bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of a physical activity intervention during and shortly after chemotherapy for testicular cancer
Authors: Thorsen Lene , Kirkegaard Camilla , Loge Jon Håvard , Kiserud Cecilie E. , Johansen Merethe Lia , Gjerset Gunhild M. , Edvardsen Elisabeth , Hamre Hanne , Ikdahl Tone , Fosså Sophie D. 
Published: June 2017

Abstract
Background
Given the risk of developing acute and long-term adverse effects in patients receiving cisplatin-based chemotherapy for testicular cancer (TC), risk-reducing interventions, such as physical activity (PA), may be relevant. Limited knowledge is available on the challenges met when conducting PA intervention trials in patients with TC during and shortly after chemotherapy. The aims of the present feasibility study are therefore to determine patient recruitment, compliance and adherence to a PA intervention.

Results
Patients with metastatic TC referred to cisplatin-based chemotherapy were eligible. They followed an individual low-threshold PA intervention, including counseling from a personal coach during and 3 months after chemotherapy. Outcomes were recruitment rate, compliance rate and adherence to the intervention including preferences for type of PA and barriers for PA. During 8 months 12 of 18 eligible patients were invited, all consented, but three dropped out. Walking and low intensity activities were preferred and nausea and feeling unwell were the most often reported barriers towards PA.

Discussion
In order to achieve adequate recruitment, compliance and complete data in future PA intervention trials, close cooperation with treating physicians, individual PA plans and availability of personalized coaching are required.
Trial registration NCT01749774, November 2012, ClinicalTrials.gov
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a
Authors: Lange Lisette , Marks Matthias , Liu Jinhua , Wittler Lars , Bauer Hermann , Piehl Sandra , Bläß Gabriele , Timmermann Bernd , Herrmann Bernhard G. 
Published: June 2017

ABSTRACTThe mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast, causing embryonic patterning defects and failure of primitive streak and mesoderm formation. By using a candidate gene approach, gene knockout by homologous recombination and genetic rescue, we have identified the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65alpha. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling.
Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Kuusela Jukka , Larsson Kim , Shah Disheet , Prajapati Chandra , Aalto-Setälä Katriina 
Published: June 2017

ABSTRACT
Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K+. Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K+ concentration ([K+]Ex) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A&gt;G mutation (LQT1B) in KCNQ1. The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K+]Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K+]Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K+]Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K+]Ex and provide a platform to study acquired LQTS.
Simultaneous stimulation of glycolysis and gluconeogenesis by feeding in the anterior intestine of the omnivorous GIFT tilapia, Oreochromis niloticus
Authors: Chen Yong-Jun , Zhang Ti-Yin , Chen Hai-Yan , Lin Shi-Mei , Luo Li , Wang De-Shou 
Published: June 2017

ABSTRACT
The present study was performed to investigate the roles of anterior intestine in the postprandial glucose homeostasis of the omnivorous Genetically Improved Farmed Tilapia (GIFT). Sub-adult fish (about 173 g) were sampled at 0, 1, 3, 8 and 24 h post feeding (HPF) after 36 h of food deprivation, and the time course of changes in intestinal glucose transport, glycolysis, glycogenesis and gluconeogenesis at the transcription and enzyme activity level, as well as plasma glucose contents, were analyzed. Compared with 0 HPF (fasting for 36 h), the mRNA levels of both ATP-dependent sodium/glucose cotransporter 1 and facilitated glucose transporter 2 increased during 1-3 HPF, decreased at 8 HPF and then leveled off. These results indicated that intestinal uptake of glucose and its transport across the intestine to blood mainly occurred during 1-3 HPF, which subsequently resulted in the increase of plasma glucose level at the same time. Intestinal glycolysis was stimulated during 1-3 HPF, while glucose storage as glycogen was induced during 3-8 HPF. Unexpectedly, intestinal gluconeogenesis (IGNG) was also strongly induced during 1-3 HPF at the state of nutrient assimilation. The mRNA abundance and enzyme activities of glutamic-pyruvic and glutamic-oxaloacetic transaminases increased during 1-3 HPF, suggesting that the precursors of IGNG might originate from some amino acids. Taken together, it was concluded that the anterior intestine played an important role in the regulation of postprandial glucose homeostasis in omnivorous tilapia, as it represented significant glycolytic potential and glucose storage. It was interesting that postprandial IGNG was stimulated by feeding temporarily, and its biological significance remains to be elucidated in fish.
Breaking the color barrier – a multi-selective antibody reporter offers innovative strategies of fluorescence detection
Authors: Gallo Eugenio , Jarvik Jonathan W. 
Published: June 2017

ABSTRACT
A novel bi-partite fluorescence platform exploits the high affinity and selectivity of antibody scaffolds to capture and activate small-molecule fluorogens. In this report, we investigated the property of multi-selectivity activation by a single antibody against diverse cyanine family fluorogens. Our fluorescence screen identified three cell-impermeant fluorogens, each with unique emission spectra (blue, green and red) and nanomolar affinities. Most importantly, as a protein fusion tag to G-protein-coupled receptors, the antibody biosensor retained full activity – displaying bright fluorogen signals with minimal background on live cells. Because fluorogen-activating antibodies interact with their target ligands via non-covalent interactions, we were able to perform advanced multi-color detection strategies on live cells, previously difficult or impossible with conventional reporters. We found that by fine-tuning the concentrations of the different color fluorogen molecules in solution, a user may interchange the fluorescence signal (onset versus offset), execute real-time signal exchange via fluorogen competition, measure multi-channel fluorescence via co-labeling, and assess real-time cell surface receptor traffic via pulse-chase experiments. Thus, here we inform of an innovative reporter technology based on tri-color signal that allows user-defined fluorescence tuning in live-cell applications.
A putative antiviral role of plant cytidine deaminases
Authors: Martín Susana , Cuevas José M. , Grande-Pérez Ana , Elena Santiago F. 
Published: June 2017

Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plantArabidopsis thalianagenome encodes nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well.Methods: Here we tested the effects of expression ofAtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nineA. thalianaAtCDAgenes inNicotianabigeloviiplants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions. Secondly, we createdA. thalianatransgenic plants expressing an artificial microRNA designed to knock-out the expression of up to sixAtCDAgenes. This and control plants were then infected with CaMV. Virus accumulation and mutational spectra where characterized in both types of plants.Results: We have shown that theA. thalianaAtCDA1gene product exerts a mutagenic activity, significantly increasing the number of G to A mutationsin vivo, with a concomitant reduction in the amount of CaMV genomes accumulated. Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level ofAtCDA1mRNA expression in the plant.Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.
Case report: Percutaneous electrical neural field stimulation in two cases of sympathetically-mediated pain
Authors: Fraser Lynn , Woodbury Anna 
Published: June 2017

Background: Fibromyalgia and complex regional pain syndrome (CRPS) are both chronic pain syndromes with pathophysiologic mechanisms related to autonomic nervous system dysregulation and central sensitization. Both syndromes are considered difficult to treat with conventional pain therapies. Case presentations: Here we describe a female veteran with fibromyalgia and a male veteran with CRPS, both of whom failed multiple pharmacologic, physical and psychological therapies for pain, but responded to percutaneous electrical neural field stimulation (PENFS) targeted at the auricular branches of the cranial nerves. Discussion: While PENFS applied to the body has been previously described for treatment of localized pain, PENFS effects on cranial nerve branches of the ear is not well-known, particularly when used for regional and full-body pain syndromes such as those described here. PENFS of the ear is a minimally-invasive, non-pharmacologic therapy that could lead to improved quality of life and decreased reliance on medication. However, further research is needed to guide clinical application, particularly in complex pain patients.
A bipedal mammalian model for spinal cord injury research: The tammar wallaby
Authors: Saunders Norman R. , Dziegielewska Katarzyna M. , Whish Sophie C. , Hinds Lyn A. , Wheaton Benjamin J. , Huang Yifan , Henry Steve , Habgood Mark D. 
Published: June 2017

Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury.Methods: We used an Australian macropod marsupial, the tammar wallaby(Macropuseugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7–60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit.Results:Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch.Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.
Enterovirus D68 in Viet Nam (2009-2015)
Authors: Ny Nguyen Thi Han , Anh Nguyen To , Hang Vu Thi Ty , Nguyet Lam Anh , Thanh Tran Tan , Ha Do Quang , Minh Ngo Ngoc Quang , Ha Do Lien Anh , McBride Angela , Tuan Ha Manh , Baker Stephen , Tam Pham Thi Thanh , Phuc Tran My , Huong Dang Thao , Loi Tran Quoc , Vu Nguyen Tran Anh , Hung Nguyen Van , Minh Tran Thi Thuy , Xang Nguyen Van , Dong Nguyen , Nghia Ho Dang Trung , Chau Nguyen Van Vinh , Thwaites Guy , van Doorn H. Rogier , Anscombe Catherine , Le Van Tan ,   VIZIONS Consortium
Published: June 2017

Background: Since 1962, enterovirus D68 (EV-D68) has been implicated in multiple outbreaks and sporadic cases of respiratory infection worldwide, especially in the USA and Europe with an increasing frequency between 2010 and 2014. We describe the detection, associated clinical features and molecular characterization of EV-D68 in central and southern Viet Nam between 2009 and 2015. Methods: Enterovirus/rhinovirus PCR positive respiratory or CSF samples taken from children and adults with respiratory/central nervous system infections in Viet Nam were tested by an EV-D68 specific PCR. The included samples were derived from 3 different observational studies conducted at referral hospitals across central and southern Viet Nam 2009-2015. Whole-genome sequencing was carried out using a MiSeq based approach. Phylogenetic reconstruction and estimation of evolutionary rate and recombination were carried out in BEAST and Recombination Detection Program, respectively. Results: EV-D68 was detected in 21/625 (3.4%) enterovirus/rhinovirus PCR positive respiratory samples but in none of the 15 CSF. All the EV-D68 patients were young children (age range: 11.8 – 24.5 months) and had moderate respiratory infections. Phylogenetic analysis suggested that the Vietnamese sequences clustered with those from Asian countries, of which 9 fell in the B1 clade, and the remaining sequence was identified within the A2 clade. One intra sub-clade recombination event was detected, representing the second reported recombination within EV-D68. The evolutionary rate of EV-D68 was estimated to be 5.12E-3 substitutions/site/year. Phylogenetic analysis indicated that the virus was imported into Viet Nam in 2008. Conclusions: We have demonstrated for the first time EV-D68 has been circulating at low levels in Viet Nam since 2008, associated with moderate acute respiratory infection in children. EV-D68 in Viet Nam is most closely related to Asian viruses, and clusters separately from recent US and European viruses that were suggested to be associated with acute flaccid paralysis.
Strategic Investment in Renewable Energy Sources: The Effect of Supply Intermittency
Authors: Aflaki Sam , Netessine Serguei 
Published: June 2017

To analyze incentives for investing in the capacity to generate renewable electricity, we model the trade-off between renewable (e.g., wind) and nonrenewable (e.g., natural gas) technology. Renewable technology has a higher investment cost and yields only an intermittent supply of electricity; nonrenewable technology is reliable and has lower investment cost but entails both fuel expenditures and carbon emission costs. With reference to existing electricity markets, we model several interrelated contexts—the vertically integrated electricity supplier, market competition, and partial market competition with long-term fixed-price contracts for renewable electricity—and examine the effect of carbon taxes on the cost and share of wind capacity in an energy portfolio. We find that the intermittency of renewable technologies drives the effectiveness of carbon pricing mechanisms, which suggests that charging more for emissions could unexpectedly discourage investment in renewables. We also show that market liberalization may reduce investment in renewable capacity while increasing the overall system’s cost and emissions. Fixed-price contracts with renewable generators can mitigate these detrimental effects, but not without possibly creating other problems. In short, actions to reduce the intermittency of renewable sources may be more effective than carbon taxes alone at promoting investment in renewable generation capacity. The online appendix is available at https://doi.org/10.1287/msom.2017.0621 .
Risk Aversion, Information Acquisition, and Technology Adoption
Authors: Smith James E. , Ulu Canan 
Published: June 2017

We use a dynamic programming model to study the impacts of risk aversion on information acquisition in technology adoption decisions. In this model, the benefit of the technology is uncertain and, in each period, the decision maker (DM) may adopt the technology, reject the technology, or pay to acquire a signal about the benefit of the technology. The dynamic programming state variables are the DM’s wealth and a probability distribution that describes the DM’s beliefs about the benefit of the technology; these distributions are updated over time using Bayes’ rule. If the signal-generating process satisfies the monotone-likelihood ratio property and the DM is risk neutral, the value functions and policies satisfy natural monotonicity properties: a likelihood-ratio improvement in the distribution on benefits leads to an increase in the value function and moves the DM away from rejection and toward adoption. With risk aversion, the value functions (now representing expected utilities) will be monotonic, but the policies need not be monotonic, even with reasonable utility functions. However, if we assume the DM exhibits decreasing absolute risk aversion and is not “too risk averse,” the policies can be shown to be monotonic. Establishing these structural properties requires the use of some novel proof techniques that may prove useful in other contexts. We also study the impact of changing risk attitudes on the optimal policy.The online appendix is available at https://doi.org/10.1287/opre.2017.1601 .
Stronger Together: Aggregated Z-values of Traditional Quality Control Measurements and Patient Medians Improve Detection of Biases
Authors: Bietenbeck Andreas , Thaler Markus A , Luppa Peter B , Klawonn Frank 
Published: June 2017

AbstractBACKGROUNDIn clinical chemistry, quality control (QC) often relies on measurements of control samples, but limitations, such as a lack of commutability, compromise the ability of such measurements to detect out-of-control situations. Medians of patient results have also been used for QC purposes, but it may be difficult to distinguish changes observed in the patient population from analytical errors. This study aims to combine traditional control measurements and patient medians for facilitating detection of biases.METHODSThe software package “rSimLab” was developed to simulate measurements of 5 analytes. Internal QC measurements and patient medians were assessed for detecting impermissible biases. Various control rules combined these parameters. A Westgard-like algorithm was evaluated and new rules that aggregate Z-values of QC parameters were proposed.RESULTSMathematical approximations estimated the required sample size for calculating meaningful patient medians. The appropriate number was highly dependent on the ratio of the spread of sample values to their center. Instead of applying a threshold to each QC parameter separately like the Westgard algorithm, the proposed aggregation of Z-values averaged these parameters. This behavior was found beneficial, as a bias could affect QC parameters unequally, resulting in differences between their Z-transformed values. In our simulations, control rules tended to outperform the simple QC parameters they combined. The inclusion of patient medians substantially improved bias detection for some analytes.CONCLUSIONSPatient result medians can supplement traditional QC, and aggregations of Z-values are novel and beneficial tools for QC strategies to detect biases.
Scale Model for Mass Flows Down an Inclined Plane in a Geotechnical Centrifuge
Authors: Cabrera M. A. , Wu W. 
Published: June 2017

Abstract
Natural mass flows are among the most dangerous geo-hazards in mountain regions. These mass flows are studied in experimental models in a wide range of model dimensions and flow configurations. However, the scale of the experiments required to bring the flowing material to a stress level close to those of field processes demands larger models. Centrifuge modelling is an attractive alternative to simulate mass flows under controlled boundary conditions while increasing the gravity-driven processes in a small scale model. This paper presented a centrifuge model developed for the simulation of dry and wet granular flows down an inclined plane. The scale model allowed measuring flow height, basal load, flow velocity, and discharge load under an augmented acceleration field. The scale model enabled studying mass flows with reduced dimensions, accounting for the stress-dependent behavior of the solid and fluid phase.