bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of single-walled carbon nanotubes on tumor cells viability and formation of multicellular tumor spheroids
Authors: Yakymchuk Olena M , Perepelytsina Olena M , Dobrydnev Alexey V , Sydorenko Mychailo V 
Published: March 2015

AbstractThis paper describes the impact of different concentrations of single-walled carbon nanotubes (SWCNTs) on cell viability of breast adenocarcinoma, MCF-7 line, and formation of multicellular tumor spheroids (MTS). Chemical composition and purity of nanotubes is controlled by Fourier transform infrared spectroscopy. The strength and direction of the influence of SWCNTs on the tumor cell population was assessed by cell counting and measurement of the volume of multicellular tumor spheroids. Effect of SWCNTs on the formation of multicellular spheroids was compared with the results obtained by culturing tumor cells with ultra dispersed diamonds (UDDs). Our results demonstrated that SWCNTs at concentrations ranging from 12.5 to 50 μg/ml did not have cytotoxic influence on tumor cells; instead, they had weak cytostatic effect. The increasing of SWCNTs concentration to 100 to 200 μg/ml stimulated proliferation of tumor cells, especially in suspension fractions. The result of this influence was in formation of more MTS in cell culture with SWCNTs compared with UDDs and control samples. In result, the median volume of MTS after cultivation with SWCNTs at 100 to 200 μg/ml concentrations is 3 to 5 times greater than that in samples which were incubated with the UDDs and is 2.5 times greater than that in control cultures. So, if SWCNTs reduced cell adhesion to substrate and stimulated formation of tumor cell aggregates volume near 7 · 10−3 mm3, at the same time, UDDs reduced adhesion and cohesive ability of cells and stimulated generation of cell spheroids volume no more than 4 · 10−3 mm3. Our results could be useful for the control of cell growth in three-dimensional culture.PACS61. 46 + w; 61.48 + c; 61.48De; 87.15-v; 87.64-t
Properties of Sodium Currents in Neonatal and Young Adult Mouse Superficial Dorsal Horn Neurons
Authors: Tadros Melissa A , Farrell Kristen E , Graham Brett A , Brichta Alan M , Callister Robert J 
Published: March 2015

Background Superficial dorsal horn (SDH) neurons process nociceptive information and their excitability is partly determined by the properties of voltage-gated sodium channels. Recently, we showed the excitability and action potential properties of mouse SDH neurons change markedly during early postnatal development. Here we compare sodium currents generated in neonate (P0-5) and young adult (≥P21) SDH neurons. Results Whole cell recordings were obtained from lumbar SDH neurons in transverse spinal cord slices (CsF internal, 32°C). Fast activating and inactivating TTX-sensitive inward currents were evoked by depolarization from a holding potential of −100 mV. Poorly clamped currents, based on a deflection in the IV relationship at potentials between −60 and −50 mV, were not accepted for analysis. Current density and decay time increased significantly between the first and third weeks of postnatal development, whereas time to peak was similar at both ages. This was accompanied by more subtle changes in activation range and steady state inactivation. Recovery from inactivation was slower and TTX-sensitivity was reduced in young adult neurons. Conclusions Our study suggests sodium channel expression changes markedly during early postnatal development in mouse SDH neurons. The methods employed in this study can now be applied to future investigations of spinal cord sodium channel plasticity in murine pain models.
Prolonged mechanical ventilation–induced neuroinflammation affects postoperative memory dysfunction in surgical mice
Authors: Chen Chang , Zhang Zongze , Chen Ting , Peng Mian , Xu Xing , Wang Yanlin 
Published: March 2015

Abstract
Introduction
Patients undergoing surgery frequently develop neuropsychological disturbances, including cognitive decline or memory impairment, and routine clinical procedures such as mechanical ventilation (MV) may affect acute-phase brain outcome. We aimed to investigate the effect of the prolonged MV on postoperative memory dysfunction in surgical mice.

Methods
Male C57BL/6 mice were randomly divided into the following three groups: (1) The control group (group C) comprised anesthetized, unventilated animals; (2) the surgery group (subgroups S1h, S3h and S6h) was unventilated animals that underwent surgery under general anesthesia; and (3) the MV group (subgroups MV1h, MV3h and MV6h) was made up of animals under MV for 1 hour, 3 hours or 6 hours after surgery. Separate cohorts of animals were tested for memory function with fear conditioning tests or were killed at 6 hours, 1 day or 3 days postsurgery or post-MV to examine levels systemic and hippocampal interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNFα), and assessed synaptic structure and microglial activation. Nuclear factor κB (NF-κB) p65, cytochrome c, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) activation were analyzed by Western blotting.

Results
The MV6h group showed increased CD11b-immunopositive cells, synapse degeneration, cytochrome c release, cleaved caspase-3 and cleaved PARP-1 activation after surgery, as well as a decrease in freezing time after surgery. At 6 hours and 1 day post-MV, MV6h increased NF-κB activation and levels of systemic and hippocampal IL-1β, IL-6 and TNFα after surgery.

Conclusions
Prolonged MV after surgery further aggravates cognitive decline that may stem from upregulation of hippocampal IL-1β, IL-6 and TNFα, partially via activation of gliocytes in the surgical mouse hippocampus.
A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes
Authors: Trogrlić Zoran , van der Jagt Mathieu , Bakker Jan , Balas Michele C , Ely E Wesley , van der Voort Peter HJ , Ista Erwin 
Published: March 2015

Abstract
Introduction
Despite recommendations from professional societies and patient safety organizations, the majority of ICU patients worldwide are not routinely monitored for delirium, thus preventing timely prevention and management. The purpose of this systematic review is to summarize what types of implementation strategies have been tested to improve ICU clinicians’ ability to effectively assess, prevent and treat delirium and to evaluate the effect of these strategies on clinical outcomes.

Method
We searched PubMed, Embase, PsychINFO, Cochrane and CINAHL (January 2000 and April 2014) for studies on implementation strategies that included delirium-oriented interventions in adult ICU patients. Studies were suitable for inclusion if implementation strategies’ efficacy, in terms of a clinical outcome, or process outcome was described.

Results
We included 21 studies, all including process measures, while 9 reported both process measures and clinical outcomes. Some individual strategies such as “audit and feedback” and “tailored interventions” may be important to establish clinical outcome improvements, but otherwise robust data on effectiveness of specific implementation strategies were scarce. Successful implementation interventions were frequently reported to change process measures, such as improvements in adherence to delirium screening with up to 92%, but relating process measures to outcome changes was generally not possible. In meta-analyses, reduced mortality and ICU length of stay reduction were statistically more likely with implementation programs that employed more (six or more) rather than less implementation strategies and when a framework was used that either integrated current evidence on pain, agitation and delirium management (PAD) or when a strategy of early awakening, breathing, delirium screening and early exercise (ABCDE bundle) was employed. Using implementation strategies aimed at organizational change, next to behavioral change, was also associated with reduced mortality.

Conclusion
Our findings may indicate that multi-component implementation programs with a higher number of strategies targeting ICU delirium assessment, prevention and treatment and integrated within PAD or ABCDE bundle have the potential to improve clinical outcomes. However, prospective confirmation of these findings is needed to inform the most effective implementation practice with regard to integrated delirium management and such research should clearly delineate effective practice change from improvements in clinical outcomes.
Granulocytic immune infiltrates are essential for the efficient formation of breast cancer liver metastases
Authors: Tabariès Sébastien , Ouellet Véronique , Hsu Brian E , Annis Matthew G , Rose April AN , Meunier Liliane , Carmona Euridice , Tam Christine E , Mes-Masson Anne-Marie , Siegel Peter M 
Published: March 2015

Abstract
Introduction
Breast cancer cells display preferences for specific metastatic sites including the bone, lung and liver. Metastasis is a complex process that relies, in part, on interactions between disseminated cancer cells and resident/infiltrating stromal cells that constitute the metastatic microenvironment. Distinct immune infiltrates can either impair the metastatic process or conversely, assist in the seeding, colonization and growth of disseminated cancer cells.

Methods
Using in vivo selection approaches, we previously isolated 4T1-derived breast cancer cells that preferentially metastasize to these organs and tissues. In this study, we examined whether the propensity of breast cancer cells to metastasize to the lung, liver or bone is associated with and dependent on distinct patterns of immune cell infiltration. Immunohistocytochemistry and immunohistofluorescence approaches were used to quantify innate immune cell infiltrates within distinct metastases and depletion of Gr1+ (Ly-6C and Ly-6G) or specifically Ly-6G+ cells was performed to functionally interrogate the role of Ly-6G+ infiltrates in promoting metastasis to these organs.

Results
We show that T lymphocytes (CD3+), myeloid-derived (Gr-1+) cells and neutrophils (Ly-6G+ or NE+) exhibit the most pronounced recruitment in lung and liver metastases, with markedly less recruitment within bone metastatic lesions. Interestingly, these infiltrating cell populations display different patterns of localization within soft tissue metastases. T lymphocytes and granulocytic immune infiltrates are localized around the periphery of liver metastases whereas they were dispersed throughout the lung metastases. Furthermore, Gr-1+ cell-depletion studies demonstrate that infiltrating myeloid-derived cells are essential for the formation of breast cancer liver metastases but dispensable for metastasis to the lung and bone. A specific role for the granulocytic component of the innate immune infiltrate was revealed through Ly-6G+ cell-depletion experiments, which resulted in significantly impaired formation of liver metastases. Finally, we demonstrate that the CD11b+/Ly-6G+ neutrophils that infiltrate and surround the liver metastases are polarized toward an N2 phenotype, which have previously been shown to enhance tumor growth and metastasis.

Conclusions
Our results demonstrate that the liver-metastatic potential of breast cancer cells is heavily reliant on interactions with infiltrating Ly-6G+ cells within the liver microenvironment.
Calling genotypes from public RNA-sequencing data enables identification of genetic variants that affect gene-expression levels
Authors: Deelen Patrick , Zhernakova Daria V , de Haan Mark , van der Sijde Marijke , Bonder Marc Jan , Karjalainen Juha , van der Velde K Joeri , Abbott Kristin M , Fu Jingyuan , Wijmenga Cisca , Sinke Richard J , Swertz Morris A , Franke Lude 
Published: March 2015

Abstract
Background
RNA-sequencing (RNA-seq) is a powerful technique for the identification of genetic variants that affect gene-expression levels, either through expression quantitative trait locus (eQTL) mapping or through allele-specific expression (ASE) analysis. Given increasing numbers of RNA-seq samples in the public domain, we here studied to what extent eQTLs and ASE effects can be identified when using public RNA-seq data while deriving the genotypes from the RNA-sequencing reads themselves.

Methods
We downloaded the raw reads for all available human RNA-seq datasets. Using these reads we performed gene expression quantification. All samples were jointly normalized and subjected to a strict quality control. We also derived genotypes using the RNA-seq reads and used imputation to infer non-coding variants. This allowed us to perform eQTL mapping and ASE analyses jointly on all samples that passed quality control. Our results were validated using samples for which DNA-seq genotypes were available.

Results
4,978 public human RNA-seq runs, representing many different tissues and cell-types, passed quality control. Even though these data originated from many different laboratories, samples reflecting the same cell type clustered together, suggesting that technical biases due to different sequencing protocols are limited. In a joint analysis on the 1,262 samples with high quality genotypes, we identified cis-eQTLs effects for 8,034 unique genes (at a false discovery rate ≤0.05). eQTL mapping on individual tissues revealed that a limited number of samples already suffice to identify tissue-specific eQTLs for known disease-associated genetic variants. Additionally, we observed strong ASE effects for 34 rare pathogenic variants, corroborating previously observed effects on the corresponding protein levels.

Conclusions
By deriving and imputing genotypes from RNA-seq data, it is possible to identify both eQTLs and ASE effects. Given the exponential growth of the number of publicly available RNA-seq samples, we expect this approach will become especially relevant for studying the effects of tissue-specific and rare pathogenic genetic variants to aid clinical interpretation of exome and genome sequencing.
Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer’s disease
Authors: Doody Rachelle S , Raman Rema , Sperling Reisa A , Seimers Eric , Sethuraman Gopalan , Mohs Richard , Farlow Martin , Iwatsubo Takeshi , Vellas Bruno , Sun Xiaoying , Ernstrom Karin , Thomas Ronald G , Aisen Paul S ,   for the Alzheimer’s Disease Cooperative Study
Published: March 2015

Abstract
Introduction
The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer’s disease (AD) included a number of biomarkers of the disease as well as safety outcomes. We analyzed these data to explore relationships between drug exposure and pharmacodynamic effects and to examine the correlations among outcome measures.

Methods
The study was a multicenter, randomized, placebo-controlled trial of two dose regimens of semagacestat and a placebo administered for 18 months to individuals with mild to moderate AD. Changes in measures of central and peripheral drug activity were compared between the three treatment groups using one-way analysis of variance. The relationship between changes in each of the outcome measures and measures of drug exposure and peripheral pharmacodynamic effect were assessed using Spearman’s correlation coefficient.

Results
Assignment to the active treatment arms was associated with reduction in plasma amyloid-β (Aβ) peptides, increase in ventricular volume, decrease in cerebrospinal fluid phosphorylated tau (p-tau) and several other laboratory measures and adverse event categories. Within the active arms, exposure to drug, as indicated by area under the concentration curve (AUC) of blood concentration, was associated with reduction in plasma Aβ peptides and a subset of laboratory changes and adverse event rates. Ventricular volume increase, right hippocampal volume loss and gastrointestinal symptoms were related to change in plasma Aβ peptide but not AUC, supporting a link to inhibition of γ-secretase cleavage of the amyloid precursor protein. Cognitive decline correlated with ventricular expansion and reduction in p-tau.

Conclusion
These findings may inform future studies of drugs targeting secretases involved in Aβ generation.

Trial registration
ClinicalTrials.gov Identifier: NCT00594568. Registered 11 January 2008.
Novel 89Zr cell labeling approach for PET-based cell trafficking studies
Authors: Bansal Aditya , Pandey Mukesh K , Demirhan Yunus E , Nesbitt Jonathan J , Crespo-Diaz Ruben J , Terzic Andre , Behfar Atta , DeGrado Timothy R 
Published: March 2015

Abstract

Background
With the recent growth of interest in cell-based therapies and radiolabeled cell products, there is a need to develop more robust cell labeling and imaging methods for in vivo tracking of living cells. This study describes evaluation of a novel cell labeling approach with the positron emission tomography (PET) isotope 89Zr (T
1/2 = 78.4 h). 89Zr may allow PET imaging measurements for several weeks and take advantage of the high sensitivity of PET imaging.

Methods
A novel cell labeling agent, 89Zr-desferrioxamine-NCS (89Zr-DBN), was synthesized. Mouse-derived melanoma cells (mMCs), dendritic cells (mDCs), and human mesenchymal stem cells (hMSCs) were covalently labeled with 89Zr-DBN via the reaction between the NCS group on 89Zr-DBN and primary amine groups present on cell surface membrane protein. The stability of the label on the cell was tested by cell efflux studies for 7 days. The effect of labeling on cellular viability was tested by proliferation, trypan blue, and cytotoxicity/apoptosis assays. The stability of label was also studied in in vivo mouse models by serial PET scans and ex vivo biodistribution following intravenous and intramyocardial injection of 89Zr-labeled hMSCs. For comparison, imaging experiments were performed after intravenous injections of 89Zr hydrogen phosphate (89Zr(HPO4)2).

Results
The labeling agent, 89Zr-DBN, was prepared in 55% ± 5% decay-corrected radiochemical yield measured by silica gel iTLC. The cell labeling efficiency was 30% to 50% after 30 min labeling depending on cell type. Radioactivity concentrations of labeled cells of up to 0.5 MBq/106 cells were achieved without a negative effect on cellular viability. Cell efflux studies showed high stability of the radiolabel out to 7 days. Myocardially delivered 89Zr-labeled hMSCs showed retention in the myocardium, as well as redistribution to the lung, liver, and bone. Intravenously administered 89Zr-labeled hMSCs also distributed primarily to the lung, liver, and bone, whereas intravenous 89Zr(HPO4)2 distributed to the liver and bone with no activity in the lung. Thus, the in vivo stability of the radiolabel on the hMSCs was evidenced.

Conclusions
We have developed a robust, general, and biostable 89Zr-DBN-based cell labeling strategy with promise for wide applications of PET-based non-invasive in vivo cell trafficking.
Expression and functional validation of heat-labile enterotoxin B (LTB) and cholera toxin B (CTB) subunits in transgenic rice (Oryza sativa)
Authors: Soh Ho Seob , Chung Ha Young , Lee Hyun Ho , Ajjappala Hemavathi , Jang Kyoungok , Park Jong-Hwa , Sim Joon-Soo , Lee Gee Young , Lee Hyun Ju , Han Young Hee , Lim Jae Wook , Choi Inchan , Chung In Sik , Hahn Bum-Soo 
Published: March 2015

Abstract
We expressed the heat-labile enterotoxin B (LTB) subunit from enterotoxigenic Escherichia coli and the cholera toxin B (CTB) subunit from Vibrio cholerae under the control of the rice (Oryza sativa) globulin (Glb) promoter. Binding of recombinant LTB and CTB proteins was confirmed based on GM1-ganglioside binding enzyme-linked immunosorbent assays (GM1-ELISA). Real-time PCR of three generations (T3, T4, and T5) in homozygous lines (LCI-11) showed single copies of LTB, CTB, bar and Tnos. LTB and CTB proteins in rice transgenic lines were detected by Western blot analysis. Immunogenicity trials of rice-derived CTB and LTB antigens were evaluated through oral and intraperitoneal administration in mice, respectively. The results revealed that LTB- and CTB-specific IgG levels were enhanced in the sera of intraperitoneally immunized mice. Similarly, the toxin-neutralizing activity of CTB and LTB in serum of orally immunized mice was associated with elevated levels of both IgG and IgA. The results of the present study suggest that the combined expression of CTB and LTB proteins can be utilized to produce vaccines against enterotoxigenic strains of Escherichia coli and Vibrio cholera, for the prevention of diarrhea.
Reactive scheduling based on actual logistics data by applying simulation-based optimization
Authors: Szczesny Kamil , König Markus 
Published: March 2015

Abstract
Background
A reasonable management and monitoring of construction projects requires accurate construction schedules. Accuracy depends highly on availability of reliable actual logistics data. Such data contain information about available material, equipment, personnel, updated delivery dates, and other data on site conditions. However, such data is often associated with different types of uncertainties due to infrequent collections, varying transport times, or manual assessments. Nonetheless, consideration of these uncertainties is important for evaluating actual data regarding their impact on the overall construction progress. Currently, the integration of such data into construction schedules is a time-consuming, manual and, thus, error-prone process. Therefore, in practice schedules are not updated as often as they should be.

Methods
To ease the handling of actual data and their integration into construction schedules, a reactive construction scheduling approach is presented. The approach is structured into four successive steps. To evaluate and systematically analyze uncertain actual data, fuzzy set theory and α-cut method are incorporated. Thus, actual data can be integrated into discrete-event simulation models. These models are used to perform simulation-based sensitivity analyzes, which evaluate impacts on construction schedules. As a result, an actual schedule is generated, such that a target-actual schedule comparison can be performed. If significant deviations or problems are identified, adaption is necessary and a new schedule needs to be generated. Thereby, different restrictions on the target schedule, such as contracted delivery dates, milestones or resource allocation must be considered. To perform this required adaption simulation-based optimization is utilized.

Results
To validate the method and show its advantages, an initial construction schedule example is created. The example is extended to incorporate uncertain actual logistics data. The proposed method shows how efficient actual data can be analyzed to update construction schedules. Further, the results show a competitive adaption of invalid construction schedules, such that contracted milestones, or other project objectives can be achieved.

Conclusion
The presented reactive construction scheduling method has the ability to improve current treatment of uncertain actual logistics data. This helps construction project managers to improve the management and monitoring of construction projects by reducing the time-consuming, error-prone process of updating inconsistent schedules.