bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey
Authors: Ma Christopher , Panaccione Remo , Fedorak Richard N , Parker Claire E , Khanna Reena , Levesque Barrett G , Sandborn William J , Feagan Brian G , Jairath Vipul
Published: June 2017

Introduction

Crohn’s disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).

Methods and analysis

The development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials.

Ethics and dissemination

Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality.
Diabetic retinopathy screening and treatment in Myanmar: a pilot study
Authors: Patel Sarju , Klein Richard M , Patel Arun , Klein Ronnie Boriskin , Aung Mya , Hoe Wilbert
Published: June 2017

Background/aims

The goals of this pilot study were (a) to demonstrate the feasibility of identifying patients with vision-threatening diabetic retinopathy (DR) in a provincial area of Myanmar and treating them with portable lasers and (b) to gather data specific to Myanmar to help design larger cross-sectional studies of DR prevalence in Myanmar.

Methods

97 consecutive patients with diabetes mellitus (DM) were identified by local ophthalmologists over a period of 1 month in Pyinmana, Myanmar and were referred to the pilot screening programme. Patients’ demographics were recorded and their eyes were examined. Those with vision-threatening DR were treated with panretinal photocoagulation (PRP).

Results

Of the 97 patients with DM, 33 (34%) had evidence of DR, 23 (23.5%) had evidence of vision-threatening DR including 13 (13.5%) with proliferative DR and 33 eyes in 23 patients (23.5%) had PRP with portable green wavelength laser. Hypertension was a significant cofactor in the development of vision-threatening DR (p<0.01). The average time since diagnosis of DM was 6.0 years in patients with vision-threatening DR.

Conclusions

This study demonstrates the feasibility of identifying and treating patients with vision-threatening DR in a provincial area of Myanmar and provides initial data to plan a larger study to assess true prevalence, a prerequisite for establishing broader screening/treatment programs.
Is it time for a review of the way that NICE guidelines are developed, presented and used to inform policy and practice?
Authors: Lowenhoff Catherine
Published: June 2017

Catherine Lowenhoff emphasises the need to share the uncertainties inherent in the National Institute for Health and Care Excellence guidelines with policy makers, commissioners, regulators, managers and clinicians to facilitate the paradigm shift from evidence-based practice to evidence-informed practice.
NADPH oxidase depletion in neutrophils from patients with cirrhosis and restoration via toll-like receptor 7/8 activation
Authors: Rolas Loïc , Boussif Abdelali , Weiss Emmanuel , Lettéron Philippe , Haddad Oualid , El-Benna Jamel , Rautou Pierre-Emmanuel , Moreau Richard , Périanin Axel
Published: June 2017

Objective

Cirrhosis downregulates phagocyte oxidant production via their antibacterial superoxide-generating system, NADPH oxidase (NOX2) and increases patients’ susceptibility to infection and mortality rate. To explore novel biochemical parameters that explain susceptibility to infections, we investigated the expression of NOX2 and partners in neutrophils of patients with severe alcoholic cirrhosis and have provided a novel approach to restore superoxide production capacity in patients’ neutrophils and blood.

Design

Neutrophils were isolated from patients with decompensated alcoholic cirrhosis. NOX2 activity was assessed after stimulation of purified neutrophils or whole blood with the bacterial-derived peptide fMet-Leu-Phe. The expression of NOX2 and partners was studied by western blot analysis, flow cytometry and reverse transcription-PCR.

Results

The impaired superoxide production by patients’ neutrophils was associated with a severe deficient expression of the NADPH oxidase catalytic core flavocytochrome-b558 (gp91phox/NOX2 and p22phox), its cytosolic partner p47phoxbut not p67phox. NOX2 expression decreased rapidly by protein degradation involving elastase released during degranulation of healthy neutrophils stimulated with fMet-Leu-Phe, or highly present in patients’ plasma. Interestingly, the deficient superoxide production was reversed by treatment of patients’ neutrophils and whole blood with toll-like receptor 7/8 (TLR7/8) agonists. This treatment stimulated a rapid NOX2 transcription and translation through a process involving mammalian target of rapamycin (mTOR) whose expression was also deficient in patients’ neutrophils. NOX2 expression was also increased by the TLR4 agonist lipopolysaccharide but with only a modest improvement of reactive oxygen species production.

Conclusion

Impairment of neutrophil oxidants production in alcoholic cirrhosis is associated with NOX2 degradation and deficient mTOR-dependent translational machinery. The NOX2 depletion can be reversed via TRL7/8 activation and might be used to restore antimicrobial responses of immunocompromised patients.
Incidence of irritable bowel syndrome and chronic fatigue following GI infection: a population-level study using routinely collected claims data
Authors: Donnachie Ewan , Schneider Antonius , Mehring Michael , Enck Paul
Published: June 2017

Objectives

To investigate the occurrence of postinfectious IBS in routine outpatient care, comparing different types of GI infection and its interaction with psychosomatic comorbidity.

Design

Retrospective cohort study using routinely collected claims data covering statutorily insured patients in Bavaria, Germany. Cases were defined as patients without prior record of functional intestinal disorder with a first-time diagnosis of GI infection between January 2005 and December 2013 and classed according to the type of infection. Each case was matched by age, sex and district of residence to a patient without history of GI infection. Prior psychological disorder (depression, anxiety or stress reaction disorder) was assessed in the 2 years prior to inclusion. Proportional hazards regression models were used to estimate the HRs for GI infection and psychological disorder. Chronic fatigue syndrome (CFS) was assessed as a comparator outcome.

Results

A total of 508 278 patients with first diagnosis of GI infection were identified, resulting in a matched cohort of 1 016 556 patients. All infection types were associated with an increased risk of IBS (HR: 2.19–4.25) and CFS (HR 1.35–1.82). Prior psychological disorder was a distinct risk factor for IBS (HR: 1.73) and CFS (HR: 2.08). Female sex was a further risk factor for both conditions.

Conclusion

Psychological disorder and GI infections are distinct risk factors for IBS. The high incidence of non-specific GI infection suggests that postinfectious IBS is a common clinical occurrence in primary care. Chronic fatigue is a further significant sequela of GI infection.
Smoking intensity and duration is associated with cardiac structure and function: the ECHOcardiographic Study of Hispanics/Latinos
Authors: Leigh J Adam , Kaplan Robert C , Swett Katrina , Balfour Pelbreton , Kansal Mayank M , Talavera Gregory A , Perreira Krista , Blaha Michael J , Benjamin Emelia J , Robertson Rosemarie , Bhartnagar Aruni , Rodriguez Carlos J
Published: June 2017

Objective

Cardiovascular disease is the leading cause of death in smokers and this relationship is complicated by the multiplicity of cardiovascular effects of smoking. However, the relationship between intensity and duration of cigarette smoking and echocardiographic measures of right and left ventricular structure and function has been poorly studied.

Methods

We examined ECHO-SOL (Echocardiographic Study of Hispanics/Latinos) participants, a subset of the Hispanic Community Health Study/Study of Latinos. Participants were administered a detailed tobacco exposure questionnaire and a comprehensive echocardiography exam. Multivariable linear regression models (adjusted for age, sex, obesity, hypertension and diabetes statuses) were performed using sampling weights. Statistical significance was defined at p<0.01.

Results

There were 1818 ECHO-SOL participants (57.4% women, mean age 56.4 years). Among current smokers (n=304), increased duration of smoking, as measured by a younger age of smoking initiation, was significantly associated with higher mean left ventricular mass (LVM) and lower right ventricular (RV) function (lower right ventricular stroke volumes). More cigarettes smoked per day was significantly associated with higher mean LVM, worse diastolic function (higher E/e′ ratio), worse LV geometry (increased relative wall thickness) and worse RV function (decreasing right ventricular stroke volume). Among current smokers, higher mean lifetime pack-years (a combined measure of smoking intensity and duration) was associated with higher LVM, worse LV geometry, worse diastolic function, greater RV dilatation and worse RV function.

Conclusions

There is a dose–response relationship between intensity and duration of cigarette tobacco smoking with unfavourable changes of multiple measures of right-sided and left-sided cardiac structure and function.
Pulmonary arterial hypertension, a novelty in idiopathic inflammatory myopathies: insights and first experiences with vasoactive therapy
Authors: Bhansing Kavish J , Vonk-Noordegraaf Anton , Oosterveer Frank PT , van Riel Piet LCM , Vonk Madelon C
Published: June 2017

To characterise the different types of pulmonary hypertension (PH) among idiopathic inflammatory myopathy (IIM). A retrospective case series with assessment of PH by right heart catheterisation, extent of interstitial lung disease (ILD) and outcome of vasoactive therapy.The group of patients with IIM with PH (n=9) showed a median age at PH diagnosis of 62 years (IQR 48–71 years; eight women), seven diagnosed with polymyositis and two with dermatomyositis; median disease duration of 5.7 years and five patients with a positive anti-Jo1 antibody. We found one patient to be classified in PH WHO group 2 (left heart disease), five patients in WHO group 3 (lung disease) and three patients in WHO group 1 (pulmonary arterial hypertension (PAH)). During median observed follow-up of 24 months, mortality for the total group was 44%. Surprisingly, we found a relevant group (33%) of patients with IIM who suffered from non-ILD-PH, which reflects the presence of PAH phenotype. This result should lead to more awareness among treating physicians that complaints of dyspnoea among patient with IIM could be related to PAH and not only ILD. The role of vasoactive therapy remains to be defined in patients with IIM suffering from PAH or PH-ILD.
Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts
Authors: Yates Max , Watts Richard , Bajema Ingeborg , Cid Maria , Crestani Bruno , Hauser Thomas , Hellmich Bernhard , Holle Julia , Laudien Martin , Little Mark A , Luqmani Raashid Ahmed , Mahr Alfred , Merkel Peter , Mills John , Mooney Janice , Segelmark Mårten , Tesar Vladimir , Westman Kerstin W A , Vaglio Augusto , Yalçındağ Nilüfer , Jayne David R , Mukhtyar Chetan
Published: June 2017

The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society—EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases.
Electronic cigarette use in restaurants and workplaces where combustible tobacco smoking is not allowed: an Internet survey in Japan
Authors: Kiyohara Kosuke , Tabuchi Takahiro
Published: June 2017

Background

The present study aimed to examine the experience of actual electronic cigarette (e-cigarette) use in smoke-free areas of restaurants and workplaces and to explore the determinants associated with such use among Japanese adults who reported any experience using e-cigarettes (e-cigarette ever-users).

Methods

An Internet-based self-reported questionnaire survey was conducted in 2015 on Japanese e-cigarette ever-users. The proportion of the respondents who had ever used or frequently used e-cigarettes in smoke-free restaurants and/or workplaces was calculated. Potential factors associated with e-cigarette use in those smoke-free areas were also examined by using multivariable logistic regression analyses.

Results

In total, 1243 e-cigarette ever-users (662 current and 581 former e-cigarette users) were analysed. The majority of them (1020/1243, 82.1%) were male and their mean age ± SD was 47.0±10.4 years. The proportion of those who had ever used e-cigarettes in smoke-free restaurants was 28.8% (358/1243) and that in smoke-free workplaces was 25.5% (317/1243), respectively. The proportion of those who had frequently used e-cigarettes in smoke-free restaurants was 18.5% (230/1243) and that in smoke-free workplaces was 16.3% (202/1243), respectively. In general, the proportion of e-cigarette use in those smoke-free areas was higher among those having a higher educational level than those having a lower educational level.

Conclusion

Among adult Japanese e-cigarette ever-users, approximately 26%–29% had ever used and 16%–19% had frequently used e-cigarettes in restaurants and/or workplaces where combustible tobacco smoking is not allowed. Policy-makers may need to establish explicit rules as to e-cigarette use in smoke-free environments.
Distributional range, ecology, and mating system of the Cape mole-rat (Georychus capensis) family Bathyergidae
Authors: Visser J.H. , Bennett N.C. , Jansen van Vuuren B.
Published: June 2017

Interpopulation variation in life-history patterns are influenced by intrinsic and extrinsic factors. Life-history patterns have been intensely studied in the eusocial African bathyergid species, largely neglecting the solitary species. Of these solitary genera, the Cape mole-rat (Georychus capensis (Pallas, 1778)) is endemic to South Africa with a disjunct distribution across its range. Knowledge regarding this species is rudimentary; therefore, this study aimed to investigate the current distribution of the species with particular attention to common ecological variables, differences in body size between localities and sexes, as well as its reproduction and mating system. Georychus is a habitat specialist restricted to specific ecological areas. A lack of sexual size dimorphism and correlation between male testis size and number of females in the population, suggests a polygynous mating system, facilitated by the spatial distribution of the sexes. A positive relationship between male testes size and percentage of females in populations sampled suggests that larger sperm reserves (i.e., larger testes) are required in populations with a higher percentage of females. In addition, mating variables (testicular size and litter size) are linked to ecological factors (elevation, aridity, soil type, and vegetation type) that could impact mate searching, mating success, and food resources.
Generalized Rogers–Ramanujan identities for twisted affine algebras
Authors: Genish Arel , Gepner Doron
Published: June 2017

The characters of parafermionic conformal field theories are given by the string functions of affine algebras, which are either twisted or untwisted algebras. Expressions for these characters as generalized Rogers–Ramanujan algebras have been established for the untwisted affine algebras. However, we study the identities for the string functions of the twisted affine Lie algebras. A conjecture for the string functions was proposed by Hatayama et al., for the unit fields, which expresses the string functions as Rogers–Ramanujan type sums. Here we propose to check the Hatayama et al. conjecture, using Lie algebraic theoretic methods. We use Freudenthal’s formula, which we computerized, to verify the identities for all the algebras at low rank and low level. We find complete agreement with the conjecture.
Constraint Test Cases Generation Based on Particle Swarm Optimization
Authors: Sheng Yunlong , Wei Changan , Jiang Shouda
Published: June 2017

The testing of configurations with constraints still faces a great challenge. Although artificial intelligence (AI)-based algorithms perform better than greedy algorithms on [Formula: see text]-way testing because of the good searching ability of optimal solutions, only a few AI-based algorithms can support constraints currently. Moreover, the AI-based algorithms can only ignore the conflicting candidate test cases subject to constraints, even though they are optimal. In this paper, we demonstrate two novel particle swarm optimization (PSO)-based constraint test cases generation (PCTG) methods. In the two methods, the strategies of avoiding the selection of conflicting test cases and replacing conflicting test cases are applied to handle constraints, respectively. They guide the process of searching for optimal solutions from different perspectives, according to different handling of constraints. We evaluate the availability of these two methods with some excellent existing strategies in terms of performance. The evaluation results indicate that our proposed methods, in most cases, outperform other strategies as far as the generated constraints covering array sizes.
Further results on the distance signless Laplacian spectrum of graphs
Authors: Alhevaz Abdollah , Baghipur Maryam , Hashemi Ebrahim
Published: June 2017

The distance signless Laplacian matrix [Formula: see text] of a connected graph [Formula: see text] is defined as [Formula: see text], where [Formula: see text] is the distance matrix of [Formula: see text] and [Formula: see text] is the diagonal matrix whose main entries are the vertex transmissions of [Formula: see text], and the spectral radius of a connected graph [Formula: see text] is the largest eigenvalue of [Formula: see text]. In this paper, first we obtain the [Formula: see text]-eigenvalues of the join of certain regular graphs. Next, we give some new bounds on the distance signless Laplacian spectral radius of a graph [Formula: see text] in terms of graph parameters and characterize the extremal graphs. Utilizing these results we present some upper and lower bounds on the distance signless Laplacian energy of a graph [Formula: see text].
Algebra cone generalized b-metric space over Banach algebra and fixed point theorems of generalized Lipschitz mappings
Authors: Ahmed Aziz , Salunke J. N.
Published: June 2017

In this paper, we introduce the concept of algebra cone generalized [Formula: see text]-metric space over Banach algebra by replacing the constant [Formula: see text] with [Formula: see text] where [Formula: see text] is the spectral radius of [Formula: see text], with this modification we shall prove Banach and Kannan fixed point results for contractive generalized Lipschitz mappings in such a space. Moreover, we present one example in support of our results.
Term Premium Dynamics and the Taylor Rule
Authors: Gallmeyer Michael , Hollifield Burton , Palomino Francisco , Zin Stanley
Published: June 2017

We explore the bond-pricing implications of an exchange economy where preference shocks result in time-varying term premiums in real yields with a Taylor rule determining inflation dynamics and nominal term premiums. We calibrate the model by matching the term structure of the means and volatilities of nominal yields. Unlike a model with exogenous inflation, a Taylor rule matching empirical properties of inflation leads to nominal term premiums that are volatile at long maturities. Increasing monetary policy aggressiveness decreases the level and volatility of nominal yields.
Testing covariance structure of large-dimensional data based on Wald’s score test
Authors: Jiang Dandan , Zhang Qibin , Hui Yongchang
Published: June 2017

This paper considers testing the covariance matrices structure based on Wald’s score test in large-dimensional setting. The tests for identity and sphericity of large-dimensional covariance matrices are reviewed by the generalized CLT for the linear spectral statistics of large-dimensional sample covariance matrices from [D. D. Jiang, Tests for large-dimensional covariance structure based on Rao’s score test, J. Multivariate Anal. 152 (2016) 28–39]. The proposed test can be applicable for large-dimensional non-Gaussian variables in a wider range. Furthermore, the simulation study is conducted to compare the proposed test with other large-dimensional covariance matrix tests. As seen from the simulation results, our proposed test is feasible for large-dimensional data without restriction of population distribution and provides the accurate and steady empirical sizes, which are almost around the nominal size.
Heavy hydrocarbon fate and transport in the environment
Authors: Brown David M. , Bonte Matthijs , Gill Richard , Dawick James , Boogaard Peter J.
Published: June 2017

Heavy hydrocarbons are a heterogeneous mixture of compounds consisting mainly of alkylated cyclics, resins and asphaltenes and, depending on the source, can form a significant proportion of crude oil. Their prevalence is expected to increase in the future as heavy oil reserves are increasingly exploited for growing worldwide energy demands. Despite their growing use, heavy hydrocarbons are generally overlooked when assessing the risk of hydrocarbons to human health, ecology and water reserves. Although their human and environmental health risks are considered low, heavy hydrocarbons are known to persist in the environment. This review considers the fate, transport and toxicity of heavy hydrocarbons. It provides a description of the possible mechanisms involved in heavy hydrocarbon attenuation and offers some interpretation of data that provides insight into their persistence in the environment.

Supplementary material:
The effect of hydrocarbon concentration and soil organic content on the partitioning of heavy hydrocarbon (EC >44) into soils is available at
https://doi.org/10.6084/m9.figshare.c.3791473
.
Tight Lower Bounds on Graph Embedding Problems
Authors: Cygan Marek , Fomin Fedor V. , Golovnev Alexander , Kulikov Alexander S. , Mihajlin Ivan , Pachocki Jakub , Socała Arkadiusz
Published: June 2017

We prove that unless the Exponential Time Hypothesis (ETH) fails, deciding if there is a homomorphism from graph
G
to graph
H
cannot be done in time |
V
(
H
)|

o
(|
V
(
G
)|)

. We also show an exponential-time reduction from Graph Homomorphism to Subgraph Isomorphism. This rules out (subject to ETH) a possibility of |
V
(
H
)|

o
(|
V
(
H
)|)

-time algorithm deciding if graph
G
is a subgraph of
H
. For both problems our lower bounds asymptotically match the running time of brute-force algorithms trying all possible mappings of one graph into another. Thus, our work closes the gap in the known complexity of these fundamental problems.

Moreover, as a consequence of our reductions, conditional lower bounds follow for other related problems such as Locally Injective Homomorphism, Graph Minors, Topological Graph Minors, Minimum Distortion Embedding and Quadratic Assignment Problem.
A Distributed (2 + ε)-Approximation for Vertex Cover in O(log Δ / ε log log Δ) Rounds
Authors: Bar-Yehuda Reuven , Censor-Hillel Keren , Schwartzman Gregory
Published: June 2017

We present a simple deterministic distributed (2 + ϵ)-approximation algorithm for minimum-weight vertex cover, which completes in
O
(log Δ/ϵlog log Δ) rounds, where Δ is the maximum degree in the graph, for any ϵ > 0 that is at most
O
(1). For a constant ϵ, this implies a constant approximation in
O
(log Δ/log log Δ) rounds, which contradicts the lower bound of [KMW10].
Adult ADHD: Questioning Diagnosis and Treatment in a Patient with Multiple Psychiatric Comorbidities
Authors: Chu Robert Karoly , Rosic Tea , Samaan Zainab
Published: June 2017

Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is a contentious diagnostic issue, which has been increasing in prevalence in recent years, and is often comorbid with other psychiatric disorders. This report presents a detailed account of a clinical case involving a middle-aged man with a history of recurrent depressive episodes and an unsubstantiated diagnosis of ADHD, treated with stimulants. There is persistent debate around the use of psychostimulants both in adult ADHD and in the treatment of depression. Despite promising activating properties, psychostimulants carry significant risks of misuse and substance use disorder. In this report, we consider the potential benefits and adverse effects of stimulants in the treatment of adult ADHD and mood disorders and review the learning points of this complicated, but not uncommon, clinical case.
Magnesium Oxide Nanoparticles Reinforced Electrospun Alginate-Based Nanofibrous Scaffolds with Improved Physical Properties
Authors: De Silva R. T. , Mantilaka M. M. M. G. P. G. , Goh K. L. , Ratnayake S. P. , Amaratunga G. A. J. , de Silva K. M. Nalin
Published: June 2017

Mechanically robust alginate-based nanofibrous scaffolds were successfully fabricated by electrospinning method to mimic the natural extracellular matrix structure which benefits development and regeneration of tissues. Alginate-based nanofibres were electrospun from an alginate/poly(vinyl alcohol) (PVA) polyelectrolyte complex. SEM images revealed the spinnability of the complex composite nanofibrous scaffolds, showing randomly oriented, ultrafine, and virtually defects-free alginate-based/MgO nanofibrous scaffolds. Here, it is shown that an alginate/PVA complex scaffold, blended with near-spherical MgO nanoparticles (⌀ 45 nm) at a predetermined concentration (10% (w/w)), is electrospinnable to produce a complex composite nanofibrous scaffold with enhanced mechanical stability. For the comparison purpose, chemically cross-linked electrospun alginate-based scaffolds were also fabricated. Tensile test to rupture revealed the significant differences in the tensile strength and elastic modulus among the alginate scaffolds, alginate/MgO scaffolds, and cross-linked alginate scaffolds (P<0.05). In contrast to cross-linked alginate scaffolds, alginate/MgO scaffolds yielded the highest tensile strength and elastic modulus while preserving the interfibre porosity of the scaffolds. According to the thermogravimetric analysis, MgO reinforced alginate nanofibrous scaffolds exhibited improved thermal stability. These novel alginate-based/MgO scaffolds are economical and versatile and may be further optimised for use as extracellular matrix substitutes for repair and regeneration of tissues.
Biology of Incidental Catch Sea Star Stellaster childreni Gray, 1840 (Echinodermata: Asteroidea), from Malaysian Borneo Exclusive Economic Zone
Authors: Hassan Ruhana , Lee Suet Yee , Morni Wan Zabidii Wan
Published: June 2017

Sea star (class Asteroidea, phylum Echinodermata) is one of the most successful marine organisms inhabiting a wide range of habitats. As one of the key stone species, sea stars are responsible for maintaining much of the local diversity of species within certain communities. Malaysian Exclusive Economic Zone (EEZ) Resource Survey had been carried out from 16th Aug to 6th Nov 2015 and one of the invertebrate by-catch organisms is sea star Stellaster childreni Gray, 1840. This study documents morphological characters and diet of the sea star, besides providing brief descriptions of the habitats based on particle size analysis and vessel log data sheet. A total of 217 individuals had been examined throughout this study. Fragments of flora and fauna were found in the gut including Mollusca (gastropod, bivalves, and scaphopods), sponge seagrass, and seaweed as well as benthic Foraminifera. Stellaster childreni were found at depth of 45 m to 185 m in the South China Sea off Sarawak Malaysia, with various sea bottom substrata. Approximately 41% of S. childreni were found at a mixture of sandy and muddy substratum, followed by mixture of sandy and coral (19.3%), muddy substratum (17.5%), coral substratum (11.5%), and sandy areas (10.6%). The widely distributed sea star on different types of sea beds suggested healthy deep sea ecosystem; thus Malaysia should explore further potential fisheries resources in the EEZ off Sarawak coast.
Simultaneous Measurements of the Vehicle, Track, and Soil Vibrations at a Surface, Bridge, and Tunnel Railway Line
Authors: Auersch Lutz
Published: June 2017

A complex measuring campaign has been performed including the simultaneous measurement of vehicle, track, and soil vibrations during train runs at 16, 25, 40, 63, 80, 100, 125, 140, and 160 km/h and impulse measurements of the passenger car, three track sections, and the soil. A ballast track on the soil surface and on a concrete bridge has been investigated as well as a slab track in a tunnel. The evaluation and comparison of all these data show a generally good agreement for all components if the strong low- and high-frequency cut-off characteristics of the layered and damped soil are incorporated. There is a strong causal correlation between the vehicle and the soil by the dynamic excitation forces and a weak relation between the track and the soil by the axle-sequence spectrum of the train. However, the similarity between the axle-impulse spectrum observed at the track and the spectra of the ground vibration leads to the special excitation component of “scattered axle impulses” which is predominant at the far field points of the soil.
On a Fourth-Order Boundary Value Problem at Resonance
Authors: Xu Man , Ma Ruyun
Published: June 2017

We investigate the spectrum structure of the eigenvalue problem u4x=λux,  x∈0,1;  u0=u1=u′0=u′1=0. As for the application of the spectrum structure, we show the existence of solutions of the fourth-order boundary value problem at resonance -u4x+λ1ux+gx,ux=hx,  x∈0,1;  u0=u1=u′0=u′1=0, which models a statically elastic beam with both end-points being cantilevered or fixed, where λ1 is the first eigenvalue of the corresponding eigenvalue problem and nonlinearity g may be unbounded.
The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System
Authors: Hansen Niels
Published: June 2017

The locus coeruleus is connected to the dorsal hippocampus via strong fiber projections. It becomes activated after arousal and novelty, whereupon noradrenaline is released in the hippocampus. Noradrenaline from the locus coeruleus is involved in modulating the encoding, consolidation, retrieval, and reversal of hippocampus-based memory. Memory storage can be modified by the activation of the locus coeruleus and subsequent facilitation of hippocampal long-term plasticity in the forms of long-term depression and long-term potentiation. Recent evidence indicates that noradrenaline and dopamine are coreleased in the hippocampus from locus coeruleus terminals, thus fostering neuromodulation of long-term synaptic plasticity and memory. Noradrenaline is an inductor of epigenetic modifications regulating transcriptional control of synaptic long-term plasticity to gate the endurance of memory storage. In conclusion, locus coeruleus activation primes the persistence of hippocampus-based long-term memory.
Prevalence and Clinical Spectrum of Liver Disease in Nepalese HIV-Sero-Positive Patients Undergoing Antiretroviral Therapy: A Cross-Sectional Hospital Based Study
Authors: Jha Roshan Kumar , Sah Shiv Kumar
Published: June 2017

Introduction. Liver enzyme abnormalities are common in HIV patients, and the prevalence varies across the nations. In Nepal, however, prevalence of liver enzyme disorder and the spectrum of these populations are lacking. Objective. The present study sheds light on prevalence and clinical spectrum of liver disease in Nepalese HIV-sero-positive patients. Methods. This cross-sectional study was conducted at OPD/ART, Clinic of Bir Hospital, NAMS. One hundred and forty-four HIV positive patients were enrolled consecutively and their clinical profiles of liver injury were investigated. Results. Of 144 recruited patients, liver enzyme injury was observed in 82 (56.9%). Majority 61 (42.4%) of these cases had hepatocellular type of liver injury. Opportunistic infections were reported in 18 cases, with 9 (6.2%) TB and 8 (5.6%) HCV. Test for significance of liver injury confirmed the absence of any tendency towards an association with coinfection, CD4 cells, ART regimen, and alcohol consumption (P>0.05). However, gender significantly linked with liver injury as well as the pattern of liver injury (P<0.05). Conclusion. The study revealed high rate of liver injury in a substantial proportion of HIV individuals, stressing that a regular clinic follow-up is necessary for the HIV individuals who are undergoing ART.
Vertebral Artery Thrombosis in Chronic Idiopathic Thrombocytopenic Purpura
Authors: Hindi Zakaria , Onteddu Nirmal , Ching Christopher A. , Khaled Abdallah A.
Published: June 2017

Introduction. Immune thrombocytopenic purpura (ITP) is an autoimmune hematological disorder that causes decreased production and destruction of platelets leading to thrombocytopenia. Although thrombocytopenia usually causes hemorrhagic problems, thrombotic events like strokes, although rare, can still occur. Management of thrombotic events in patients with ITP differs from that of patients with normal platelet count function and count.Case Description. A 32-year-old female with a history of ITP presented with ischemic stroke. The patient was treated in the hospital with IV immunoglobulin, discharged to a rehabilitation facility, and had complete resolution of symptoms when examined at a follow-up visit 3 months later.Conclusion. Although stroke in patients with ITP is very rare due to thrombocytopenia, it has been reported in several other published cases and is likely associated with increased platelet microparticle levels, a byproduct of platelet destruction. While usage of antiplatelet therapy in such patients is debated, immunosuppression therapy has been the mainstay treatment in all published cases.
Evaluation of Serum Posaconazole Concentrations in Patients with Hematological Malignancies Receiving Posaconazole Suspension Compared to the Delayed-Release Tablet Formulation
Authors: Belling Morgan , Kanate Abraham S. , Shillingburg Alexandra , Lu Xiaoxiao , Wen Sijin , Shah Nilay , Craig Michael , Cumpston Aaron
Published: June 2017

Posaconazole (PCZ) is frequently used for prophylaxis against invasive fungal infections (IFI) in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is commercially available as an oral suspension (PCZ-susp) and as a delayed-release tablet (PCZ-tab). Differences in absorption and bioavailability between these formulations may result in variability in serum posaconazole concentrations. The primary objective of this retrospective analysis was to compare attainment of goal serum posaconazole steady state concentrations (Css) ≥ 700 ng/ml in patients with AML/MDS undergoing induction chemotherapy receiving PCZ-susp 600–800 mg per day (N=118) versus PCZ-Tablet 300 mg twice daily for one day, followed by 300 mg daily (N=64). Sixty-two patients (97%) in the PCZ-tab group compared to 20 patients (17%) in the PCZ-susp group achieved goal Css  (P<0.0001). Median posaconazole serum Css was 1,665 ng/ml (522–3,830 mg/ml) in the PCZ-tab group versus 390 ng/ml (51–1,870 ng/ml) in the PCZ-susp group (P<0.0001). There was no difference in hepatotoxicity, QTc prolongation, or breakthrough IFI. Patients receiving PCZ-tab were significantly more likely to achieve goal Css and demonstrated higher Css versus patients receiving PCZ-susp. Prospective studies are needed to assess the potential correlation of serum concentrations with efficacy and toxicity.
Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia “Yuza 1” by High-Throughput Sequencing
Authors: Deng Minjie , Cao Yabing , Zhao Zhenli , Yang Lu , Zhang Yanfang , Dong Yanpeng , Fan Guoqiang
Published: June 2017

Understanding the role of miRNAs in regulating the molecular mechanisms responsive to drought stress was studied in Paulownia “yuza 1.” Two small RNA libraries and two degradome libraries were, respectively, constructed and sequenced in order to detect miRNAs and their target genes associated with drought stress. A total of 107 miRNAs and 42 putative target genes were identified in this study. Among them, 77 miRNAs were differentially expressed between drought-treated Paulownia “yuza 1” and the control (60 downregulated and 17 upregulated). The predicted target genes were annotated using the GO, KEGG, and Nr databases. According to the functional classification of the target genes, Paulownia “yuza 1” may respond to drought stress via plant hormone signal transduction, photosynthesis, and osmotic adjustment. Furthermore, the expression levels of seven miRNAs (ptf-miR157b, ptf-miR159b, ptf-miR398a, ptf-miR9726a, ptf-M2153, ptf-M2218, and ptf-M24a) and their corresponding target genes were validated by quantitative real-time PCR. The results provide relevant information for understanding the molecular mechanism of Paulownia resistance to drought and reference data for researching drought resistance of other trees.
Immunomodulating and Revascularizing Activity of Kalanchoe pinnata Synergize with Fungicide Activity of Biogenic Peptide Cecropin P1
Authors: Zakharchenko N. S. , Belous A. S. , Biryukova Y. K. , Medvedeva O. A. , Belyakova A. V. , Masgutova G. A. , Trubnikova E. V. , Buryanov Y. I. , Lebedeva A. A.
Published: June 2017

Previously transgenic Kalanchoe pinnata plants producing an antimicrobial peptide cecropin P1 (CecP1) have been reported. Now we report biological testing K. pinnata extracts containing CecP1 as a candidate drug for treatment of wounds infected with Candida albicans. The drug constitutes the whole juice from K. pinnata leaves (not ethanol extract) sterilized with nanofiltration. A microbicide activity of CecP1 against an animal fungal pathogen in vivo was demonstrated for the first time. However, a favorable therapeutic effect of the transgenic K. pinnata extract was attributed to a synergism between the fungicide activity of CecP1 and wound healing (antiscar), revascularizing, and immunomodulating effect of natural biologically active components of K. pinnata. A commercial fungicide preparation clotrimazole eliminated C. albicans cells within infected wounds in rats with efficiency comparable to CecP1-enriched K. pinnata extract. But in contrast to K. pinnata extract, clotrimazole did not exhibit neither wound healing activity nor remodeling of the scar matrix. Taken together, our results allow assumption that CecP1-enriched K. pinnata extracts should be considered as a candidate drug for treatment of dermatomycoses, wounds infected with fungi, and bedsores.
Sustained Remission in Patients with Primary Immune Thrombocytopenia after Romiplostim Tapering and Discontinuation: A Case Series in Real Life Management in Spain
Authors: Mingot-Castellano María-Eva , Grande-García Carlos , Valcárcel-Ferreiras David , Conill-Cortés Clara , de Olivar-Oliver Loreto
Published: June 2017

Romiplostim, a thrombopoietin-receptor agonist (TPO-ra), is a highly effective option in primary immune thrombocytopenia (ITP), with 80–90% of patients achieving platelet responses after few weeks of treatment. The evidence showing remissions, that is, sustained platelet counts after romiplostim discontinuation, in patients with ITP refractory to immunosuppressive therapy is steadily increasing. However, there is a lack of guidelines or recommendations addressing how and when to taper romiplostim in clinical practice in patients maintaining elevated and stable platelet counts. Furthermore, given the high heterogeneity of ITP patients, no associated predictive factors have been currently identified. Here, we present 4 representative clinical cases of the daily clinical practice in Spain comprising newly diagnosed, persistent, and both splenectomized and nonsplenectomized chronic ITP patients treated with romiplostim, achieving and maintaining clinical remission (platelet count ≥ 50×109/L for 24 consecutive weeks in the absence of any treatment for ITP) after treatment tapering and discontinuation, without observed safety concerns. Prospective studies identifying clinical and biological predictive factors of sustained response are warranted.
Tanshinone IIA Inhibits Glutamate‐Induced Oxidative Toxicity through Prevention of Mitochondrial Dysfunction and Suppression of MAPK Activation in SH‐SY5Y Human Neuroblastoma Cells
Authors: Li Haifeng , Han Wenjing , Wang Hongyu , Ding Fei , Xiao Lingyun , Shi Ruona , Ai Liping , Huang Zebo
Published: June 2017

Glutamate excitotoxicity is associated with many neurological diseases, including cerebral ischemia and neurodegenerative diseases. Tanshinone IIA, a diterpenoid naphthoquinone from Salvia miltiorrhiza, has been shown to suppress presynaptic glutamate release, but its protective mechanism against glutamate‐induced neurotoxicity is lacking. Using SH‐SY5Y human neuroblastoma cells, we show here that excessive glutamate exposure decreases cell viability and proliferation and increases LDH release. Pretreatment with tanshinone IIA, however, prevents the decrease in cell viability and proliferation and the increase in LDH release induced by glutamate. Tanshinone IIA also attenuates glutamate‐induced oxidative stress by reducing reactive oxygen species level and malondialdehyde and protein carbonyl contents and by enhancing activities and protein levels of superoxide dismutase and catalase. We then show that tanshinone IIA prevents glutamate‐induced mitochondrial dysfunction by increasing mitochondrial membrane potential and ATP content and by reducing mitochondrial protein carbonyl content. Moreover, tanshinone IIA can inhibit glutamate‐induced apoptosis through regulation of apoptosis‐related protein expression and MAPK activation, including elevation of Bcl‐2 protein level, decrease in Bax and cleaved caspase‐3 levels, and suppression of JNK and p38 MAPK activation. Collectively, our findings demonstrate that tanshinone IIA protects SH‐SY5Y cells against glutamate toxicity by reducing oxidative stress and regulating apoptosis and MAPK pathways.
Weak and Strong Solutions for a Strongly Damped Quasilinear Membrane Equation
Authors: Hwang Jin-soo
Published: June 2017

We consider a strongly damped quasilinear membrane equation with Dirichlet boundary condition. The goal is to prove the well-posedness of the equation in weak and strong senses. By setting suitable function spaces and making use of the properties of the quasilinear term in the equation, we have proved the fundamental results on existence, uniqueness, and continuous dependence on data including bilinear term of weak and strong solutions.
Nasolabial Cyst: A Case Report with Ultrasonography and Magnetic Resonance Imaging Findings
Authors: Ocak Ali , Duman Suayip Burak , Bayrakdar Ibrahim Sevki , Cakur Binali
Published: June 2017

Nasolabial cysts are uncommon nonodontogenic lesions that occur in the nasal alar region. These lesions usually present with asymptomatic swelling but can cause pain if infected. In this case report, we describe the inadequacy of conventional radiography in a nasolabial cyst case, as well as the magnetic resonance imaging (MRI) and ultrasonography (US) findings in a 54-year-old female patient.
Proximal Femoral Fracture in Hip Arthrodesis Treated with Double Reconstruction Plates
Authors: Asakawa Shunsuke , Mammoto Takeo , Hirano Atsushi
Published: June 2017

We present a rare clinical case of a 90-year-old female who sustained a proximal femoral neck fracture following long-standing hip arthrodesis. Since the fracture occurred relatively proximally and involved the pelvis, double-plate fixation was chosen to achieve rigid fixation. The reconstruction plate was placed at the posterior and anterior columns individually through single vertical incision. She was treated successfully, and she attained preinjury activity level. Proximal femoral fractures in arthrodesed hips need to be recognized as a fracture between the pelvis and femur. Rotational stress from the trunk and lower extremity requires rigid fixation to minimize the increase of displacement and the risk for nonunion.