bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long‐Term Anti–Tumor Necrosis Factor Treatment: Six‐Year Results of Continuous Treatment With Etanercept
Authors: Rios Rodriguez Valeria , Hermann Kay‐Geert , Weiß Anja , Listing Joachim , Haibel Hildrun , Althoff Christian , Proft Fabian , Behmer Olaf , Sieper Joachim , Poddubnyy Denis
Published: January 2019

Objective

To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long‐term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA).

Methods

Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0–4 per SI joint). A sacroiliitis sum score (total range 0–8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system.

Results

Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow‐up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, −0.27 ± 0.76, and −0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C‐reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score.

Conclusion

Our findings indicate that long‐term anti‐TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression.
Identification of Low‐Abundance Urinary Biomarkers in Lupus Nephritis Using Electrochemiluminescence Immunoassays
Authors: Stanley Samantha , Mok Chi Chiu , Vanarsa Kamala , Habazi Deena , Li Jennifer , Pedroza Claudia , Saxena Ramesh , Mohan Chandra
Published: January 2019

Objective

To investigate the utility of a sensitive platform using electrochemiluminescence (ECL) for the identification of low‐abundance urinary protein biomarkers in lupus nephritis (LN).

Methods

Forty‐eight urine samples were obtained from subjects in 2 independent cohorts, each consisting of 3 groups (matched for age, sex, and race) of 8 patients with active LN (renal Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] >0), 8 patients with inactive SLE (renal SLEDAI 0), and 8 healthy controls. Samples were tested using a preexisting 40‐plex ECL panel. A custom 5‐plex ECL panel was then developed for further validation studies and used to test 140 urine samples (from 44 patients with active LN, 41 patients with inactive SLE, 28 healthy controls, and 27 patients with other kidney diseases).

Results

Levels of 17 urinary proteins were elevated (P < 0.05 by 2‐tailed Mann‐Whitney U test) in samples from patients with active LN compared to samples from patients with inactive SLE and healthy controls in cohort 1, while 9 were similarly elevated in cohort 2. Of these, interleukin‐7 (IL‐7), IL‐12p40, IL‐15, interferon‐γ–inducible protein 10 (IP‐10), and thymus and activation–regulated chemokine (TARC) were chosen for further validation. These 5 proteins were undetectable by enzyme‐linked immunosorbent assay (ELISA). Hence, a custom 5‐plex ECL panel was developed and used to validate the results from the initial 40‐plex screening panel. Urinary IL‐7, IL‐12p40, IL‐15, IP‐10, and TARC levels were again significantly elevated in patients with active LN compared to those with inactive SLE and healthy controls, and correlated well with the renal SLEDAI and physician's global assessment of disease activity (R > 0.67, P < 0.05). All 5 urinary proteins were more frequently elevated in LN compared to controls with other chronic kidney diseases, although overall group differences attained significance only for urinary IL‐7 and IL‐15.

Conclusion

Urinary levels of IL‐7, IL‐12p40, IL‐15, IP‐10, and TARC are potentially useful diagnostic tools in LN. The use of ECL assays may allow detection of urinary biomarkers that are below ELISA detection limits.
Synergy in the knowledge base of U.S. innovation systems at national, state, and regional levels: The contributions of high‐tech manufacturing and knowledge‐intensive services
Authors: Leydesdorff Loet , Wagner Caroline S. , Porto‐Gomez Igone , Comins Jordan A. , Phillips Fred
Published: January 2019

Using information theory, we measure innovation systemness as synergy among size‐classes, ZIP Codes, and technological classes (NACE‐codes) for 8.5 million American companies. The synergy at the national level is decomposed at the level of states, Core‐Based Statistical Areas (CBSA), and Combined Statistical Areas (CSA). We zoom in to the state of California and in more detail to Silicon Valley. Our results do not support the assumption of a national system of innovations in the U.S.A. Innovation systems appear to operate at the level of the states; the CBSA are too small, so that systemness spills across their borders. Decomposition of the sample in terms of high‐tech manufacturing (HTM), medium‐high‐tech manufacturing (MHTM), knowledge‐intensive services (KIS), and high‐tech services (HTKIS) does not change this pattern, but refines it. The East Coast—New Jersey, Boston, and New York—and California are the major players, with Texas a third one in the case of HTKIS. Chicago and industrial centers in the Midwest also contribute synergy. Within California, Los Angeles contributes synergy in the sectors of manufacturing, the San Francisco area in KIS. KIS in Silicon Valley and the Bay Area—a CSA composed of seven CBSA—spill over to other regions and even globally.
Variable‐Temperature Resonance Raman Studies to Probe Interchain Ordering for Semiconducting Conjugated Polymers with Different Chain Curvature
Authors: Sutton Joshua J. , Nguyen Thanh Luan , Woo Han Young , Gordon Keith C.
Published: January 2019

The morphology and crystallinity of the polymers used to fabricate bulk heterojuction (BHJ) solar cells significantly influences the efficiency of the cells. We have used variable‐temperature (VT) spectroscopy techniques, namely VT emission and VT resonance Raman spectroscopy (VT‐RRS), to examine how the backbone linearity of a conducting polymer affects its electronic response to temperature and variations in solution behavior. We have studied two types of donor–acceptor polymers used in BHJ cells with differing backbone structures; they are poly‐{5,6‐bis(tetradecyloxy)‐4‐(thiophen‐2‐yl)benzo[c]‐1,2,5‐thiadiazole} (PTBT) which has a curved backbone and poly‐{5,6‐bis(tetradecyloxy)‐4‐(thieno[3,2‐b]‐thiophen‐2‐yl)benzo[c]‐1,2,5‐thiadiazole} (PTTBT) which has a linear chain structure. Time‐dependent density functional theory (TD‐DFT) calculations and resonance Raman spectra (RRS) of PTTBT revealed the presence of three electronic transitions, with character that varies between π to π*, mixed π to π*/charge transfer and pure charge transfer in nature. Emission spectra of PTTBT showed spectral changes at 650 and 710 nm with varied temperature (−10 to 60 °C). Variable‐temperature RRS was measured in resonance with the lowest and highest energy electronic transitions. The changes were interpreted using two‐dimensional correlation spectroscopy (2DCOS) analysis. PTTBT showed gradual shifts to lower wavenumbers of modes at around 1425, 1450 and 1500 cm−1. For PTBT larger and more rapid spectral changes are observed at 1440 and 1460 cm−1 consistent with greater variation in the electronic nature upon heating. Further study into the influence of polymer linearity on crystallinity and long range order was carried out using low‐frequency Raman (LFR) to examine drop cast films under a variety of different conditions. LFR spectra showed that PTTBT has a band at 73 cm−1. This is observed under a variety of film‐forming conditions. PTBT does not show distinct low frequency modes, consistent with its low crystallinity.
Synthesis of Bioactive Side‐Chain Analogues of TAN‐2483B
Authors: Somarathne Kalpani K. , McCone Jordan A. J. , Brackovic Amira , Rivera José Luis Pinedo , Fulton J. Robin , Russell Euan , Field Jessica J. , Orme Christopher L. , Stirrat Hedley L. , Riesterer Jasmin , Teesdale‐Spittle Paul H. , Miller John H. , Harvey Joanne E.
Published: January 2019

The fungal metabolite TAN‐2483B has a 2,6‐trans‐relationship across the pyran ring of its furo[3,4‐b]pyran‐5‐one core, which has thwarted previous attempts at its synthesis. We have now developed a chiral pool approach to this core and prepared side‐chain analogues of TAN‐2483B. The synthesis relies on ring expansion of a reactive furan ring‐fused dibromocyclopropane and alkynylation of the resulting pyran. The furan ring is constructed by palladium‐catalysed carbonylative lactonisation. Various side‐chains are appended through Wittig‐type chemistry. The prepared analogues showed micromolar activity towards cancer cell lines HL‐60, 1A9 and MCF‐7 and certain human disease‐relevant kinases, including Bruton's tyrosine kinase (Btk).
Prepregnancy asthma and the subsequent risk of central nervous system defects in offspring
Authors: Auger Nathalie , Arbour Laura , Kabageni Adeline , Healy‐Profitós Jessica , Ayoub Aimina , Fraser William D.
Published: January 2019

Background

The relationship between childhood asthma and central nervous system defects in offspring is poorly understood. We assessed if childhood asthma was associated with the risk of having an infant with neural tube or other nervous system defects compared with asthma during pregnancy.

Methods

We analyzed a longitudinal cohort of 128,060 women who were 5 years or less at study entry and later delivered an infant in Quebec, Canada (1989–2014). We identified women hospitalized for asthma before pregnancy, including childhood and adolescence, and determined if asthma was present during pregnancy based on obstetric records. Main outcomes were neural tube and non‐neural tube defects in pregnancy. We used log‐binomial regression models to determine risk ratios (RR) and 95% confidence intervals (CI) for the association between asthma and risk of nervous system defects, adjusting for patient characteristics.

Results

Asthma was associated with a greater risk of neural tube defects in offspring (RR 2.39, 95% CI 1.03–5.53) compared with no asthma, but not non‐neural tube defects (RR 1.10, 95% CI 0.71–1.71). Women whose asthma resolved before pregnancy had a greater risk of neural tube defects (RR 3.43, 95% CI 1.35–8.69), while women with asthma during pregnancy were at greater risk of non‐neural tube defects, especially microcephaly (RR 2.80, 95% CI 1.23–6.40).

Conclusions

Asthma that resolved before pregnancy was associated with an increased risk of neural tube defects in offspring but not non‐neural tube defects. Further investigation is needed to determine the pathophysiology connecting childhood asthma with nervous system defects in offspring.
Metabolite Profiling of Anti‐Addictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae)
Authors: Krengel Felix , Chevalier Quentin , Dickinson Jonathan , Herrera Santoyo Josefina , Reyes Chilpa Ricardo
Published: January 2019

Ibogaine and other ibogan type alkaloids present anti‐addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography‐mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, ibogamine, voacangine, and ibogaine. While T. iboga mainly presented high concentrations of ibogaine, Tabernaemontana samples either showed a predominance of voacangine and ibogaine, or coronaridine and ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti‐addictive compounds.
Promotion of Glycerol Oxidation by Selective Ru Decoration of (100) Domains at Nanostructured Pt Electrodes
Authors: Tam Brian , Duca Matteo , Wang Andrew , Fan Mengyang , Garbarino Sébastien , Guay Daniel
Published: January 2019

Glycerol (GlOH) electrooxidation is a potential route to GlOH valorisation. In this work, we show that GlOH oxidation can be enhanced at bimetallic Pt−Ru electrodes with respect to bare Pt in sulphuric acid. We electrodeposited high‐surface area Pt electrodes comprising of 40 % (100) sites, along with a smaller amount of (111) domains. Spontaneous Ru deposition was carried out by immersion in a RuCl3 solution for a varying amount of time. Voltammetric methods demonstrated that (100) sites are decorated most readily. Pt−Ru electrodes display an earlier onset potential for COads oxidation, which translates into an anticipation of the main GlOH oxidation wave. Under prolonged Ru deposition, Ru decoration also proceeds close to (111) Pt domains, as highlighted by CO stripping. We suggest that such ensembles may play a critical role in achieving optimal GlOH activity at Pt−Ru.
Thermally Activated Multilayered Carbon Cloth as Flexible Supercapacitor Electrode Material with Significantly Enhanced Areal Energy Density
Authors: Wang Qinghua , Ren Wenhao , Gao Feng , Qiu Chunyu , Wang Qingxiang , Gao Fei , Zhao Chuan
Published: January 2019

Carbon cloth, an inexpensive and conductive textile, holds great promise as substrate for constructing electrical double‐layer capacitors due to its mechanical and electrochemical superiority. However, its widespread application is significantly hampered by the intrinsic low specific capacity. In this work, we demonstrate that the areal capacitance of commercial carbon cloth is raised for 800‐folds by a direct thermal activation strategy. When evaluated as the symmetric supercapacitor electrodes, thermally activated carbon cloth (TACC) displays the outstanding performance with areal capacitance up to 3291 mF cm−2 and the energy density of 740 μW h cm−2 at a power density of 9000 μW cm−2. In addition, the TACC‐based electrode reserves 95.2 % capacitance after 10,000 charge‐discharge cycles in a neutral NaBF4 electrolyte, showing outstanding cycle durability of the material. This work offers a foolproof and scalable method to prepare flexible electrode materials for wearable energy storage devices.
Polyaniline‐Intercalated FeOCl Cathode Material for Chloride‐Ion Batteries
Authors: Yu Tingting , Yang Renjie , Zhao Xiangyu , Shen Xiaodong
Published: January 2019

Iron oxychloride is regarded as a promising cathode material for chloride‐ion batteries, owing to its high theoretical capacity and abundant elemental resources. Its cycling stability, however, is limited by the intrinsic low conductivity and large volume change during cycling. Herein, the polyaniline‐intercalated iron oxychloride, in which the interlayer spacing along the b‐axis direction is greatly expanded from 0.79 to 1.4 nm, is developed as a cathode material for chloride‐ion batteries. Benefiting from the uniform expanded laminated structure and high structural integrity, the fully polyaniline‐intercalated iron oxychloride cathode delivers a short activation process, significantly improved charge transfer, and superior cycling stability. For example, a high reversible capacity of 120 mAh g−1, owing to the redox reaction based on chloride ion transfer, is achieved after 50 cycles, showing good capacity retention of 82 %. In contrast, the pure iron oxychloride cathode suffers from severe capacity decay and only 61 mAh g−1 (42 % capacity retention) is kept. This work demonstrates a new strategy for designing high‐performance layered electrodes of chloride ion batteries.
Treatment burden and long‐term health deficits of patients with low‐grade gliomas or glioneuronal tumors diagnosed during the first year of life
Authors: Liu Anthony P. Y. , Hastings Camden , Wu Shengjie , Bass Johnnie K. , Heitzer Andrew M. , Ashford Jason , Vestal Robert , Hoehn Mary E. , Ghazwani Yahya , Acharya Sahaja , Conklin Heather M. , Boop Frederick , Merchant Thomas E. , Gajjar Amar , Qaddoumi Ibrahim
Published: January 2019

Background

Low‐grade gliomas (LGGs) and low‐grade glioneuronal tumors (LGGNTs) diagnosed during the first year of life carry unique clinical characteristics and challenges in management. However, data on the treatment burden, outcomes, and morbidities are lacking.

Methods

A retrospective study of LGGs and LGGNTs diagnosed in patients younger than 12 months at St. Jude Children’s Research Hospital (1986‐2015) was conducted.

Results

For the 51 patients (including 31 males), the mean age at diagnosis was 6.47 months (range, 0.17‐11.76 months), and the mean follow‐up period was 11.8 years (range, 0.21‐29.19 years). Tumor locations were hypothalamic/optic pathway (61%), hemispheric (12%), brainstem (12%), cerebellar (8%), and spinal (8%). There were 41 patients with histological diagnoses: 28 had World Health Organization grade 1 tumors, 6 had grade 2 tumors, and 7 had an LGG/LGGNT not definitively graded. Forty‐one patients required an active intervention at diagnosis. Throughout their treatment course, 41 patients eventually underwent tumor‐directed surgeries (median, 2 surgeries; range, 1‐6), 39 received chemotherapy (median, 2 regimens; range, 1‐13), and 21 received radiotherapy. Forty patients experienced disease progression (median, 2 progressions; range, 1‐18). Ten patients died of progression (n = 5), malignant transformation (n = 2), a second cancer (n = 2), or a shunt infection (n = 1). The 10‐year overall survival, progression‐free survival, and radiation‐free survival rates were 85% ± 5.3%, 16.9% ± 5.3%, and 51.2% ± 7.5%, respectively. Forty‐nine patients experienced health deficits (eg, endocrinopathies, obesity, seizures, visual/hearing impairments, neurocognitive impairments, and cerebrovascular disease). Predictors of progression and toxicities were defined.

Conclusions

Infantile LGG/LGGNT is a chronic, progressive disease universally associated with long‐term morbidities and requires multidisciplinary intervention.
The role of vascular endothelial growth factor, interleukin 8, and insulinlike growth factor in sustaining autophagic DIRAS3‐induced dormant ovarian cancer xenografts
Authors: Mao Weiqun , Peters Haley L. , Sutton Margie N. , Orozco Aaron F. , Pang Lan , Yang Hailing , Lu Zhen , Bast Robert C.
Published: January 2019

Background

Re‐expression of the imprinted tumor suppressor gene DIRAS family GTPase 3 (DIRAS3) (aplysia ras homology member I [ARHI]) induces autophagy and tumor dormancy in ovarian cancer xenografts, but drives autophagic cancer cell death in cell culture. The current study explored the tumor and host factors required to prevent autophagic cancer cell death in xenografts and the use of antibodies against those factors or their receptors to eliminate dormant autophagic ovarian cancer cells.

Methods

Survival factors (insulinlike growth factor 1 [IGF‐1], vascular endothelial growth factor [VEGF], and interleukin 8 [IL‐8]) were detected with growth factor arrays and measured using enzyme‐linked immunoadsorbent assay analysis. Phosphorylation of protein kinase B (AKT), phosphorylation of extracellular signal‐regulated kinase (ERK), nuclear localization of translocation factor EB (TFEB) or forkhead box O3a (FOXo3a), and expression of microtubule‐associated proteins 1A/1B light chain 3B (MAPLC3B; LC3B) were examined using Western blot analysis. The effect of treatment with antibodies against survival factors or their receptors was studied using DIRAS3‐induced dormant xenograft models.

Results

Ovarian cancer cells grown subcutaneously in nude mice exhibited higher levels of phosphorylated ERK/AKT activity and lower levels of nuclear TFEB/FOXo3a, MAPLC3B, and autophagy compared with cells grown in culture. Induction of autophagy and dormancy with DIRAS3 was associated with decreased ERK/AKT signaling. The addition of VEGF, IGF‐1, and IL‐8 weakened the inhibitory effect of DIRAS3 on ERK/AKT activity and reduced DIRAS3‐mediated TFEB or FOXo3a nuclear localization and MAPLC3B expression in ovarian cancer cells. Treatment with antibodies against VEGF, IL‐8, and IGF receptor inhibited the growth of dormant xenografts, thereby prolonging survival from 99 to >220 days (P < .05) and curing a percentage of mice.

Conclusions

Treatment with a combination of anti‐VEGF, anti–IL‐8, and anti‐IGF receptor antibodies prevented the outgrowth of dormant cells and prolonged survival in a preclinical model.
A Single Nonblinking Cs4PbBr6 Nanoparticle as a Nanothermometer
Authors: Lei Yanyu , Yang Jie , Hong Daocheng , Wan Sushu , Hua Yan , Xie Mingcai , Tang Xiaosheng , Tian Yuxi
Published: January 2019

Inorganic perovskite materials have attracted broad interest in the last several years due to their stability and promising applications as photovoltaic and light‐emitting materials. In this work, we prepared Cs4PbBr6 nanoparticles showing stable photoluminescence (PL) without blinking and studied the PL properties of individual Cs4PbBr6 nanoparticles in the biological temperature range. We found that both PL intensity and lifetime of a single Cs4PbBr6 particle strongly depends on the temperature. The PL intensity and lifetime decrease almost linearly with the increasing of the temperature. The slopes of the PL intensity and lifetime versus temperature were as high as 2% and 3% per degree centigrade, respectively. The photostability and thermal stability were also checked for individual particles. With these results, we proposed that the sensitivity of PL intensity and lifetime of a single Cs4PbBr6 nanoparticle on temperature showed the potential application of a single particle as a nanothermometer for thermal detection in a local environment.
An Open‐Label, Randomized, Pivotal Bioequivalence Study of Oral Rolapitant
Authors: Zhang Zhi‐Yi , Wang Jing , Arora Sujata , Lu Sharon , Powers Dan , Kansra Vikram , Wang Xiaodong
Published: January 2019

Rolapitant, a selective and long‐acting neurokinin‐1 receptor antagonist, is approved in an oral formulation for prevention of delayed chemotherapy‐induced nausea and vomiting in adults. This pivotal open‐label, randomized, single‐dose, multicenter, parallel‐group study assessed the bioequivalence of a single oral dose of 180 mg of rolapitant administered in tablet (2 × 90‐mg tablets) or capsule (4 × 45‐mg capsules) form in healthy male and female subjects. Blood samples for pharmacokinetic analysis were collected predose and at times up to 912 hours postdose. The rolapitant tablet was considered bioequivalent to the rolapitant capsule if the 90% confidence intervals for the ratios of the geometric means for rolapitant, observed maximum plasma concentration (Cmax), and area under the curve from time 0 extrapolated to infinity (AUC0‐∞) were within the 0.80–1.25 range. The pharmacokinetic profiles of the capsule group (n = 43) and tablet group (n = 44) were similar. The geometric mean ratios of Cmax and AUC0‐∞ were 0.99 (0.89–1.11) and 1.05 (0.92–1.19), respectively, establishing bioequivalence of the rolapitant tablet and capsule formulations. Both formulations were well tolerated, with a similar incidence of treatment‐emergent adverse events in the 2 groups.
Expression and Preparation of a G‐Protein‐Coupled Cannabinoid Receptor CB2 for NMR Structural Studies
Authors: Yeliseev Alexei
Published: January 2019

Cannabinoid receptor type II, or CB2, is an integral membrane protein that belongs to a large class of G‐protein‐coupled receptors (GPCR)s. CB2 is a part of the endocannabinoid system, which plays an important role in the regulation of immune response, inflammation, and pain. Information about the structure and function of CB2 is essential for the development of specific ligands targeting this receptor. We present here a methodology for recombinant expression of CB2 and its stable isotope labeling, purification, and reconstitution into liposomes, in preparation for its characterization by nuclear magnetic resonance (NMR). Correctly folded, functional CB2 labeled with [13C,15N]tryptophan or uniformly labeled with 13C and 15N is expressed in a medium of defined composition, under controlled aeration, pH, and temperature conditions. The receptor is purified by affinity chromatography and reconstituted into lipid bilayers in the form of proteoliposomes suitable for analysis by NMR spectroscopy. © 2019 by John Wiley & Sons, Inc.
Isolation and Flow Cytometry Characterization of Extracellular‐Vesicle Subpopulations Derived from Human Mesenchymal Stromal Cells
Authors: Gorgun Cansu , Reverberi Daniele , Rotta Gianluca , Villa Federico , Quarto Rodolfo , Tasso Roberta
Published: January 2019

This unit describes protocols for isolating subpopulations of extracellular vesicles (EVs) purified from human adipose tissue–derived mesenchymal stromal cells by density gradient centrifugation and for characterizing them by flow cytometry (FCM). Determining the optimal strategy for isolating EVs is a critical step toward retrieving the maximal amount while ensuring the recovery of different vesicular subtypes. The first protocol details density gradient centrifugation to isolate both exosomes and microvesicles. In the second protocol, characterization of EV subpopulations by FCM is depicted, taking advantage of non‐conventional modalities, in accordance with the latest technical indications. The procedures described here can be easily reproduced and can be employed regardless of the cell type used to obtain EVs. © 2019 by John Wiley & Sons, Inc.
A High‐Density Azobenzene Side Chain Polymer Brush for Azimuthal and Zenithal Orientational Photoswitching of a Nematic Liquid Crystal
Authors: Mukai Koji , Imai Kenjiro , Hara Mitsuo , Nagano Shusaku , Seki Takahiro
Published: January 2019

The azimuthal and zenithal orientational switching of nematic liquid crystals (NLCs) can be performed by photoresponsive azobenzene alignment layers called command surfaces. Such photoresponsive layers have been prepared by molecular assembly methods or by spincasting of polymer materials. This work reports on the photoswitching orientation behavior of an NLC on a high‐density brush of an azobenzene‐containing side chain liquid crystalline polymer. On the high‐density polymer brush surface, the zenithal homeotropic/planar photoalignment switching modes triggered by UV/visible light irradiation are reversed from those observed for traditional command surface systems, reflecting the azobenzene side chain orientation directing parallel to the substrate surface. Because the thermally stable trans‐azobenzene provides the in‐plane orientation of the NLC, irradiation with linearly polarized visible light readily switches the azimuthal direction to an arbitrary direction, and the resulting orientation is retained persistently. This paper discusses the features of the architecture of a high‐density polymer brush as the command surface for NLC orientation.
SGMR: A spatial geometry–based multipath routing method on overlay networks
Authors: Guan Yunchong , Lei Weimin , Zhang Wei , Li Hao , Zhang Songyang
Published: January 2019

Multipath transmission (MT) promotes transmission quality effectively. Path diversity (PD) impacts MT quality by aggregating capabilities of paths with little correlation. Enough PD contributes to improving concurrent link utilization and weakening negative impacts from a single path so that abilities of congestion and failure tolerance are enhanced. However, PD is hard to guarantee on overlay networks due to little awareness of underlay networks and few evaluation methods. In this paper, we propose the spatial geometry–based multipath routing (SGMR) method to improve PD for MT on overlay networks. Considering that paths are composed of overlay nodes and network coordinates effectively characterize node diversity (ND), we employ some geometric mechanisms on the spatial coordinate–based view to convert ND to PD. Firstly, coordinates are generated to match the overlay and underlay networks and meanwhile to characterize ND. Then, for generating multiple paths, transmission direction facilitates the path convergence, transmission surface constrains intermediate nodes, and deviation angle guarantees link diversity. Simulation and real‐world evaluations demonstrate that SGMR guarantees PD better, and the multipath transmission quality is improved thanks to enough PD.
Cluster‐based emergency message dissemination strategy for VANET using V2V communication
Authors: Benkerdagh Saliha , Duvallet Claude
Published: January 2019

Data dissemination in vehicular ad hoc network (VANET) is emerging as a critical area of research. One of the challenges posed by this domain is the reliability of connection, which depends on many parameters, such as the bandwidth consumption, transmission delay, and data quality of service (QoS). Dissemination of emergency messages is very critical since the network topology is changing frequently and rapidly, which leads to data loss. So, it is necessary to develop new protocols and enhance dissemination schemes in VANET to avoid more emergencies and hazards cases. In this regard, we have proposed a new strategy, which consists of data handling before dissemination process as the first step of our scheme. In this phase, the original message is optimized in order to reduce the number of exchanged packets. The second part of this proposition consists of constructing fast and stable clusters to improve the message delivery time and to procure efficient bandwidth consumption. This approach is based on a Fitness function, which takes into account different parameters such as the transmission period, the connectivity degree, the relative velocity, and the link lifetime validity. Since exchanging data in VANET is an important process, routing phase is proposed to perform data exchange among clusters. It is based on a rapid and real‐time heuristic (real‐time adaptive A* [RTAA*]). To evaluate the reliability of the proposed approach, an urban scenario is used with different simulation parameters. The simulation results show that our proposed approach presents a better stability and efficiency performance compared with the discussed approaches. The proposed approach improves the performance of cluster duration (5% − 25%), delivery rate (2% − 8%), and the overhead (5% − 35%) on average compared with the discussed approaches.
Fine‐scale vegetation mosaics in Pyrenean mires are driven by complex hydrological regimes and threatened by extreme weather events
Authors: Colomer Joana , Pérez‐Haase Aaron , Carrillo Empar , Ventura Marc , Ninot Josep M.
Published: January 2019

Holarctic mires are systems of great ecological value and limited alpine distribution. Their southernmost European boundary borders the Mediterranean region. Understanding how environmental factors influence the plant community distribution and its response to disturbances, especially in the water regime, is a key step for their management and conservation. Here, we report our study of the main ecological gradients that determine the distribution of different plant community types in the Trescuro mire system and their response to variations in the environmental conditions such as summer drought. We set up 30 sampling points across the vegetation mosaic where pH, electrical conductivity, water table depth, and ion concentration were recorded during the 2014 and 2015 summers. The results revealed that variation in the water table level is what most drives the vegetation distribution at the local scale, followed by the ion concentration. Soligenous communities, which are highly dependent on water run‐off, were the most affected by the drought event in 2015. Because these communities are generally situated in the marginal parts of mire systems, summer drought periods may facilitate invasion by trees into the areas they occupy, which may eventually lead to a reduction of mire area. This study contributes to the understanding of the dynamics of these unique and complex systems through elucidating the relationship between the vegetation and climatic variations.
Differences in nutritional status and activities of daily living and mobility in elderly hospitalized patients with heart failure
Authors: Kitamura Masahiro , Izawa Kazuhiro P. , Yaekura Masakazu , Mimura Yumi , Nagashima Hitomi , Oka Koichiro
Published: January 2019

Aims

This study aims to examine the effect of differences in nutritional status on activities of daily living (ADL) and mobility recovery of hospitalized elderly patients with heart failure (HF).

Methods and results

From among 377 consecutive HF patients who underwent rehabilitation at one acute‐care hospital from January 2013 to August 2015, those who were aged ≥ 65 years could walk with assistance before hospitalization and who were hospitalized for the first time were included in this retrospective cohort study. Exclusion criteria were pacemaker surgery during hospitalization, change to other departments, death during hospitalization, and unmeasured ADL. We investigated patient characteristics, basic attributes, Geriatric Nutritional Risk Index (GNRI), ADL [motor Functional Independence Measure (motor FIM)], and Rivermead Mobility Index (RMI). Of these 377 patients, 96 met the inclusion criteria and were divided into the low GNRI group (n = 38, 83.5 ± 8.3 years, 44.7% male) and high GNRI group (n = 58, 81.0 ± 6.6 years, 55.2%). Patient characteristics and the difference between motor ADL and motility recovery and nutrition data were analysed with unpaired t‐test, χ2 test, and two‐way analysis of covariance. In comparing the two groups, the following parameters were significantly lower in the low GNRI group than in the high GNRI group: body mass index (18.7 ± 2.2 vs. 23.2 ± 2.7 kg/m2, P < 0.01), albumin (3.4 ± 0.4 vs. 3.8 ± 0.4 g/dL, P < 0.01), diabetes mellitus ratio (21.1% vs. 50.0%, P < 0.01), RMI at discharge (6.8 ± 2.6 vs. 8.2 ± 2.2, P = 0.01), and motor FIM at discharge (67.2 ± 19.5 vs. 75.6 ± 13.3, P = 0.02). RMI showed a significant group and term main effect and interaction effect (P < 0.05). Motor FIM showed a significant main effect of group and term (P < 0.05), and no significant interaction effect.

Conclusions

Low nutritional status in hospitalized elderly HF patients affected their recovery of mobility but did not appear to affect the recovery of ADL.
A Bismuth–Arene σ‐Complex – On the Edge of Menshutkin‐Type Complexes
Authors: Bresien Jonas , Schulz Axel , Thomas Max , Villinger Alexander
Published: January 2019

Mes*N(SiMe3)BiCl2 (1, Mes* = 2,4,6‐tri‐tert‐butylphenyl) can be referred to as a hidden iminobismuthane, Mes*N=BiCl, which was thought to be generated in‐situ upon Me3SiCl elimination triggered by a Lewis acid such as GaCl3. Therefore, the reactivity of aminobismuthane 1 was studied to find a synthesis route for the formation of a tetrazabismuthole in a [3+2] cycloaddition reaction with a covalently bound azide. However, reaction of 1 with GaCl3 cleanly led to [Mes*N(SiMe3)BiCl][GaCl4] (2[GaCl4]), a compound with a Bi‐arene σ‐complex. Utilizing Ag[WCA] salts (WCA = weakly coordinating anion) for chloride abstraction, a C–C coupling product (3) was identified. The diiodide species Mes*N(SiMe3)BiI2 (4) as precursor for a diazido species and the azido‐chloride compound Mes*N(SiMe3)Bi(N3)Cl (5) were also prepared to explore the possibility of a BiN4 heterocycle formation, again upon Me3SiX elimination (X = halogen, N3), but 4 and 5 were unstable towards decomposition into a black precipitate and a complex product mixture. The structure and bonding of all isolated bismuth species is discussed.
Observers’ impression of the person in pain influences their pain estimation and tendency to help
Authors: Khatibi Ali , Mazidi Mahdi
Published: January 2019

Background

Estimation of a patient's pain may have a considerable impact on the level of care that patient receives. Many studies have shown that contextual factors may influence an observer's pain estimation. Here, we investigate the effect of an observer's impression of a person in pain and justification of his/her pain on the observer's pain estimation, tendency to help and perceived empathy.

Methods

Thirty healthy individuals (half females) read scenarios aimed to manipulate the reader's impression of characters who ultimately were fired from their work (four positive characters and four negative; half females). Then they observed 1‐s videos of four levels of pain expression (neutral, mild, moderate, strong) in those characters during an examination. Subsequently, they rated pain estimation, tendency to help and perceived empathy. Afterwards, they rated their likability of characters and how just they find the end of story.

Results

People rated pain in positive characters higher than the pain in negative characters. They also expressed more tendency to help and a higher level of perceived empathy towards positive characters than negative characters. For the highest level of pain in positive characters, perceived injustice towards that person was the best predictor of the observer's pain estimation, tendency to help and perceived empathy. For negative characters, dislikeability was the best predictor of tendency to help and perceived empathy. Justification of their pain was a predictor of pain estimation and tendency to help.

Conclusion

Observers used different information to evaluate pain in positive and negative individuals.

Significance

Observers’ estimation of pain, perceived empathy and tendency to help biases by their understanding of the characteristics of the person in pain. In clinical settings, these biases may influence the quality of care and well‐being of patients. Understanding the underlying mechanisms of these biases can help us improve the quality of care and control the effect of prejudices on pain assessment.
Standards for the diagnosis and management of complex regional pain syndrome: Results of a European Pain Federation task force
Authors: Goebel Andreas , Barker Chris , Birklein Frank , Brunner Florian , Casale Roberto , Eccleston Chris , Eisenberg E. , McCabe Candy S. , Moseley G. Lorimer , Perez R. , Perrot Serge , Terkelsen Astrid , Thomassen Ilona , Zyluk Andrzey , Wells Chris
Published: January 2019

Background

Complex regional pain syndrome is a painful and disabling post‐traumatic primary pain disorder. Acute and chronic complex regional pain syndrome (CRPS) are major clinical challenges. In Europe, progress is hampered by significant heterogeneity in clinical practice. We sought to establish standards for the diagnosis and management of CRPS.

Methods

The European Pain Federation established a pan‐European task force of experts in CRPS who followed a four‐stage consensus challenge process to produce mandatory quality standards worded as grammatically imperative (must‐do) statements.

Results

We developed 17 standards in 8 areas of care. There are 2 standards in diagnosis, 1 in multidisciplinary care, 1 in assessment, 3 for care pathways, 1 in information and education, 4 in pain management, 3 in physical rehabilitation and 2 on distress management. The standards are presented and summarized, and their generation and consequences were discussed. Also presented are domains of practice for which no agreement on a standard could be reached. Areas of research needed to improve the validity and uptake of these standards are discussed.

Conclusion

The European Pain Federation task force present 17 standards of the diagnosis and management of CRPS for use in Europe. These are considered achievable for most countries and aspirational for a minority of countries depending on their healthcare resource and structures.

Significance

This position statement summarizes expert opinion on acceptable standards for CRPS care in Europe.
Potential use of leukocytosis and anion gap elevation in differentiating psychogenic nonepileptic seizures from epileptic seizures
Authors: Li Yi , Matzka Liesl , Flahive Julie , Weber Daniel
Published: January 2019

Epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) can be difficult to differentiate from each other in the emergency department (ED) setting. We have previously shown that the anion gap (AG) can help differentiate between ES and PNES in the ED. In this study, we explored whether additionally considering leukocytosis can help better differentiate between ES and PNES. We screened a total of 1354 subjects seen in the ED of a tertiary care medical center; 27 PNES and 27 ES patients were identified based on clinical description and subsequent electroencephalography (EEG). Multivariable logistic regression analysis was used to model the association between ES, leukocytosis, and AG. Our results indicated that within 9 hours after the index event, serum AG (adjusted odds ratio [aOR] 2.07) and white blood cell (WBC) count (aOR 1.61) were both independently associated with ES. We derived an equation to help differentiate between ES and PNES: 1.5*AG+WBC. A score >24.8 indicated a >90% likelihood of ES. A score <15.5 indicated a <10% likelihood of ES (ie, the alternate diagnosis of PNES should be considered). This study for the first time provides evidence to help differentiate PNES and ES utilizing acidosis and leukocytosis.
Efficacy of psychotherapy for bulimia nervosa and binge‐eating disorder on self‐esteem improvement: Meta‐analysis
Authors: Linardon Jake , Kothe Emily J. , Fuller‐Tyszkiewicz Matthew
Published: January 2019

Objectives

This meta‐analysis examined the effects of psychotherapy for bulimia nervosa (BN) and binge‐eating disorder (BED) on self‐esteem improvement.

Method

Randomized controlled trials (RCTs) of psychological treatments that assessed self‐esteem change in eating disorders were included. Thirty‐four RCTs were included; most sampled BED and then BN. Hedge's g effects were entered into random effects models.

Results

Psychotherapy for BN led to significantly greater post‐treatment improvements in self‐esteem than control conditions (g = 0.45; 95% CI [0.17, 0.73]). This effect was smaller when only analysing low risk of bias trials (g = 0.28; 95% CI [0.05, 0.51]). Psychotherapy for BED also led to significantly greater post‐treatment improvements in self‐esteem than controls (g = 0.20; 95% CI [0.05, 0.35]), with some evidence that guided self‐help was associated with the largest effects. This effect, however, was overestimated after adjustment for publication bias (g = 0.10; 95% CI [−0.05, 0.26]). There was no evidence that cognitive‐behavioural therapy was superior to non‐cognitive‐behavioural therapy interventions in improving self‐esteem. There was no relationship between symptom improvement and self‐esteem improvement in a meta‐regression.

Conclusions

Psychotherapy may lead to small improvements in self‐esteem in BN and BED. Additional RCTs with follow‐up assessments are required to make more definitive conclusions about the effects of psychotherapy for eating disorders on self‐esteem in the long‐term.
Netzwerk des Überlebens
Authors: Rössler Patrick , Droste Magdalena , Blümm Anke
Published: January 2019

Vor 100 Jahren gegründet, gilt das Bauhaus als der erfolgreichste deutsche Kulturexport des 20. Jahrhunderts. Eine Studie verdeutlicht, wie der kommunikative Austausch zwischen den Bauhaus‐Angehörigen die Institution auch nach ihrer Schließung 1933 als eine frühe Form „virtueller Gemeinschaft” fortleben ließ. Ein neuer Blick jenseits üblicher, von stilistischen Überlegungen geprägter Betrachtungen.
Flexible model for patient engagement: Achieving quality outcomes and building a research agenda for head and neck cancer
Authors: Iwata Ayaka J. , Olden Heather A. , Kippen Karen E. , Swegal Warren C. , Johnson Christine C. , Chang Steven S.
Published: January 2019

Background

This article describes the benefits of patient‐driven research in the field of head and neck oncology, reviews lessons learned from establishing partnerships with patients and caregivers, and serves as a model for further patient‐driven research endeavors.

Methods

Head and neck cancer survivors underwent training including that of effective communication and the basics of research methodology. They then drove the agendas for monthly meetings that included a multidisciplinary team of providers, facilitated by a physician champion (S.S.C.).

Results

The advisors reported concrete areas for improvement of the clinical flow, including the formation of a dental oncology clinic and a post‐treatment survivorship clinic. They also refined research topics of interest, such as treatment regret. The advisors have also driven efforts to increase public awareness and have participated in cancer symposiums and local presentations.

Conclusion

Patient‐driven research improves the relevance and implementation of head and neck oncology research and clinical processes.
Trade‐off Analytics: Creating and Evaluating the Tradespace
Authors: Parnell Gregory S.
Published: January 2019

The INCOSE Corporate Advisory Board documented the need for a guidebook on best practices for trade studies. They wanted a book that covered the system lifecycle and aligned with INCOSE process guidance (ISO/IEC 15288, Systems Engineering Handbook, and the “Systems Engineering Body of Knowledge”). The INCOSE Decision Analysis Working Group supported the book project. Members of the Decision Analysis Working Group began by writing the decision management sections of the Systems Engineering Handbook and the “Systems Engineering Body of Knowledge” (SEBoK). We decided to develop a textbook in the Wiley Systems Engineering and Management Series to meet this need (note: the authors provide all proceeds from sale of the textbook directly to the INCOSE Foundation). Our goal was to describe and illustrate sound trade‐off analysis techniques to identify value and risk to help decision makers make the necessary trade‐offs to provide affordable systems that meet performance and schedule objectives. We recruited sixteen leading systems engineering experts with significant academic and industry experience. The textbook audience is undergraduate students (systems engineering, industrial, engineering management, other engineering); graduate students (systems, industrial, engineering management, other engineering); and professional systems engineers, project managers, and engineering managers. The textbook can also be used as a professional reference. Wiley offers a 25% discount to INCOSE Corporate Advisory Board members.