bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Treatment With Exenatide and Cyclosporine A or Parstatin 1-26 Results in Enhanced Reduction of Infarct Size in a Rabbit Model
Authors: Alexopoulos Panagiotis , Panoutsopoulou Konstantina , Vogiatzis George , Koletsis Efstratios , Dougenis Dimitrios , Tsopanoglou Nikos E.
Published: April 2017

Exenatide and cyclosporine A have been shown to moderately protect against myocardial reperfusion injury leading to reduction of infarct size in patients. Our objective was to investigate whether the combined treatment with exenatide (glucagon-like peptide 1 receptor agonist) and cyclosporine A or parstatin 1-26 (inhibitors of mitochondrial permeability transition pore and/or inflammation) is more beneficial than either agent alone. Rabbits underwent 40 minutes of ischemia and 120 minutes of reperfusion. Intravenous bolus administration of exenatide or cyclosporine A, 10 minutes before reperfusion, reduced infarct size by 38% (P < 0.05) and 40% (P < 0.05), and cardiac troponin I (cTnI) plasma levels by 48% (P < 0.05) and 36% (P < 0.05), respectively, compared with control. The combined administration of both agents resulted in an additive decrease of infarct size by 55% (P < 0.05) and cTnI release by 61% (P < 0.05). Also, combined treatment of exenatide and parstatin 1-26 enhanced infarct size reduction (62%, P < 0.05), compared with monotherapies (41% for parstatin 1-26, P < 0.05; 43% for exenatide, P < 0.05). In contrast, the combined administration of parstatin 1-26 and cyclosporine A canceled out the cardioprotective effects observed by monotherapies. These results suggest that, for the therapy of myocardial reperfusion injury the combined administration of exenatide and cyclosporine A or parstatin 1-26 is more effective than monotherapies and may provide advantageous clinical outcome.
Scleral Lens Prescription and Management Practices: The SCOPE Study
Authors: Harthan Jennifer , Nau Cherie B. , Barr Joseph , Nau Amy , Shorter Ellen , Chimato Nicolette T. , Hodge David O. , Schornack Muriel M.
Published: April 2017

Objectives:

To assess current scleral lens prescription and management practices by conducting an international online survey of eye care providers.

Methods:

The SCOPE (Scleral Lenses in Current Ophthalmic Practice: an Evaluation) study group designed and administered an online survey regarding current scleral lens prescription and management practices. The survey was open from January 15 to March 31, 2015, and generated 723 responses from individuals who had fit at least 5 patients with scleral lenses.

Results:

Respondents (n=663) prescribed scleral lenses that ranged from 15 to 17 mm in diameter (65%), smaller than 15 mm (18%), and larger than 18 mm (17%). More than 50 lens designs were identified. Average daily wearing time of 11.8 hr was consistent across 651 respondents, and 475/651 (73%) recommended midday removal on some, most, or all days. Most respondents recommended nonpreserved saline to fill the bowl of the lens before application (single-use vials, 392/653 [60%]; bottled products, 372/653 [57%]). A hydrogen peroxide-based disinfection system was the most commonly recommended care product (397/651 [61%]).

Conclusions:

A reasonable degree of consensus exists regarding some aspects of scleral lens prescription and management (average lens diameter, daily wearing time, and use of nonpreserved products for lens application). Further study is needed to develop evidence-based guidelines for scleral lens prescription and management.
Glaucoma Drainage Device Erosion Following Ptosis Surgery
Authors: Bae Steven S. , Campbell Robert J.
Published: April 2017

Purpose:

To highlight the potential risk of glaucoma drainage device erosion following ptosis surgery.

Methods:

Case report.

Results:

A 71-year-old man underwent uncomplicated superotemporal Ahmed glaucoma valve implantation in the left eye in 2008. Approximately 8 years later, the patient underwent bilateral ptosis repair, which successfully raised the upper eyelid position. Three months postoperatively, the patient’s glaucoma drainage implant tube eroded through the corneal graft tissue and overlying conjunctiva to become exposed. A graft revision surgery was successfully performed with no further complications.

Conclusions:

Caution and conservative lid elevation may be warranted when performing ptosis repair in patients with a glaucoma drainage implant, and patients with a glaucoma implant undergoing ptosis surgery should be followed closely for signs of tube erosion.
Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model
Authors: Shih Hsi-Chien , Kuan Yung-Hui , Shyu Bai-Chung
Published: April 2017

Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area. Nociceptive activity in the medial thalamus (MT) and the coherence coefficient of spontaneous field potential oscillations in the anterior cingulate cortex were enhanced in CPSP animals, and these enhancements were blocked by an acute injection of TrkB-Fc and TrkB antagonist Tat Cyclotraxin-B. Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.
The postoperative Model for End stage Liver Disease score as a predictor of short-term outcome after transplantation of extended criteria donor livers
Authors: Benko Tamas , Gallinat Anja , Minor Thomas , Saner Fuat H. , Sotiropoulos Georgios C. , Paul Andreas , Hoyer Dieter P.
Published: April 2017

Background

Recently, the postoperative Model for End stage Liver Disease score (POPMELD) was suggested as a definition of postoperative graft dysfunction and a predictor of outcome after liver transplantation (LT).

Aim

The aim of the present study was to validate this concept in the context of extended criteria donor (ECD) organs.

Patients and methods

Single-center prospectively collected data (OPAL study/01/11-12/13) of 116 ECD LTs were utilized. For each recipient, the Model for End stage Liver Disease (MELD) score was calculated for 7 postoperative days (PODs). The ability of international normalized ratio, bilirubin, aspartate aminotransferase, Donor Risk Index, a recent definition of early allograft dysfunction, and the POPMELD was compared to predict 90-day graft loss. Predictive abilities were compared by receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values.

Results

The median Donor Risk Index was 1.8. In all, 60.3% of recipients were men [median age of 54 (23–68) years]. The median POD1–7 peak-aspartate aminotransferase value was 1052 (194–17 577) U/l. The rate of early allograft dysfunction was 22.4%. The 90-day graft survival was 89.7%. Out of possible predictors of the 90-day graft loss MELD on POD5 was the best predictor of outcome (area under the curve=0.84). A MELD score of 16 or more on POD5 predicted the 90-day graft loss with a specificity of 80.8%, a sensitivity of 81.8%, and a positive and negative predictive value of 31 and 97.7%.

Conclusion

A MELD score of 16 or more on POD5 is an excellent predictor of outcome in ECD donor LT. Routine evaluation of POPMELD scores might support clinical decision-making and should be reported routinely in clinical trials.
Risks and Benefits of Swaddling Healthy Infants
Authors: Nelson Antonia M.
Published: April 2017

Background:

Swaddling has been practiced since antiquity; however, there is controversy about its safety.

Objectives:

The purpose of this review is to update and build upon previous reviews and synthesize evidence on risks and benefits of swaddling in healthy-term, near-term, or older infants.

Data Sources:

MEDLINE (1960–May 13, 2016) and CINAHL (1963–May 13, 2016) searches were conducted, relevant articles retrieved, and citation lists reviewed for other references.

Synthesis Methods:

A table summarizes study details. Selected older references and supporting literature are integrated into the synthesis to provide context.

Results:

Swaddling calms infants and promotes sleep, but it is equally or less effective than other nonpharmacological methods in managing pain. There may be a slight risk for sudden infant death syndrome associated with supine swaddling, although the impact of confounding variables is unclear. Early skin-to-skin contact supports early breastfeeding, but swaddling does not have a negative impact on breastfeeding long term. Swaddling tightly around the hips is strongly associated with developmental dysplasia of the hip. More research is needed on the impact of swaddling on pain in term infants, infant vital signs, arousal thresholds, and a possible association between swaddling, vitamin D deficiency, and acute lower respiratory tract infection.

Limitations:

The number of studies was small, with few randomized control trials, and researchers used different definitions of swaddling.

Conclusions:

If a few precautions are taken, such as swaddling securely to minimize risk of unwrapping, avoiding overheating, placing infants to sleep supine, and discontinuing swaddling when infants first show signs of rolling over, swaddling presents minimal risk.

Clinical Implications:

Maternity and neonatal nurses should model swaddling practices based on the evidence and promote informed decision-making among infant caregivers.
Cardiac Computed Tomography for Planning Revascularization Procedures
Authors: Opolski Maksymilian P.
Published: April 2017

Coronary computed tomography angiography (coronary CTA) is being increasingly used to detect and rule out coronary artery stenoses. Beyond stenosis detection, the abundance of anatomic, morphologic, and physiological information incorporated from a single one-stop-shop CT study has generated considerable interest in the context of preprocedural planning for coronary revascularization. Specifically, preprocedural CTA data sets can assist interventional cardiologists with selective catheter placement, appropriate guidewire choice, accurate stent size selection, and, most importantly, development of a stepwise revascularization strategy plan. This is particularly salient in cases in which noninvasive CTA exceeds the characterization of coronary lesions compared with invasive angiogram and has been successfully used to predict the likelihood of procedural outcome (eg, coronary chronic total occlusions). Unlike invasive angiography, coronary CTA can characterize “adverse” plaque characteristics (eg, low-attenuation plaque) that increase the risk for periprocedural complications and may thus require tailored revascularization strategies. In addition, the procedure itself may be facilitated by projection of 3-dimensional CTA data sets directly to the catheterization laboratory. Finally, the ability of CTA-derived computational fluid dynamics to pinpoint lesion-specific ischemia can be used to predict the functional outcome of coronary revascularization by “virtual stenting” algorithms. Continuous research is clearly needed, but many experienced operators have already integrated CTA into planning and guiding of coronary revascularization.
Formin-Dependent Adhesions are Required for Invasion by Epithelial Tissues
Authors: Fessenden Tim B. , Beckham Yvonne , Perez-Neut Mathew , Chourasia Aparajita H. , Macleod Kay F. , Oakes Patrick W. , Gardel Margaret L.
Published: April 2017

Developing tissues change shape, and tumors initiate spreading, through collective cell motility. Conserved mechanisms by which tissues initiate motility into their surroundings are not known. We investigated cytoskeletal regulators during collective invasion by mouse tumor organoids and epithelial MDCK acini undergoing branching morphogenesis. Inhibition of formins, but not Arp2/3, prevented the formation of migrating cell fronts in both cell types. MDCK cells depleted of the formin protein Dia1 formed polarized acini and could execute planar cell motility, either within the acinus or in 2D scattering assays. However, Dia1 was required to form protrusions into the collagen matrix. Live imaging of actin, myosin, and collagen in control acini revealed adhesions that deformed individual collagen fibrils, while Dia1-depleted acini exhibited unstable adhesions with minimal collagen deformation. This work identifies Dia1-mediated adhesions as essential regulators of tissue shape changes, through their role in focal adhesion maturation.
Resolving drug effects in patient-derived cancer cells links organoid responses to genome alterations
Authors: Neugebauer Julia , Zickgraf Franziska M. , Park Jeongbin , Wagner Steve , Jiang Xiaoqi , Jechow Katharina , Kleinheinz Kortine , Toprak Umut H. , Schneider Marc A. , Meister Michael , Spaich Saskia , Sütterlin Marc , Schlesner Matthias , Trumpp Andreas , Sprick Martin , Eils Roland , Conrad Christian
Published: April 2017

Cancer drug screening in patient-derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developedDeathPro, an automated microscopy-based assay to resolve drug-induced cell death and proliferation inhibition. UsingDeathPro, we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs. Drug-induced growth arrest and efficacy of cytostatic drugs differed between the two culture systems. Interestingly, drug effects in organoids were more diverse and had lower therapeutic potential. Genomic analysis revealed novel links between drug sensitivity and DNA repair deficiency in organoids that were undetectable in monolayers. Thus, our results highlight the dependency of cytostatic drugs and pharmacogenomic associations on culture systems, and guide culture selection for drug tests.
Disruption of perineuronal nets increases the frequency of sharp wave ripples
Authors: Sun ZhiYong , Bozzelli P. Lorenzo , Caccavano Adam , Allen Megan , Balmuth Jason , Vicini Stefano , Wu Jian-Young , Conant Katherine
Published: April 2017

Hippocampal sharp wave ripples (SWRs) represent irregularly occurring synchronous neuronal population events that are observed during phases of rest and slow wave sleep. SWR activity that follows learning involves sequential replay of training-associated neuronal assemblies and is critical for systems level memory consolidation. SWRs are initiated by CA2 or CA3 pyramidal cells and require initial excitation of CA1 pyramidal cells as well as subsequent participation of parvalbumin (PV) expressing fast spiking (FS) inhibitory interneurons. These interneurons are relatively unique in that they represent the major neuronal cell type known to be surrounded by perineuronal nets (PNNs), lattice like structures composed of a hyaluronin backbone that surround the cell soma and proximal dendrites. Though the function of the PNN is not completely understood, previous studies suggest it may serve to localize glutamatergic input to synaptic contacts and thus influence the activity of ensheathed cells. Noting that FS PV interneurons impact the activity of pyramidal cells thought to initiate SWRs, and that their activity is critical to ripple expression, we examine the effects of PNN integrity on SWR activity in the hippocampus. Extracellular recordings from the stratum radiatum of 490 micron horizontal murine hippocampal hemisections demonstrate SWRs that occur spontaneously in CA1. As compared to vehicle, pretreatment (120 min) of paired hemislices with hyaluronidase, which cleaves the hyaluronin backbone of the PNN, decreases PNN integrity and increases SWR frequency. Pretreatment with chondroitinase, which cleaves PNN side chains, also increases SWR frequency. Together, these data contribute to an emerging appreciation of extracellular matrix as a regulator of neuronal plasticity and suggest that one function of mature perineuronal nets could be to modulate the frequency of SWR events.
Host traits drive viral life histories across phytoplankton viruses
Authors: Edwards Kyle F. , Steward Grieg F.
Published: April 2017

Viruses are integral to ecological and evolutionary processes, but we have a poor understanding of what drives variation in key traits across diverse viruses. For lytic viruses, burst size, latent period, and genome size are primary characteristics controlling host-virus dynamics. Burst size and latent period are analogous to organismal traits of fecundity and generation time, and genome size affects the size of the virion as well as viral control of host metabolism. Here we synthesize data on these traits for 75 strains of phytoplankton viruses, which play an important role in global biogeochemistry. We find that primary traits of the host (genome size, growth rate) are major ecological drivers, explaining 40-50% of variation in burst size and latent period. We analyze an eco-evolutionary model to explore mechanisms underlying these patterns. We find that burst size may be set by the host genomic resources available for viral construction, while latent period evolves to permit this maximal burst size, modulated by host metabolic rate. These results suggest that general mechanisms may underlie the evolution of diverse viruses, which will facilitate our understanding of viral community processes, ecosystem impacts, and coevolutionary dynamics.
Cortical Representations of Speech in a Multi-talker Auditory Scene
Authors: Puvvada Krishna C. , Simon Jonathan Z.
Published: April 2017

The ability to parse a complex auditory scene into perceptual objects is facilitated by a hierarchical auditory system. Successive stages in the hierarchy transform an auditory scene of multiple overlapping sources, from peripheral tonotopically-based representations in the auditory nerve, into perceptually distinct auditory-objects based representation in auditory cortex. Here, using magnetoencephalography (MEG) recordings from human subjects, both men and women, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in distinct hierarchical stages of auditory cortex. Using systems-theoretic methods of stimulus reconstruction, we show that the primary-like areas in auditory cortex contain dominantly spectro-temporal based representations of the entire auditory scene. Here, both attended and ignored speech streams are represented with almost equal fidelity, and a global representation of the full auditory scene with all its streams is a better candidate neural representation than that of individual streams being represented separately. In contrast, we also show that higher order auditory cortical areas represent the attended stream separately, and with significantly higher fidelity, than unattended streams. Furthermore, the unattended background streams are more faithfully represented as a single unsegregated background object rather than as separated objects. Taken together, these findings demonstrate the progression of the representations and processing of a complex acoustic scene up through the hierarchy of human auditory cortex.

Significance Statement

Using magnetoencephalography (MEG) recordings from human listeners in a simulated cocktail party environment, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in separate hierarchical stages of auditory cortex. We show that the primary-like areas in auditory cortex use a dominantly spectro-temporal based representation of the entire auditory scene, with both attended and ignored speech streams represented with almost equal fidelity. In contrast, we show that higher order auditory cortical areas represent an attended speech stream separately from, and with significantly higher fidelity than, unattended speech streams. Furthermore, the unattended background streams are represented as a single undivided background object rather than as distinct background objects.
Accounting for cell lineage and sex effects in the identification of cell-specific DNA methylation using a Bayesian model selection algorithm
Authors: White Nicole M. , Benton Miles C. , Kennedy Daniel W. , Fox Andrew , Griffiths Lyn R. , Lea Rodney A. , Mengersen Kerrie L.
Published: April 2017

Cell- and sex-specific differences in DNA methylation are major sources of epigenetic variation in whole blood. Failure to account for these confounders may lead to substantial bias in the identification of differentially methylated CpGs and predicted levels of differential methylation. Previous studies have provided evidence of cell-specific methylation, but all of these have been restricted to the detection of differential methylation in a single cell type. We developed a Bayesian model selection algorithm for the identification of cell-specific methylation profiles that incorporates knowledge of shared cell lineage, to accommodate differential methylation in one or more cell types. Under the proposed methodology, sex-specific differences in methylation by cell type are also assessed. Using publicly available cell-sorted methylation data, we show that 51.3% of female CpG markers and 61.4% of male CpG markers identified were associated with differential methylation in more than one cell type. The impact of cell lineage on differential methylation was also highlighted. An evaluation of sex-specific differences revealed marked differences in CD56+NK methylation, within both single and multi-cell dependent methylation patterns. Our findings demonstrate the need to account for cell lineage in studies of differential methylation and associated sex effects.
Insight and Inference for DVARS
Authors: Afyouni Soroosh , Nichols Thomas E.
Published: April 2017

Estimates of functional connectivity using resting state functional Magnetic Resonance Imaging (rs-fMRI) are acutely sensitive to artifacts and large scale nuisance variation. As a result much effort is dedicated to preprocessing rs-fMRI data and using diagnostic measures to identify bad scans. One such diagnostic measure is DVARS, the spatial standard deviation of the data after temporal differencing. A limitation of DVARS however is the lack of concrete interpretation of the absolute values of DVARS, and finding a threshold to distinguish bad scans from good. In this work we describe a variance decomposition of the entire 4D dataset that shows DVARS to be just one of three sources of variation we refer to asD-var (closely linked to DVARS),S-var andE-var.D-var andS-var partition the variance at adjacent time points, whileE-var accounts for edge effects; each can be used to make spatial and temporal summary diagnostic measures. Extending the partitioning to global (and non-global) signal leads to a rs-fMRI DSE ANOVA table, which decomposes the total and global variability into fast (D-var), slow (S-var) and edge (E-var) components. We find expected values for each component under nominal models, showing howD-var (and thus DVARS) scales with overall variability and is diminished by temporal autocorrelation. Finally we propose a null sampling distribution for DVARS-squared and robust methods to estimate this null model, allowing computation of DVARS p-values. We propose that these diagnostic time series, images, p-values and ANOVA table will provide a succinct summary of the quality of a rs-fMRI dataset that will support comparisons of datasets over preprocessing steps and between subjects.
FiloQuant reveals increased filopodia density during DCIS progression
Authors: Jacquemet Guillaume , Paatero Ilkka , Carisey Alexandre F. , Padzik Artur , Orange Jordan S. , Hamidi Hellyeh , Ivaska Johanna
Published: April 2017

Filopodia are commonly observed cellular protrusions in vitro and in vivo. Defective filopodia formation is linked to several pathologies including cancer, wherein actively protruding filopodia, at the invasive front, and filopodia-mediated probing of the microenvironment accompanies cancer cell dissemination. Despite wide biological significance, delineating the function of these finger-like protrusions in more complex systems remains technically challenging, particularly hindered by lack of compatible methods to quantify filopodia properties. Here, we present FiloQuant, a freely available ImageJ plugin, to detect filopodia and filopodia-like protrusions in both fixed and live-cell microscopy data. We demonstrate that FiloQuant can extract quantifiable information including protrusion dynamics, density and length from multiple cell types and in a range of microenvironments, such as during collective or single cancer cell migration in 2D and 3D, in fixed neuronal cultures, in activated natural killer cells and in sprouting endothelial cells in vivo. In cellular models of breast ductal carcinoma in situ (DCIS) we reveal a link between filopodia formation at the cell-matrix interface, during collective invasion and in 3D tumour spheroids, with the previously reported local invasive potential of these breast cancer models in vivo. Finally, using intravital microscopy, we observed that tumour spheroids display prominent filopodia in vivo, supporting a potential role for these protrusions during tumorigenesis.
Burst activation of dopamine neurons produces prolonged post-burst availability of actively released dopamine
Authors: Lohani Sweyta , Martig Adria K. , Underhill Suzanne M. , DeFrancesco Alicia , Roberts Melanie J. , Rinaman Linda , Amara Susan , Moghaddam Bita
Published: April 2017

Both phasic and tonic modes of neurotransmission are implicated in critical functions assigned to dopamine. In learning, for example, sub-second phasic responses of ventral tegmental area (VTA) dopamine neurons to salient events serve as teaching signals, but learning is also interrupted by dopamine antagonists administered minutes after training. Our findings bridge the multiple timescales of dopamine neurotransmission by demonstrating that burst stimulation of VTA dopamine neurons produces a prolonged post-burst increase (> 20 min) of extracellular dopamine in nucleus accumbens and prefrontal cortex. This elevation is not due to spillover from the stimulation surge but depends on impulse flow-mediated dopamine release. We identified Rho-mediated internalization of dopamine transporter as a mechanism responsible for prolonged availability of actively released dopamine. These results demonstrate that phasic and tonic dopamine neurotransmission can be a continuum and may explain why both modes of signaling are critical for motivational and cognitive functions associated with dopamine.
Post-transcriptional regulation of adult CNS axonal regeneration by Cpeb1
Authors: Pak-Kin Lou Wilson , Mateos Alvaro , Koch Marta , Klussman Stefan , Yang Chao , Lu Na , Limpert Stefanie , Göpferich Manuel , Zschaetzsch Marlen , Maillo Carlos , Senis Elena , Grimm Dirk , Mendez Raul , Liu Kai , Hassan Bassem A. , Martin-Villalba Ana
Published: April 2017

Adult mammalian CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we study the transcriptome and proteome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identify a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were downregulated in the total RNA-fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovers a global conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.
ZINB-WaVE: A general and flexible method for signal extraction from single-cell RNA-seq data
Authors: Risso Davide , Perraudeau Fanny , Gribkova Svetlana , Dudoit Sandrine , Vert Jean-Philippe
Published: April 2017

Single-cell RNA sequencing (scRNA-seq) is a powerful high-throughput technique that enables researchers to measure genome-wide transcription levels at the resolution of single cells. Because of the low amount of RNA present in a single cell, some genes may fail to be detected even though they are expressed; these genes are usually referred to as dropouts. Here, we present a general and flexible zero-inflated negative binomial model (ZINB-WaVE), which leads to low-dimensional representations of the data that account for zero inflation (dropouts), over-dispersion, and the count nature of the data. We demonstrate, with simulated and real data, that the model and its associated estimation procedure are able to give a more stable and accurate low-dimensional representation of the data than principal component analysis (PCA) and zero-inflated factor analysis (ZIFA), without the need for a preliminary normalization step.
Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model
Authors: Zhang Fanshuang , Ni Yanying , Yuan Yuan , Yin Wei , Gao Youhe
Published: April 2017

Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis, which results from the deposition of extracellular matrix (ECM) components, is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide (TAA) liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS). A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins in the TAA 1-week, 3-week, 6-week and 8-week groups. A total of 40 urinary proteins were statistically significant (fold change >2 and p<0.05), 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase (ALT) and aspartate transaminase (AST) changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Masson’s staining.
Comprehensive statistical inference of the clonal structure of cancer from multiple biopsies
Authors: Liu Jie , Halloran John T. , Bilmes Jeffrey A. , Daza Riza M. , Lee Choli , Mahen Elisabeth M. , Prunkard Donna , Song Chaozhong , Blau Sibel , Dorschner Michael O. , Gadi Vijayakrishna K. , Shendure Jay , Blau C. Anthony , Noble William S.
Published: April 2017

A comprehensive characterization of tumor genetic heterogeneity is critical for understanding how cancers evolve and escape treatment. Although many algorithms have been developed for capturing tumor heterogeneity, they are designed for analyzing either a single type of genomic aberration or individual biopsies. Here we present THEMIS (Tumor Heterogeneity Extensible Modeling via an Integrative System), which allows for the joint analysis of different types of genomic aberrations from multiple biopsies taken from the same patient, using a dynamic graphical model. Simulation experiments demonstrate higher accuracy of THEMIS over its ancestor, TITAN. The heterogeneity analysis results from THEMIS are validated with single cell DNA sequencing from a clinical tumor biopsy. When THEMIS is used to analyze tumor heterogeneity among multiple biopsies from the same patient, it helps to reveal the mutation accumulation history, track cancer progression, and identify the mutations related to treatment resistance. We implement our model via an extensible modeling platform, which makes our approach open, reproducible, and easy for others to extend.
Asian wild rice is a hybrid swarm with extensive gene flow and feralization from domesticated rice
Authors: Wang Hongru , Vieira Filipe G. , Crawford Jacob E. , Chu Chengcai , Nielsen Rasmus
Published: April 2017

The domestication history of rice remains controversial, with multiple studies reaching different conclusions regarding its origin(s). These studies have generally assumed that populations of living wild rice, O. rufipogon, are descendants of the ancestral population that gave rise to domesticated rice, but relatively little attention has been paid to the origins and history of wild rice itself. Here, we investigate the genetic ancestry of wild rice by analyzing a diverse panel of rice genomes consisting of 203 domesticated and 435 wild rice accessions. We show that most modern wild rice is heavily admixed with domesticated rice through both pollen- and seed-mediated gene flow. In fact, much presumed wild rice may simply represent different stages of feralized domesticated rice. In line with this hypothesis, many presumed wild rice varieties show remnants of the effects of selective sweeps in previously identified domestication genes, as well as evidence of recent selection in flowering genes possibly associated with the feralization process. Furthermore, there is a distinct geographical pattern of gene flow from aus, indica, and japonica varieties into colocated wild rice. We also show that admixture from aus and indica is more recent than gene flow from japonica, possibly consistent with an earlier spread of japonica varieties. We argue that wild rice populations should be considered a hybrid swarm, connected to domesticated rice by continuous and extensive gene flow.
Radiography registration for mosaic tomography
Authors: Vescovi R. F. C. , Cardoso M. B. , Miqueles E. X.
Published: April 2017

A hybrid method of stitching X-ray computed tomography (CT) datasets is proposed and the feasibility to apply the scheme in a synchrotron tomography beamline with micrometre resolution is shown. The proposed method enables the field of view of the system to be extended while spatial resolution and experimental setup remain unchanged. The approach relies on taking full tomographic datasets at different positions in a mosaic array and registering the frames using Fourier phase correlation and a residue-based correlation. To ensure correlation correctness, the limits for the shifts are determined from the experimental motor position readouts. The masked correlation image is then minimized to obtain the correct shift. The partial datasets are blended in the sinogram space to be compatible with common CT reconstructors. The feasibility to use the algorithm to blend the partial datasets in projection space is also shown, creating a new single dataset, and standard reconstruction algorithms are used to restore high-resolution slices even with a small number of projections.
On the Penrose and Taylor–Socolar hexagonal tilings
Authors: Lee Jeong-Yup , Moody Robert V.
Published: April 2017

The intimate relationship between the Penrose and the Taylor–Socolar tilings is studied, within both the context of double hexagon tiles and the algebraic context of hierarchical inverse sequences of triangular lattices. This unified approach produces both types of tilings together, clarifies their relationship and offers straightforward proofs of their basic properties.
C—I...N short contacts as tools for the construction of the crystal packing in the crystal structure of 3,3′-(ethane-1,2-diyl)bis(6-iodo-3,4-dihydro-2H-1,3-benzoxazine)
Authors: Rivera Augusto , Rojas Jicli José , Ríos-Motta Jaime , Bolte Michael
Published: April 2017

The asymmetric unit of the title compound, C18H18I2N2O2, consists of one half-molecule, completed by the application of inversion symmetry. The molecule adopts the typical structure for this class of bis-benxozazines, characterized by an anti orientation of the two benzoxazine rings around the central C—C bond. The oxazinic ring adopts a half-chair conformation. In the crystal, molecules are linked by C—I...N short contacts [I...N = 3.378 (2) Å], generating layers lying parallel to the bc plane.
trans-Dichloridobis(dimethyl sulfoxide-κO)bis(4-fluorobenzyl-κC
1)tin(IV): crystal structure and Hirshfeld surface analysis
Authors: Amin Nur Adibah Binti Mohd , Hussen Rusnah Syahila Duali , Lee See Mun , Halcovitch Nathan R. , Jotani Mukesh M. , Tiekink Edward R. T.
Published: April 2017

The SnIV atom in the title diorganotin compound, [Sn(C7H6F)2Cl2(C2H6OS)2], is located on a centre of inversion, resulting in the C2Cl2O2 donor set having an all-trans disposition of like atoms. The coordination geometry approximates an octahedron. The crystal features C—H...F, C—H...Cl and C—H...π interactions, giving rise to a three-dimensional network. The respective influences of the Cl...H/H...Cl and F...H/H...F contacts to the molecular packing are clearly evident from the analysis of the Hirshfeld surface.
From K-Pop to K-Preparedness: Korea confronts disaster reduction
Authors: Oliver Kasdan David , Kim Kyehyun
Published: April 2017

Purpose

The purpose of this paper is to describe a recent effort by the South Korean Government to stimulate a domestic disaster risk reduction (DRR) technology industry for the export market. The project is a novel form of public-private partnership (PPP) that simultaneously fulfills the mandates of the Sendai Framework for Disaster Risk Reduction while promoting Korea’s economic development agenda.

Design/methodology/approach

The research is primarily a review study of the Global DRR Technology project as it is situated in the literature of PPP research from both the public administration and disaster management disciplines.

Findings

Korea’s approach to address DRR through a PPP targeting the needs of East Asian countries is unique. The overall effectiveness of the effort will take time to assess, but the model is an interesting and potentially fruitful mean of advancing DRR technology dissemination.

Practical implications

Korea may position itself as a global leader of DRR technology through this effort in terms of both market share and support of the Sendai Framework’s objectives. If successful, the PPP approach may be adopted as a viable means of improving DRR for other countries.

Social implications

Using PPPs for various aspects of DRR can be win-win situation for economic development and disaster management outcomes.

Originality/value

This paper presents a distinct application of the PPP model for DRR that other countries may appreciate and/or adopt for their own DRR needs.
Developing best practice in psychologically informed environments
Authors: Westaway Coral , Nolte Lizette , Brown Rachel
Published: April 2017

Purpose

The purpose of this paper is to extend our understanding of the issues facing those who experience multiple moves around homelessness projects. It considers these issues and how they relate to best practice, informing the delivery of psychologically informed environments (PIEs).

Design/methodology/approach

A qualitative design was employed, with interviews undertaken with men currently residing in hostels for those with additional needs. These men had already experienced multiple moves within the hostel system. Interpretative phenomenological analysis was used to analyse the data.

Findings

Main themes consider issues and challenges associated with hope and moving forward; help and the conditional or temporal nature of this; identity and stigma; and intimacy and relationships. Clinical implications of these findings are discussed.

Research limitations/implications

Implications include best practice for future planning with service users, the relational nature of hope, how best to manage endings and practical guidance for service developments in these settings.

Originality/value

These findings further the understanding of the challenges faced by service users with complex needs and how best to address them. They build on PIE guidance, offering tangible advice for practice.
Factors affecting the success of women’s entrepreneurship: a review of literature
Authors: Cabrera Ezilda María , Mauricio David
Published: April 2017

Purpose

Women entrepreneurship has grown significantly all over the world, and it is widely established that entrepreneurship is important for economic growth and wealth. Despite those facts, women’s participation in entrepreneurship is lower than men’s in almost all societies. Those phenomena get the attention of scholars from diverse disciplines, all of them interested in the behaviour and profile of female entrepreneurs and their business success rates. Several isolated factors were studied, with positive and negative effects on each stage of the entrepreneur process, for women entrepreneurs, so the purpose of this research is identify, classify by their impact and organise those factors in relation to the stages of the entrepreneur process.

Design/methodology/approach

The literature on factors affecting female entrepreneurship produced since January 2010 until October 2015 is analysed to define entrepreneurial success, identify factors affecting success at each stage of the entrepreneurial process and propose and organise those factors at individual and environment levels.

Findings

Several factors affecting female entrepreneurial success at each stage of the entrepreneurship process were found and organised at the internal (individual), micro, meso and macro environment level. In the literature reviewed, the most considered factors are: at the internal level, human capital, education and experience, with effects on the opportunity identification stage of the entrepreneurial process, and at the micro environment level, access to resources with effects on the opportunity recognition, acquiring resources and entrepreneurial performance stages, both with influence on quantitative and qualitative indicators of success.

Originality/value

This paper proposes an integrated classification and an array for all those factors that have an influence on women’s entrepreneurship and its success, relating those to the entrepreneurship process.
Promotional support: a formative scale development
Authors: R.M. Harindranath , Jacob Jayanth
Published: April 2017

Purpose

In pharmaceutical marketing, salespeople require promotional instruments to satisfy and retain their customers (physicians), but companies ignore the need because of the costs involved. It appears that the importance of promotional support is understood differently by managers and sales representatives. This study aims at developing a new construct called “promotional support”, as a resource support provided to salespeople to help them satisfy customer needs and achieve sales goals.

Design/methodology/approach

A detailed review of literature is followed by in-depth interviews to create items for the construct “promotional support”. Substantive validity is performed for identification of items measuring the construct. To initially validate the measures, a vignette study is performed. Formative index development procedure is followed. Data from a sample of 124 pharmaceutical sales representatives are collected and analyzed.

Findings

A formative construct is developed which possesses convergent (redundancy analysis) and nomological validity. The results of post hoc validation tests like confirmatory tetrad analysis and inter-item correlation are satisfactory and confirm the authors’ conceptualization.

Research limitations/implications

The scale requires external validation by testing it with different samples such as managers of pharmaceutical firms.

Practical implications

This study will help managers of pharmaceutical firms gain insights into the role and importance of promotional inputs given to their sales representatives.

Originality/value

This study uses the formative scale development procedure to develop promotional support. This construct can be used to understand the effect of promotional support given to pharmaceutical sales representatives on other constructs, which in turn helps in theory-building.
Physicians’ attitude towards direct to consumer advertising of pharmaceutical drugs
Authors: Siddiqi Arslan Ahmad , Shah Syed Zulfiqar Ali
Published: April 2017

Purpose

Pharmaceutical marketers and manufactures create hype of demand among patients towards a specific brand of drug or disease through drug advertisements. It induces the patients to seek additional information of the brand and ask for its prescription generation by the physician. The paper aims to determine the attitude of the physicians towards direct to consumer advertising (DTCA) and to examine the extent of patients’ request for a specific brand which leads to actual prescription generation.

Design/methodology/approach

Quantitative study, data was collected from field setting general practicing Doctors/Physicians in the leading hospitals. Quantitative data was collected from physicians working in leading hospitals. Doctors were selected on judgmental basis with high patient turnover. Sample size consists of 250 doctors, and questionnaire were adopted from two authors. Attitude of physicians towards DTCA and information inquired by the patient are two independent variables, whereas prescription generation by the physicians is dependent variable. SPSS was tool for data analysis.

Findings

Physicians have positive attitude towards DTCA and information provision to patient and consider it supplementary in overall health-care system. Advertising induces patients to visit physician and seek appropriate treatment and get induced to ask for further information.

Research limitations/implications

Time and resources were limited.

Practical implications

First, it contributes towards knowledge, second, it shows the importance of DTCA and its impact on prescription generation and, third, it will help in devising drug advertising policy.

Social implications

Highlights the issue are of not only misuse of drugs but also malpractice of drug prescription.

Originality/value

First, it explores the impact of the attitude of physicians along with the patients’ request on prescription generation behaviour. Second, it examines the impact of inquiring additional information about specific brand from the physician that might lead to the prescription generation. Finally, there is no study from the developing countries like Pakistan.