bluuebunny/crossref_metadata_2025 huggingface dataset:
Multinucleotide mutations cause false inferences of lineage-specific positive selection
Authors: Venkat Aarti , Hahn Matthew W. , Thornton Joseph W.
Published: July 2017

Phylogenetic tests of adaptive evolution, which infer positive selection from an excess of nonsynonymous changes, assume that nucleotide substitutions occur singly and independently. But recent research has shown that multiple errors at adjacent sites often occur in single events during DNA replication. These multinucleotide mutations (MNMs) are overwhelmingly likely to be nonsynonymous. We therefore evaluated whether phylogenetic tests of adaptive evolution, such as the widely used branch-site test, might misinterpret sequence patterns produced by MNMs as false support for positive selection. We explored two genome-wide datasets comprising thousands of coding alignments – one from mammals and one from flies – and found that codons with multiple differences (CMDs) account for virtually all the support for lineage-specific positive selection inferred by the branch-site test. Simulations under genome-wide, empirically derived conditions without positive selection show that realistic rates of MNMs cause a strong and systematic bias in the branch-site and related tests; the bias is sufficient to produce false positive inferences approximately as often as the branch-site test infers positive selection from the empirical data. Our analysis indicates that genes may often be inferred to be under positive selection simply because they stochastically accumulated one or a few MNMs. Because these tests do not reliably distinguish sequence patterns produced by authentic positive selection from those caused by neutral fixation of MNMs, many published inferences of adaptive evolution using these techniques may therefore be artifacts of model violation caused by unincorporated neutral mutational processes. We develop an alternative model that incorporates MNMs and may be helpful in reducing this bias.
Context-dependent Requirements for FimH and Other Canonical Virulence Factors in Gut Colonization by Extraintestinal PathogenicEscherichia coli
Authors: Russell Colin W. , Fleming Brittany A. , Stenquist Alan T. , Wambaugh Morgan A. , Bronner Mary P. , Mulvey Matthew A.
Published: July 2017

Extraintestinal pathogenicEscherichia coli(ExPEC) act as commensals within the mammalian gut, but can induce pathology upon dissemination to other host environments such as the urinary tract and bloodstream. It is thought that ExPEC genomes are shaped in large part by evolutionary forces encountered within the gut where the bacteria spend much of their time, provoking the question of how their extraintestinal virulence traits arose. The principle of coincidental evolution, in which a gene that evolved in one niche happens to be advantageous in another, has been used to argue that ExPEC virulence factors originated in response to selective pressures within the gut ecosystem. As a test of this hypothesis, the fitness of ExPEC mutants lacking canonical virulence factors was assessed within the intact murine gut in the absence of any antibiotic treatment. We found that most of the tested factors—including CNF1, Usp, colibactin, flagella, and the plasmid pUTI89—were dispensable for gut colonization. Deletion of genes encoding the adhesin PapG or the toxin HlyA caused transient defects, but did not affect longer-term persistence. In contrast, a mutant missing the type 1 pilus-associated adhesin FimH displayed reduced persistence within the gut. However, this phenotype was variable, being dependent on the presence of specific competing strains and partially attributable to aberrant flagellin expression by thefimHmutant. These data indicate that FimH and other key ExPEC-associated factors are not strictly required for gut colonization, suggesting that selective pressures within the gut do not drive the development of all extraintestinal virulence traits.
Whole genome optical mapping reveals multiple fusion events chained by large novel sequences in cancer
Authors: Chan Eva K.F. , Petersen Desiree C. , Lyons Ruth J. , Baldi Benedetta F. , Papenfuss Anthony T. , Thomas David M. , Hayes Vanessa M.
Published: July 2017

Genomic rearrangements are common in cancer, with demonstrated links to disease progression and treatment response. These rearrangements can be complex, resulting in fusions of multiple chromosomal fragments and generation of derivative chromosomes. While methods exist for detecting individual fusions, they are generally unable to reconstruct complex chained events. To overcome these limitations, we adopted a new optical mapping approach, allowing for megabase length DNA to be captured, and in turn rearranged genomes to be visualized without loss of integrity. Whole genome mapping (Bionano Genomics) of a well-studied highly rearranged liposarcoma cell line, resulted in 3,338 assembled haploid genome maps, including 101 fusion maps. These fusion maps represent 175 Mb of highly rearranged genomic regions, illuminating the complex architecture of chained fusions, including content, order, orientation, and size. Spanning the junction of 151 chromosomal translocations, we found a total of 32 Mb of novel interspersed sequences that were not detected from short-read sequencing. We demonstrate that optical mapping provides a powerful new approach for capturing a higher level of complex genomic architecture, creating a scaffold for renewed interpretation of sequencing data of particular relevance to human cancer.
Genome expansion and lineage-specific genetic innovations in the world’s largest organisms (Armillaria)
Authors: Sipos György , Prasanna Arun N. , Walther Mathias C. , O’Connor Eoin , Bálint Balázs , Krizsán Krisztina , Kiss Brigitta , Hess Jaqueline , Varga Torda , Slot Jason , Riley Robert , Bóka Bettina , Rigling Daniel , Barry Kerrie , Lee Juna , Mihaltcheva Sirma , Labutti Kurt , Lipzen Anna , Waldron Rose , Moloney Nicola M. , Sperisen Christoph , Kredics László , Vágvölgyi Csaba , Patrigniani Andrea , Fitzpatrick David , Nagy István , Doyle Sean , Anderson James B. , Grigoriev Igor V. , Güldener Ulrich , Münsterkötter Martin , Nagy László G
Published: July 2017

Armillariaspecies are both devastating forest pathogens and some of the largest terrestrial organisms on Earth. They forage for hosts and achieve immense colony sizes using rhizomorphs, root-like multicellular structures of clonal dispersal. Here, we sequenced and analyzed genomes of fourArmillariaspecies and performed RNA-Seq and quantitative proteomic analysis on seven invasive and reproductive developmental stages of A. ostoyae. Comparison with 22 related fungi revealed a significant genome expansion inArmillaria, affecting several pathogenicity-related genes, lignocellulose degrading enzymes and lineage-specific genes likely involved in rhizomorph development. Rhizomorphs express an evolutionarily young transcriptome that shares features with the transcriptomes of fruiting bodies and vegetative mycelia. Several genes show concomitant upregulation in rhizomorphs and fruiting bodies and shared cis-regulatory signatures in their promoters, providing genetic and regulatory insights into complex multicellularity in fungi. Our results suggest that the evolution of the unique dispersal and pathogenicity mechanisms ofArmillariamight have drawn upon ancestral genetic toolkits for wood-decay, morphogenesis and complex multicellularity.
Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control
Authors: Carroni Marta , Franke Kamila B. , Maurer Michael , Jäger Jasmin , Hantke Ingo , Gloge Felix , Linder Daniela , Gremer Sebastian , Turgay Kürşad , Bukau Bernd , Mogk Axel
Published: July 2017

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.
The importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis
Authors: Tan Queenie K.-G. , McConkie-Rosell Allyn , Juusola Jane , Gustafson Kathryn E. , Pizoli Carolyn E. , Buckley Anne F. , Jiang Yong-hui
Published: July 2017

GLE1 encodes a protein important for mRNA export and appears to play roles in translation initiation and termination as well. Pathogenic variants in GLE1 mutations have been associated with lethal contracture syndrome and lethal arthrogryposis with anterior horn cell disease; phenotypes reported in individuals include fetal akinesia and a severe form of motor neuron disease, typically presenting with prenatal symptoms and perinatal lethality. In this article, we identified biallelic missense mutations in GLE1 by trio whole-exome sequencing in an individual affected with congenital motor weakness and contractures as well as feeding and respiratory difficulties. Muscle biopsy was consistent with anterior horn cell disease and supported the pathogenicity of the sequence variants. Importantly, this individual survived past the perinatal period with respiratory support and currently demonstrates age-appropriate cognition and slow but steady motor developmental progress. We propose that pathogenic variants in GLE1 can be associated with a nonperinatal lethal motor phenotype, and affected individuals can demonstrate motor skill progression, unlike prototypical anterior horn cell diseases such as spinal muscular atrophy.
Ethyl 2-(4-methoxyphenyl)-6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate: crystal structure and Hirshfeld analysis
Authors: Zukerman-Schpector Julio , Sugiyama Fabricia H. , Garcia Ariel L. L. , Correia Carlos Roque D. , Jotani Mukesh M. , Tiekink Edward R. T.
Published: July 2017

The title compound, C14H17NO4, features an epoxide-O atom fused to a pyrrolidyl ring, the latter having an envelope conformation with the N atom being the flap. The 4-methoxyphenyl group is orthogonal to [dihedral angle = 85.02 (6)°] and lies to the opposite side of the five-membered ring to the epoxide O atom, while the N-bound ethyl ester group (r.m.s. deviation of the five fitted atoms = 0.0187 Å) is twisted with respect to the ring [dihedral angle = 17.23 (9)°]. The most prominent interactions in the crystal are of the type methine-C—H...O(carbonyl) and these lead to the formation of linear supramolecular chains along the c axis; weak benzene-C—H...O(epoxide) and methine-C—H...O(methoxy) interactions connect these into a three-dimensional architecture. The analysis of the Hirshfeld surface confirms the presence of C—H...O interactions in the crystal, but also the dominance of H...H dispersion contacts.
Crystal structures of three 1-[4-(4-bromobutoxy)phenyl] chalcone derivatives: (E)-1-[4-(4-bromobutoxy)phenyl]-3-phenylprop-2-en-1-one, (E)-1-[4-(4-bromobutoxy)phenyl]-3-(4-methoxyphenyl)prop-2-en-1-one and (E)-1-[4-(4-bromobutoxy)phenyl]-3-(3,4-dimethoxyphenyl)prop-2-en-1-one
Authors: Maragatham Gunasekaran , Selvarani Sivasamy , Rajakumar Perumal , Lakshmi Srinivasakannan
Published: July 2017

The crystal structures of three chalcones with a bromo-substituted butoxy side chain, viz. (E)-1-[4-(4-bromobutoxy)phenyl]-3-phenylprop-2-en-1-one, C19H19BrO2, (I), (E)-1-[4-(4-bromobutoxy)phenyl]-3-(4-methoxyphenyl)prop-2-en-1-one, C20H21BrO3, (II), and (E)-1-[4-(4-bromobutoxy)phenyl]-3-(3,4-dimethoxyphenyl)prop-2-en-1-one, C21H23BrO4, (III), are reported. In all molecules, the conformation of the keto group with respect to the olefinic bond is s-cis. Molecules of (I) and (II) are nearly planar, while molecule (III) is not planar. In the crystal of compounds (I) and (II), molecules are linked into chains parallel to the c axis by C—H...π interactions. In the crystal of compound (III), molecules are linked by a pairs of C—H...O hydrogen bonds, forming inversion dimers. Weak C—Br...π interactions are also observed in (III).
Crystallographic and spectroscopic characterization of 5-chloropyridine-2,3-diamine
Authors: Sulovari Aron , Tanski Joseph M.
Published: July 2017

The two ortho-amino groups of the title compound, C5H6ClN3, twist out of the plane of the molecule to minimize intramolecular interaction between the amino hydrogen atoms. In the crystal, the amino groups and the pyridine N atom engage in intermolecular hydrogen bonding. The molecules pack into spiral hydrogen-bonded columns with offset face-to-face π-stacking.
Structure of Equilenin at 100 K: an estrone-related steroid
Authors: Frampton Christopher S. , MacNicol David D.
Published: July 2017

The structure of the estrone-related steroid, Equilenin, C18H18O2 (systematic name 3-hydroxy-13-methyl-11,12,13,14,15,16-hexahydrocyclopenta[a]phenanthren-17-one), has been determined at 100 K. The crystals are orthorhombic, P212121, and the absolute structure of the molecule in the crystal has been determined by resonant scattering [Flack parameter = −0.05 (4)]. The C atoms of the A and B rings are almost coplanar, with an r.m.s. deviation from planarity of 0.0104 Å. The C ring has a sofa conformation, while the D ring has an envelope conformation with the methine C atom as the flap. The keto O atom and the methyl group are translated 0.78 and 0.79 Å, respectively, from the equivalent positions on 17β-estrone. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming chains parallel to the c-axis direction.
Bis(tetra-n-butylammonium) bis(5,6-dicyanopyrazine-2,3-dithiolato-κ2
S,S′)nickelate(II)
Authors: Tomura Masaaki
Published: July 2017

In the title salt, (C16H36N)2[Ni(C6N4S2)2], the centrosymmetric complex dianion is planar, with an r.m.s. deviation of 0.031 (1) Å. The NiII atom, lying on an inversion centre, has an almost undistorted square-planar coordination geometry, with Ni—S bond lengths of 2.1606 (5) and 2.1759 (5) Å.
The molecular ecology of Microcystis sp. blooms in the San Francisco Estuary
Authors: Otten Timothy G. , Paerl Hans W. , Dreher Theo W. , Kimmerer Wim J. , Parker Alexander E.
Published: July 2017

Harmful blooms of the cyanobacterium Microcystis sp. have become increasingly pervasive in the San Francisco Estuary Delta (USA) since the early 2000s and their rise has coincided with substantial decreases in several important fish species. Direct and indirect effects Microcystis blooms may have on the Delta food web were investigated. The Microcystis population was tracked for 2 years at six sites throughout the Delta using quantitative PCR. High‐throughput amplicon sequencing and colony PCR sequencing revealed the presence of 10 different strains of Microcystis, including 6 different microcystin‐producing strains. Shotgun metagenomic analysis identified a variety of Microcystis secondary metabolite pathways, including those for the biosynthesis of: aeruginosin, cyanopeptolin, microginin, microviridin and piricyclamide. A sizable reduction was observed in microbial community diversity during a large Microcystis bloom (H′ = 0.61) relative to periods preceding (H′ = 2.32) or following (H′ = 3.71) the bloom. Physicochemical conditions of the water column were stable throughout the bloom period. The elevated abundance of a cyanomyophage with high similarity to previously sequenced isolates known to infect Microcystis sp. was implicated in the bloom's collapse. Network analysis was employed to elucidate synergistic and antagonistic relationships between Microcystis and other bacteria and indicated that only very few taxa were positively correlated with Microcystis.
‘I cover myself in the blood of Jesus’: Born Again heritage making in Sierra Leone
Authors: Zetterström‐Sharp Johanna
Published: July 2017

This article concerns the risky terrain of heritage management in Sierra Leone and its navigation by devout Born Again Pentecostal Christians. It engages with the ever‐expanding Born Again movement and its narrative of rupture, on the one hand, and the increasingly visible heritage sector and its focus on cultural continuity, on the other. These positions appear irreconcilable: one experiences the past as a dangerous satanic realm, the other as a valuable resource. However, as this article explores, they frequently meet in the workplace as many heritage professionals are also Born Again believers. I am interested in this meeting‐point as demonic channels and godly practices converge. I argue that Freetown's Born Again heritage professionals do not succeed in their roles despite their religion, but because of it.
Writing against loss: Kurdish women, subaltern authorship, and the politics of voice in contemporary Turkey
Authors: Schäfers Marlene
Published: July 2017

This article focuses on the appeal that writing and authorship hold for Kurdish women singers in contemporary Turkey. It argues that authorship has come to the fore as an object of aspiration at a moment when a history of political silencing intersects with a more recent commodification of Kurdish culture. In this context, authorship constitutes an avenue for Kurdish women to insert themselves into struggles for political rights, discourses of history writing, and an emerging cultural market. Yet, as the analysis shows, becoming an author centrally relies on gaining access to means that allow materially inscribing voices and making them durable. Authorship therefore needs to be recognized as a fragile achievement, especially for subaltern authors, whose position is marked by restricted access to inscriptive means. Tracing Kurdish women's attempts at making their voices, quite literally, matter, the article contributes to our understanding of the politics of voice in the contemporary world.
Mycotoxin Contamination of Maize in China
Authors: Sun Xiang Dong , Su Ping , Shan Hong
Published: July 2017

China is a major cereal‐producing country and almost one third of the annual cereal yield is maize. The maize plant and kernel are prone to infection by fungal attack and are most likely to be contaminated with mycotoxins under suitable temperature and humidity conditions, during both the growing and storage period. A number of investigations conducted in China have demonstrated that maize had been infected by fungi and contaminated with mycotoxins to varying degrees. Although most of the maize produced in China is used as feed and raw materials for the chemistry industry, a small amount of maize is consumed directly by humans and the hazards of mycotoxin to humans cannot be ignored. The state of mycotoxin contamination of maize in China is analyzed in this review. Due to unfavorable weather and poor storage conditions, the high incidences of mycotoxin contamination of maize are of great concern to the Chinese. It is imperative for the national and local governments to increase investments on building large‐scale modern warehouses and instructing farmers to grow, harvest, and store maize safely. Meanwhile, due to accumulative toxic effects of mycotoxins, quality control should be enforced to guarantee that animal products are safe for human consumption.
Characterization of Metabolic Pathways and Absorption of Sea Cucumber Saponins, Holothurin A and Echinoside A, in Vitro and in Vivo
Authors: Song Shanshan , Zhang Lingyu , Cao Jian , Xiang Gao , Cong Peixu , Dong Ping , Li Zhaojie , Xue Changhu , Xue Yong , Wang Yuming
Published: July 2017

Sea cucumber saponins (SCSs) exhibit a wide spectrum of bioactivities, but their metabolic characteristics are not well elucidated. In this study, the metabolism of holothurin A (HA) and echinoside A (EA), 2 major saponins in sea cucumber, by gut microflora were investigated. First, we conducted an in vitro study, where in the SCSs were incubated with intestinal microflora and the metabolites were detected by high pressure liquid chromatography–high resolution mass spectrometry. We also conducted an in vivo study on rats, where in the intestinal contents, serum, urine, and feces were collected and evaluated after oral administration of SCSs. In the in vitro study, we identified 6 deglycosylated metabolites of HA and EA, assigned M1‐M6. In the in vivo study, we found all the deglycosylated metabolites in the intestinal contents after oral administration, and both the metabolites and their prototype components could be absorbed. Four metabolites were identified in the serum, 6 in the urine, and 4 in the feces. The saponins with different structures showed different absorption characteristics in rats. According to our results, deglycosylation is the main intestinal microflora‐mediated metabolic pathway for SCSs, and both the SCSs and deglycosylated metabolites can be absorbed by intestine. This study improves the understanding of the metabolism of HA and EA by gut flora, which will be useful for further analysis of the bioactivity mechanism of SCSs.
Characteristic Flavor of Traditional Soup Made by Stewing Chinese Yellow‐Feather Chickens
Authors: Qi Jun , Liu Deng‐yong , Zhou Guang‐hong , Xu Xing‐lian
Published: July 2017

The traditional recipe for Chinese chicken soup creates a popular taste of particular umami and aroma. The present study investigated the effects of stewing time (1, 2, and 3 h) on the principal taste‐active and volatile compounds and the overall flavor profile of traditional Chinese chicken soup by measuring the contents of free amino acids (FAAs), 5′‐nucleotides, minerals and volatile compounds and by evaluating the taste and aroma profiles using an electronic nose, an electronic tongue and a human panel. Results showed that the major umami‐related compounds in the chicken soup were inosine 5′‐monophosphate (IMP) and chloride, both of which increased significantly (P < 0.05) during stewing. The taste active values (TAVs) of the equivalent umami concentration (EUC) increased from 4.08 to 9.93 (P < 0.05) after stewing for 3 h. Although the FAA and mineral contents increased significantly (P < 0.05), their TAVs were less than 1. The volatile compounds were mainly hexanal, heptanal, octanal, nonanal, (E)‐2‐nonanal, (E)‐2‐decenal, (E,E)‐2,4‐decadienal, 1‐hexanol, and 2‐pentyl furan. With the prolonged stewing time, the aldehydes first increased and then decreased significantly (P < 0.05), while 1‐hexanol and 2‐pentyl furan increased steadily (P < 0.05). The aroma scores of the chicken soup reached the maximum after stewing for 3 h. The discrepancy in overall flavor characteristics tended to stabilize after 2 h of stewing. In general, stewing time has a positive effect on improving the flavor profiles of chicken soup, especially within the first 2 h.
Relating switching rates between normal and persister cells to substrate and antibiotic concentrations: a mathematical modelling approach supported by experiments
Authors: Carvalho Gabriel , Guilhen Cyril , Balestrino Damien , Forestier Christiane , Mathias Jean‐Denis
Published: July 2017

We developed and compared two mathematical models of variable phenotypic switching rates between normal and persister cells that depend on substrate concentration and antibiotic presence. They could be used to simulate the formation of persisters in environments with concentration gradients such as biofilms. Our models are extensions of a previous model of the dynamics of normal and persistent cell populations developed by Balaban et al. (2004, Science 305: 1622). We calibrated the models’ parameters with experimental killing curves obtained after ciprofloxacin treatment of samples regularly harvested from planktonic batch cultures of Klebsiella pneumoniae. Our switching models accurately reproduced the dynamics of normal and persistent populations in planktonic batch cultures and under antibiotic treatment. Results showed that the models are valid for a large range of substrate concentrations and for zero or high doses of antibiotics.
Psoriatic arthritis treatment regimens, therapy duration and reasons for cessation in the biologics era: a multi‐centre Australian study
Authors: Tymms Kathleen , Kelly Ayano , Bird Paul , Griffiths Hedley , de Jager Julien , Littlejohn Geoff , Louw Sandra , Roberts Lynden , Youssef Peter , Zochling Jane , Nichols Dave
Published: July 2017

Aim

To describe the treatment regimens, duration of therapy and reasons for disease‐modifying antirheumatic drug (DMARD) cessation in a large psoriatic arthritis (PsA) cohort.

Methods

A retrospective non‐interventional multi‐centre study using Audit4 electronic medical records, with de‐identified, routinely collected clinical data from rheumatology practices in the OPAL consortium (Optimising Patient outcomes in Australian rheumatoLogy) during November 2015. Baseline characteristics, type and duration of conventional and biologic DMARDs (cDMARD and bDMARD, respectively), disease activity (Disease Activity Score of 28 joints C‐reactive protein [DAS28‐CRP]), and reasons for treatment cessation were recorded.

Results

A total of 3422 rheumatologist‐diagnosed PsA patients were included: 60% female, mean age 54 years and disease duration 10 years. Of patients with treatment recorded (n = 2948), 46% were on cDMARD monotherapy, 19% bDMARD monotherapy, 13% combination bDMARD and cDMARDs, 11% combination cDMARDs and 10% no DMARDs. Of those with DAS28‐CRP results (n = 494), the highest mean DAS28‐CRP was 3.32 on combination cDMARDs, and the lowest was 2.19 on bDMARD monotherapy. Median duration on cDMARD monotherapy was 33.5 months (n = 2232), on bDMARD monotherapy 110.1 months (n = 751), on combination bDMARD and cDMARDs 68.5 months (n = 559). The most common reasons for cessation of cDMARD monotherapy was adverse reactions (41%), for bDMARD monotherapy lack of efficacy (26%), and for combination bDMARD and cDMARDs treatment completed or no longer required (37%).

Conclusion

Most PsA patients were prescribed DMARD therapies with a large proportion receiving cDMARDs. Patients on combination cDMARD therapies had the highest DAS28‐CRP results. Adverse reactions were the most common reason for cessation of cDMARD monotherapy, whereas for bDMARD monotherapy it was lack of efficacy.
2016 updated Thai Rheumatism Association Recommendations for the use of biologic and targeted synthetic disease‐modifying anti‐rheumatic drugs in patients with rheumatoid arthritis
Authors: Louthrenoo Worawit , Kasitanon Nuntana , Katchamart Wanruchada , Aiewruengsurat Duangkamol , Chevaisrakul Parawee , Chiowchanwisawakit Praveena , Dechanuwong Pornchai , Hanvivadhanakul Punchong , Mahakkanukrauh Ajanee , Manavathongchai Siriporn , Muangchan Chayawee , Narongroeknawin Pongthorn , Phumethum Veerapong , Siripaitoon Boonjing , Suesuwan Anawat , Suwannaroj Siraphop , Uea‐Areewongsa Parichat , Ukritchon Sittichai , Asavatanabodee Paijit , Koolvisoot Ajchara , Nanagara Ratanavadee , Totemchokchyakarn Kitti , Nuntirooj Kanokrut , Kitumnuaypong Tasanee
Published: July 2017

Aim

In June 2015, the Thai Rheumatism Association (TRA) approved an update of its recommendation for the use of biologic disease‐modifying anti‐rheumatic drugs (bDMARDs) and targeted synthetic (tsDMARD) in the treatment of rheumatoid arthritis (RA) to cover those currently available in Thailand (etanercept, infliximab, golimumab, rituximab, tocilizumab, abatacept and tofacitinib).

Method

A search of the literature was performed between January 2000 and June 2015. Existing RA recommendations, in relation to the use of bDMARDs and tsDMARD, were identified and evaluated by the AGREE II instrument prior to their use as a ‘guide’ for developing this TRA recommendation. An additional literature search was performed in order to answer specific clinical questions that could not be found in existing guidelines.

Result

Thirteen recommendations were developed. They covered the use of RA classification criteria, the aim of RA treatment, when to initiate bDMARDs/tsDMARD or taper or switch them to other medications, as well as monitoring these drugs during their use. In addition, specific issues including their use and vaccination, malignancies, pregnancy and lactation, and perioperative period also were addressed. Public hearings were performed at the annual meeting of the TRA and of the Royal College of Physicians of Thailand. The recommendations were distributed to other professional associations related to RA management, as well as government sectors associated with the reimbursement policy, prior to development of the final version.

Conclusion

These recommendations will help Thai rheumatologists prescribe bDMARDs and tsDMARD more appropriately when treating RA patients.
Effect of excessive gestational weight gain on trial of labour after caesarean: A retrospective cohort study
Authors: McDonald Anna C. E. , Wise Michelle R. , Thompson John M.
Published: July 2017

Background

Counselling women for and managing birth after caesarean section are important. Research is needed on evaluation of antenatal factors that predict likelihood of successful trial of labour after caesarean section (TOLAC).

Aim

To evaluate the effect of gestational weight gain on mode of delivery in women having TOLAC.

Materials and methods

A retrospective cohort study of eligible women who underwent TOLAC (January 2012 to July 2015) at a large urban hospital. Gestational weight gain was classified as ‘excessive’ or ‘not excessive’ based on calculated pre‐pregnancy body mass index. Multivariable logistic regression analysis was performed to estimate the association of gestational weight gain and vaginal birth, adjusting for socio‐demographic and pregnancy‐related factors.

Results

Of 534 women, those who gained excessive weight were less likely to have a vaginal birth as women who did not (adjusted odds ratio (aOR) 0.48, 95% confidence interval (CI) 0.29–0.81)). Women with previous vaginal birth were more likely to have a vaginal birth (aOR 3.74, 95% CI 1.90–7.36), while women ≥35, women who had an epidural, and women who delivered at 40 weeks, were less likely (aOR 0.58, 95% CI 0.35–0.97, aOR 0.12, 95% CI 0.07–0.22, and aOR 0.53, 95% CI 0.31–0.91, respectively).

Conclusions

Gaining excessive weight in pregnancy is potentially modifiable, and can be incorporated into individual antenatal counselling, and into risk prediction models, to assist with informed decision making around planned mode of delivery in women with previous caesarean section. Future research could focus on interventions to reduce gestational weight gain in women planning TOLAC.
Extending the Use and Prediction Precision of Subnational Public Opinion Estimation
Authors: Leemann Lucas , Wasserfallen Fabio
Published: July 2017

The comparative study of subnational units is on the rise. Multilevel regression and poststratification (MrP) has become the standard method for estimating subnational public opinion. Unfortunately, MrP comes with stringent data demands. As a consequence, scholars cannot apply MrP in countries without detailed census data, and when such data are available, the modeling is restricted to a few variables. This article introduces multilevel regression with synthetic poststratification (MrsP), which relaxes the data requirement of MrP to marginal distributions, substantially increases the prediction precision of the method, and extends its use to countries without census data. The findings of Monte Carlo, U.S., and Swiss analyses show that, using the same predictors, MrsP usually performs in standard applications as well as the currently used standard approach, and it is superior when additional predictors are modeled. The better performance and the more straightforward implementation promise that MrsP will further stimulate subnational research.
Apparent and standardized ileal digestibility of amino acids in diverse barley cultivars fed to growing pigs
Authors: Wang Hongliang , Ma Xiaokang , Xu Xiao , Shi Meng , Piao Xiangshu
Published: July 2017

The objectives of this study were to determine the chemical composition, ileal amino acid (AA) digestibility of barley varieties and to develop equations to predict the AA digestibility based on the chemical characteristics of individual barley. A wide selection of nine barley varieties in the main growing regions of China was used in the experiment. Ten crossbred pigs (30.9 ± 1.8 kg) were allotted to a 6 × 10 Youden Square. The treatments included a nitrogen‐free diet and nine barley test diets. Considerable variation was observed in the content of neutral detergent fiber, acid detergent fiber, crude protein (CP) and all AAs among the barley samples. The standardized ileal digestibility (SID) of indispensable AAs with the exception of arginine, phenylalanine and threonine were different (P < 0.05) among the nine barley sources tested. With R2 values exceeding 0.50, significant linear regression equations for CP and threonine were obtained. In conclusion, significant differences existed in the ileal digestibility of CP and AAs among barley varieties. It is difficult to predict the SID of most of the amino acids in barely based upon chemical characteristics.
Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis
Authors: Fábián Katalin , Puskás Rita , Kakuk Tímea , Prés László , Fejes Dorottya , Szegedi Zsolt , Rojkó Lívia , Szállási Zoltán , Döme Balázs , Pipek Orsolya , Moldvay Judit
Published: July 2017

Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Comorbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model. In patients suffering from hypertension, both median serum creatinine and blood urea nitrogen (BUN) were higher (81.9 versus 75.8 μmol/L, p < 0.001 and 6.0 versus 5.7 mmol/L, p = 0.005, respectively). Such a difference could not be observed in patients with diabetes. In patients with COPD, only serum creatinine was higher (81.1 versus 77.3 μmol/L, p = 0.004). In the whole cohort, we found that while at the time of lung cancer diagnosis the ratio of patients in the pathological range (PRR) was 8.67% for serum creatinine (median: 75 μmol/L) and 14.16% for BUN (median: 5.4 mmol/L), at the time of bone metastasis the PRR for serum creatinine increased to 16.11% (median: 77.0 μmol/L) and for BUN to 24.07% (median: 6.0 mmol/L), which is a significant increase for both parameters (p < 0.001). For the whole cohort, the last laboratory results showed a 26.37% PRR for serum creatinine and 45.66% PRR for BUN (significant increase for both, p < 0.001). Multivariate analysis revealed that patients with hypertension had a higher chance for switching to the pathological range sooner (p = 0.033, HR: 1.372, CI: 1.025–1.835). Also, the appearance of the bone metastasis correlated with an acceleration of the onset of such a switch (p < 0.001, HR: 2.655, CI: 1.581–4.456). Our results suggest that renal function is impaired in a significant proportion of patients with lung cancer and highlight the importance of non‐nephrotoxic drug in the management of bone metastases.
Big data for open innovation in SMEs and large corporations: Trends, opportunities, and challenges
Authors: Del Vecchio Pasquale , Di Minin Alberto , Petruzzelli Antonio Messeni , Panniello Umberto , Pirri Salvatore
Published: July 2017

The notion of ‘Big Data’ has recently been attracting an increasing degree of attention from scholars and practitioners in an attempt to identify how it may be leveraged to create innovative solutions and business opportunities. Specifically, Big Data may come from a variety of sources, especially sources outside the usual boundaries of organizations, and it represents an interesting and emerging opportunity for sustaining and enhancing the effectiveness of the so‐called open innovation paradigm. However, to the best of our knowledge, no prior works have provided a broad overview of the use of Big Data for open innovation strategies. We aim to fill this gap. In particular, we have focused our investigation on two types of companies: small and medium‐sized enterprises (SMEs) and big corporations, reviewing the major academic works published so far and analysing the main industrial applications on this topic. As a result, we provide a relevant list of the main trends, opportunities, and challenges faced by SMEs and large corporations when dealing with Big Data for open innovation strategies.
IS THE REVENUE ALLOCATION SCHEME OF FORMULA ONE MOTOR RACING A CASE FOR EUROPEAN COMPETITION POLICY?
Authors: Budzinski Oliver , Müller‐Kock Anika
Published: July 2017

Recent allegations from participants of the FIA Formula One World Championship (F1) suggest that its authorities violate European competition law in two ways. First, they allegedly abuse market power by forcing unfavorable contracts on media revenue allocation upon teams as a whole and on smaller teams in particular (vertical allocation of media revenue). Second, they allegedly form a cartel with selected teams to the detriment of smaller teams by providing unjustified extra payments to these teams (horizontal allocation of media revenues). In doing so, the cartel members allegedly secure supracompetitive rents from the authorities and cement an unfair competitive advantage over the outsider teams. Employing concentration measures from empirical economics, we present an assessment of whether the current antitrust allegations against F1 may be considered valid or not. We show that the allocation scheme employed in F1 considerably differs from those in other professional sports championships. We find the empirical picture to be consistent with an anticompetitive interpretation of F1 media revenue structures and policies. We conclude that there is merit in initiating an in‐depth antitrust investigation of Formula One motor racing. (JEL K21, L12, L40, L83, Z20)
Cell‐derived micro‐environment helps dental pulp stem cells promote dental pulp regeneration
Authors: Zhang Xuexin , Li Hui , Sun Jingjing , Luo Xiangyou , Yang Hefeng , Xie Li , Yang Bo , Guo Weihua , Tian Weidong
Published: July 2017

Objectives

The function of the dental pulp is closely connected to the extracellular matrix (ECM) structure, and ECM has received significant attention due to its biological functions for regulating cells. As such, the interaction between the ECM niche and cells is worth exploring for potential clinical uses.

Materials and methods

In this study, dental pulp stem cell (DPSC)‐derived ECM (DPM) was prepared through cell culture and decellularization to function as the cell niche, and changes in DPSC behaviour and histological analysis of dental pulp tissue regeneration were evaluated following the DPM culture. DPM promoted the replication of DPSCs and exhibited retention of their mineralization. Then, the DPM‐based culture strategy under odontogenic culture medium was further investigated, and the mineralization‐related markers showed that DPSCs were regulated towards odontogenic differentiation. Dental pulp‐like tissue with well‐arranged ECM was harvested after a 2‐month subcutaneous implantation in nude mice with DPM application. Additionally, DPSCs cultured on the plastic culture surface showed the up‐regulation of mineralization makers in vitro, but there was a disorder in matrix formation and mineralization when the cells were cultured in vivo.

Results and Conclusions

DPM‐based cultivation could serve as a cell niche and modulate DPSC behaviour, and this method also provided an alternative to harvest tissue‐specific ECM and provided a strategy for ECM‐cell interaction.
ERP System versus Stand‐Alone Enterprise Applications in the Mitigation of Operational Glitches
Authors: Tenhiälä Antti , Rungtusanatham M. Johnny , Miller Jason W.
Published: July 2017

Business function‐specific stand‐alone enterprise applications (SEAs) are displacing functionally integrated enterprise resource planning (ERP) systems, despite strong empirical support for the business benefits of the latter. This study explores the conditions under which it may be more effective to use a set of SEAs instead of a single‐suite ERP system, and vice versa. Based on Organizational Information Processing Theory, we expect differences in effectiveness to grow in prominence when the uncertainty of the operating environment increases, that is, when operational glitches in production processes become more frequent. Extending the existing literature, we postulate that high functional differentiation is a precondition for SEAs to be more effective than an ERP system, hypothesizing that the level of functional interdependence ultimately determines which type of software is superior for a given production process. We test our hypotheses using data collected from 163 make‐to‐order (MTO) production processes nested within 73 manufacturing plants and seven supply chains of complex, high‐tech machinery. Results show that when functional interdependence is low, the negative effect of operational glitches on delivery performance is effectively mitigated in MTO production processes wherein process‐related information is managed predominantly using SEAs; conversely, when functional interdependence is high, using an ERP system is more effective. Our findings offer practical guidelines as to when to use SEAs versus an ERP system while also integrating and updating the findings of earlier empirical research, in which each has been analyzed separately.
Endoscopic surgical technique for benign fibrotic strictures of the upper esophageal sphincter
Authors: Chitose Shun‐ichi , Sato Kiminori , Fukahori Mioko , Hamakawa Sachiyo , Koga Akari , Sueyoshi Shintaro , Umeno Hirohito
Published: July 2017

A 43‐year‐old man with complaints of increased difficulty swallowing and weight loss underwent videofluorographic examination of swallowing, which revealed severely reduced cricopharyngeal opening. Endoscopic cricopharyngeal myotomy was carried out using a modified technique (mECPM). A benign fibrotic stricture of the upper esophageal sphincter (UES) was identified under visualization of a distending operating laryngoscope. A vertical midline incision in the strictured mucosa and submucosal resection of the cricopharyngeal muscle were done using a CO2 laser. The initial vertical mucosal incision was tightly sutured in the horizontal direction with absorbable surgical sutures. Histopathological examination of the cricopharyngeal muscle revealed infiltration of inflammatory cells. The patient started oral intake on postoperative day 7. He has been symptom free for 2 years with an improved body mass index, and postoperative laryngoscopy revealed no salivary retention in the piriform sinuses. The technique presented here provides sufficient opening of the UES by eliminating the problem of restenosis. mECPM will be useful for treating benign fibrotic strictures of the UES.
Insulin secretion and action in North Indian women during pregnancy
Authors: Arora G. P. , Almgren P. , Thaman R. G. , Pal A. , Groop L. , Vaag A. , Prasad R. B. , Brøns C.
Published: July 2017

Aim

The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1‐h glucose value, in a high‐risk Indian population from Punjab.

Methods

Insulin secretion (HOMA2‐B) and insulin action (HOMA2‐IR) were assessed in 4665 Indian women with or without gestational diabetes defined by the GDM1999 or adapted GDM2013 criteria.

Results

Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were independently associated with increased insulin resistance.

Conclusions

Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more severe impairments of insulin secretion and action.
European Studies and the European Crisis: Legal and Political Science between Critique and Complacency
Authors: Joerges Christian , Kreuder‐Sonnen Christian
Published: July 2017

European Studies used to be dominated by legal and political science approaches which hailed the progress of European integration and its reliance on law. The recent set of crises that struck the EU have highlighted fundamental problems in the ways and means by which European integration unfolds. The quasi‐authoritarian emergency politics deployed in the euro crisis is a radical expression of the fading prevalence of democratic processes to accommodate economic and social diversity in the Union. As we argue in this paper, however, the mainstreams in both disciplines retain a largely affirmative and apologetic stance on the EU's post‐democratic and extra‐constitutional development. While political science contributions mostly content themselves with a revival of conventional integration theories and thus turn a blind eye to normatively critical aspects of European crisis governance, legal scholarship is in short supply of normatively convincing theoretical paradigms and thus aligns itself with the functionalist reasoning of the EU's Court of Justice. Yet, we also identify critical peripheries in both disciplines which intersect in their critical appraisal of the authoritarian tendencies that inhere in the crisis‐ridden state of European integration. Their results curb the prevailing optimism and underline that the need for fundamental reorientations in both the theory and practice of European integration has become irrefutable.
Community‐based monitoring of small‐scale fisheries with digital devices in Brazilian Amazon
Authors: Oviedo A. F. P. , Bursztyn M.
Published: July 2017

Fisheries management is potentially a short‐term measure for reducing floodplain fisheries degradation. This objective can only be achieved if adequate measures to improve fishery governance and ecosystem conservation are taken. The monitoring of fisheries management is likely to be important for understanding the effectiveness of local rules and the impacts on aquatic biodiversity. Given that monitoring is the periodic assessment of fish stock characteristics regarding reference data, adopting tools and procedures for monitoring at different scales is a challenging task. Information and Communication Technologies (ICT) have enabled local communities to gather data on key resources in a cost‐effective way. This article presents a community‐based monitoring of fisheries based of smartphones that supports the annual fishing quotas and legal harvest permits procedures. The precision of community‐based monitoring data is assessed and a model to integrate these data into a large‐scale monitoring scheme examined. Data collection performance was evaluated at communities in the Kaxinawá Nova Olinda Indigenous Territory, in the State of Acre, where fishery management was monitored. The results indicate that voluntary collectors are able to provide data with precision comparable with government agency measurements, but at lower cost.