bluuebunny/crossref_metadata_2025 huggingface dataset:
Xenobiotic pregnane X receptor promotes neointimal formation in balloon‐injured rat carotid arteries
Authors: Zhang Meiqian , Zhang Zihui , Xie Xinya , Yao Qinyu , Liu Jia , Lai Baochang , Xiao Lei , Wang Nanping
Published: August 2018

Pregnane X receptor (PXR) is a member of nuclear receptor superfamily and responsible for the detoxification of xenobiotics. Recent studies demonstrated that PXR was also expressed in the vasculature and protected the vessels from endogenous and exogenous insults, thus representing a novel gatekeeper in vascular defense. In this study, we examined the potential function of PXR in the neointimal formation following vascular injury. In the rat carotid artery after balloon injury, overexpression of a constitutively active PXR increased the intima‐to‐media ratio in the injured region. PXR increased cell proliferation and migration in cultured rat aortic smooth muscle cells (SMCs) by inducing the expressions of cyclins (cyclin A, D1, and E) and cyclin‐dependent kinase 2. In addition, PXR increased the phosphorylation and activation of extracellular‐signal‐regulated kinase 1/2 (ERK1/2) and p38 mitogen‐activated protein kinase (MAPK). Inactivation of ERK1/2 and p38 MAPK pathways using selective inhibitors (U0126 and SB203580) abrogated PXR‐induced SMC proliferation and migration. Furthermore, cigarette smoke particles (CSP) activated PXR in SMCs. Knockdown of PXR by small interfering RNA suppressed the cell proliferation, migration, and activation of the MAPK pathways by CSP. These findings suggested a novel role for PXR in promoting SMC proliferation and migration, and neointimal hyperplasia. Therefore, PXR may be a potential therapeutic target for vascular disease related to xenobiotics such as cigarette smoking and other environmental pollutants.
Insight into the large‐scale upstream fermentation environment using scaled‐down models
Authors: Olughu Williams , Deepika Gurjot , Hewitt Chris , Rielly Chris
Published: August 2018

Scaled‐down models are small‐scale bioreactors, used to mimic the chemical (pH, nutrient and dissolved oxygen) and physical (pressure, viscosity and temperature) gradients known to occur in the large‐scale fermenter. Conventionally, before scaling up any bioprocess, small‐scale bioreactors are used for strain selection, characterisation and optimisation. The typical small‐scale environment is homogenous, hence all the cells held within the small‐scale bioreactor can be assumed to experience the same condition at any point in time. However, for the large‐scale bioreactor, this is not the case, due to its inhomogeneous environment. Three different scaled‐down models are reviewed here, and the results suggest that a bacterium responds to changes in its environment rapidly and the magnitude of response to environmental oscillations is organism‐specific. The reaction and adaption of a bacterium to an inhomogeneous environment in most cases result in productivity and quality losses. This review concludes that consideration of fermentation gradients should be paramount when researchers screen for high yielding mutants in bioprocess development and doing this would help mitigate performance loss on scale‐up. © 2018 Society of Chemical Industry
A suspensory way of life: Integrating locomotion, postures, limb movements, and forces in two‐toed sloths Choloepus didactylus (Megalonychidae, Folivora, Pilosa)
Authors: Granatosky Michael C. , Karantanis Nikolaos E. , Rychlik Leszek , Youlatos Dionisios
Published: August 2018

Over the last decade, we have learned much about the anatomy, evolutionary history, and biomechanics of the extant sloths. However, most of this study has involved studying sloths in controlled conditions, and few studies have explored how these animals are behaving in a naturalistic setting. In this study, we integrate positional activities in naturalistic conditions with kinematic and kinetic observations collected on a simulated runway to best capture the biomechanical behavior of Linnaeus’s two‐toed sloths. We confirm that the dominant positional behaviors consist of hanging below the support using a combination of forelimbs and hindlimbs, and walking quadrupedally below the branches. The majority of these behaviors occur on horizontal substrates that are approximately 5–10 cm in diameter. The kinematics of suspensory walking observed both in the naturalistic settings and on simulated arboreal runways are dominated by movement of the proximal limb elements, while distal limb elements tend to show little excursion. Joint kinematics are similar between the naturalistic setting and the simulated runway, but movements of the shoulder and hip tend to be exaggerated while moving in simulated conditions. Kinetic patterns of the two‐toed sloth can be explained almost entirely by considering them as an inverted linked strut. However, medially directed forces toward the substrate were more frequent than expected in the forelimb, which may help sloths maintain a better “grip” on the substrate. This study serves as a model of how to gain a comprehensive understanding of the functional‐adaptive profile of a particular species.
The association between polymorphism of theBDNFgene and cigarette smoking in the Iranian population
Authors: Rajabi Abdolhalim , Khosravi Pedram , Motevalian Seyed Abbas , Farjam Mojtaba , Shojaei Azadeh
Published: August 2018

Background

Cigarette smoking remains a serious public health problem. Environmental and genetic factors both play critical roles in the process of cigarette smoking. We aimed to investigate the associations between single nucleotide polymorphisms (SNP) in theBDNFgene and cigarette smoking in the Iranian population.

Methods

We conducted a case–control study. In total, 932 case and control subjects aged > 15 years were recruited in the present study in a simple random manner, including 523 lifetime cigarette smokers, 466 cigarette smokers within a 12‐month period, 409 never cigarette smokers in their lifetime and 466 never cigarette smokers within a 12‐month period. The rs6265 SNP genotypes were determined by a polymerase chain reaction followed by restriction fragment length polymorphism. To examine the association of smoking with theBDNFgene polymorphism, odds ratios (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and sex.

Results

In total, 932 participants (758 males and 174 females) were selected. Using a chi‐squared test, we found that rs6265 with OR = 1.41 and 95% CI = 1.07–1.87 (p = 0.009) and OR = 1.41 and 95% CI = 1.08–1.85 (p = 0.008) in theBNDFwas associated with an increased odds of lifetime cigarette smoking and cigarette smoking within a 12‐month period, respectively. Also, the allele “A” of rs6265 inBDNFhad a significant elevating effect for cigarette smoking in a recessive model (p < 0.05).

Conclusions

These results suggest that polymorphisms ofBDNFplay an important role in lifetime cigarette smoking and cigarette smoking within a 12‐month period of susceptibility in the Iranian population.
Progressive mechanical confinement of chemotactic neutrophils induces arrest, oscillations, and retrotaxis
Authors: Wang Xiao , Jodoin Emily , Jorgensen Julianne , Lee Jarone , Markmann James J , Cataltepe Sule , Irimia Daniel
Published: August 2018

Neutrophils reach the sites of inflammation and infection in a timely manner by navigating efficiently through mechanically complex interstitial spaces, following the guidance of chemical gradients. However, our understanding of how neutrophils that follow chemical cues overcome mechanical obstacles in their path is restricted by the limitations of current experimental systems. Observations in vivo provide limited insights due to the complexity of the tissue environment. Here, we developed microfluidic devices to study the effect of progressive mechanical confinement on the migration patterns of human neutrophils toward chemical attractants. Using these devices, we identified four migration patterns: arrest, oscillation, retrotaxis, and persistent migration. The proportion of these migration patterns is different in patients receiving immunosuppressant treatments after kidney transplant, patients in critical care, and neonatal patients with infections and is distinct from that in healthy donors. The occurrence of these migration patterns is independent of the nuclear lobe number of the neutrophils and depends on the integrity of their cytoskeletal components. Our study highlights the important role of mechanical cues in moving neutrophils and suggests the mechanical constriction-induced migration patterns as potential markers for infection and inflammation.

Confined mechanical environment rivals chemical cues and alters the migratory behavior of neutrophils during chemotaxis.
Convolutional Neural Network Using a Breast MRI Tumor Dataset Can Predict Oncotype Dx Recurrence Score
Authors: Ha Richard , Chang Peter , Mutasa Simukayi , Karcich Jenika , Goodman Sarah , Blum Elyse , Kalinsky Kevin , Liu Michael Z. , Jambawalikar Sachin
Published: August 2018

Background

Oncotype Dx is a validated genetic analysis that provides a recurrence score (RS) to quantitatively predict outcomes in patients who meet the criteria of estrogen receptor positive / human epidermal growth factor receptor‐2 negative (ER+/HER2–)/node negative invasive breast carcinoma. Although effective, the test is invasive and expensive, which has motivated this investigation to determine the potential role of radiomics.

Hypothesis

We hypothesized that convolutional neural network (CNN) can be used to predict Oncotype Dx RS using an MRI dataset.

Study Type

Institutional Review Board (IRB)‐approved retrospective study from January 2010 to June 2016.

Population

In all, 134 patients with ER+/HER2– invasive ductal carcinoma who underwent both breast MRI and Oncotype Dx RS evaluation. Patients were classified into three groups: low risk (group 1, RS <18), intermediate risk (group 2, RS 18–30), and high risk (group 3, RS >30).

Field Strength/Sequence

1.5T and 3.0T. Breast MRI, T1 postcontrast.

Assessment

Each breast tumor underwent 3D segmentation. In all, 1649 volumetric slices in 134 tumors (mean 12.3 slices/tumor) were evaluated. A CNN consisted of four convolutional layers and max‐pooling layers. Dropout at 50% was applied to the second to last fully connected layer to prevent overfitting. Three‐class prediction (group 1 vs. group 2 vs. group 3) and two‐class prediction (group 1 vs. group 2/3) models were performed.

Statistical Tests

A 5‐fold crossvalidation test was performed using 80% training and 20% testing. Diagnostic accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) area under the curve (AUC) were evaluated.

Results

The CNN achieved an overall accuracy of 81% (95% confidence interval [CI] ± 4%) in three‐class prediction with specificity 90% (95% CI ± 5%), sensitivity 60% (95% CI ± 6%), and the area under the ROC curve was 0.92 (SD, 0.01). The CNN achieved an overall accuracy of 84% (95% CI ± 5%) in two‐class prediction with specificity 81% (95% CI ± 4%), sensitivity 87% (95% CI ± 5%), and the area under the ROC curve was 0.92 (SD, 0.01).

Data Conclusion

It is feasible for current deep CNN architecture to be trained to predict Oncotype DX RS.

Level of Evidence: 4

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:518–524.
Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France
Authors: Jordier François , Deligny Marie‐Laurence , Barré Romain , Robert Catherine , Galicher Vital , Uch Rathviro , Fournier Pierre‐Edouard , Raoult Didier , Biagini Philippe
Published: August 2018

Human pegivirus (HPgV, formerly GBV‐C) is a member of the genus Pegivirus, family Flaviviridae. Despite its identification more than 20 years ago, both natural history and distribution of this viral group in human hosts remain under exploration. Analysis of HPgV genomes characterized up to now points out the scarcity of French pegivirus sequences in databases. To bring new data regarding HPgV genomic diversity, we investigated 16 French isolates obtained from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations following deep sequencing and coupled molecular protocols. Initial phylogenetic analysis of 5′‐untranslated region (5′‐UTR)/E2 partial sequences permitted to assign HPgV isolates to genotypes 2 (n = 15) and 1 (n = 1), with up to 16% genetic diversity observed for both regions considered. Seven nearly full‐length representative genomes were characterized subsequently, with complete polyprotein coding sequences exhibiting up to 13% genetic diversity; closest nucleotide (nt) divergence with available HPgV sequences was in the range 7% to 11%. A 36 nts deletion located on the NS4B coding region (N‐terminal part, 12 amino acids) of the genotype 1 HPgV genome characterized was identified, along with single nucleotide deletions in two genotype 2, 5′‐UTR sequences.
Influence of spatial information resolution on the relation between elevation and temperature
Authors: Joly Daniel , Castel Thierry , Pohl Benjamin , Richard Yves
Published: August 2018

The association between elevation and temperature is analysed by simple linear correlations across several spatial scales. The minimum (tn) and maximum (tx) temperatures (response variables), expressed at two time scales (monthly and daily), are observed for 102 weather stations in east central France from 1980 to 2014 (12,784 days). Elevation (explanatory variable) is provided at 10 resolutions: 50, 100, 200, 500 m, 1, 2, 4, 8, 12, and 16 km. The coefficient of determination, R2, is used to determine which resolution gives the best results. The slope given by the regression is used to assess the drop in temperature per unit of elevation (temperature lapse rate [TLR]). In most situations, monthly and daily temperatures are optimally explained by the finest (50 m) resolution: the R2 is, respectively, 0.53 and 0.24 for tn and 0.78 and 0.39 for tx. The coarser resolutions produce results of much lower quality. However, in one circumstance (monthly mean of tn), the highest R2 value is obtained for the 4‐km resolution, which is a meaningful result as current regional climate models now achieve similar resolutions. Both monthly and daily TLRs of tn and tx are, on average, slightly lower than −0.5 °C/100 m at 50‐m resolution. The TLR decreases with resolution: it is only −0.23 °C/100 m for tn and −0.13 °C/100 m for tx at 16‐km resolution. Other insightful results involve the influence of the topographical context, which shows some additional effect with that of elevation and which was quantified through partial correlations.
Effect of different CT scanners and settings on femoral failure loads calculated by finite element models
Authors: Eggermont Florieke , Derikx Loes C. , Free Jeffrey , van Leeuwen Ruud , van der Linden Yvette M. , Verdonschot Nico , Tanck Esther
Published: August 2018

In a multi‐center patient study, using different CT scanners, CT‐based finite element (FE) models are utilized to calculate failure loads of femora with metastases. Previous studies showed that using different CT scanners can result in different outcomes. This study aims to quantify the effects of (i) different CT scanners; (ii) different CT protocols with variations in slice thickness, field of view (FOV), and reconstruction kernel; and (iii) air between calibration phantom and patient, on Hounsfield Units (HU), bone mineral density (BMD), and FE failure load. Six cadaveric femora were scanned on four CT scanners. Scans were made with multiple CT protocols and with or without an air gap between the body model and calibration phantom. HU and calibrated BMD were determined in cortical and trabecular regions of interest. Non‐linear isotropic FE models were constructed to calculate failure load. Mean differences between CT scanners varied up to 7% in cortical HU, 6% in trabecular HU, 6% in cortical BMD, 12% in trabecular BMD, and 17% in failure load. Changes in slice thickness and FOV had little effect (≤4%), while reconstruction kernels had a larger effect on HU (16%), BMD (17%), and failure load (9%). Air between the body model and calibration phantom slightly decreased the HU, BMD, and failure loads (≤8%). In conclusion, this study showed that quantitative analysis of CT images acquired with different CT scanners, and particularly reconstruction kernels, can induce relatively large differences in HU, BMD, and failure loads. Additionally, if possible, air artifacts should be avoided. © 2018 Orthopaedic Research Society. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2288–2295, 2018.
Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review
Authors: Nickien Mieke , Heuijerjans Ashley , Ito Keita , van Donkelaar Corrinus C.
Published: August 2018

Methodological differences between in vitro and in vivo studies on cartilage overloading complicate the comparison of outcomes. The rationale of the current review was to (i) identify consistencies and inconsistencies between in vitro and in vivo studies on mechanically‐induced structural damage in articular cartilage, such that variables worth interesting to further explore using either one of these approaches can be identified; and (ii) suggest how the methodologies of both approaches may be adjusted to facilitate easier comparison and therewith stimulate translation of results between in vivo and in vitro studies. This study is anticipated to enhance our understanding of the development of osteoarthritis, and to reduce the number of in vivo studies. Generally, results of in vitro and in vivo studies are not contradicting. Both show subchondral bone damage and intact cartilage above a threshold value of impact energy. At lower loading rates, excessive loads may cause cartilage fissuring, decreased cell viability, collagen network de‐structuring, decreased GAG content, an overall damage increase over time, and low ability to recover. This encourages further improvement of in vitro systems, to replace, reduce, and/or refine in vivo studies. However, differences in experimental set up and analyses complicate comparison of results. Ways to bridge the gap include (i) bringing in vitro set‐ups closer to in vivo, for example, by aligning loading protocols and overlapping experimental timeframes; (ii) synchronizing analytical methods; and (iii) using computational models to translate conclusions from in vitro results to the in vivo environment and vice versa. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2076–2086, 2018.
Lower risk of fractures under methylphenidate treatment for ADHD: A dose–response effect
Authors: Schermann Haggai , Gurel Ron , Ankory Ran , Kadar Assaf , Yoffe Victoria , Snir Nimrod , Sternheim Amir , Karakis Isabella
Published: August 2018

Methylphenidate (MP), a widely used and abused stimulant medication for ADHD, negatively affects bone mass. However, previous epidemiological studies demonstrated that MP is not associated with increased incidence of fractures in children, and may even have a protective effect due to behavior modification. This study aimed to investigate the association between MP and fracture risk in a retrospective cohort of healthy military recruits, aged 18–25, with at least 1 year of service between 2008 and 2017. Subjects were divided into five groups: subjects without ADHD; untreated subjects with ADHD; and subjects with ADHD and prescriptions of 1–90, 91–180, or 181+ tablets during the study period. The primary outcome was at least one fracture diagnosis during the study. Among 682,110 subjects (409,175 men [60%]), 50,999 (7.5%) had fractures. MP was used by 1,681 (0.4%) men and 2.828 (1%) women. The fracture rates in the no ADHD, untreated ADHD, ADHD 0–90, ADHD 91–180, and ADHD 181+ groups were 10.4%, 16.4%, 8.7%, 4.8% and 5.8% in men, and 3.6%, 7.1%, 4.6%, 4.4% and 3% in women, respectively. Multivariate regression analysis confirmed an inverse dose–response association between MP and fractures in men (p < 0.001). In women, untreated ADHD was associated with a significantly higher fracture risk, compared to healthy controls (OR = 1.82, p < 0.001). The study confirms previous literature and demonstrates an inverse dose–response association between MP and fracture risk in men. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3328–3333, 2018.
Effects of high‐molecular‐weight glutenin subunit combination in common wheat on the quality of crumb structure
Authors: Jiang Peihong , Xue Jiesheng , Duan Luning , Gu Yunsong , Mu Junyi , Han Shichen , Chen Lin , Li Yaxuan , Ma Wujun , Yan Yueming , Li Xiaohui
Published: August 2018

BACKGROUND

High‐molecular‐weight glutenin subunits (HMW‐GSs) have important effects on bread‐making quality. Allelic variations of HMW‐GS in bread wheat varieties contribute in different ways to dough properties and bread volume. However, no systematic analysis has been done on the effects of allelic variation on bread‐crumb structure, an important parameter when evaluating bread‐making quality. In this study, seven Glu‐1 deletion lines and one intact line harboring different encoding loci and derived from a cross between two spring wheat cultivars were used to investigate the contribution of a single Glu‐1 locus, or combination of Glu‐1 loci, to the crumb structure.

RESULTS

Deletion of HMW‐GS locus combinations resulted in a decline in slice size, brightness, and fineness of the bread crumb. A desirable crumb structure correlated well with preferred subunit combinations: high levels of GMPs, superior dough properties, and loaf volume. The effects of the HMW‐GS combinations were ranked as Dx5 + Dy10 > Bx17 + By18 > Ax1 + Null. The Ax1 + Null allele affected the crumb structure by interacting with the Bx17 + By18 or Dx5 + Dy10.

CONCLUSION

High‐molecular‐weight glutenin subunits had significant effects on the loaf volume and crumb structure; varying effects from different subunit combinations were observed. © 2018 Society of Chemical Industry
Effect of preharvest fruit bagging on fruit quality characteristics and incidence of fruit physiopathies in fully irrigated and water stressed pomegranate trees
Authors: Griñán Isabel , Morales Donaldo , Galindo Alejandro , Torrecillas Arturo , Pérez‐López David , Moriana Alfonso , Collado‐González Jacinta , Carbonell‐Barrachina Ángel A , Hernández Francisca
Published: August 2018

Background

This report studied the response of pomegranate fruit under full irrigation (FI) and water stress conditions to bagging with externally glossy, single‐layer, cellulosic paper bags, open at the bottom, from the end of fruit thinning to harvest time.

Results

Bagging decreased fruit size and the maturity index, and increased antioxidant activity in FI conditions. Moreover, fruit bagging substantially reduced the incidence of peel sunburn in both irrigation conditions.

Conclusion

The delay in fruit growth and ripening as a result of pomegranate fruit bagging is outweighed by the very important commercial benefit in terms of the reduced incidence of peel sunburn and the increase in fruit antioxidant activity. © 2018 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Authorship order
Authors: Helgesson Gert , Eriksson Stefan
Published: August 2018

Considering the fact that authorship order plays such a significant role as a basis for scientific merit, this paper looks into the practices of authorship order from a research ethical perspective. We conclude that there is a wide variety of practices and no common understanding of what the different authorship positions signify. Authorship guidelines do not provide much help. We recognize that, regardless of what system for valuing authorship positions is used, it will be misleading and unfair in most applications because relative contributions vary in ways that are not captured by fixed value assignments to authorship positions. In theory, assigning percentage figures reflecting the relative contributions of the authors would solve that problem, but we argue that such a scheme is not likely to work in practice. It can also be questioned whether relative, rather than absolute, contributions should be the basis for scientific merit. Contributorship is discussed as an alternative, but is recognized to be insufficient both in communicating absolute and relative contributions, as standardly used. However, there may be a way forward with contributorship, but then, the level of detail needs to increase considerably and its application be standardized.
Fewer blue lakes and more murky lakes across the continental U.S.: Implications for planktonic food webs
Authors: Leech Dina M. , Pollard Amina I. , Labou Stephanie G. , Hampton Stephanie E.
Published: August 2018

Elevated allochthonous inputs of organic matter are increasingly recognized as a driver of ecosystem change in lakes, particularly when concurrent with eutrophication. Evaluation of lakes in a nutrient‐color paradigm (i.e., based on total phosphorus and true color) enables a more robust approach to research and management. To assess temporal and spatial patterns in nutrient‐color status for U.S. lakes and associated food web attributes, we analyzed the U.S. Environmental Protection Agency's National Lakes Assessment (NLA) data. With 1000+ lakes sampled in 2007 and 2012 in a stratified random sampling design, the NLA enables rigorous assessment of lake condition across the continental U.S. We demonstrate that many U.S. lakes are simultaneously experiencing eutrophication and brownification to produce an abundance of “murky” lakes. Overall, “blue” lakes decreased by ~ 18% (46% of lakes in 2007 to 28% in 2012) while “murky” lakes increased by almost 12% (24% of lakes in 2007 to 35.4% in 2012). No statistical differences were observed in the proportions of “green” or “brown” lakes. Regionally, murky lakes significantly increased in the Northern Appalachian, Southern Plains, and Xeric ecoregions. Murky lakes exhibited the highest epilimnetic chlorophyll a concentrations, cyanobacterial densities, and microcystin concentrations. Total zooplankton biomass was also highest in murky lakes, primarily due to increased rotifer and copepod biomass. However, zooplankton : phytoplankton biomass ratios were low, suggesting reduced energy transfer to higher trophic levels. These results emphasize that many lakes in the U.S. are simultaneously “greening” and “browning”, with potentially negative consequences for water quality and food web structure.
Longterm Survival and Cost‐Effectiveness of Immunosuppression Withdrawal After Liver Transplantation
Authors: Manzia Tommaso Maria , Angelico Roberta , Toti Luca , Angelico Cristina , Quaranta Claudia , Parente Alessandro , Blasi Francesca , Iesari Samuele , Sforza Daniele , Baiocchi Leonardo , Lerut Jan , Tisone Giuseppe
Published: August 2018

Lifelong immunosuppression (IS) after liver transplantation is associated with severe adverse effects and increased recipients’ morbidity and mortality. Clinical operational tolerance has been reported in up to 40% in very well‐selected recipients. Longterm survival and cost savings within the Italian national health system in operational tolerant recipients is reported. Seventy‐five liver recipients were enrolled for IS withdrawal at our institution during the period from April 1998 to December 2015. The study population comprised 32 (42.7%) tolerant patients; 41 (54.7%) nontolerant patients needing uptake of IS after clinical or biopsy‐proven rejection; and 2 (2.7%) immediate nontolerant patients who developed early rejection after the first drug reduction. The primary endpoint of the study was to assess the longterm patients and graft outcome; the secondary endpoint was the assessment of cost savings in the context of IS withdrawal. The follow‐up was 95.0 months (interquartile range, 22.5‐108.5 months). IS withdrawal did not result in patient nor graft loss and resulted in a major cost savings reaching about €630,000. In conclusion, longterm IS withdrawal represents a remarkable cost savings in the health care of liver recipients without exposing them to graft loss.
Hyponatremia in Cirrhosis: Implications for Liver Transplantation
Authors: Leise Michael , Cárdenas Andrés
Published: August 2018

Hyponatremia in cirrhosis is defined as a serum sodium level ≤130 mEq/L and occurs in approximately 22% of patients with cirrhosis. The appearance of hyponatremia in patients with cirrhosis portends a poor prognosis before liver transplantation (LT), independent of the Model for End‐Stage Liver Disease (MELD) score. With the development of the MELD‐sodium score, the management of hyponatremia has become more relevant than ever before. Overcorrection of hyponatremia before LT or perioperatively can lead to the devastating neurologic condition known as osmotic demyelination syndrome, which is often irreversible and fatal. Therefore, the most important tenet of hyponatremia is to avoid correcting the serum sodium by ≥8 mEq/L in a 24‐hour period. Treatment of hyponatremia is highly challenging. The vast majority of patients with cirrhosis have chronic hypervolemic hyponatremia. Fluid restriction increases serum sodium levels, but tolerance and compliance are significant barriers. Diuretic withdrawal is helpful but contributes to worsening fluid overload. There are limited data to support use of intravenous concentrated albumin solutions. The use of the arginine vasopressin antagonists (“vaptans”) is contentious; however, they may have a limited role. Risk factors for intraoperative overcorrection of serum sodium include increased utilization of packed red blood cell and fresh frozen plasma transfusions, which are often unavoidable. Intraoperative management is evolving, and more data are needed in regard to the use of sodium‐reduced continuous venovenous hemofiltration and the use of trishydroxymethylaminomethane (Tris) to avoid excess sodium rebound. A thorough discussion of the current treatment options before and during LT is given in this review.
Singular Hamiltonian elliptic systems with critical exponential growth in dimension two
Authors: Monari Soares Sergio H. , Santaria Leuyacc Yony R.
Published: August 2018

We will focus on the existence of nontrivial solutions to the following Hamiltonian elliptic system
urn:x-wiley:0025584X:media:mana201700215:mana201700215-math-0001where are numbers belonging to the interval [0, 2), V is a continuous potential bounded below on by a positive constant and the functions f and g possess exponential growth range established by Trudinger–Moser inequalities in Lorentz–Sobolev spaces. The proof involves linking theorem and a finite‐dimensional approximation.
Explicit uniform bounds on integrals of Bessel functions and trace theorems for Fourier transforms
Authors: Kalf Hubert , Okaji Takashi , Yamada Osanobu
Published: August 2018

Explicit and partly sharp estimates are given of integrals over the square of Bessel functions with an integrable weight which can be singular at the origin. They are uniform with respect to the order of the Bessel functions and provide explicit bounds for some smoothing estimates as well as for the L2 restrictions of Fourier transforms onto spheres in which are independent of the radius of the sphere. For more special weights these restrictions are shown to be Hölder continuous with a Hölder constant having this independence as well. To illustrate the use of these results a uniform resolvent estimate of the free Dirac operator with mass in dimensions is derived.
FBLIM1 enhances oral cancer malignancy via modulation of the epidermal growth factor receptor pathway
Authors: Toeda Yuriko , Kasamatsu Atsushi , Koike Kazuyuki , Endo‐Sakamoto Yosuke , Fushimi Kazuaki , Kasama Hiroki , Yamano Yukio , Shiiba Masashi , Tanzawa Hideki , Uzawa Katsuhiro
Published: August 2018

Filamin‐binding LIM protein 1 (FBLIM1) is related to regulation of inflammatory responses, such as chronic recurrent multifocal osteomyelitis; however, the relevance of FBLIM1 in oral squamous cell carcinoma (OSCC) is unknown. The aim of the current study was to elucidate the possible role of FBLIM1 in the carcinogenesis of OSCC. We analyzed FBLIM1 expression using quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR), immunoblot analysis, and immunohistochemistry. The expression levels of FBLIM1 were up‐regulated significantly (P < 0.05) in OSCC‐derived cell lines and primary OSCCs specimens compared with normal counterparts. FBLIM1 expression also was correlated with the primary tumoral size (P < 0.05) and vascular invasion (P < 0.05). We then assessed tumoral progression after treatment with FBLIM1 siRNA and clopidogrel, an antiplatelet agent. Similar to the FBLIM1 knockdown effect, clopidogrel‐treated cells had attenuated functions of proliferation, migration, and invasiveness. Interestingly, clopidogrel treatment led to down‐regulation of epidermal growth factor receptor (EGFR) and FBLIM1. These findings identify FBLIM1 as a putative therapeutic target by using clopidogrel for inhibiting over activation of EGFR signaling to prevent OSCC malignancy.
Cinnamyl Isobutyrate Decreases Plasma Glucose Levels and Total Energy Intake from a Standardized Breakfast: A Randomized, Crossover Intervention
Authors: Hochkogler Christina M. , Hoi Julia K. , Lieder Barbara , Müller Nicole , Hans Joachim , Widder Sabine , Ley Jakob P. , Somoza Veronika
Published: August 2018

Scope

Cinnamon is associated with anti‐obesity effects, regulating food intake, improving plasma glucose levels and lipid profiles in vivo. In the present study, the impact of cinnamyl isobutyrate (CIB), one constituent of cinnamon, on ad libitum food intake from a standardized breakfast and outcome measures of hormonal regulation of appetite were investigated.

Methods and results

In this randomized, short‐term crossover intervention study, a 75 g per 300 mL glucose solution solely (control) or supplemented with 0.45 mg CIB was administered to 26 healthy volunteers. Prior to and 2 h after receiving control or CIB treatment, subjective hunger perceptions were rated using a visual analog scale. Food intake from a standardized breakfast was assessed 2 h after treatments. Plasma peptide YY3–36, glucagon‐like‐peptide1, ghrelin, and serotonin as well as plasma glucose and insulin were measured in blood samples drawn at fasting and 15, 30, 60, 90, and 120 min after treatment. CIB administration decreased total energy intake and delta area under curve plasma glucose by 4.64 ± 3.51% and 49.3 ± 18.5% compared to control treatment, respectively.

Conclusions

CIB, administered at a 0.45 mg bolus in 75 g glucose–water solution, decreased ad libitum energy intake from a standardized breakfast and postprandial plasma glucose levels.
Monte Carlo dosimetry modeling of focused kV x‐ray radiotherapy of eye diseases with potential nanoparticle dose enhancement
Authors: Yan Huagang , Ma Xiangyu , Sun Weiyuan , Mendez Stacy , Stryker Stefan , Starr‐Baier Sean , Delliturri Gianpiero , Zhu Dengsong , Nath Ravinder , Chen Zhe , Roberts Kenneth , MacDonald Carolyn A. , Liu Wu
Published: August 2018

Purpose

Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel‐focused kV x‐ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling.

Methods

A polycapillary x‐ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x‐ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype‐focused x‐ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x‐ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor.

Results

The MC‐simulated full width at half maximum (FWHM) and central‐axis depth dose of the focused kV x‐ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x‐ray beams can concentrate the high‐dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x‐ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I‐125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively.

Conclusion

Compared to eye plaque brachytherapy, the proposed focused kV x‐ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.
Toward a novel dosimetry system using acrylic disk radiation sensor for proton pencil beam scanning
Authors: Cho Shinhaeng , Lee Nuri , Song Sanghyeon , Son Jaeman , Kim Haksoo , Jeong Jong Hwi , Lee Se Byeong , Lim Youngkyung , Moon Sunyoung , Yoon Myonggeun , Shin Dongho
Published: August 2018

Purpose

Fabricate an acrylic disk radiation sensor (ADRS) and characterize the photoluminescence signal generated from the optical device as basis for the development and evaluation of a new dosimetry system for pencil beam proton therapy.

Methods

Based on the characteristics of the proposed optical dosimetry sensor, we established the relation between the photoluminescence output and the applied dose using an ionization chamber. Then, we obtained the relative integral depth dose profiles using the photoluminescence signal generated by pencil beam irradiation at energies of 99.9 and 162.1 MeV, and compared the results with the curve measured using a Bragg peak ionization chamber.

Results

The relation between the photoluminescence output and applied dose was linear. In addition, the ADRS was dose independent for beam currents up to 6 Gy/min, and the calibration factor for energy was close to 1. Hence, the energy dependence on the optical device can be disregarded. The integral depth dose profiles obtained for the ADRS suitable agreed with the curve measured in the Bragg peak ionization chamber without requiring correction.

Conclusions

These results suggest that the ADRS is suitable for dosimetry measurements in pencil beam scanning, and it will be employed as a low‐cost and versatile dosimetry sensor in upcoming developments.
Discourse analysis of health providers' experiences using service design
Authors: Eines Trude Fløystad , Angelo Elin , Vatne Solfrid
Published: August 2018

Background

Municipal healthcare organizations are facing increasing challenges to developing more cost‐effective organizations and services, particularly in nursing homes. The background for this article is an attempt in this concern; implementing service design in a nursing home.

Aim

The aim of the study is to explore nurses and nurse assistants' experiences using service design in a nursing home.

Design

A qualitative design was applied.

Method

Data were collected through focus group interviews with 17 nurses and nurse assistants in 2015. Thematic discourse analysis was conducted to analyse their discussed experiences.

Results

The employees had positive attitudes towards incorporating a service design approach that focused on the patients' needs, which thus encouraged creative solutions and promoted employee involvement. The study shows that involving service designers and employees in the entire process, from planning to implementation of new and innovative solutions, requires closer collaboration between the service designers, managers, and employees to achieve the final goal. We consider that the results of this study will be of relevance to the future development of health care and nursing in nursing homes.
Finite‐volume scheme for a degenerate cross‐diffusion model motivated from ion transport
Authors: Cancès Clément , Chainais‐Hillairet Claire , Gerstenmayer Anita , Jüngel Ansgar
Published: August 2018

An implicit Euler finite‐volume scheme for a degenerate cross‐diffusion system describing the ion transport through biological membranes is proposed. The strongly coupled equations for the ion concentrations include drift terms involving the electric potential, which is coupled to the concentrations through the Poisson equation. The cross‐diffusion system possesses a formal gradient‐flow structure revealing nonstandard degeneracies, which lead to considerable mathematical difficulties. The finite‐volume scheme is based on two‐point flux approximations with “double” upwind mobilities. The existence of solutions to the fully discrete scheme is proved. When the particles are not distinguishable and the dynamics is driven by cross diffusion only, it is shown that the scheme preserves the structure of the equations like nonnegativity, upper bounds, and entropy dissipation. The degeneracy is overcome by proving a new discrete Aubin–Lions lemma of “degenerate” type. Numerical simulations of a calcium‐selective ion channel in two space dimensions show that the scheme is efficient even in the general case of ion transport.
SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents
Authors: Beus Maja , Rajić Zrinka , Maysinger Dusica , Mlinarić Zvonimir , Antunović Maja , Marijanović Inga , Fontinha Diana , Prudêncio Miguel , Held Jana , Olgen Sureyya , Zorc Branka
Published: August 2018

We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding. It includes the following steps: coupling reaction between primaquine and a dicarboxylic acid monoester, hydrolysis, a new coupling reaction with O‐protected hydroxylamine, and deprotection. SAHAquines 5 a–d showed significant reduction in cell viability. Among the three human cancer cell lines (U2OS, HepG2, and MCF‐7), the most responsive were the MCF‐7 cells. The antibodies against acetylated histone H3K9/H3K14 in MCF‐7 cells revealed a significant enhancement following treatment with N‐hydroxy‐N′‐{4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}pentanediamide (5 b). Ethyl (2E)‐3‐({4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}carbamoyl)prop‐2‐enoate (2 b) and SAHAquines were the most active compounds against both the hepatic and erythrocytic stages of Plasmodium parasites, some of them at sub‐micromolar concentrations. The results of our research suggest that SAHAquines are promising leads for new anticancer and antimalarial agents.
Mechanisms and treatment of heart failure in diabetes
Authors: Timmons Joseph , Fisher Miles
Published: August 2018

Heart failure is an increasingly common cause of cardiovascular morbidity and mortality in people with diabetes. The pathophysiology of heart failure in diabetes includes factors related to coronary heart disease, with myocardial ischaemia and myocardial scarring following myocardial infarction. Non‐ischaemic mechanisms are also important, including structural, metabolic, and biochemical abnormalities. Treatment of heart failure in people with diabetes is in essence the same as for other patients, along with optimised diabetic control. ACE inhibitors and beta blockers should be commenced in all patients with a diagnosis of heart failure with reduced ejection fraction regardless of NYHA class. Aldosterone antagonists, cardiac resynchronisation therapy and heart transplantation all have a role in management of patients of NYHA class III and IV. In patients with heart failure with preserved ejection fraction, which is more common in people with diabetes, there is unfortunately no evidence of benefit for these therapies and a diuretic‐based regimen is used to alleviate symptoms. Copyright © 2018 John Wiley & Sons.
QEEG phenotypes, depression and TMS
Authors: Hackett Natalia
Published: August 2018

In 2017, depression became recognised as the leading cause of ill health and disability worldwide.1 In England, 1 in 6 people experience mental health problems every week,2 75%3 of whom may not be able to access the treatment they need. There is a growing interest in electroencephalogram (EEG) analysis to identify anomalous patterns of electrical activity in the brains of depressed patients. These patterns are known as EEG phenotypes.
17th Latest Advances in Psychiatry Symposium 2018
Authors: David Felix
Published: August 2018

The 2018 Latest Advances in Psychiatry Symposium was held in March at the Royal College of Physicians, London, with the theme ‘causes, correlates and consequences of mental ill health’. Here, Felix David covers highlights on perinatal guidelines, inflammation and depression, and the association between proteostasis and schizophrenia.
Robust Synthesis of High‐Performance N‐Graphite Hollow Nanocatalysts Based on the Ostwald Ripening Mechanism for Oxygen Reduction Reaction Electrocatalysis
Authors: Ai Kelong , Li Zelun , Li Weiwei , Fan Jinchang , Cui Xiaoqiang , Zheng Weitao
Published: August 2018

N‐doped carbon nanomaterials have received increasing attention as one of the most attractive candidates to replace Pt/C catalysts for the oxygen reduction reaction (ORR) in energy conversion and storage devices. The graphitization degree and the surface area are widely recognized as two fundamentally crucial factors for the catalytic performance of N‐doped carbon nanomaterials. However, there are no effective strategies to produce N‐doped carbon materials with a high degree of graphitization and a large surface area, simultaneously. As a result, currently studied N‐doped carbon materials exhibit much lower activity, durability, and stability than expected. Herein, an Ostwald ripening mechanism‐driven method to produce monodisperse N‐graphite hollow nanoparticles with significantly improved graphitization and a dramatically enlarged surface area is developed. Exhaustive measurements demonstrate that the N‐graphite hollow nanoparticles exhibit higher catalytic activity, stability, and methanol tolerance in the alkaline media, as compared to the commercial Pt/C. These nanoparticles are further assembled into a cell. Impressively, the cell shows a power density of 47.2 mW cm−2, which is almost twice the value of Pt/C‐based cell, and also much higher than those of previously reported nonprecious catalyst‐based cells. The N‐graphite hollow nanoparticles are expected to be a promising candidate for the next generation of ORR catalysts.