bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemically synthesized highly crystalline nitrogen doped graphene nanosheets with exceptional biocompatibility
Authors: Suhag Deepa , Kumar Sharma Arun , Rajput Satyendra K. , Saini Gajender , Chakrabarti Sandip , Mukherjee Monalisa 
Published: March 2017

AbstractThis work reports first electrochemical preparation of exceptionally biocompatible, highly crystalline, and well exfoliated nitrogen doped graphene nanosheets (eNGS) from carbon nanosheets for the development of mighty platforms in the field of modern biosensing and other biological applications for human welfare. eNGS displayed exceptional biocompatibility. Administration of the as-synthesized eNGS to rat models did not lead to any significant deviation or inimical consequences in its functional observation battery (FOB) tests, GSH levels or the histology of the vital organs of the rat models. The pictomicrographs of myocytes nuclei and myofibrillar for heart, hippocampus (CA1) section for brain, central vein, and hepatocytes for liver and parenchyma, tubules and glomeruli for kidney also remained unaffected. Moreover, the resultant nanoelectrocatalyst displayed enhanced electrochemical performance towards real-time sensing of dopamine (DA) from human urine sample in the presence of interferences, such as ascorbic acid (AA) and uric acid (UA).
Dynamics of single human embryonic stem cells and their pairs: a quantitative analysis
Authors: Wadkin L. E. , Elliot L. F. , Neganova I. , Parker N. G. , Chichagova V. , Swan G. , Laude A. , Lako M. , Shukurov A. 
Published: March 2017

AbstractNumerous biological approaches are available to characterise the mechanisms which govern the formation of human embryonic stem cell (hESC) colonies. To understand how the kinematics of single and pairs of hESCs impact colony formation, we study their mobility characteristics using time-lapse imaging. We perform a detailed statistical analysis of their speed, survival, directionality, distance travelled and diffusivity. We confirm that single and pairs of cells migrate as a diffusive random walk for at least 7 hours of evolution. We show that the presence of Cell Tracer significantly reduces hESC mobility. Our results open the path to employ the theoretical framework of the diffusive random walk for the prognostic modelling and optimisation of the growth of hESC colonies. Indeed, we employ this random walk model to estimate the seeding density required to minimise the occurrence of hESC colonies arising from more than one founder cell and the minimal cell number needed for successful colony formation. Our prognostic model can be extended to investigate the kinematic behaviour of somatic cells emerging from hESC differentiation and to enable its wide application in phenotyping of pluripotent stem cells for large scale stem cell culture expansion and differentiation platforms.
Double-stacked hyperbolic metamaterial waveguide arrays for efficient and broadband terahertz quarter-wave plates
Authors: Ke Xianmin , Zhu Hua , Li Junhao , Chen Lin , Li Xun 
Published: March 2017

AbstractWe demonstrate how it is possible to achieve weak dispersion in the phase delay between two orthogonal polarization states by using double-stacked hyperbolic metamaterial (HMM) waveguide arrays. The weak dispersion in the phase delay originates from the different signs of phase delay from the two different HMM waveguide arrays. The condition of dispersion-free phase delay for the transmitted waves has been theoretically derived from the transmission matrix as the propagation characteristic of the HMM waveguide is involved. We further reveal that the designed double-stacked HMM waveguide array can function as an efficient quarter-wave plate that enables the conversion of linearly polarized light to circularly polarized light within a broad frequency band. In addition, the bandwidth over which the degree of linear polarization is nearly unity and over which the angle of linear polarization is kept at approximately 45° is basically consistent with the phase bandwidth. This offers a promising approach for developing a practical polarization converter in the terahertz domain.
Adventitial lymphatic capillary expansion impacts on plaque T cell accumulation in atherosclerosis
Authors: Rademakers Timo , van der Vorst Emiel P. C. , Daissormont Isabelle T. M. N. , Otten Jeroen J. T. , Theodorou Kosta , Theelen Thomas L. , Gijbels Marion , Anisimov Andrey , Nurmi Harri , Lindeman Jan H. N. , Schober Andreas , Heeneman Sylvia , Alitalo Kari , Biessen Erik A. L. 
Published: March 2017

AbstractDuring plaque progression, inflammatory cells progressively accumulate in the adventitia, paralleled by an increased presence of leaky vasa vasorum. We here show that next to vasa vasorum, also the adventitial lymphatic capillary bed is expanding during plaque development in humans and mouse models of atherosclerosis. Furthermore, we investigated the role of lymphatics in atherosclerosis progression. Dissection of plaque draining lymph node and lymphatic vessel in atherosclerotic ApoE−/− mice aggravated plaque formation, which was accompanied by increased intimal and adventitial CD3+ T cell numbers. Likewise, inhibition of VEGF-C/D dependent lymphangiogenesis by AAV aided gene transfer of hVEGFR3-Ig fusion protein resulted in CD3+ T cell enrichment in plaque intima and adventitia. hVEGFR3-Ig gene transfer did not compromise adventitial lymphatic density, pointing to VEGF-C/D independent lymphangiogenesis. We were able to identify the CXCL12/CXCR4 axis, which has previously been shown to indirectly activate VEGFR3, as a likely pathway, in that its focal silencing attenuated lymphangiogenesis and augmented T cell presence. Taken together, our study not only shows profound, partly CXCL12/CXCR4 mediated, expansion of lymph capillaries in the adventitia of atherosclerotic plaque in humans and mice, but also is the first to attribute an important role of lymphatics in plaque T cell accumulation and development.
Checking behavior in rhesus monkeys is related to anxiety and frontal activity
Authors: Bosc Marion , Bioulac Bernard , Langbour Nicolas , Nguyen Tho Hai , Goillandeau Michel , Dehay Benjamin , Burbaud Pierre , Michelet Thomas 
Published: March 2017

AbstractWhen facing doubt, humans can go back over a performed action in order to optimize subsequent performance. The present study aimed to establish and characterize physiological doubt and checking behavior in non-human primates (NHP). We trained two rhesus monkeys (Macaca mulatta) in a newly designed “Check-or-Go” task that allows the animal to repeatedly check and change the availability of a reward before making the final decision towards obtaining that reward. By manipulating the ambiguity of a visual cue in which the reward status is embedded, we successfully modulated animal certainty and created doubt that led the animals to check. This voluntary checking behavior was further characterized by making EEG recordings and measuring correlated changes in salivary cortisol. Our data show that monkeys have the metacognitive ability to express voluntary checking behavior similar to that observed in humans, which depends on uncertainty monitoring, relates to anxiety and involves brain frontal areas.
Quantifying edge significance on maintaining global connectivity
Authors: Qian Yuhua , Li Yebin , Zhang Min , Ma Guoshuai , Lu Furong 
Published: March 2017

AbstractGlobal connectivity is a quite important issue for networks. The failures of some key edges may lead to breakdown of the whole system. How to find them will provide a better understanding on system robustness. Based on topological information, we propose an approach named LE (link entropy) to quantify the edge significance on maintaining global connectivity. Then we compare the LE with the other six acknowledged indices on the edge significance: the edge betweenness centrality, degree product, bridgeness, diffusion importance, topological overlap and k-path edge centrality. Experimental results show that the LE approach outperforms in quantifying edge significance on maintaining global connectivity.
Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts
Authors: Yam Gary Hin-Fai , Williams Geraint P. , Setiawan Melina , Yusoff Nur Zahirah Binte M. , Lee Xiao-wen , Htoon Hla Myint , Zhou Lei , Fuest Matthias , Mehta Jodhbir S. 
Published: March 2017

AbstractLaser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using anin vitrochick dorsal root ganglion model. The neurite growth was assessed by a validated concentric circle intersection count method. Serum-free conditioned media (CM) from SFs promoted neurite growth dose-dependently, compared to that from CSKs. We detected neurotrophic and pro-inflammatory factors (interleukin-8, interleukin-15, monocyte chemoattractant protein-1, eotaxin, RANTES) in SFCM by Bio-Plex Human Cytokine assay. More than 130 proteins in SFCM and 49 in CSKCM were identified by nanoLC-MS/MS. Proteins uniquely present in SFCM had reported neuro-regulatory activities and were predicted to regulate neurogenesis, focal adhesion and wound healing. Conclusively, this was the first study showing a physiological relationship between nerve growth and the metabolically active SFs versus quiescent CSKs from the same cornea source. The dose-dependent effect on neurite growth indicated that nerve regeneration could be influenced by SF density.
Inelastic electron injection in a water chain
Authors: Rizzi Valerio , Todorov Tchavdar N. , Kohanoff Jorge J. 
Published: March 2017

AbstractIrradiation of biological matter triggers a cascade of secondary particles that interact with their surroundings, resulting in damage. Low-energy electrons are one of the main secondary species and electron-phonon interaction plays a fundamental role in their dynamics. We have developed a method to capture the electron-phonon inelastic energy exchange in real time and have used it to inject electrons into a simple system that models a biological environment, a water chain. We simulated both an incoming electron pulse and a steady stream of electrons and found that electrons with energies just outside bands of excited molecular states can enter the chain through phonon emission or absorption. Furthermore, this phonon-assisted dynamical behaviour shows great sensitivity to the vibrational temperature, highlighting a crucial controlling factor for the injection and propagation of electrons in water.
When trainees reach competency in performing endoscopic ultrasound: a systematic review
Authors: Shahidi Neal , Ou George , Lam Eric , Enns Robert , Telford Jennifer 
Published: March 2017

Abstract
Background/Study aim The American Society for Gastrointestinal Endoscopy (ASGE) recommends that trainees complete 150 endoscopic ultrasound (EUS) procedures before assessing competency. However, this recommendation is largely based on limited evidence and expert opinion. With new evidence suggesting that this historical threshold is underestimating training requirements, we evaluated the learning curve for achieving competency in EUS.
Patients/Materials and methods Two investigators independently searched MEDLINE for full-text citations assessing the learning curve for achieving competency in EUS in the period 1946 to 25 March 2016. A learning curve was defined as either a tabulated or graphic representation of competency as a function of increasing EUS experience.
Results Eight studies assessing 28 trainees and 7051 EUS procedures were included. When stratifying studies based on procedural indication: three studies assessed competency in evaluating mucosal lesions, three studies assessed competency in EUS fine-needle aspiration (EUS-FNA), and two studies assessed comprehensive competency. Among studies assessing mucosal lesion T-staging accuracy, competency was achieved by 65 to 231 procedures. Among studies assessing EUS-FNA, competency was achieved by 30 to 40 procedures. Among the two studies assessing comprehensive competency in EUS, competency was not achieved in either study across all trainees. Only four of 17 trainees reached competency by 225 to 295 EUS procedures.
Conclusion As EUS competency assessment has evolved to more closely reflect independent clinical practice, the number of procedures required to achieve competency has risen well above ASGE recommendations. Advanced endoscopy training programs and specialty societies need to re-assess the structure of EUS training.
Metabolic evolution and the self-organization of ecosystems
Authors: Braakman Rogier , Follows Michael J. , Chisholm Sallie W. 
Published: March 2017

SignificanceUnderstanding what drives self-organization in complex systems and how it arises is a major challenge. We addressed this challenge using dominant oceanic photosynthetic and heterotrophic microbes as a model system. Reconstructing the metabolic evolution of this system suggests that its self-organization and self-amplification were coupled and driven by an increasing cellular energy flux. Specifically, the evolution of cells steadily increased their metabolic rate and excretion of organic carbon. We describe how this increases cellular nutrient uptake and thereby ecosystem biomass. The release of organic carbon, in turn, promotes positive feedbacks among species that reinforce this evolutionary drive at the ecosystem level. We propose the evolutionary self-organization of oceanic microbial ecosystems contributed to the oxygenation of Earth.
Cooperative Extension as a Framework for Health Extension: The Michigan State University Model
Authors: Dwyer Jeffrey W. , Contreras Dawn , Eschbach Cheryl L. , Tiret Holly , Newkirk Cathy , Carter Erin , Cronk Linda 
Published: March 2017

Problem
The Affordable Care Act charged the Agency for Healthcare Research and Quality to create the Primary Care Extension Program, but did not fund this effort. The idea to work through health extension agents to support health care delivery systems was based on the nationally known Cooperative Extension System (CES). Instead of creating new infrastructure in health care, the CES is an ideal vehicle for increasing health-related research and primary care delivery.

Approach
The CES, a long-standing component of the land-grant university system, features a sustained infrastructure for providing education to communities. The Michigan State University (MSU) Model of Health Extension offers another means of developing a National Primary Care Extension Program that is replicable in part because of the presence of the CES throughout the United States. A partnership between the MSU College of Human Medicine and MSU Extension formed in 2014, emphasizing the promotion and support of human health research. The MSU Model of Health Extension includes the following strategies: building partnerships, preparing MSU Extension educators for participation in research, increasing primary care patient referrals and enrollment in health programs, and exploring innovative funding.

Outcomes
Since the formation of the MSU Model of Health Extension, researchers and extension professionals have made 200+ connections, and grants have afforded savings in salary costs.

Next Steps
The MSU College of Human Medicine and MSU Extension partnership can serve as a model to promote health partnerships nationwide between CES services within land-grant universities and academic health centers or community-based medical schools.
Validating Domains of Patient Contextual Factors Essential to Preventing Contextual Errors: A Qualitative Study Conducted at Chicago Area Veterans Health Administration Sites
Authors: Binns-Calvey Amy E. , Malhiot Alex , Kostovich Carol T. , LaVela Sherri L. , Stroupe Kevin , Gerber Ben S. , Burkhart Lisa , Weiner Saul J. , Weaver Frances M. 
Published: March 2017

Purpose
“Patient context” indicates patient circumstances and characteristics or states that are essential to address when planning patient care. Specific patient “contextual factors,” if overlooked, result in an inappropriate plan of care, a medical error termed a “contextual error.” The myriad contextual factors that constitute patient context have been grouped into broad domains to create a taxonomy of challenges to consider when planning care. This study sought to validate a previously identified list of contextual domains.

Method
This qualitative study used directed content analysis. In 2014, 19 Department of Veterans Affairs (VA) providers (84% female) and 49 patients (86% male) from two VA medical centers and four outpatient clinics in the Chicago area participated in semistructured interviews and focus groups. Topics included patient-specific, community, and resource-related factors that affect patients’ abilities to manage their care. Transcripts were analyzed with a previously identified list of contextual domains as a framework.

Results
Analysis of responses revealed that patients and providers identified the same 10 domains previously published, plus 3 additional ones. Based on comments made by patients and providers, the authors created a revised list of 12 domains from themes that emerged. Six pertain to patient circumstances such as access to care and financial situation, and 6 to patient characteristics/states including skills, abilities, and knowledge.

Conclusions
Contextual factors in patients’ lives may be essential to address for effective care planning. The rubric developed can serve as a “contextual differential” for clinicians to consider when addressing challenges patients face when planning their care.
Loss of E-cadherin as Part of a Migratory Phenotype in Melanoma Is Associated With Ulceration
Authors: Bønnelykke-Behrndtz Marie L. , Steiniche Torben , Nørgaard Peter , Danielsen Allan V. , Damsgaard Tine E. , Christensen Ib J. , Bastholt Lars , Møller Holger J. , Schmidt Henrik 
Published: March 2017

Abstract:
It has been suggested that embryogenic properties of migratory cells are reactivated during wound healing and metastasis in adults. This might explain the association between wound-induced inflammation and poor survival in patients with ulcerated melanoma. Linking inflammation with a migratory phenotype, we characterize the infiltration of innate inflammatory cells, loss of cell-to-cell adhesion (E-cadherin), factors associated with extracellular matrix degradation [matrix metalloproteinase-9 (MMP-9), and neutrophil elastase (NE)], and spindle-shaped cell morphology, between ulcerated (n = 179) and nonulcerated (n = 206) melanoma. In addition, the presence of “extravascular migratory metastasis” (angiotropism) and tumor-vessel density were evaluated as important factors for tumor cell dispersal in ulcerated melanoma. We showed a correlation between expression of the granulocyte marker cd66b+ and the expression of NE and MMP-9, reflecting activated neutrophils. Ulcerated melanoma correlated with a low global E-cadherin score (P = 0.041) and weak-spot score (P = 0.0004). Thus, 28% of the nonulcerated, 42% of the minimally/moderately ulcerated melanoma, and 53% of the excessively ulcerated melanoma presented low scores as opposed to a high E-cadherin score. In addition, the presence of ulceration was correlated with angiotropism (P < 0.0001) and spindle-shaped morphology (P = 0.021). There were no differences in MMP-9 expression or intratumoral vessel density between the ulcerated and nonulcerated group. In conclusion, expression of migratory cell properties showed a highly heterogeneous pattern, which was associated with ulcerated areas and inflammatory cells, in general and with neutrophils in particular. We, therefore, suggest that wound-associated inflammation may be involved in the induction of migratory cell transition and tumor cell dispersal in ulcerated melanoma.
Exercise Training in a Patient With a Left Ventricular Assist Device and Large Aortic Valve Thrombus
Authors: Wuliya Mijiti , Peyrot Sandrine , Radu Costin , Deux Jean-François , Ben Elhaj Habib , Lellouche Nicolas , Damy Thibaud , Guendouz Soulef , Gellen Barnabas 
Published: March 2017

Details of the Clinical Case:
An aortic valve thrombus (AVT) is a rare complication after HeartMate II implantation. In a 44-year-old man, a large AVT was discovered 6 weeks after implantation of a HeartMate II for severe dilated cardiomyopathy. The aortic valve was permanently closed.

Discussion:
After a followup of 3 months without embolic events, the patient started a cardiac rehabilitation (CR) program involving aerobic exercise, resistance exercises, group gymnastics, and relaxation exercise, and completed the program without any complications, resulting in a significant functional benefit.

Summary:
CR might not be systematically contraindicated in patients with HeartMate II and an AVT, in particular, if there is no opening of the aortic valve at rest.
Aripiprazole Lauroxil
Authors: Hard Marjie L. , Mills Richard J. , Sadler Brian M. , Turncliff Ryan Z. , Citrome Leslie 
Published: March 2017

Abstract

Background
Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice.

Methods
Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations.

Findings
The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441–882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing.

Conclusions
This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.