteriorated by a background of radioxenon emitted by civilian sources. One of the possible approaches to deal with this issue, is to simulate the daily radioxenon concentrations from these civilian sources at noble gas stations by using atmospheric transport models. In order to accurately quantify the contribution from these civilian sources, knowledge on the releases is required. However, such data are often not available and furthermore it is not clear what temporal resolution such data should have. In this paper, we assess which temporal resolution is required to best model the 133Xe contribution from civilian sources at noble gas stations in an operational context. We consider different sampling times of the noble gas stations and discriminate between nearby and distant sources. We find that for atmospheric transport and dispersion problems on a scale of 1000 km or more, emission data with subdaily temporal resolution is generally not necessary. However, when the source-receptor distance decreases, time-resolved emission data become more important. The required temporal resolution of emission data thus depends on the transport scale of the problem. In the context of the Comprehensive Nuclear-Test-Ban Treaty, where forty noble gas stations will monitor the whole globe, daily emission data are generally sufficient, but for certain meteorological conditions, better temporally resolved emission data are required.



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Chemical properties and colors of fermenting materials in salmon fish sauce production

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Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Mitsutoshi Nakano, Yoshimasa Sagane, Ryosuke Koizumi, Yozo Nakazawa, Masao Yamazaki, Toshihiro Watanabe, Katsumi Takano, Hiroaki Sato
This data article reports the chemical properties (moisture, pH, salinity, and soluble solid content) and colors of fermenting materials in salmon fish sauce products. The fish sauce was produced by mixing salt with differing proportions of raw salmon materials and fermenting for three months; the salmon materials comprised flesh, viscera, an inedible portion, and soft roe. Chemical properties and colors of the unrefined fish sauce (moromi), and the refined fish sauce, were analyzed at one, two, and three months following the start of fermentation. Data determined for all products are provided in table format.



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The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing

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Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Robert J. Rabelo-Fernandez, Kevin Santiago-Morales, Luis Morales-Vale, Carlos Rios-Velazquez
Studies underestimate the microbial diversity and genotypic traits in the snails' microbiome. Caracolus marginella, a land snail native to Caribbean islands, can adapt to different environments. Our research focused on the generation of a metagenomic library from C. marginella gut, to further explore the diversity and functional traits. Thirty specimens of C. marginella were collected from the four regions of Puerto Rico. High molecular weight (40kb) metagenomic libraries were generated using a direct DNA isolation method. DNA was end-repaired and ligated into a pCCFOS1 fosmid vector; then, the cloned DNA was transduced into Escherichia coli EPI300. The master pool library contains approximately 60,200 clones and restriction enzyme digestion showed that 90% of the library contains insert. After removing the fosmid and host genome sequences, 567,015 sequences were analyzed using the MG-RAST online server. The Bacteria domain was the most abundant (82.15%), followed by viruses (16.49%), eukaryotes (0.83%) and archaea (0.31%). The Proteobacteria (51.47%) was predominant in the gut environment, followed by unidentified virus (16.28%), and Actinobacteria (8.52%). Escherichia coli, Streptomyces avermitilis, and Burkholderia sp. were the most abundant species present. Subsystem functional analysis showed that 35.00% of genes belong to transposable elements, 10.00% of genes belong to clustering-based subsystems, 4.00% of genes belong to the production of cofactors and secondary metabolites, and 2.00% resistance to antibiotics and toxic compounds. The data generated in this research is the first metagenomic examination of a snail gut in Puerto Rico, and will serve as a baseline to start understanding of C. marginella gut microbiome.



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Magnetic record of Mio-Pliocene red clay and Quaternary loess-paleosol sequence in the Chinese Loess Plateau

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Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Yougui Song
This article presents magnetic data of a 300-m-thick Mio-Pliocene red clay and Quaternary loess-paleosol sequence near Chaona town in the Central Chinese Loess Plateau. Detailed magnetostratigraphy shows that the aeolian red clay began to accumulate at ca. 8.1Ma. Here, we presented a high-resolution rock magnetic data at 20–40cm intervals within 4.5–8ka span per sample of this section, which has been published in Song et al. (2014) [1] and (2017) [2]. The dataset including the following magnetic parameters: mass magnetic susceptibility (χ), frequency-dependent susceptibility (χfd), saturation magnetization (Ms), saturation remanent magnetization (Mrs), coercive force (Bc), remanent coercivity (Bcr), saturation isothermal remanent magnetization (SIRM) and S-ratio. Magnetic susceptibility and hysteresis parameters were measured at Lanzhou University and Kyoto University, respectively. This data provides a high-resolution rock magnetic evidences for understanding East Asia Monsoon change, Asian interior aridification and tectonic effect of the uplift of the Tibetan Plateau since middle Miocene period.



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Draft genomes of Enterococcus faecium strains isolated from human feces before and after eradication therapy against Helicobacter pylori

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Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Nikita A. Prianichnikov, Maja V. Malakhova, Vlad V. Babenko, Andrei K. Larin, Evgenii I. Olekhnovich, Elizaveta V. Starikova, Dmitry I. Chuvelev, Oksana E. Glushchenko, Andrei E. Samoilov, Alexander I. Manolov, Boris A. Kovarsky, Alexander V. Tyakht, Alexander V. Pavlenko, Elena N. Ilina, Elena S. Kostryukova
The abundance of Enterococci in the human intestinal microbiota environment is usually < 0.1% of the total bacterial fraction. The multiple resistance to antibiotics of the opportunistic Enterococcus spp. is alarming for the world medical community because of their high prevalence among clinically significant strains of microorganisms. Enterococci are able to collect different mobile genetic elements and transmit resistance to antibiotics to wide range of Gram-positive and Gram-negative species of microorganisms, including the transmission of vancomycin resistance to methicillin-resistant strains of Staphylococcus aureus. The number of infections caused by antibiotics resistant strains of Enterococcus spp. is increasing. Here we present a draft genomes of Enterococcus faecium strains. These strains were isolated from human feces before and after (1 month) Helicobacter pylori eradication therapy. The samples were subject to whole-genome sequencing using Illumina HiSeq. 2500 platform. The data is available at NCBI http://ift.tt/2nDbgHS.



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Can we refine body mass estimations based on femoral head breadth?

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Publication date: Available online 7 December 2017
Source:Journal of Human Evolution
Author(s): Markku Niskanen, Juho-Antti Junno, Heli Maijanen, Brigitte Holt, Vladimir Sladék, Margit Berner
Femoral head breadth is widely used in body mass estimation in biological anthropology. Earlier research has demonstrated that reduced major axis (RMA) equations perform better than least squares (LS) equations. Although a simple RMA equation to estimate body size from femoral head breadth is sufficient in most cases, our experiments with male skeletons from European data (including late Pleistocene and Holocene skeletal samples) and the Forensic Anthropology Data Bank data (including the W. M. Bass Donated Skeletal Collection sample) show that including femoral length or anatomically estimated stature in an equation with femoral head breadth improves body mass estimation precision. More specifically, although directional bias related to body mass is not reduced within specific samples, the total estimation error range, directional bias related to stature, and temporal fluctuation in estimation error are markedly reduced. The overall body mass estimation precision of individuals representing different temporal periods and ancestry groups (e.g., African and European ancestry) is thus improved.



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Multi-agent chemotherapy in advanced soft tissue sarcoma (STS) – A systematic review and meta-analysis

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Publication date: Available online 6 December 2017
Source:Cancer Treatment Reviews
Author(s): Alona Zer, Rebecca M. Prince, Eitan Amir, Albiruni R Abdul Razak
BackgroundDespite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.MethodsWe conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.ResultsWe identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p=0.02), and borderline improvement in PFS (HR:0.86, p=0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference=0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference=0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference=0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta=0.70, p=0.053).ConclusionMulti-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.



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What motivates women to breastfeed in Lebanon: An exploratory qualitative analysis

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Publication date: 1 April 2018
Source:Appetite, Volume 123
Author(s): Sarah BouDiab, Carolina Werle
This exploratory qualitative study examined the influence of injunctive and descriptive norms on breastfeeding, a health-improving behaviour related to a highly committed personal decision. The research explores the different mechanisms through which social norms impact breastfeeding behaviour pre or post-adoption of breastfeeding practice.A qualitative approach was used by performing in-depth analysis of cross-sectional accounts of women in Lebanon contemplating adoption of breastfeeding practice and women who already breastfed. Interviews were also conducted with medical professionals, lactation specialists, and breastfeeding activists.On one hand, the attitude of the medical professionals and the government efforts are two mechanisms that stimulate the injunctive norms. On the other hand, the descriptive norms are defined by community attitude aggregated with societal beliefs and expectations on women's image and role in society. Both types of social norms are in constant interplay with personal norms and each type becomes more salient at different periods over time.The findings suggest that social norms are major determinants of breastfeeding behaviour. The influence of the type of social norm—descriptive or injunctive—on the decision to breastfeed varies according to the moment of life the mother is living. Theoretical and practical implications are discussed.



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Initial validation of the Nine Item Avoidant/Restrictive Food Intake disorder screen (NIAS): A measure of three restrictive eating patterns

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Publication date: 1 April 2018
Source:Appetite, Volume 123
Author(s): Hana F. Zickgraf, Jordan M. Ellis
Avoidant/Restrictive Food Intake Disorder (ARFID) is an eating or feeding disorder characterized by inadequate nutritional or caloric intake leading to weight loss, nutritional deficiency, supplement dependence, and/or significant psychosocial impairment. DSM-5 lists three different eating patterns that can lead to symptoms of ARFID: avoidance of foods due to their sensory properties (e.g., picky eating), poor appetite or limited interest in eating, or fear of negative consequences from eating. Research on the prevalence and psychopathology of ARFID is limited by the lack of validated instruments to measure these eating behaviors. The present study describes the development and validation of the nine-item ARFID screen (NIAS), a brief multidimensional instrument to measure ARFID-associated eating behaviors. Participants were 455 adults recruited on Amazon's Mechanical Turk, 505 adults recruited from a nationally-representative subject pool, and 311 undergraduates participating in research for course credit. Exploratory and confirmatory factor analyses provided evidence for three factors. The NIAS subscales demonstrated high internal consistency, test-retest reliability, invariant item loadings between two samples, and convergent/discriminant validity with other measures of picky eating, appetite, fear of negative consequences, and psychopathology. The scales were also correlated with measures of ARFID-like symptoms (e.g., low BMI, low fruit/vegetable variety and intake, and eating-related psychosocial interference/distress), although the picky eating, appetite, and fear scales had distinct independent relationships with these constructs. The NIAS is a brief, reliable instrument that may be used to further investigate ARFID-related eating behaviors.



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Blocking IL4- and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer

Publication date: Available online 7 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Omar M. Rahal, Adam R. Wolfe, Pijus K. Mandal, Richard Larson, Sanda Tin, Cristina Jimenez, Dadong Zhang, Janet Horton, James M. Reuben, John S. McMurray, Wendy A. Woodward
PurposeThe purpose of this study was to determine the role of macrophage polarization on the response of IBC cells to radiation and whether modulation of macrophage plasticity can alter radiation response.Methods and MaterialsThe human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "anti-tumor" (M1) or a "pro-tumor" (M2) phenotype. These polarized macrophages were co-cultured with IBC cells (SUM149, KPL4, MDA-IBC3, or SUM190) without direct contact for 24 h, then subjected to irradiation (0, 2, 4, or 6 Gy). Interleukin (IL)4/IL13-induced activation of STAT6 signaling was measured by Western blotting of phospho-STAT6 (Tyr641), and expression of M2 polarization gene markers (CD206, fibronectin, and CCL22) was measured by qPCR.ResultsExpression of M2 polarization markers was higher in M2-polarized macrophages after IL4/IL13 treatment than in control (M0) or M1-polarized macrophages. Co-culture of IBC cell lines with M1-polarized THP-1 macrophages mediated radiosensitivity of IBC cells, while co-culture with M2-polarized macrophages mediated radioresistance. Phosphopeptide mimetic PM37, targeting the SH2 domain of STAT6, prevented and reversed IL4/IL13-mediated STAT6 phosphorylation (Tyr641) and decreased the expression of M2 polarization markers. Pretreatment of M2-THP1 macrophages with PM37 reduced the radioresistance they induced in IBC cells after co-culture. Targeted proteomics analysis of IBC KPL4 cells using a kinase antibody array revealed induction of PRKCZ in these cells only after co-culture with M2-THP1 macrophages, which was prevented by PM37 pretreatment. KPL4 cells with stable shRNA knockdown of PRKCZ exhibited lower radioresistance after M2-THP1 co-culture.ConclusionsThese data suggest that inhibition of M2 polarization of macrophages by PM37 can prevent radioresistance of IBC by downregulating PRKCZ.

Teaser

Here we show that M2-polarized macrophages upon co-culture with IBC cells, promote radioresistance of IBC cells, and this effect was inhibited by PM37, a phosho-STAT6 inhibitor. M2-macrophages mediated radioresistance of KPL4 IBC cells is associated with increased protein expression of PRKCZ kinase in KPL4 cells, after M2-macrophage co-culture, and this was prevented by PM37-mediated inhibition of M2 polarization of THP1 macrophages prior to coculture with KPL4 cells.


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Effects of miR-200a and FH535 combined with taxol on proliferation and invasion of gastric cancer

Publication date: Available online 6 December 2017
Source:Pathology - Research and Practice
Author(s): Xi Liu, Ping Du, Lei Han, Anling Zhang, Kui Jiang, Qingyu Zhang
Gastric cancer is one of the most common cancers in the world; taxol displayed modest efficacy as first-line chemotherapy for gastric cancer, conversely, it has limitations used alone. β-catenin is a multifunctional oncogenic protein and the elevation in expression and activity of β-catenin has been implicated in many cancers. Therefore, we assume that the inhibition of β-catenin can enhanced the efficacy of taxol. The purpose of this study was to investigate the inhibitory effect of miR-200a mimics, FH535 combined with taxol on proliferation and invasion of human gastric cancer cell lines SGC-7901 and BGC-823. In the current study, we identified that the combination of FH535 and miR-200a with taxol had potent growth-inhibitory and pro-apoptotic effects. Further, similar results were also observed in vivo, intratumoral injection of FH535, taxol and miR-200a mimics which also delayed tumor growth in nude mice harboring subcutaneous SGC-7901 xenografts. Collectively, miR-200a and FH535 can enhance the inhibitory effect of taxol on cell proliferation and moderate the invasion of human gastric cancer.



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Rare frameshift mutations of putative tumor suppressor genes CSMD1 and SLX4 in colorectal cancers

Publication date: Available online 6 December 2017
Source:Pathology - Research and Practice
Author(s): Ju Hwa Lee, Chang Hyeok An, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee




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Immunophenotypic profile of tumor buds in breast cancer

Publication date: Available online 5 December 2017
Source:Pathology - Research and Practice
Author(s): C Laedrach, Bodour Salhia, N Cihoric, I Zlobec, C Tapia
BackgroundTumor buds are associated with lympho-vascular invasion and lymph node metastases leading to the assumption that they are involved in the early metastatic process. Hence, it would be important to know if tumor buds can be targeted with the most widely used targeted therapies in breast cancer (BC) and if changes in hormone and Her2 status occur. The aim of this study was to answer these questions by determining whether hormone receptor (HR) and Her2 status are expressed in the tumor buds of a large cohort of BCs.DesignWe constructed a tumor bud next-generation tissue microarray (ngTMA) consisting of n=199 BCs of non-special type. Generally, two 1mm punches were taken from the tumor bud areas in the periphery (PTB) and within the tumor center (ITB). HR and Her2 status was assessed using immunohistochemistry and fluorescence in situ hybridization, respectively. HR status was positive if ≥1% of tumor bud cells were positive. Her2 status was considered positive if bud cells showed strong complete membranous Her2 over-expression or Her2 amplification.ResultsMost tumor buds were positive for estrogen (ER) (PTB: 86%; ITB: 88.3) and progesterone receptor (PgR) (PTB: 72%; ITB: 72.8%) and Her2 was positive in: PTB 11.5% and ITB 11%. A difference between the main tumor mass and tumor buds (PTB and ITB) was seen for PgR in 3.5% of cases (n=7). No differences were seen for ER and Her2 between tumor buds and main tumor mass.ConclusionMost tumor buds (96.5%) share the same HR and Her2 expression profile of the main tumor mass, implying that tumor buds relay on the same pathways as the main tumor mass and might be equally responsive to targeted therapies.



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Use of 2,3,5-triphenyltetrazolium chloride-stained brain tissues for immunofluorescence analyses after focal cerebral ischemia in rats

Publication date: Available online 21 November 2017
Source:Pathology - Research and Practice
Author(s): Li Li, Qiong Yu, Weimin Liang
The middle cerebral artery occlusion (MCAO) model in rodents has been widely used as model for studying brain ischemic stroke. TTC (2,3,5-triphenyltetrazolium chloride) staining in fresh tissues is used to evaluate the size of the infarct in MCAO model, and TTC-stained brain tissues are considered to be possible to bring a damage to the anatomical structure of neuronal cells and unsuitable for immunofluorescence analyses of cytology, and discarded after evaluation of infarct volume. Another group of models with in Vivo fixation was required to the pathological or histological analyses of the infarct brains, which lead to double the numbers of animals in researches. However, some evidences indicate that if we properly optimized staining protocol, TTC-stained brain tissues might be suitable for cytological analyses. In this work, we have optimized the immunofluorescent staining methods of TTC-stained brain slices, and found that TTC-stained brain tissues are suitable for quantitative and qualitative analyses of microglia, astrocytes and neuroblasts, the morphology of theses cell were nearly identical to the in-vivo fixed models. Our optimized-protocol provide two advantages over traditional methods one of them is providing the precise the infarct region, which reduces the differences within groups, the other one is decreasing the total number of animals in research dramatically.



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Juvenile myelomonocytic leukemia with t(3;5)(q25;q35), Auer rods and marked myelodysplasia

Publication date: Available online 5 December 2017
Source:Pathology - Research and Practice
Author(s): Weijie Li, Linda D. Cooley, Keith August
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive childhood leukemia characterized by an excess proliferation of cells of granulocytic and monocytic lineages. The WHO classifies JMML with the myelodysplastic/myeloproliferative neoplasms. Myelodysplasia in JMML is usually minimal to mild. Auer rods have never been reported in JMML. We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis. Conventional cytogenetic analysis showed a sole abnormality of t(3;5)(q25;q35). Microarray analysis showed a terminal 21 Mb region of copy-neutral loss of heterozygosity on 19q. Disease-related somatic NRAS mutation was detected. This case represents an unusual JMML with Auer rods and marked myelodysplasia. These unusual histopathologic features may be related to the t(3;5)(q25;q35). A t(3;5) with variable breakpoints has been reported in a small proportion of acute myeloid leukemias and myelodysplastic syndromes. To our knowledge, this is the first JMML case reported with this translocation.



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Bone marrow miR-10a overexpression is associated with genetic events but not affects clinical outcome in acute myeloid leukemia

Publication date: Available online 5 December 2017
Source:Pathology - Research and Practice
Author(s): Ting-juan Zhang, Hong Guo, Jing-dong Zhou, Xi-xi Li, Wei Zhang, Ji-chun Ma, Xiang-mei Wen, Xin-yu Yao, Jiang Lin, Jun Qian
BackgroundAccumulating studies have linked the disruptions of microRNA-10 (miR-10) to acute myeloid leukemia (AML) with NPM1 mutation. However, miR-10 expression and its clinical implication in AML remain poorly defined. Although a recent report showed high serum level of miR-10a was associated with adverse prognosis in AML, herein, we found bone marrow (BM) miR-10 overexpression was not a prognostic biomarker in AML.MethodsBM miR-10 expression was examined by real-time quantitative PCR in BM mononuclear cells in 115 de novo AML patients and 45 controls.ResultsBM miR-10 (miR-10a/b) expression was significantly up-regulated in AML patients, and was positively correlated with each other. Overexpression of miR-10a was associated with lower percentage of BM blasts, whereas miR-10b overexpression tended to correlate with higher percentage of BM blasts. Importantly, miR-10a overexpression was significantly associated with FAB-M3/t(15;17) subtypes and NPM1 mutation, meanwhile, overexpression of miR-10b was correlated with NPM1 and DNMT3A mutations. However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation.ConclusionsBM miR-10 overexpression is associated with genetic events but not affects clinical outcome in AML.



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