bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multinational Arab Genome‐Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis
Authors: Saxena Richa , Plenge Robert M. , Bjonnes Andrew C. , Dashti Hassan S. , Okada Yukinori , Gad El Haq Wessam , Hammoudeh Mohammed , Al Emadi Samar , Masri Basel K. , Halabi Hussein , Badsha Humeira , Uthman Imad W. , Margolin Lauren , Gupta Namrata , Mahfoud Ziyad R. , Kapiri Marianthi , Dargham Soha R. , Aranki Grace , Kazkaz Layla A. , Arayssi Thurayya
Published: January 2017

Objective

Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome‐wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab‐specific genetic loci.

Methods

The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single‐nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population.

Results

Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome‐wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA–DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10−16), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10−5) and with seropositive RA (P = 1.48 × 10−6) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci.

Conclusion

This first RA GWAS in Arab populations confirms that established HLA‐region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population‐specific insights into the pathophysiology of RA.
Synthesis and luminescence properties of polymer–rare earth complexes containing salicylaldehyde‐type bidentate Schiff base ligand
Authors: Zhang Dandan , Gao Baojiao , Li Yanbin
Published: January 2017

Using molecular design and polymer reactions, two types of bidentate Schiff base ligands, salicylaldehyde–aniline (SAN) and salicylaldehyde–cyclohexylamine (SCA), were synchronously synthesized and bonded onto the side chain of polysulfone (PSF), giving two bidentate Schiff base ligand‐functionalized PSFs, PSF–SAN and PSF–SCA, referred to as macromolecular ligands. Following coordination reactions between the macromolecular ligands and Eu(III) and Tb(III) ions (the reaction occurred between the bonded ligands SAN or SCA and the lanthanide ion), two series of luminescent polymer–rare earth complexes, PSF–SAN–Eu(III) and PSF–SCA–Tb(III), were obtained. The two macromolecular ligands were fully characterized by Fourier transform infrared (FTIR), 1H NMR and UV absorption spectroscopy, and the prepared complexes were also characterized by FTIR, UV absorption spectroscopy and thermo‐gravity analysis. On this basis, the photoluminescence properties of these complexes and the relationships between their structure and luminescence were investigated in depth. The results show that the bonded bidentate Schiff base ligands, SAN and SCA, can effectively sensitize the fluorescence emission of Eu(III) and Tb(III) ions, respectively. PSF–SAN–Eu(III) series complexes, namely the binary complex PSF–(SAN)3–Eu(III) and the ternary complex PSF–(SAN)3–Eu(III)–(Phen)1 (Phen is the small‐molecule ligand 1,10‐phenanthroline), produce strong red luminescence, suggesting that the triplet state energy level of SAN is lower and well matched with the resonant energy level of the Eu(III) ion. By contrast, PSF–SAN–Eu(III) series complexes, namely the binary complex PSF–(SCA)3–Tb(III) and the ternary complex PSF–(SCA)3–Tb(III)–(Phen)1, display strong green luminescence, suggesting that the triplet state energy level of SCA is higher and is well matched with the resonant energy level of Tb(III).
Development of a Paste‐type Certified Reference Material of Tomato for Elemental Analysis: Certification and Long‐term Stability Study
Authors: Choi Jiha , Hwang Euijin , Yim Yong‐Hyeon , Jo Hang Mi , Lim Youngran , Kim Tae Kyu , Lee Kyoung‐Seok
Published: January 2017

A paste‐type certified reference material (CRM) of tomato was developed for accurate elemental analysis of canned foods. Accurate mass fractions of cadmium (Cd), lead (Pb), and tin (Sn) in the tomato paste CRM were determined by isotope dilution inductively coupled plasma mass spectrometry. The certified values and their expanded uncertainties (k=2 at approximately 95% level of confidence) for Cd, Pb, and Sn were (0.297 ± 0.015) mg/kg, (0.213 ± 0.010) mg/kg, and (221.2 ± 9.5) mg/kg, respectively. Homogeneity of the CRM was 0.3%, 1.8%, and 0.2% for Cd, Pb, and Sn, respectively, which were estimated using the relative standard deviation of the measurement results of 10 separate sample bottles from one batch of the CRM. Major contributions to the measurement uncertainties for Cd and Sn were the uncertainties of the isotope ratios of Cd and Sn in the sample and the elemental standards. The uncertainty for Pb was mainly affected by sample homogeneity. Stability tests were conducted for 6 and 12 months at −20, 4, and 25°C, and the storage temperature for the CRM was determined to be −20°C. To investigate long‐term storage, the mass fractions of Cd, Pd, and Sn in the CRM were re‐determined after storage for 7 years. The results were in good agreement with the certified results implying that this CRM is stable for 7 years if kept at an appropriate storage condition with vacuum packaging the amber glass bottles in aluminum‐coated polymer bag.
Urocortin suppresses endometrial cancer cell migration via CRFR2 and its system components are differentially modulated by estrogen
Authors: Owens Gemma L. , Lawrence Kevin M. , Jackson Tom R. , Crosbie Emma J. , Sayan Berna S. , Kitchener Henry C. , Townsend Paul A.
Published: January 2017

Urocortin (UCN1) peptide shares structural and functional homology with corticotropin‐releasing factor (CRF). UCN1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of UCN1 in the endometrium, or how it is modulated. We used proliferation and transwell assays to determine the effect of UCN1 on the proliferation and migration of Ishikawa and HEC1A cells. We also determined the expression levels of UCN1 and its receptors produced by estrogen receptor agonists, and the effect of UCN1 on estrogen receptor expression, using quantitative polymerase chain reaction. UCN1 suppressed migration of endometrial cancer cells in vitro. This effect appears to be specific to CRF receptor 2 (CRFR2), as selective antagonism of CRFR2 but not CRFR1 completely eliminated suppression of migration. Activation of ERA reduced UCN1 expression, but only had a small effect on the expression of CRFR1. However, expression of CRFR2 was more notably reduced at both the mRNA and protein levels by activation of ERB. UCN1 in turn reduced both ERA and ERB expression, as assessed by real‐time quantitative PCR. We demonstrate that UCN1 significantly suppresses the migration of endometrial cancer cells but has no effect on their proliferation. Thus, loss of UCN1 in endometrial cancer may promote invasion and metastatic spread. There is a complex relationship between the UCN1 system and estrogen receptors, which may provide insights into endometrial carcinogenesis, a disease known to be driven by estrogen excess.
Robust standing control with posture optimization
Authors: Kavafoglu Zumra , Kavafoglu Ersan , Egges Arjan
Published: January 2017

Humans need to shift their center of mass during standing for several purposes such as preparing for the upcoming motion or increasing their stability. In this paper, we present a control strategy for robust center of mass shifting motions during standing. In our strategy, the desired posture can be defined with only a few high level features, such as the desired character center of mass position and the foot configurations. An online optimization process is designed for generating a kinematic lower body and pelvis posture that satisfies these high level features together with some criteria that guide a natural standing pose. Natural knee bending behaviours automatically arise as a result of this optimization process. Internal joint torques for tracking this optimized posture together with the given desired upper body pose are calculated by the physics‐based control framework. Moreover, a physics‐based arm control strategy that regulates the angular momentum of the character is devised in order to increase the robustness of the character under external disturbances. Several experiments are conducted to demonstrate the effectiveness of the proposed strategy. Because the strategy does not include any off‐line parameter optimization, equations of motion, or inverse dynamics, it is highly suitable for online applications.
Chemical Variability, Antioxidant and Antifungal Activities of Essential Oils and Hydrosol Extract of Calendula arvensis L. from Western Algeria
Authors: Belabbes Rania , Dib Mohammed El Amine , Djabou Nassim , Ilias Faiza , Tabti Boufeldja , Costa Jean , Muselli Alain
Published: January 2017

The chemical composition of the essential oils and hydrosol extract from aerial parts of Calendula arvensis L. was investigated using GC‐FID and GC/MS. Intra‐species variations of the chemical compositions of essential oils from 18 Algerian sample locations were investigated using statistical analysis. Chemical analysis allowed the identification of 53 compounds amounting to 92.3 – 98.5% with yields varied of 0.09 – 0.36% and the main compounds were zingiberenol 1 (8.7 – 29.8%), eremoligenol (4.2 – 12.5%), β‐curcumene (2.1 – 12.5%), zingiberenol 2 (4.6 – 19.8%) and (E,Z)‐farnesol (3.5 – 23.4%). The study of the chemical variability of essential oils allowed the discrimination of two main clusters confirming that there is a relation between the essential oil compositions and the harvest locations. Different concentrations of essential oil and hydrosol extract were prepared and their antioxidant activity were assessed using three methods (2,2‐diphenyl‐1‐picrylhydrazyl, Ferric‐Reducing Antioxidant Power Assay and β‐carotene). The results showed that hydrosol extract presented an interesting antioxidant activity. The in vitro antifungal activity of hydrosol extract produced the best antifungal inhibition against Penicillium expansum and Aspergillus niger, while, essential oil was inhibitory at relatively higher concentrations. Results showed that the treatments of pear fruits with essential oil and hydrosol extract presented a very interesting protective activity on disease severity of pears caused by P. expansum.
Intracoronary optical coherence tomography: Clinical and research applications and intravascular imaging software overview
Authors: Tenekecioglu Erhan , Albuquerque Felipe N. , Sotomi Yohei , Zeng Yaping , Suwannasom Pannipa , Tateishi Hiroki , Cavalcante Rafael , Ishibashi Yuki , Nakatani Shimpei , Abdelghani Mohammad , Dijkstra Jouke , Bourantas Christos , Collet Carlos , Karanasos Antonios , Radu Maria , Wang Ancong , Muramatsu Takashi , Landmesser Ulf , Okamura Takayuki , Regar Evelyn , Räber Lorenz , Guagliumi Giulio , Pyo Robert T. , Onuma Yoshinobu , Serruys Patrick W.
Published: January 2017

By providing valuable information about the coronary artery wall and lumen, intravascular imaging may aid in optimizing interventional procedure results and thereby could improve clinical outcomes following percutaneous coronary intervention (PCI). Intravascular optical coherence tomography (OCT) is a light‐based technology with a tissue penetration of approximately 1 to 3 mm and provides near histological resolution. It has emerged as a technological breakthrough in intravascular imaging with multiple clinical and research applications. OCT provides detailed visualization of the vessel following PCI and provides accurate assessment of post‐procedural stent performance including detection of edge dissection, stent struts apposition, tissue prolapse, and healing parameters. Additionally, it can provide accurate characterization of plaque morphology and provides key information to optimize post‐procedural outcomes. This manuscript aims to review the current clinical and research applications of intracoronary OCT and summarize the analytic OCT imaging software packages currently available. © 2017 Wiley Periodicals, Inc.
Angiographic assessment of aortic regurgitation by video‐densitometry in the setting of TAVI: Echocardiographic and clinical correlates
Authors: Abdelghani Mohammad , Tateishi Hiroki , Miyazaki Yosuke , Cavalcante Rafael , Soliman Osama I. I. , Tijssen Jan G. , de Winter Robbert J. , Baan Jan , Onuma Yoshinobu , Campos Carlos M. , Leite Rogério S. , Mangione José A. , Abizaid Alexandre , Lemos Pedro A. , de Brito Fabio S. , Serruys Patrick W.
Published: January 2017

Objectives

We sought to investigate a new angiographic method for aortic regurgitation (AR) severity assessment in the setting of transcatheter aortic valve implantation (TAVI).

Background

AR after TAVI is common but challenging to quantitate, especially in the cath‐lab.

Methods

In 228 patients, AR was quantitated before and after TAVI by echocardiography and by video‐densitometric analysis of aortograms. Contrast time–density curves for the aortic root (the reference region) and the left ventricular outflow tract, LVOT were generated. LVOT‐AR was calculated as the area under the curve of the LVOT as a fraction of the area under the curve of the reference region.

Results

LVOT‐AR was 0.10 ± 0.08, 0.13 ± 0.10 and 0.28 ± 0.14 in none‐trace, mild and moderate‐severe post‐TAVI AR as defined by echocardiography (P < 0.001) and a cutpoint of >0.17 corresponded to moderate‐severe AR on echocardiography (area under the curve = 0.84). At follow‐up (median, 496 days), patients with LVOT‐AR ≤ 0.17 showed a significant reduction of LV mass index (LVMi; 121 [95–148] vs. 140 [112–169] g/m2, P = 0.009) and the prevalence of LV hypertrophy (LVH; 64 vs. 88%, P = 0.001) compared to baseline. In patients with LVOT‐AR > 0.17, LVMi (149 [121–178] vs. 166 [144–188] g/m2, P = 0.14) and the prevalence of LVH (74 vs. 87%, P = 0.23) did not show a significant change. Compared to patients with LVOT‐AR ≤ 0.17, those with LVOT‐AR > 0.17 had an increased 30‐day (16.4% vs. 7.1%, P = 0.035) and one year mortality (32.9 vs. 14.2%, log rank P value = 0.001; HR: 2.690 [1.461–4.953], P = 0.001).

Conclusions

LVOT‐AR > 0.17 corresponds to greater than mild AR as defined by echocardiography and predicts impaired LV reverse remodeling and increased early and midterm mortality after TAVI. © 2017 Wiley Periodicals, Inc.
Pressurized liquid extraction of macauba pulp oil
Authors: Trentini Caroline Portilho , da Silva Sandra Beserra , Rodrigues Giovana Menezes , dos Santos Garcia Vitor Augusto , Cardozo‐Filho Lúcio , da Silva Camila
Published: January 2017

The aim of this study was to investigate the extraction of oil from macauba pulp using ethanol and isopropanol as pressurized solvents. Experiments were carried out in a semi‐continuous extractor system at various temperatures (40, 60, and 80 °C) maintaining the pressure fixed at 10 000 kPa and the solvent flow at 3 mL/min and also using conventional extraction (in a Soxhlet). For both methods assessed, higher yields were obtained with the use of ethanol as the solvent. In the pressurized liquid extraction (PLE), an increase in temperature from 40 to 60 °C provided higher yields at 72 min of extraction, which was not influenced by the extraction carried out at 80 °C. This temperature effect was also observed in the extraction kinetics data. The maximum yields obtained by PLE were 44.78 % and 37.12 % with ethanol and isopropanol, respectively, which represents ∼77 % of the yield obtained by conventional extraction. Oleic and palmitic acids are the main fatty acids identified in macauba pulp oil, representing ∼88 % of the fatty acids composition, which was not influenced by the extraction method and solvent used. PLE with ethanol provides oils with higher levels of β‐carotene. The flavonoid content was higher with the use of isopropanol; however, it was not influenced by the method used.
Comminution of biogenic materials
Authors: Eisenlauer Moritz , Teipel Ulrich
Published: January 2017

Renewable resources have been gaining increasing importance for energy generation in recent years. Lignocellulosic biomass, as an alternative to limited crude oil, can be utilized to produce these chemicals. The upstream process of comminution is a key element in the use of renewable raw materials. However, comminution is a highly energy consumptive process, making it necessary to assess the benefits of fine comminution in terms of reducing energy consumption by an adequate characterization of the products. The key factors to increased energy efficiency are, besides the mill type and the mill operation factors, the species of the renewable resource, in terms of water content and the mechanical properties which are the dominant factors in biomass size reduction. A better understanding of these interdependencies can help to improve the adjustment of particle size distribution and particle shape. As well as the total specific surface area and the energy demand for the comminution process, which impacts the overall efficiency of the supply chain process, disintegration, and the conversion. This work, therefore, focuses on the comminution of woody biomass in a cutting mill. It reports the effects of the influencing parameter of the biomass on the comminution process, the energy consumption, and the physical properties of the products regarding their particle size. Furthermore, selected experiments have been carried out on a swing hammer mill to compare the influence of the type of stressing.
Effect of storms during drought on post‐wildfire recovery of channel sediment dynamics and habitat in the southern California chaparral, USA
Authors: Florsheim Joan L. , Chin Anne , Kinoshita Alicia M. , Nourbakhshbeidokhti Samira
Published: January 2017

Current global warming projections suggest a possible increase in wildfire and drought, augmenting the need to understand how drought following wildfire affects the recovery of stream channels in relation to sediment dynamics. We investigated post‐wildfire geomorphic responses caused by storms during a prolonged drought following the 2013 Springs Fire in southern California (USA), using multi‐temporal terrestrial laser scanning and detailed field measurements. After the fire, a dry‐season dry‐ravel sediment pulse contributed sand and small gravel to hillslope‐channel margins in Big Sycamore Creek and its tributaries. A small storm in WY 2014 generated sufficient flow to mobilize a portion of the sediment derived from the dry‐ravel pulse and deposited the fine sediment in the channel, totaling ~0.60 m3/m of volume per unit length of channel. The sediment deposit buried step‐pool habitat structure and reduced roughness by over 90%. These changes altered sediment transport characteristics of the bed material present before and after the storm; the ratio of available to critical shear stress (τo/τc) increased by five times. Storms during WY 2015 contributed additional fine sediment from tributaries and lower hillslopes and hyperconcentrated flow transported and deposited additional sediment in the channel. Together these sources delivered sediment on the order of six times that in 2014, further increasing τo/τc. These storms during multi‐year drought following wildfire transformed channel dynamics. The increased sediment transport capacity persisted during the drought period characterized by the longer residence time of relatively fine‐grained post‐fire channel sedimentation. This contrasts with wetter years, when post‐fire sediment is transported from the fluvial system during the same season as the post‐fire sediment pulse. Results of this short‐term study highlight the complex and substantial effects of multi‐year drought on geomorphic responses following wildfire. These responses influence pool habitat that is critical to longer‐term post‐wildfire riparian ecosystem recovery. Copyright © 2017 John Wiley & Sons, Ltd.
An evolve‐then‐filter regularized reduced order model for convection‐dominated flows
Authors: Wells D. , Wang Z. , Xie X. , Iliescu T.
Published: January 2017

In this paper, we propose a new evolve‐then‐filter reduced order model (EF‐ROM). This is a regularized ROM (Reg‐ROM), which aims to add numerical stabilization to proper orthogonal decomposition (POD) ROMs for convection‐dominated flows. We also consider the Leray ROM (L‐ROM). These two Reg‐ROMs use explicit ROM spatial filtering to smooth (regularize) various terms in the ROMs. Two spatial filters are used: a POD projection onto a POD subspace (Proj) and a POD differential filter (DF). The four Reg‐ROM/filter combinations are tested in the numerical simulation of the three‐dimensional flow past a circular cylinder at a Reynolds number Re=1000. Overall, the most accurate Reg‐ROM/filter combination is EF‐ROM‐DF. Furthermore, the spatial filter has a higher impact on the Reg‐ROM than the regularization used. Indeed, the DF generally yields better results than Proj for both the EF‐ROM and L‐ROM. Finally, the CPU times of the four Reg‐ROM/filter combinations are orders of magnitude lower than the CPU time of the DNS. Copyright © 2017 John Wiley & Sons, Ltd.
The membrane‐bound O‐acyltransferase domain‐containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B
Authors: Thabet Khaled , Chan Henry Lik Yuen , Petta Salvatore , Mangia Alessandra , Berg Thomas , Boonstra Andre , Brouwer Willem P. , Abate Maria Lorena , Wong Vincent Wai‐Sun , Nazmy Maiiada , Fischer Janett , Liddle Christopher , George Jacob , Eslam Mohammed
Published: January 2017

Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane‐bound O‐acyltransferase domain‐containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty‐two patients underwent gene expression analysis to assess the functional consequences of rs641738 on hepatic MBOAT7 expression. The minor allele (T) of rs641738 was associated with greater inflammation (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06‐1.95; P = 0.001) and fibrosis (OR = 1.31; 95% CI, 1.19‐1.92; P = 0.01). Risk allele frequency in whites (0.43) was greater than in Chinese (0.24), translating to a larger size effect in the former. The rs641738 (T) allele was associated with lower hepatic MBOAT7 expression (P = 0.008), and the latter was associated with serum liver enzymes and inflammation. Neither patatin‐like phospholipase domain‐containing protein 3 rs738409 nor transmembrane 6 superfamily member 2 rs58542926 polymorphisms influenced disease severity. Conclusion: In patients with CHB, MBOAT7 rs641738 influences hepatic inflammation and fibrosis stage. (Hepatology 2017;65:1840‐1850).
Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation
Authors: Steinmetz Caroline , Kashyap Anubha , Zhivkova Nataliya , Alizor Henry , Ernst Isabell , Gottfried‐Brand Daniela , Janssen Henning , Teufel Andreas , Schulze‐Bergkamen Henning , Lotz Johannes , Kuball Jürgen , Theobald Matthias , Heise Michael , Lang Hauke , Galle Peter R. , Strand Dennis , Strand Susanne
Published: January 2017

Incidence and prevalence of inflammatory liver diseases has increased over the last years, but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune hepatitis (AIH). We investigated the immune‐suppressive mechanisms of the human pregnancy hormone, chorionic gonadotropin (hCG), in the liver. hCG signaling activates silent mating type information regulation 2 homolog 1 (SIRT1), which deacetylates forkhead box o3 (FOXO3a), leading to repression of proapoptotic gene expression, because the immunosuppressive consequence attributed to the absence of caspase‐3 activity of hepatocellular interleukin 16 (IL‐16) is no longer processed and released. Thus, serum levels of IL‐16, a key chemotactic factor for CD4+ lymphocytes, were reduced and migration to injured hepatocytes prevented. Furthermore, elevated IL‐16 levels are found in the sera from patients with AIH, hepatitis B virus, hepatitis C virus, and nonalcoholic steatohepatitis. Conclusion: Here, we report that hCG regulates the SIRT1/FOXO3a axis in hepatocytes, resulting in immune suppression by attenuating caspase‐3–dependent IL‐16 processing and release, which concomitantly prevents autoaggressive T‐cell infiltration of the liver. Considering the low toxicity profile of hCG in humans, interrupting the inflammatory cycle by hCG opens new perspectives for therapeutic intervention of inflammatory liver diseases. (Hepatology 2017;65:2074‐2089).
Implementation of the 7th edition AJCC staging system: Effects on staging and survival for pT1 melanoma. A Dutch population based study
Authors: Oude Ophuis Charlotte M.C. , Louwman Marieke W.J. , Grünhagen Dirk J. , Verhoef Kees , van Akkooi Alexander C.J.
Published: January 2017

In the 7th edition of the AJCC staging system, the mitotic rate criterion replaced Clark level to increase correct classification of high‐risk thin melanoma patients (pT1B). Additionally, sentinel node biopsy (SNB) was recommended for nodal staging of pT1B melanomas. The aim of this article was to evaluate the effects on pT1 substaging and clinical implications in the national pT1 melanoma population. All pT1 melanomas diagnosed in the Netherlands between 2003 and 2014 were selected from the Netherlands Cancer Registry (IKNL). Patients were stratified by cohort according to AJCC edition: (1) 2003–2009 (6th) and (2) 2010–2014 (7th). Relative survival was calculated to estimate melanoma‐specific survival. A total of 29.546 pT1 melanoma patients were included. The pT1b proportion increased from 10.1% in Cohort 1 to 21.5% in Cohort 2. The proportion of performed SNBs per cohort increased: for pT1b melanomas alone from 4.5% to 13.0%. SNB positivity rate decreased from 10.5% to 8.8% for the entire pT1 population, and for pT1b melanomas from 11.3% to 8.6%. At 5 years, the relative survival rate was similar for pT1a and pT1b in both cohorts, namely, pT1a 100% vs pT1b 97% (Cohort 1), and pT1a 100% vs pT1b 98% (Cohort 2). The 7th edition of the AJCC staging system has caused an increased number of patients to undergo SNB, without an increase in SNB positivity rate. Survival between pT1 subgroups remains similar. The mitotic rate criterion for pT1b classification and the recommendation to perform SNB for pT1b melanomas should be reconsidered.
Risk of high‐grade precancerous lesions and invasive cancers in high‐risk HPV‐positive women with normal cervix or CIN 1 at baseline—A population‐based cohort study
Authors: Mittal Srabani , Basu Partha , Muwonge Richard , Banerjee Dipanwita , Ghosh Ishita , Sengupta Mitali Mukherjee , Das Pradip , Dey Priatosh , Mandal Ranajit , Panda Chinmay , Biswas Jaydip , Sankaranarayanan Rengaswamy
Published: January 2017

Infection with high‐risk human papillomavirus (HR‐HPV) is transient and clears on its own in majority of the women. Only a few women who have persistent infection may finally develop cervical intraepithelial neoplasia (CIN) or cervical cancer in later years. The risk of progression in the HR‐HPV‐positive women with normal cervix or low‐grade lesion on colposcopy and histopathology at baseline is less studied. We performed a longitudinal study on 650 HR‐HPV‐positive women with colposcopy and/or histopathology‐proved normal or CIN1 diagnosis at baseline to assess the cumulative risk of development of high‐grade CIN. After a mean follow‐up of 2.1 person years of observation (PYO) (range 0.1–5.1), the cumulative incidence of CIN2+ (6.4%; 3.0/100 PYO) was significantly higher in women who had persistent HR‐HPV infection compared to those who cleared the infection (adjusted HR 6.28; 95% CI 2.87–13.73). The risk of viral persistence in women aged 50–60 years was two times higher compared to women aged 40–49 years and three times higher compared to women aged 30–39 years. The probability of having persistent infection increased progressively with higher viral load at baseline (adjusted HR 3.29, 95% CI 2.21–4.90 for RLU ≥100; adjusted HR 2.69, 95% CI 1.71–4.22 for RLU 10–100). Women with increasing viral load at follow‐up had four times higher risk of developing CIN2 or worse lesions as compared to those with decreasing load (20.9% vs 4.8%; p < 0.001). In the context of developing countries where cytology or genotyping triaging is not feasible, colposcopy referral of HR‐HPV‐positive women with advancing age, viral persistence, and increasing viral load may be considered.
Inhibition of group 1 p21‐activated kinases suppresses pancreatic stellate cell activation and increases survival of mice with pancreatic cancer
Authors: Yeo Dannel , Phillips Phoebe , Baldwin Graham S. , He Hong , Nikfarjam Mehrdad
Published: January 2017

Pancreatic cancer remains one of the most lethal of all solid tumors. Pancreatic stellate cells (PSCs) are primarily responsible for the fibrosis that constitutes the stroma and p21‐activated kinase 1 (PAK1) may have a role in signalling pathways involving PSCs. This study aimed to examine the role of PAK1 in PSCs and in the interaction of PSCs with pancreatic cancer cells. Human PSCs were isolated using the modified outgrowth method. The effect of inhibiting PAK1 with group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively. The effect of depleting host PAK1 on the survival of mice with pancreatic Pan02 cell tumors was evaluated using PAK1 knockout (KO) mice. PAK1 was expressed in isolated PSCs. FRAX597 reduced the activation of PSCs, inhibited PSC proliferation, and increased PSC apoptosis at least in partial by inhibiting PAK1 activity. The decreased expression and activity of PAK1 in PAK1 KO mice tumors was associated with an increased mouse survival. These results implicate PAK1 as a regulator of PSC activation, proliferation and apoptosis. Targeting stromal PAK1 could increase therapeutic response and survival of patients with pancreatic cancer.
Ab initio Modelling of Plasmons in Metal‐semiconductor Bilayer Transition‐metal Dichalcogenide Heterostructures
Authors: Sen Huseyin Sener , Xian Lede , H. da Jornada Felipe , Louie Steven G. , Rubio Angel
Published: January 2017

Two‐dimensional transition‐metal dichalcogenides (TMDs) have attracted enormous interest, due to the richness of their optical and electronic properties. Here, we consider two prototypical two‐dimensional TMD metal‐semiconductor bilayer heterostructures, VSe2‐MoSe2 and VSe2‐WSe2, and investigate the effect of the semiconducting layer on the plasmons supported by the metallic layer using first principles time‐dependent density functional theory (TDDFT) calculations. We focus on the flat region of the plasmon dispersion, where momentum transfer is larger than 0.05 Å−1 and the interband transitions gain importance. With the addition of the semiconducting layer, we show that the electronic band structure undergoes significant changes close to the Fermi level, and hybridization occurs, which leads to strengthening of the interband transitions and a significant redshift in the plasmon energy.
Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats
Authors: de Bakker Chantal MJ , Altman-Singles Allison R , Li Yihan , Tseng Wei-Ju , Li Connie , Liu X Sherry
Published: January 2017

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on postmenopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, whereas other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration, which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that whereas rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. © 2017 American Society for Bone and Mineral Research.
Serotonin transporter protects the placental cells against apoptosis in caspase 3‐independent pathway
Authors: Hadden Coedy , Fahmi Tariq , Cooper Anthonya , Savenka Alena V. , Lupashin Vladimir V. , Roberts Drucilla J. , Maroteaux Luc , Hauguel‐de Mouzon Sylvie , Kilic Fusun
Published: January 2017

Serotonin (5‐HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT‐knock out (KO), peripheral 5‐HT (TPH1)‐KO, and wild‐type (WT) mice, we explored the role of 5‐HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT‐KO placentas appeared only moderately in TPH1‐KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT. The etiology of these findings was tested with TUNEL assays. The placentas from SERT‐KO and TPH1‐KO showed 49‐ and 8‐fold increase in TUNEL‐positive cells without a concurrent change in the DNA repair or cell proliferation compared to WT placentas. While the proliferation rate in the embryos of TPH1‐KO mice was 16‐fold lower than the rate in gestational age matched embryos of WT or SERT‐KO mice. These findings highlight an important role of continuous 5‐HT signaling on trophoblast cell viability. SERT may contribute to protecting trophoblast cells against cell death via terminating the 5‐HT signaling which changes cell death ratio in trophoblast as well as proliferation rate in embryos. However, the cell death in SERT‐KO placentas is in caspase 3‐independent pathway.
The prognostic and therapeutic application of microRNAs in breast cancer: Tissue and circulating microRNAs
Authors: Bahrami Afsane , Aledavood Amir , Anvari Kazem , Hassanian Seyed Mahdi , Maftouh Mina , Yaghobzade Ali , Salarzaee Omid , ShahidSales Soodabeh , Avan Amir
Published: January 2017

Breast cancer is the second most common malignancy diagnosed in women, supporting the need for identification of novel prognostic and diagnostic biomarkers. Recently, microRNAs have emerged as molecular regulators that can have key roles in pathogenesis and progression of different malignancies, including breast cancer. Micro‐RNAs can be circulated in body fluid, suggesting their values as non‐invasive marker. There is growing body of evidence showing the aberrant activation of some known circulating miRNAs, for example let‐151a, miR‐21, miR‐155, miR‐,145 miR‐18a, miR‐16 as well as tissue specific‐miRNAs, for example miR‐182, miR‐145, miR‐21, miR‐155/154, miR‐203, miR‐213, miR‐7 in patients affected by breast cancer. In addition, there is growing body of evidences on the value of miRNAs to be associated with drug‐resistance, suggesting their values as a potential approach to overcome chemo‐resistance. Attuned with these facts, this review highlights recent preclinical and clinical investigation performed on tissue‐specific miRNAs and circulating as novel promising biomarkers for detection of patients at early stages, prediction of prognosis, and monitoring of the patients in response to therapy.
VSL#3 probiotic differently influences IEC‐6 intestinal epithelial cell status and function
Authors: Cinque Benedetta , La Torre Cristina , Lombardi Francesca , Palumbo Paola , Evtoski Zoran , Jr Santini Silvano , Falone Stefano , Cimini Annamaria , Amicarelli Fernanda , Cifone Maria Grazia
Published: January 2017

The data here reported introduce the wound‐healing assay as a tool for testing probiotics aimed at protecting gastrointestinal mucosal surfaces and to verify the consistency of their manufacturing. At the scope, we compared the in vitro effects of two multi‐strain high concentration formulations both commercialized under the same brand VSL#3 but sourced from different production sites (USA and Italy) on a non‐transformed small‐intestinal epithelial cell line, IEC‐6. The effects on cellular morphology, viability, migration, and H2O2‐induced damage, were assessed before and after the treatment with both VSL#3 formulations. While the USA‐sourced product (“USA‐made”) VSL#3 did not affect monolayer morphology and cellular density, the addition of bacteria from the Italy‐derived product (“Italy‐made”) VSL#3 caused clear morphological cell damage and strongly reduced cellularity. The treatment with “USA‐made” lysate led to a higher rate of wounded monolayer healing, while the addition of “Italy‐made” bacterial lysate did not influence the closure rate as compared to untreated cells. While lysates from “USA‐made” VSL#3 clearly enhanced the formation of elongated and aligned stress fibers, “Italy‐made” lysates had not similar effect. “USA‐made” lysate was able to cause a total inhibition of H2O2‐induced cytotoxic effect whereas “Italy‐made” VSL#3 lysate was unable to protect IEC‐6 cells from H2O2‐induced damage. ROS generation was also differently influenced, thus supporting the hypotesis of a protective action of “USA‐made” VSL#3 lysates, as well as the idea that “Italy‐made” formulation was unable to prevent significantly the H2O2‐induced oxidative stress.
A 250‐year drought catalogue for the island of Ireland (1765–2015)
Authors: Noone S. , Broderick C. , Duffy C. , Matthews T. , Wilby R.L. , Murphy C.
Published: January 2017

This work created a 250‐year historic drought catalogue by applying the Standardized Precipitation Index (SPI) to the Island of Ireland precipitation network (1850–2015) and a reconstructed precipitation series from 1765. Documentary sources from newspaper archives spanning the last 250 years, together with other historical sources are used to (1) add confidence to the quantitative detection of drought episodes and (2) gain insight to the socio‐economic impacts of historic droughts. The results show that Ireland is drought prone but recent decades are unrepresentative of the longer‐term drought climatology. A large decline in 30‐year accumulated SPI‐12 values is evident from around the 1990s onwards. During the years 1850–2015 seven major drought rich periods were identified with an island‐wide fingerprint in 1854–1860, 1884–1896, 1904–1912, 1921–1923, 1932–1935, 1952–1954 and 1969–1977. These events exhibit substantial diversity in terms of drought development, severity and spatial occurrence. Two exceptionally long events are found in the record: the continuous drought of 1854–1860 and the drought of 1800–1809 (in fact a series of three droughts with brief interludes). Over the last 250 years, droughts have resulted in agricultural hardship, water resource crises and failures and preceded some of the major famines of the eighteenth and nineteenth centuries. This work shows that newspaper archives can be used to trace the progression of drought events and impacts and we thus advocate their wider use in corroborating quantitative assessments. The resulting catalogue challenges prevailing perceptions about drought in Ireland while strengthening the evidence base for future drought and water resource planning across the island.
Lack of critical thinking skills leading to research crisis in developing countries: A case of Pakistan
Authors: Nauman Sarwat
Published: January 2017

Key points

Increasing funding for research may not improve the quality of research.

Pakistan is investing heavily in research with commensurate increases in publications.

Pakistan's increase in article output is not being matched with increased quality – is this due to a fundamental problem with critical thinking skills?

All developing countries need to focus on critical thinking skills to realize the best use of their research funding.
Versatility of Pyrylium Salt/Vinyl Ether Initiating System for Epoxide Dual‐Cure Polymerization: Kick‐Starting Effect of the Coinitiator
Authors: Lecompère Maxime , Allonas Xavier , Maréchal David , Criqui Adrien
Published: January 2017

Pyrylium salts combined with vinyl ethers are shown to act as new versatile dual‐cure initiating systems for both photochemical and thermal initiation of oxirane monomers. The combination of both possibilities allows the curing of thick samples through photoinduced frontal polymerization. On the basis of quantum calculations and photochemical experiments, some clues are given about the reaction mechanisms involved. Interestingly, a sequential kick‐starting effect is observed in the presence of vinyl ether enabling the curing of oxetane monomers. Thereby, this communication presents a short overview of potential of pyrylium salts in cationic polymerization of oxiranes.

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A Simplified Version of the Psychogenic Movement Disorders Rating Scale: The Simplified Functional Movement Disorders Rating Scale (S‐FMDRS)
Authors: Nielsen Glenn , Ricciardi Luciana , Meppelink Anne Marthe , Holt Kate , Teodoro Tiago , Edwards Mark
Published: January 2017

Background

The Psychogenic Movement Disorders Rating Scale (PMDRS) has potential as a useful objective assessment in clinical research, but the current scale has limitations. We developed a simplified version (S‐FMDRS) and assessed inter‐rater reliability, concurrent validity, and sensitivity.

Methods

Fifty‐two videos of subjects with functional (psychogenic) movement disorders (FMD) were rated according to the PMDRS and S‐FMDRS by three neurologists. Inter‐rater reliability was assessed using intraclass correlation coefficient (ICC). Agreement of symptomatic body regions and movement disorder classification was assessed using Light's kappa. Spearman's correlation coefficient was used to assess concurrent validity. A physiotherapist also rated videos on the S‐FMDRS. The simplified scale was piloted in a feasibility study of physiotherapy for FMD to assess sensitivity.

Results

ICC of total scores was 0.84 for the original scale and 0.85 for the simplified scale. Light's kappa for agreement of symptomatic body regions and movement disorder classification was moderate to low. Concurrent validity was demonstrated by Spearman's correlation between the two scales ranging from 0.84 to 0.95. The simplified scale was sensitive to change, with an effect size in the feasibility study of 0.79. Inter‐rater reliability between physiotherapist and neurologist was high (ICC 0.85).

Discussion

Both versions of the scale had good inter‐rater reliability for the total score. Low agreement on movement disorder classification and identification of symptomatic body regions support our argument for a simplified scale.

Conclusions

The S‐FMDRS has high inter‐rater reliability and good sensitivity to change. Further psychometric evaluation is warranted.
Constant risk aversion in stochastic contests with exponential completion times
Authors: Canbolat Pelin G. , Rothblum Uriel G.
Published: January 2017

This article analyzes a class of stochastic contests among multiple players under risk‐averse exponential utility. In these contests, players compete over the completion of a task by simultaneously deciding on their investment, which determines how fast they complete the task. The completion time of the task for each player is assumed to be an exponentially distributed random variable with rate linear in the player's investment and the completion times of different players are assumed to be stochastically independent. The player that completes the task first earns a prize whereas the remaining players earn nothing. The article establishes a one‐to‐one correspondence between the Nash equilibrium of this contest with respect to risk‐averse exponential utilities and the nonnegative solution of a nonlinear equation. Using the properties of the latter, it proves the existence and the uniqueness of the Nash equilibrium, and provides an efficient method to compute it. It exploits the resulting representation of the equilibrium investments to determine the effects of risk aversion and the differences between the outcome of the Nash equilibrium and that of a centralized version.© 2016 Wiley Periodicals, Inc. Naval Research Logistics 66:4–14, 2019
PEG‐based organic–inorganic hybrid coatings prepared by the sol–gel dip‐coating process for biomedical applications
Authors: Catauro Michelina , Papale Ferdinando , Piccirillo Giusi , Bollino Flavia
Published: January 2017

In the present work, the application of functional coatings on metallic implants was proposed to delay implant failure by improving tissue tolerance and implant osseointegration. Three bioactive and biocompatible organic–inorganic hybrid nanocomposites, consisting of polyethylene glycol (PEG) embedded in a SiO2, ZrO2, and TiO2 matrix, respectively, were synthesized via the sol–gel method. Materials in the sol phase were used to dip‐coat titanium grade 4 substrates for use as dental and orthopedic implant models. To investigate the influence of the glass matrix and the polymer amount on the coating structure, and thus on their biological properties, several hybrids were obtained by adding different weight percentages of PEG to each glass matrix. Attenuated total reflectance Fourier transform infrared spectroscopy confirmed the presence of the polymer in the nanocomposites and scanning electron microscopy showed that an increase in the PEG content allows crack‐free coatings to be obtained. Moreover, the bioactivity and biocompatibility of both the uncoated and coated titanium implants were investigated and compared by an in vitro test. The results revealed that coated substrates have more enhanced biological performance than the uncoated ones. The bioactivity is not significantly affected by either the inorganic matrix or the PEG amount, whereas the presence of polymer makes the films more biocompatible. POLYM. ENG. SCI., 57:478–484, 2017. © 2017 Society of Plastics Engineers