bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual clinics in glaucoma care: face-to-face versus remote decision-making
Authors: Clarke Jonathan , Puertas Renata , Kotecha Aachal , Foster Paul J , Barton Keith
Published: October 2016

Background/aims

To examine the agreement in clinical decisions of glaucoma status made in a virtual glaucoma clinic with those made during a face-to-face consultation.

Methods

A trained nurse and technicians entered data prospectively for 204 patients into a proforma. A subsequent face-to-face clinical assessment was completed by either a glaucoma consultant or fellow. Proformas were reviewed remotely by one of two additional glaucoma consultants, and 12 months later, by the clinicians who had undertaken the original clinical examination. The interobserver and intraobserver decision-making agreements of virtual assessment versus standard care were calculated.

Results

We identified adverse disagreement between face-to-face and virtual review in 7/204 (3.4%, 95% CI 0.9% to 5.9%) patients, where virtual review failed to predict a need to accelerated follow-up identified in face-to-face review. Misclassification events were rare, occurring in 1.9% (95% CI 0.3% to 3.8%) of assessments. Interobserver κ (95% CI) showed only fair agreement (0.24 (0.04 to 0.43)); this improved to moderate agreement when only consultant decisions were compared against each other (κ=0.41 (0.16 to 0.65)). The intraobserver agreement κ (95% CI) for the consultant was 0.274 (0.073 to 0.476), and that for the fellow was 0.264 (0.031 to 0.497).

Conclusions

The low rate of adverse misclassification, combined with the slowly progressive nature of most glaucoma, and the fact that patients will all be regularly reassessed, suggests that virtual clinics offer a safe, logistically viable option for selected patients with glaucoma.
Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial
Authors: Huhn E A , Fischer T , Göbl C S , Todesco Bernasconi M , Kreft M , Kunze M , Schoetzau A , Dölzlmüller E , Eppel W , Husslein P , Ochsenbein-Koelble N , Zimmermann R , Bäz E , Prömpeler H , Bruder E , Hahn S , Hoesli I
Published: October 2016

Introduction

As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an ‘early’ oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort.

Methods and analysis

In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an ‘early’ OGTT 75 g and/or the new biomarker, glyFn, at 12–15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24–28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on ‘early’ OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014.

Ethics and dissemination

This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered underhttp://www.ClinicalTrials.gov(NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals.

Trial registration number

NCT02035059.
Therapeutic appropriation: a new concept in the ethics of clinical research
Authors: McDougall Rosalind , Martin Dominique , Gillam Lynn , Hallowell Nina , Brookes Alison , Guillemin Marilys
Published: October 2016

Ethical concerns about therapeutic misconception have been raised since the early 1980s. This concept was originally described as research participants' assumptions that decisions relating to research interventions are made on the basis of their individual therapeutic needs. The term has since been used to refer to a range of ‘misunderstandings’ that research participants may have. In this paper, we describe a new concept—therapeutic appropriation. Therapeutic appropriation occurs when patients, or clinicians, actively reframe research participation as an opportunity to enhance patients' clinical care, while simultaneously acknowledging the generalised research aims. To illustrate the concept of therapeutic appropriation, we draw on data from an interview study which we conducted to investigate the experiences of patients and general practitioners involved in clinical trials in primary care. We argue that therapeutic appropriation has two key elements: comprehension that the research project is not necessarily aiming to benefit participants and the deliberate use of incidental features of the research for personal therapeutic benefit of various kinds. We conclude that therapeutic appropriation is a useful concept that refines understanding of potential ethical problems in clinical research, and points to strategies to address them.
Rationing conscience
Authors: Wilkinson Dominic
Published: October 2016

Decisions about allocation of limited healthcare resources are frequently controversial. These decisions are usually based on careful analysis of medical, scientific and health economic evidence. Yet, decisions are also necessarily based on value judgements. There may be differing views among health professionals about how to allocate resources or how to evaluate existing evidence. In specific cases, professionals may have strong personal views (contrary to professional or societal norms) that treatment should or should not be provided. Could these disagreements rise to the level of a conscientious objection? If so, should conscientious objections to existing allocation decisions be accommodated? In the first part of this paper, I assess whether resource allocation could be a matter of conscience. I analyse conceptual and normative models of conscientious objection and argue that rationing could be a matter for conscience. I distinguish between negative and positive forms: conscientious non-treatment and conscientious treatment. In the second part of the paper, I identify distinctive challenges for conscientious objections to resource allocation. Such objections are almost always inappropriate.
Republished: Pipeline embolization device thrombosis induced peri-construct collateral channels
Authors: Chiu Albert Ho Yuen , Marotta Thomas R
Published: October 2016

More than half a decade of experience and follow-up has now been accumulated with regard to flow diversion as a treatment for intracranial aneurysms; however, many uncertainties, such as the nature of aneurysmal remnants and the meaning of non-regressed, non-perfused aneurysmal masses, are still unknown. Here we discuss a 22-year-old man who presented with a grade 1 subarachnoid hemorrhage secondary to a dissecting right anterior cerebral artery aneurysm who was subsequently treated with a Pipeline Embolization Device construct. After ceasing dual antiplatelet therapy himself, he was found on MRI to have an area of increased aneurysmal remnant reperfusion. This was found to connect to multiple channels which reconstituted flow within the distal construct on angiography. The central area of construct thrombosis could not be visualized on MRI. The finding suggests that non-opacified aneurysmal remnants that have not regressed are biologically active and raises concerns regarding using MRI for long term follow-up.
Building on a bioveterinary sciences degree
Authors: Kazemi‐Egbunike Lilia
Published: October 2016

Lilia Kazemi‐Egbunike completed a bioveterinary sciences degree at the Royal Veterinary College and is now an information scientist and business support manager with the Veterinary Poisons Information service based in London
Fine-structure energy levels and radiative rates in Al-like molybdenum
Authors: Hu Feng , Sun Yan , Mao Meifei
Published: October 2016

Based on relativistic wavefunctions from multiconfigurational Dirac–Hartree–Fock and configuration interaction calculations, energy levels, radiative rates, and wavelengths are evaluated for all levels of 3s23p, 3s3p2, 3s23d, 3p3, 3s3p3d, 3p23d, and 3s3d2 configurations of Al-like molybdenum ion (Mo XXX). Transition probabilities are reported for E1 and M2 transitions from the ground level. The valence–valence and core–valence correlation effects are accounted for in a systematic way. Breit interactions and quantum electrodynamics effects are estimated in subsequent relativistic configuration interaction calculations. Comparisons are made with the available data in the literature and good agreement has been found, which confirms the reliability of our results.
Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats
Authors: Ateyya Hayam , Nader Manar A. , Attia Ghalia M. , El-Sherbeeny Nagla A.
Published: October 2016

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA–nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.
Low-ℓ CMB from string-scale SUSY breaking?
Authors: Sagnotti A.
Published: October 2016

Models of inflation are instructive playgrounds for supersymmetry (SUSY) breaking in Supergravity and String Theory. In particular, combinations of branes and orientifolds that are not mutually BPS can lead to brane SUSY breaking, a phenomenon where nonlinear realizations are accompanied, in tachyon-free vacua, by the emergence of steep exponential potentials. When combined with milder terms, these exponentials can lead to slow-roll after a fast ascent and a turning point. This leaves behind distinctive patterns of scalar perturbations, where pre-inflationary peaks can lie well apart from an almost scale invariant profile. I review recent attempts to connect these power spectra to the low-[Formula: see text] cosmic microwave background (CMB), and a corresponding one-parameter extension of Lambda cold dark matter ([Formula: see text]CDM) with a low-frequency cut [Formula: see text]. A detailed likelihood analysis led to [Formula: see text], at 99.4% confidence level, in an extended Galactic mask with [Formula: see text], to be compared with a nearby value at 88.5% in the standard Planck 2015 mask with [Formula: see text]. In these scenarios, one would be confronted, in the CMB, with relics of an epoch of deceleration that preceded the onset of slow-roll.
Investigation on microstructure and martensitic transformation of neodymium-added NiTi shape memory alloys
Authors: Maashaa Dovchinvanchig , Dorj Ulzii-Orshikh , Lee Malrey , Lee Min Hi , Zhao Chunwang , Dashjav Munguntsetseg , Woo Seon-Mi
Published: October 2016

The effect of rare earth element neodymium (Nd) addition on the microstructure and martensitic transformation behavior of Ni[Formula: see text]Ti[Formula: see text]Nd[Formula: see text] ([Formula: see text] = 0, 0.1, 0.3, 0.5 and 0.7 at.%) shape memory alloy was investigated by scanning electronic microscope, X-ray diffraction and differential scanning calorimetry. The results show that the microstructure of Ni–Ti–Nd ternary alloy consists of NiNd phase, NiTi2 and the NiTi matrix. A one-step martensitic transformation is observed in the alloys. The martensitic transformation temperature Ms increases sharply increasing 0.1–0.7 at.% Nd content is added.
Quantum consciousness in warm, wet and noisy brain
Authors: Sbitnev Valeriy I.
Published: October 2016

The emergence of quantum consciousness stems from dynamic flows of hydrogen ions in brain liquid. This liquid contains vast areas of the fourth phase of water with hexagonal packing of its molecules, the so-called exclusion zone (EZ) of water. The hydrogen ion motion on such hexagonal lattices shows as the hopping of the ions forward and the holes (vacant places) backward, caused by the Grotthuss mechanism. By supporting this motion using external infrasound sources, one may achieve the appearance of the superfluid state of the EZ water. Flows of the hydrogen ions are described by the modified Navier–Stokes equation. It, along with the continuity equation, yields the nonlinear Schrödinger equation, which describes the quantum effects of these flows, such as the tunneling at long distances or the interference on gap junctions.
VirtualSoC
Authors: Bortolotti Daniele , Marongiu Andrea , Benini Luca
Published: October 2016

Architectural heterogeneity has proven to be an effective design paradigm to cope with an ever-increasing demand for computational power within tight energy budgets, in virtually every computing domain. Programmable manycore accelerators are currently widely used not only in high-performance computing systems, but also in embedded devices, in which they operate as coprocessors under the control of a general-purpose CPU (the
host
processor). Clearly, such powerful hardware architectures are paired with sophisticated and complex software ecosystems, composed of operating systems, programming models plus associated runtime engines, and increasingly complex user applications with related libraries. System modeling has always played a key role in early architectural exploration or software development when the real hardware is not available. The necessity of efficiently coping with the huge HW/SW design space provided by the described heterogeneous Systems on Chip (SoCs) calls for advanced full-system simulation methodologies and tools, capable of assessing various metrics for the functional and nonfunctional properties of the target system. In this article, we describe VirtualSoC, a simulation tool targeting the full-system simulation of massively parallel heterogeneous SoCs. We also describe how VirtualSoC has been successfully adopted in several research projects.
GPUrpc
Authors: Iida Yuki , Fujii Yusuke , Azumi Takuya , Nishio Nobuhiko , Kato Shinpei
Published: October 2016

Graphics processing units (GPUs) are increasingly used for high-performance computing. Programming frameworks for general-purpose computing on GPUs (GPGPU), such as CUDA and OpenCL, are also maturing. Driving this trend is the recent proliferation of mobile devices such as smartphones and wearable computers. These devices are increasingly incorporating computationally intensive applications that involve some form of environmental recognition such as augmented reality (AR) or voice recognition. However, devices with low computational power cannot satisfy such demanding computing requirements. The CPU load of these devices could be reduced by offloading computation onto GPUs on the cloud. This paper presents GPUrpc, a remote procedure call (RPC) extension to Gdev, which is a rich set of runtime libraries and device drivers for achieving first-class GPU resource management. GPUrpc allows developers to use CUDA for GPGPU development work. Existing research uses RPCs based on the CUDA application programming interfaces (APIs); hence, all CUDA APIs require communication. To reduce communication overhead, we use an RPC based on a low-level API than CUDA API and reduced API that does not require communication. Our evaluation conducted on Linux and NVIDIA GPUs shows that the basic performance of our prototype implementation is reliable in comparison with the existing method. Evaluation using the Rodinia benchmark suite designed for research in heterogeneous parallel computing showed that GPUrpc is effective for applications such as image processing and data mining. GPUrpc also can improve power consumption to approximately 1/6 that of CPU processing for performing 512 × 512 matrix multiplication.
An Antifolk Theorem for Large Repeated Games
Authors: Pai Mallesh M. , Roth Aaron , Ullman Jonathan
Published: October 2016

In this article, we study infinitely repeated games in settings of imperfect monitoring. We first prove a family of theorems showing that when the signals observed by the players satisfy a condition known as (ϵ, γ)-differential privacy, the folk theorem has little bite: for values of ϵ and γ sufficiently small, for a fixed discount factor, any equilibrium of the repeated game involves players playing approximate equilibria of the stage game in every period. Next we argue that in large games (
n
player games in which unilateral deviations by single players have only a small impact on the utility of other players), many monitoring settings naturally lead to signals that satisfy (ϵ, γ)-differential privacy for ϵ and γ tending to zero as the number of players
n
grows large. We conclude that in such settings, the set of equilibria of the repeated game collapses to the set of equilibria of the stage game.

Our results nest and generalize previous results of Green [1980] and Sabourian [1990], suggesting that differential privacy is a natural measure of the “largeness” of a game. Further, techniques from the literature on differential privacy allow us to prove quantitative bounds, where the existing literature focuses on limiting results.
The Truth, The Whole Truth, and Nothing But the Truth
Authors: Blackburn Stephen M. , Diwan Amer , Hauswirth Matthias , Sweeney Peter F. , Amaral José Nelson , Brecht Tim , Bulej Lubomír , Click Cliff , Eeckhout Lieven , Fischmeister Sebastian , Frampton Daniel , Hendren Laurie J. , Hind Michael , Hosking Antony L. , Jones Richard E. , Kalibera Tomas , Keynes Nathan , Nystrom Nathaniel , Zeller Andreas
Published: October 2016

An unsound claim can misdirect a field, encouraging the pursuit of unworthy ideas and the abandonment of promising ideas. An inadequate description of a claim can make it difficult to reason about the claim, for example, to determine whether the claim is sound. Many practitioners will acknowledge the threat of unsound claims or inadequate descriptions of claims to their field. We believe that this situation is exacerbated, and even encouraged, by the lack of a systematic approach to exploring, exposing, and addressing the source of unsound claims and poor exposition.

This article proposes a framework that identifies three sins of reasoning that lead to unsound claims and two sins of exposition that lead to poorly described claims and evaluations. Sins of exposition obfuscate the objective of determining whether or not a claim is sound, while sins of reasoning lead directly to unsound claims.

Our framework provides practitioners with a principled way of critiquing the integrity of their own work and the work of others. We hope that this will help individuals conduct better science and encourage a cultural shift in our research community to identify and promulgate sound claims.
A Scriptable Standard-Compliant Reporting and Logging Framework for SystemC
Authors: Meyer Rolf , Wagner Jan , Farkas Bastian , Horsinka Sven , Siegl Patrick , Buchty Rainer , Berekovic Mladen
Published: October 2016

With the ever-increasing complexity of digital designs, debugging and evaluation face likewise increasing challenges. While recent advances in hardware/software co-simulation have been made, solutions for corresponding debugging and evaluation did not mature and improve in a similar fashion. In this article, we present a dedicated solution to ease the debugging and evaluation efforts, particularly focusing on full-system simulation. Improving significantly over existing solutions, the presented approach features a standards-compliant powerful and flexible method of deriving, logging, and filtering detailed status information from SystemC-based models. At the core of this approach are flexible scripting capabilities that may change all logging parameters during runtime, thus not requiring re-compiling the to-be-simulated model, as in many competing solutions. The approach is tested and benchmarked with a real-world full-system example, demonstrating the overall benefits. The presented solution is published as open source via github (see text) and, by strictly adhering to existing standards, is generally compatible with existing SystemC simulation environments.
Interorgan Communication Pathways in Physiology: Focus on Drosophila
Authors: Droujinine Ilia A. , Perrimon Norbert
Published: October 2016

Studies in mammals and Drosophila have demonstrated the existence and significance of secreted factors involved in communication between distal organs. In this review, primarily focusing on Drosophila, we examine the known interorgan communication factors and their functions, physiological inducers, and integration in regulating physiology. Moreover, we describe how organ-sensing screens in Drosophila can systematically identify novel conserved interorgan communication factors. Finally, we discuss how interorgan communication enabled and evolved as a result of specialization of organs. Together, we anticipate that future studies will establish a model for metazoan interorgan communication network (ICN) and how it is deregulated in disease.
Introduction to the Theme “New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology”
Authors: Insel Paul A. , Amara Susan G. , Blaschke Terrence F. , Meyer Urs A.
Published: October 2016

Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen “New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology” as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.
Global Testing and Large-Scale Multiple Testing for High-Dimensional Covariance Structures
Authors: Cai T. Tony
Published: October 2016

Driven by a wide range of contemporary applications, statistical inference for covariance structures has been an active area of current research in high-dimensional statistics. This review provides a selective survey of some recent developments in hypothesis testing for high-dimensional covariance structures, including global testing for the overall pattern of the covariance structures and simultaneous testing of a large collection of hypotheses on the local covariance structures with false discovery proportion and false discovery rate control. Both one-sample and two-sample settings are considered. The specific testing problems discussed include global testing for the covariance, correlation, and precision matrices, and multiple testing for the correlations, Gaussian graphical models, and differential networks.
Acute hypercapnic hyperoxia stimulates reactive species production in the caudal solitary complex of rat brain slices but does not induce oxidative stress
Authors: Ciarlone Geoffrey E. , Dean Jay B.
Published: October 2016

Central CO2 chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2 during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in the production of key RONS, as well as colorimetric assays to measure levels of oxidized and nitrated lipids and proteins. We also examined the effects of CO2 narcosis and hypoxia before euthanasia and brain slice harvesting, as these neurons are CO2 sensitive and hypothesized to employ CO2/H+ mechanisms that exacerbate RONS production and potentially oxidative stress. Our findings show that hyperoxia ± HA increases the production of peroxynitrite and its derivatives, whereas increases in Fenton chemistry are most prominent during hyperoxia + HA. Using CO2 narcosis before euthanasia modulates cellular sensitivity to HA postmortem and enhances the magnitude of the peroxynitrite pathway, but blunts the activity of Fenton chemistry. Overall, hyperoxia and HA do not result in increased production of markers of oxidative and nitrosative stress as expected. We postulate this is due to antioxidant and proteosomal removal of damaged lipids and proteins to maintain cell viability and avoid death during protracted hyperoxia.
Intestinal inflammation without weight loss decreases bone density and growth
Authors: Irwin Regina , Raehtz Sandi , Parameswaran Narayanan , McCabe Laura R.
Published: October 2016

Increasing evidence indicates a strong link between intestinal health and bone health. For example, inflammatory bowel disease can cause systemic inflammation, weight loss, and extra-intestinal manifestations, such as decreased bone growth and density. However, the effects of moderate intestinal inflammation without weight loss on bone health have never been directly examined; yet this condition is relevant not only to IBD but to conditions of increased intestinal permeability and inflammation, as seen with ingestion of high-fat diets, intestinal dysbiosis, irritable bowel syndrome, metabolic syndrome, and food allergies. Here, we induced moderate intestinal inflammation without weight loss in young male mice by treating with a low dose of dextran sodium sulfate (1%) for 15 days. The mice displayed systemic changes marked by significant bone loss and a redistribution of fat from subcutaneous to visceral fat pad stores. Bone loss was caused by reduced osteoblast activity, characterized by decreased expression of osteoblast markers (runx2, osteocalcin), histomorphometry, and dynamic measures of bone formation. In addition, we observed a reduction in growth plate thickness and hypertrophic chondrocyte matrix components (collagen X). Correlation analyses indicate a link between gut inflammation and disease score, but more importantly, we observed that bone density measures negatively correlated with intestinal disease score, as well as colon and bone TNF-α levels. These studies demonstrate that colitis-induced bone loss is not dependent upon weight loss and support a role for inflammation in the link between gut and bone health, an important area for future therapeutic development.
Sensorimotor integration of vision and proprioception for obstacle crossing in ambulatory individuals with spinal cord injury
Authors: Malik Raza Naseem , Cote Rachel , Lam Tania
Published: October 2016

Skilled walking, such as obstacle crossing, is an essential component of functional mobility. Sensorimotor integration of visual and proprioceptive inputs is important for successful obstacle crossing. The objective of this study was to understand how proprioceptive deficits affect obstacle-crossing strategies when controlling for variations in motor deficits in ambulatory individuals with spinal cord injury (SCI). Fifteen ambulatory individuals with SCI and 15 able-bodied controls were asked to step over an obstacle scaled to their motor abilities under full and obstructed vision conditions. An eye tracker was used to determine gaze behaviour and motion capture analysis was used to determine toe kinematics relative to the obstacle. Combined, bilateral hip and knee proprioceptive sense (joint position sense and movement detection sense) was assessed using the Lokomat and customized software controls. Combined, bilateral hip and knee proprioceptive sense in subjects with SCI varied and was significantly different from able-bodied subjects. Subjects with greater proprioceptive deficits stepped higher over the obstacle with their lead and trail limbs in the obstructed vision condition compared with full vision. Subjects with SCI also glanced at the obstacle more frequently and with longer fixation times compared with controls, but this was not related to proprioceptive sense. This study indicates that ambulatory individuals with SCI rely more heavily on vision to cross obstacles and show impairments in key gait parameters required for successful obstacle crossing. Our data suggest that proprioceptive deficits need to be considered in rehabilitation programs aimed at improving functional mobility in ambulatory individuals with SCI.

NEW & NOTEWORTHY This work is unique since it examines the contribution of combined, bilateral hip and knee proprioceptive sense on the recovery of skilled walking function, in addition to characterizing gaze behavior during a skilled walking task in people with motor-incomplete spinal cord injury.
Modulation of Synovial Fluid‐Derived Mesenchymal Stem Cells by Intra‐Articular and Intraosseous Platelet Rich Plasma Administration
Authors: Muiños-López Emma , Delgado Diego , Sánchez Pello , Paiva Bruno , Anitua Eduardo , Fiz Nicolás , Aizpurua Beatriz , Guadilla Jorge , Padilla Sabino , Granero-Moltó Froilán , Prósper Felipe , Sánchez Mikel
Published: October 2016

The aim of this study was to evaluate the effect of intra‐articular (IA) or a combination of intra‐articular and intraosseous (IO) infiltration of Platelet Rich Plasma (PRP) on the cellular content of synovial fluid (SF) of osteoarthritic patients. Thirty‐one patients received a single infiltration of PRP either in the IA space (n = 14) or in the IA space together with two IO infiltrations, one in the medial femoral condyle and one in the tibial plateau (n = 17). SF was collected before and after one week of the infiltration. The presence in the SF of mesenchymal stem cells (MSCs), monocytes, and lymphocytes was determined and quantified by flow cytometry. The number and identity of the MSCs were further confirmed by colony‐forming and differentiation assays. PRP infiltration into the subchondral bone (SB) and the IA space induced a reduction in the population of MSCs in the SF. This reduction in MSCs was further confirmed by colony‐forming (CFU‐F) assay. On the contrary, IA infiltration alone did not cause variations in any of the cellular populations by flow cytometry or CFU‐F assay. The SF of osteoarthritic patients contains a population of MSCs that can be modulated by PRP infiltration of the SB compartment.
l1- andl2-Norm Joint Regularization Based Sparse Signal Reconstruction Scheme
Authors: Liu Chanzi , Chen Qingchun , Zhou Bingpeng , Li Hengchao
Published: October 2016

Many problems in signal processing and statistical inference involve finding sparse solution to some underdetermined linear system of equations. This is also the application condition of compressive sensing (CS) which can find the sparse solution from the measurements far less than the original signal. In this paper, we proposel1- andl2-norm joint regularization based reconstruction framework to approach the originall0-norm based sparseness-inducing constrained sparse signal reconstruction problem. Firstly, it is shown that, by employing the simple conjugate gradient algorithm, the new formulation provides an effective framework to deduce the solution as the original sparse signal reconstruction problem withl0-norm regularization item. Secondly, the upper reconstruction error limit is presented for the proposed sparse signal reconstruction framework, and it is unveiled that a smaller reconstruction error thanl1-norm relaxation approaches can be realized by using the proposed scheme in most cases. Finally, simulation results are presented to validate the proposed sparse signal reconstruction approach.
Psychosocial and Somatosensory Factors in Women with Chronic Migraine and Painful Temporomandibular Disorders
Authors: Gil-Martínez Alfonso , Grande-Alonso Mónica , La Touche Roy , Lara-Lara Manuel , López-López Almudena , Fernández-Carnero Josué
Published: October 2016

Introduction. Psychosocial and somatosensory factors are involved in the pathophysiology of chronic migraine (CM) and chronic temporomandibular disorders (TMD).Objective. To compare and assess the relationship between pain catastrophizing and kinesiophobia in patients with CM or chronic TMD.Method. Cross-sectional study of 20 women with CM, 19 with chronic TMD, and 20 healthy volunteers. Pain catastrophizing and kinesiophobia were assessed. The level of education, pain intensity, and magnitude of temporal summation of stimuli in the masseter (STM) and tibialis (STT) muscles were also evaluated.Results. There were significant differences between the CM and chronic TMD groups, compared with the group of asymptomatic subjects, for all variables (p<.05) except kinesiophobia when comparing patients with CM and healthy women. Moderate correlations between kinesiophobia and catastrophizing (r=0.46;p<.01) were obtained, and the strongest association was between kinesiophobia and magnification (r=0.52;p<.01). The strongest associations among physical variables were found between the STM on both sides (r=0.93;p<.01) and between the left and right STT (r=0.76;p<.01).Conclusion. No differences were observed in pain catastrophizing and kinesiophobia between women with CM and with chronic TMD. Women with CM or chronic TMD showed higher levels of pain catastrophizing than asymptomatic subjects.
Osteogenic Differentiation of Human Amniotic Fluid Mesenchymal Stem Cells Is Determined by Epigenetic Changes
Authors: Glemžaitė Monika , Navakauskienė Rūta
Published: October 2016

Osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells (AF‐MSCs) has been widely studied in vitro and in vivo as a potential tool for regenerative medicine and tissue engineering. While most of the studies analyze changes in transcriptional profile during differentiation to date there is not much information regarding epigenetic changes in AF‐MSCs during differentiation. The aim of our study was to evaluate epigenetic changes during osteogenic differentiation of AF‐MS cells. Isolated AF‐MSCs were characterized morphologically and osteogenic differentiation was confirmed by cell staining and determining expression of alkaline phosphatase and osteopontin by RT‐qPCR. Variation in gene expression levels of pluripotency markers and specific microRNAs were also evaluated. Analysis of epigenetic changes revealed that levels of chromatin modifying enzymes such as Polycomb repressive complex 2 (PRC2) proteins (EZH2 and SUZ12), DNMT1, HDAC1, and HDAC2 were reduced after osteogenic differentiation of AF‐MSCs. We demonstrated that the level of specific histone markers keeping active state of chromatin (H3K4me3, H3K9Ac, and others) increased and markers of repressed state of chromatin (H3K27me3) decreased. Our results show that osteogenic differentiation of AF‐MSCs is conducted by various epigenetic alterations resulting in global chromatin remodeling and provide insights for further epigenetic investigations in human AF‐MSCs.
Disseminated Cerebrospinal Embryonal Tumor in the Adult
Authors: Caporlingua Alessandro , Armocida Daniele , Caporlingua Federico , Lapadula Gennaro , Elefante Grazia Maria , Antonelli Manila , Salvati Maurizio
Published: October 2016

Introduction. According to the 2016 World Health Organization classification of Tumors of the Central Nervous System, the term Primitive Neuroectodermal Tumor has been replaced by the term Embryonal Tumor (ET). We present a case of disseminated cerebrospinal ET presenting in an adult patient.Illustrative Case. A 49-year-old male presenting with low back pain, dysuria, and hypoesthesia of the lower extremities referred to our emergency department. Brain and whole spine contrast-enhanced MRI documented a diffusively disseminated heterogeneous neoplasm with intradural extra- and intramedullary involvement of the cervicothoracic tract and cauda equina. A primary biopsy of the lumbosacral localization was performed through L5 bilateral laminectomy. Histologic diagnosis was Embryonal Tumor Not Otherwise Specified. The patient underwent chemotherapy with postoperative adjuvant alternating Vincristine-Doxorubicin-Ifosfamide (VAI) and Ifosfamide-Etoposide (IE).Discussion. Spinal ETs are exceedingly rare especially when presenting in the adult patient. Neurosurgical and oncologic management is still unclear. When feasible, surgical removal should always be performed to obtain a histologic diagnosis. Postoperative adjuvant therapy might entail both chemo- and radiotherapy; however a consensus on this matter is still lacking.
Electrically Induced Calcium Handling in Cardiac Progenitor Cells
Authors: Maxwell Joshua T. , Wagner Mary B. , Davis Michael E.
Published: October 2016

For nearly a century, the heart was viewed as a terminally differentiated organ until the discovery of a resident population of cardiac stem cells known as cardiac progenitor cells (CPCs). It has been shown that the regenerative capacity of CPCs can be enhanced by ex vivo modification. Preconditioning CPCs could provide drastic improvements in cardiac structure and function; however, a systematic approach to determining a mechanistic basis for these modifications founded on the physiology of CPCs is lacking. We have identified a novel property of CPCs to respond to electrical stimulation by initiating intracellular Ca2+ oscillations. We used confocal microscopy and intracellular calcium imaging to determine the spatiotemporal properties of the Ca2+ signal and the key proteins involved in this process using pharmacological inhibition and confocal Ca2+ imaging. Our results provide valuable insights into mechanisms to enhance the therapeutic potential in stem cells and further our understanding of human CPC physiology.
Transcriptome-Wide Analysis Reveals the Role of PPARγControlling the Lipid Metabolism in Goat Mammary Epithelial Cells
Authors: Shi Hengbo , Zhao Wangsheng , Zhang Changhui , Shahzad Khuram , Luo Jun , Loor Juan J.
Published: October 2016

To explore the large-scale effect of peroxisome proliferator-activated receptorγ(PPARG) in goat mammary epithelial cells (GMEC), an oligonucleotide microarray platform was used for transcriptome profiling in cells overexpressingPPARGand incubated with or without rosiglitazone (ROSI, a PPARγagonist). A total of 1143 differentially expressed genes (DEG) due to treatment were detected. The Dynamic Impact Approach (DIA) analysis uncovered the most impacted and induced pathways “fatty acid elongation in mitochondria,” “glycosaminoglycan biosynthesis-keratan sulfate,” and “pentose phosphate pathway.” The data highlights the central role ofPPARGin milk fatty acid metabolism via controlling fatty acid elongation, biosynthesis of unsaturated fatty acid, lipid formation, and lipid secretion; furthermore, its role related to carbohydrate metabolism promotes the production of intermediates required for milk fat synthesis. Analysis of upstream regulators indicated thatPPARGparticipates in multiple physiological processes via controlling or cross talking with other key transcription factors such asPPARDandNR1H3(also known as liver-X-receptor-α). This transcriptome-wide analysis represents the first attempt to better understand the biological relevance of PPARG expression in ruminant mammary cells. Overall, the data underscored the importance of PPARG in mammary lipid metabolism and transcription factor control.
Identification of the Most Commonly Used Laboratory Techniques in Regenerative Medicine: A Roadmap for Developing a Competency Based Education Curriculum
Authors: Rego Stephen L. , Burrell Cheryl , Nielsen Melissa , Grove Tatjana , Kidiyoor Amritha , Flournoy Vatashea , Silverman Cheri , Hill Shawn , Beard Grady , Davis Dwaine , Tajkarimi Mehrdad , Harrington Courtney , Byrum Janice , Ayers Michael
Published: October 2016

Here, we are proposing and testing the use of literature reviews as a method to identify essential competencies for specific fields. This has implications in how educators develop and structure both traditional and competency based curricula. Our focus will be on utilizing this method to identify the most relevant and commonly used techniques in the field of regenerative medicine. This publication review method may be used to develop competency based education (CBE) programs that focus on commonly utilized skills. CBE is an emerging trend in higher education that will greatly enhance student learning experiences. CBE works by providing students with field specific skills and knowledge; thus, it is imperative for educators to identify the most essential competencies in a given field. Therefore, we reason that a literature review of the techniques performed in studies published in prevalent peer reviewed journals for a given field offers an ideal method to identify and rank competencies that should be delivered to students by a respective curriculum. Here, we reviewed recent articles published on topics in the field of regenerative medicine as a proof of concept for the use of literature reviews as a guide for the development of a regenerative medicine CBE curriculum.
Associations of A-FABP with Anthropometric and Metabolic Indices and Inflammatory Cytokines in Obese Patients with Newly Diagnosed Type 2 Diabetes
Authors: Niu Guifen , Li Jian , Wang Huaiguo , Ren Yuan , Bai Jie
Published: October 2016

The study aimed to evaluate the relationship between anthropometric and metabolic indices, inflammatory cytokines, and adipocyte fatty acid-binding protein (A-FABP) in obese patients with newly diagnosed type 2 diabetes. The study included 48 nonobese subjects with newly diagnosed type 2 diabetes, 42 obese subjects with newly diagnosed type 2 diabetes, 30 simple obese subjects, and 30 matched normal subjects. Serum A-FABP was assessed by enzyme-linked immunosorbent assay. Pearson’s correlations and multiple linear regression stepwise analysis were used to analyze correlations of A-FABP with anthropometric and metabolic indices and inflammatory cytokines. Obese subjects with newly diagnosed type 2 diabetes had elevated A-FABP compared to normal control, nondiabetic obese patients, and nonobese diabetic patients. A-FABP was significantly correlated with glycated hemoglobin A1C (HbA1C), BMI, triglyceride, Homeostasis Model Assessment Index (HOMA-IR), waist hip rate, C-reactive protein, IL-6, and HDL-C in obese subjects with type 2 diabetes. In multiple linear regression stepwise analysis, BMI, HbA1C, and HOMA-IR were significantly independent determinants for A-FABP. BMI, HbA1C, and HOMA-IR are independently associated with A-FABP in obese subjects with newly diagnosed type 2 diabetes. A-FABP may be related to insulin resistance and inflammation in type 2 diabetes and concomitant obesity.
TLR Adaptor Protein MYD88 Mediates Sensitivity to HDAC Inhibitors via a Cytokine-Dependent Mechanism
Authors: New Maria , Sheikh Semira , Bekheet Mina , Olzscha Heidi , Thezenas Marie-Laetitia , Care Matthew A. , Fotheringham Susan , Tooze Reuben M. , Kessler Benedikt , La Thangue Nicholas B.
Published: October 2016

Histone deacetylase (HDAC) inhibitors have proven useful therapeutic agents for certain hematologic cancers. However, HDAC inhibition causes diverse cellular outcomes, and identification of cancer-relevant pathways within these outcomes remains unresolved. In this study, we utilized an unbiased loss-of-function screen and identified the Toll-like receptor (TLR) adaptor protein MYD88 as a key regulator of the antiproliferative effects of HDAC inhibition. High expression of MYD88 exhibited increased sensitivity to HDAC inhibitors; conversely, low expression coincided with reduced sensitivity. MYD88-dependent TLR signaling controlled cytokine levels, which then acted via an extracellular mechanism to maintain cell proliferation and sensitize cells to HDAC inhibition. MYD88 activity was directly regulated through lysine acetylation and was deacetylated by HDAC6. MYD88 was a component of a wider acetylation signature in the ABC subgroup of diffuse large B-cell lymphoma, and one of the most frequent mutations in MYD88, L265P, conferred increased cell sensitivity to HDAC inhibitors. Our study defines acetylation of MYD88, which, by regulating TLR-dependent signaling to cytokine genes, influences the antiproliferative effects of HDAC inhibitors. Our results provide a possible explanation for the sensitivity of malignancies of hematologic origin to HDAC inhibitor–based therapy. Cancer Res; 76(23); 6975–87. ©2016 AACR.
Time-Degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among Hepatitis C Virus Patients: A Model for Prioritization of Treatment
Authors: Yu Ming-Lung , Huang Chung-Feng , Yeh Ming-Lun , Tsai Pei-Chien , Huang Ching-I. , Hsieh Meng-Hsuan , Hsieh Ming-Yen , Lin Zu-Yau , Chen Shinn-Cherng , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long
Published: October 2016

Purpose: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular carcinoma among chronic hepatitis C (CHC) patients.

Experimental Design: A total of 1,281 biopsy-proven CHC patients receiving IFN-based therapy were followed for a mean period of 5.5 years.

Results: The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non–sustained virological response (SVR) and SVR patients who were <40 years old (7.7% vs. 0.5%, P = 0.1) but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P < 0.001) and >55 years old (15.1% vs. 7.9%, P = 0.03). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients 40 to 55 years old [HR/95% confidence intervals (CI), 10.92/3.78–31.56; P < 0.001] and >55 years old (HR/CI, 1.96/1.06–3.63; P = 0.03) but not in patients <40 years old (HR/CI, 2.76/0.41–18.84; P = 0.3). The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-SVR and SVR patients whose fibrosis stage was F0–1 (4.6% vs. 1.9%, P = 0.25) but was higher in non-SVR patients with F2–3 (21.4% vs. 4.3%, P < 0.001) or F4 (33.5% vs. 8.4%, P = 0.002). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients with F2–3 (HR/CI, 4.36/2.10–9.03; P < 0.001) and F4 (HR/CI, 3.84/1.59–9.30; P = 0.03) but not in those with F0–1 (HR/CI, 1.53/0.49–4.74; P = 0.47).

Conclusions: Delayed hepatitis C virus clearance for patients with CHC >40 years old or with a fibrosis stage >2 increases the risk of hepatocellular carcinoma over time. Clin Cancer Res; 23(7); 1690–7. ©2016 AACR.