bluuebunny/crossref_metadata_2025 huggingface dataset:
A Drug-Side Effect Context-Sensitive Network approach for drug target prediction
Authors: Zhou Mengshi , Chen Yang , Xu Rong
Published: November 2018

Computational drug target prediction has become an important process in drug discovery. Network-based approaches are commonly used in computational drug–target interaction (DTI) prediction. Existing network-based approaches are limited in capturing the contextual information on how diseases, drugs and genes are connected. Here, we proposed a context-sensitive network (CSN) model for DTI prediction by modeling contextual drug phenotypic relationships. We constructed a Drug-Side Effect Context-Sensitive Network (DSE-CSN) of 139 760 drug-side effect pairs, representing 1480 drugs and 5868 side effects. We also built a protein–protein interaction network (PPIN) of 15 267 gene nodes and 178 972 weighted edges. A heterogeneous network was built by connecting the DSE-CSN and the PPIN through 3684 known DTIs. For each drug on the DSE-CSN, its genetic targets were predicted and prioritized using a network-based ranking algorithm. Our approach was evaluated in both de novo and leave-one-out cross-validation analysis using known DTIs as the gold standard. We compared our DSE-CSN-based model to the traditional similarity-based network (SBN)-based prediction model. The results suggested that the DSE-CSN-based model was able to rank known DTIs highly. In a de novo cross-validation, the area under the receiver operating characteristic (ROC) curve was 0.95. In a leave-one-out cross-validation, the average rank was top 3.2% for known DTIs. When it was compared to the SBN-based model using the Precision-Recall curve, our CSN-based model achieved a higher mean average precision (MAP) (0.23 versus 0.19, P-value<1e−4) in a de novo cross-validation analysis. We further improved the CSN-based DTI prediction by differentially weighting the drug-side effect pairs on the network and showed a significant improvement of the MAP (0.29 versus 0.23, P-value<1e−4). We also showed that the CSN-based model consistently achieved better performances than the traditional SBN-based model across different drug classes. Moreover, we demonstrated that our novel DTI predictions can be supported by published literature. In summary, the CSN-based model, by modeling the context-specific inter-relationships among drugs and side effects, has a high potential in drug target prediction.

Availability and implementation

nlp/case/edu/public/data/DSE/CSN_DTI.
SeQuiLa: an elastic, fast and scalable SQL-oriented solution for processing and querying genomic intervals
Authors: Wiewiórka Marek , Leśniewska Anna , Szmurło Agnieszka , Stępień Kacper , Borowiak Mateusz , Okoniewski Michał , Gambin Tomasz
Published: November 2018

Efficient processing of large-scale genomic datasets has recently become possible due to the application of ‘big data’ technologies in bioinformatics pipelines. We present SeQuiLa—a distributed, ANSI SQL-compliant solution for speedy querying and processing of genomic intervals that is available as an Apache Spark package. Proposed range join strategy is significantly (∼22×) faster than the default Apache Spark implementation and outperforms other state-of-the-art tools for genomic intervals processing.

Availability and implementation

The project is available at http://biodatageeks.org/sequila/.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Na+/H+ Exchanger Nhe1 Modulates Network Excitability via GABA Release
Authors: Bocker Hartmut T , Heinrich Theresa , Liebmann Lutz , Hennings J Christopher , Seemann Eric , Gerth Melanie , Jakovčevski Igor , Preobraschenski Julia , Kessels Michael M , Westermann Martin , Isbrandt Dirk , Jahn Reinhard , Qualmann Britta , Hübner Christian A
Published: November 2018

Brain functions are extremely sensitive to pH changes because of the pH-dependence of proteins involved in neuronal excitability and synaptic transmission. Here, we show that the Na+/H+ exchanger Nhe1, which uses the Na+ gradient to extrude H+, is expressed at both inhibitory and excitatory presynapses. We disrupted Nhe1 specifically in mice either in Emx1-positive glutamatergic neurons or in parvalbumin-positive cells, mainly GABAergic interneurons. While Nhe1 disruption in excitatory neurons had no effect on overall network excitability, mice with disruption of Nhe1 in parvalbumin-positive neurons displayed epileptic activity. From our electrophysiological analyses in the CA1 of the hippocampus, we conclude that the disruption in parvalbumin-positive neurons impairs the release of GABA-loaded vesicles, but increases the size of GABA quanta. The latter is most likely an indirect pH-dependent effect, as Nhe1 was not expressed in purified synaptic vesicles itself. Conclusively, our data provide first evidence that Nhe1 affects network excitability via modulation of inhibitory interneurons.
No Singular Modulus Is a Unit
Authors: Bilu Yuri , Habegger Philipp , Kühne Lars
Published: November 2018

A result of the 2nd-named author states that there are only finitely many complex multiplication (CM)-elliptic curves over $\mathbb{C}$ whose $j$-invariant is an algebraic unit. His proof depends on Duke’s equidistribution theorem and is hence noneffective. In this article, we give a completely effective proof of this result. To be precise, we show that every singular modulus that is an algebraic unit is associated with a CM-elliptic curve whose endomorphism ring has discriminant less than $10^{15}$. Through further refinements and computer-assisted arguments, we eventually rule out all remaining cases, showing that no singular modulus is an algebraic unit. This allows us to exhibit classes of subvarieties in ${\mathbb{C}}^n$ not containing any special points.
Algebraic Tangent Cones of Reflexive Sheaves
Authors: Chen Xuemiao , Sun Song
Published: November 2018

We study the notion of algebraic tangent cones at singularities of reflexive sheaves. These correspond to extensions of reflexive sheaves across a negative divisor. We show the existence of optimal extensions in a constructive manner, and we prove the uniqueness in a suitable sense. The results here are an algebro-geometric counterpart of our previous study on singularities of Hermitian–Yang–Mills connections.
High Constitutive Interleukin 10 Level Interferes With the Immune Response to Varicella-Zoster Virus in Elderly Recipients of Live Attenuated Zoster Vaccine
Authors: Gershon Anne A , Brooks David , Stevenson Donald D , Chin William K , Oldstone Michael B A , Gershon Michael D
Published: November 2018

Introduction

Live attenuated zoster vaccine (Zostavax) was used to test the hypothesis that constitutive level of interleukin 10 (IL-10), which may be high in elderly subjects, impairs vaccine efficacy. If constitutive IL-10 impairs vaccine efficacy, the effectiveness of viral vaccines might be improved by transient inhibition of IL-10 before vaccination.

Methods

Zostavax was given to 26 patients (age, 60–80 years). IL-10 and immunity to varicella zoster virus (VZV) were measured at baseline and after vaccination. Fluorescent antibody to membrane antigen (FAMA) assays and glycoprotein enzyme-linked immunosorbent assays (gpELISAs) were used to assess humoral immunity; anti–varicella virus T-cell responses were studied in a subset of subjects. In a prospective animal model, T-cell responses to chimeric vaccines against lymphocytic choriomeningitis virus (LCMV) were assessed in mice that express or lack IL-10.

Results

FAMA assays revealed significant boosting (by 4-fold) of humoral immunity, which occurred only in subjects (10 of 26) with a low constitutive IL-10 level (ie, <20 pg/mL); moreover, the Zostavax-induced FAMA and gpELISA responses were inversely related to the constitutive IL-10 level. Significant VZV-specific T-cell responses followed vaccination only in subjects with a low constitutive IL-10 level. Vaccine-induced LCMV-specific T-cell responses in mice lacking IL-10 were greater than in wild-type animals.

Conclusions

A high constitutive IL-10 level adversely affects vaccine efficacy.
‘Responsibility’, change, and rising powers’ role conceptions: comparing Indian foreign policy roles in global climate change negotiations and maritime security
Authors: Plagemann Johannes , Prys-Hansen Miriam
Published: November 2018

Strong economic growth and assertive political leadership have made India an increasingly prominent player in global governance. Whereas conventional scholarship of India’s foreign policy underlines continuity, this article explores how India’s self-conception has changed across two policy fields (climate change and maritime security). Adopting a role-theoretical approach, we analyze official statements as a mirror of both India’s self-understanding and its view on the roles of significant other actors. Although both issue-areas exhibit change, India’s self-ascribed role has been transformed more profoundly in the maritime domain. Our comparison suggests three factors to particularly induce transformation of rising powers’ roles toward ‘more responsibility’: First, power-sharing is more conducive than burden-sharing; second, issue-areas with strong regional anchors are more likely to induce the adoption of a more responsible role than those areas situated primarily at the global level of politics; and third, positive external role ascriptions are more effective than negative ones.
Automated and flexible identification of complex disease: building a model for systemic lupus erythematosus using noisy labeling
Authors: Murray Sara G , Avati Anand , Schmajuk Gabriela , Yazdany Jinoos
Published: November 2018

Accurate and efficient identification of complex chronic conditions in the electronic health record (EHR) is an important but challenging task that has historically relied on tedious clinician review and oversimplification of the disease. Here we adapt methods that allow for automated “noisy labeling” of positive and negative controls to create a “silver standard” for machine learning to automate identification of systemic lupus erythematosus (SLE). Our final model, which includes both structured data as well as text processing of clinical notes, outperformed all existing algorithms for SLE (AUC 0.97). In addition, we demonstrate how the probabilistic outputs of this model can be adapted to various clinical needs, selecting high thresholds when specificity is the priority and lower thresholds when a more inclusive patient population is desired. Deploying a similar methodology to other complex diseases has the potential to dramatically simplify the landscape of population identification in the EHR.

MeSH terms

Electronic Health Records, Machine Learning, Lupus Erythematosus, Phenotype, Algorithms
Pregnancy-Associated Plasma Protein-A (PAPP-A) in Ewing Sarcoma: Role in Tumor Growth and Immune Evasion
Authors: Heitzeneder Sabine , Sotillo Elena , Shern Jack F , Sindiri Sivasish , Xu Peng , Jones Robert , Pollak Michael , Noer Pernille R , Lorette Julie , Fazli Ladan , Alag Anya , Meltzer Paul , Lau Ching , Conover Cheryl A , Oxvig Claus , Sorensen Poul H , Maris John M , Khan Javed , Mackall Crystal L
Published: November 2018

Background

Ewing sarcoma (EWS) manifests one of the lowest somatic mutation rates of any cancer, leading to a scarcity of druggable mutations and neoantigens. Immunotherapeutics targeting differentially expressed cell surface antigens could provide therapeutic benefit for such tumors. Pregnancy-associated plasma protein A (PAPP-A) is a cell membrane-associated proteinase produced by the placenta that promotes fetal growth by inducing insulinlike growth factor (IGF) signaling.

Methods

By comparing RNA expression of cell surface proteins in EWS (n = 120) versus normal tissues (n = 42), we comprehensively characterized the surfaceome of EWS to identify highly differentially expressed molecules. Using CRISPR/Cas-9 and anti-PAPP-A antibodies, we investigated biological roles for PAPP-A in EWS in vitro and in vivo in NSG xenograft models and performed RNA-sequencing on PAPPA knockout clones (n = 5) and controls (n = 3). All statistical tests were two-sided.

Results

EWS surfaceome analysis identified 11 highly differentially overexpressed genes, with PAPPA ranking second in differential expression. In EWS cell lines, genetic knockout of PAPPA and treatment with anti-PAPP-A antibodies revealed an essential survival role by regulating local IGF-1 bioavailability. MAb-mediated PAPPA inhibition diminished EWS growth in orthotopic xenografts (leg area mm2 at day 49 IgG2a control (CTRL) [n = 14], mean = 397.0, SD = 86.1 vs anti-PAPP-A [n = 14], mean = 311.7, SD = 155.0; P = .03; median OS anti-PAPP-A = 52.5 days, 95% CI = 46.0 to 63.0 days vs IgG2a = 45.0 days, 95% CI = 42.0 to 52.0 days; P = .02) and improved the efficacy of anti-IGF-1R treatment (leg area mm2 at day 49 anti-PAPP-A + anti-IGF-1R [n = 15], mean = 217.9, SD = 148.5 vs IgG2a-CTRL; P < .001; median OS anti-PAPP-A + anti-IGF1R = 63.0 days, 95% CI = 52.0 to 67.0 days vs IgG2a-CTRL; P < .001). Unexpectedly, PAPPA knockout in EWS cell lines induced interferon (IFN)-response genes, including proteins associated with antigen processing/presentation. Consistently, gene expression profiles in PAPPA-low EWS tumors were enriched for immune response pathways.

Conclusion

This work provides a comprehensive characterization of the surfaceome of EWS, credentials PAPP-A as a highly differentially expressed therapeutic target, and discovers a novel link between IGF-1 signaling and immune evasion in cancer, thus implicating shared mechanisms of immune evasion between EWS and the placenta.
Pediatric Office Delivery of Smoking Cessation Assistance for Breast-Feeding Mothers
Authors: Drehmer Jeremy E , Ossip Deborah J , Nabi-Burza Emara , Hipple Walters Bethany , Gorzkowski Julie A , Winickoff Jonathan P
Published: November 2018

Introduction

National and international organizations have done an excellent job of advocating and promoting breast feeding for all mothers. This study assessed to what extent an intervention increased delivery of cessation assistance to breast-feeding mothers who smoke.

Methods

Data were collected between April and October 2015 in five US states as part of a cluster randomized controlled trial in 10 pediatric practices. Practices were randomized to the Clinical Effort Against Secondhand Smoke Exposure (CEASE) intervention or usual care control arms. Mothers were asked about their smoking status and breast-feeding history during a screening interview upon exiting the practice and eligible mothers who agreed to participate in an enrollment interview were asked if they received smoking cessation assistance during their child’s visit. Mothers with a child 1 year old and younger were included in the analyses.

Results

Current breast feeding was associated with a reduced likelihood of current smoking (adjusted odds ratio [aOR] = 0.38, 95% confidence interval [95% CI] = 0.25 to 0.57) and a greater likelihood of quitting smoking (aOR = 2.33, 95% CI = 1.29 to 4.21) after controlling for known confounders. Mothers who concurrently smoked and breast-fed were more likely to be asked about smoking (66.7% vs. 28.6%, p = .01), advised to quit (61.1% vs. 21.4%, p < .01), prescribed nicotine replacement therapy (50.0% vs. 0%, p < .001), and enrolled into the quitline (27.8% vs. 0%, p < .01) at CEASE practices compared to control practices.

Conclusion

Breast-feeding mothers were less likely to be current smokers and more likely to have recently quit smoking. Among mothers who continue to smoke and breast feed, the CEASE intervention enhances delivery of smoking cessation assistance.

Implications

Breast feeding and eliminating infants’ exposure to tobacco smoke are important protective factors for serious pediatric health risks including sudden infant death. This study shows that breast feeding was positively associated with desirable tobacco control outcomes, specifically that breast feeding was associated with a lower likelihood of smoking among ever smokers and a greater likelihood of recently quitting smoking. This is also the first study to look specifically at delivery of smoking cessation assistance to breast-feeding mothers seen at pediatric offices and demonstrates the effectiveness of delivering evidence-based smoking cessation assistance to them in this context.

Trial Registration

www.ClinicalTrials.gov (identifier NCT01882348).
Secular trends in the incidence and prevalence of gout in Denmark from 1995 to 2015: a nationwide register-based study
Authors: Zobbe Kristian , Prieto-Alhambra Daniel , Cordtz René , Højgaard Pil , Hindrup Jens Skøt , Kristensen Lars Erik , Dreyer Lene
Published: November 2018

Objective

To investigate temporal trends in the incidence and prevalence of gout in the adult Danish population.

Methods

Using the nationwide Danish National Patient Registry, we calculated the number of incident gout patients (per 100 000 person-years) within each 1 year period from 1995 to 2015 and the prevalence of gout in 2000 and 2015. Further, we calculated age- and gender-specific incidence rates of gout from 1995 to 2015.

Results

We identified a total of 45 685 incident gout patients (72.9% males) with a mean age of 65 years (s.d. 16) at diagnosis. In both genders, an increase in age-standardized incidence rates was observed from 32.3/100 000 (95% CI 30.7, 33.9) in 1995 to 57.5/100 000 (95% CI 55.6, 59.5) in 2015 (P < 0.001). Similar trends were observed for 8950 cases diagnosed in rheumatology departments. We likewise observed an increase in the prevalence of gout from 0.29% (95% CI 0.29, 0.30) in 2000 to 0.68% (95% CI 0.68, 0.69) in 2015.

Conclusions

The annual incidence rate of gout increased by almost 80% in Denmark between 1995 and 2015. The prevalence increased by nearly 130% between 2000 and 2015. Reasons for this are unknown but may include an increase in risk factors (e.g. obesity, diabetes mellitus), longer life expectancy and increased awareness of the disease among patients and/or health professionals.
External Validity and Policy Adaptation: From Impact Evaluation to Policy Design
Authors: Williams Martin J
Published: November 2018

With the growing number of impact evaluations worldwide, the question of how to apply this evidence in policy making processes has arguably become the main challenge for evidence-based policy making. How can policy makers predict whether a policy will have the same impact in their context as it did elsewhere, and how should this influence the policy’s design and implementation? This paper suggests that failures of external validity (both in transporting and scaling up policy) can be understood as arising from an interaction between a policy’s theory of change and a dimension of the context in which it is being implemented. The paper surveys existing approaches to analyzing external validity, and suggests that there has been more focus on the generalizability of impact evaluation results than on the applicability of evidence to specific contexts. To help fill this gap, the study develops a method of “mechanism mapping” that maps a policy’s theory of change against salient contextual assumptions to identify external validity problems and suggest appropriate policy adaptations. In deciding whether and how to adapt a policy, there is a fundamental informational trade-off between the strength of evidence on the policy from other contexts and the policy maker’s information about the local context.
Deoxynivalenol Detoxification in Transgenic Wheat Confers Resistance to Fusarium Head Blight and Crown Rot Diseases
Authors: Mandalà Giulia , Tundo Silvio , Francesconi Sara , Gevi Federica , Zolla Lello , Ceoloni Carla , D’Ovidio Renato
Published: November 2018

Fusarium diseases, including Fusarium head blight (FHB) and Fusarium crown rot (FCR), reduce crop yield and grain quality and are major agricultural problems worldwide. These diseases also affect food safety through fungal production of hazardous mycotoxins. Among these, deoxynivalenol (DON) acts as a virulence factor during pathogenesis on wheat. The principal mechanism underlying plant tolerance to DON is glycosylation by specific uridine diphosphate–dependent glucosyltransferases (UGTs), through which DON-3-β-d-glucoside (D3G) is produced. In this work, we tested whether DON detoxification by UGT could confer to wheat a broad-spectrum resistance against Fusarium graminearum and F. culmorum. These widespread Fusarium species affect different plant organs and developmental stages in the course of FHB and FCR. To assess DON-detoxification potential, we produced transgenic durum wheat plants constitutively expressing the barley HvUGT13248 and bread wheat plants expressing the same transgene in flower tissues. When challenged with F. graminearum, FHB symptoms were reduced in both types of transgenic plants, particularly during early to mid-infection stages of the infection progress. The transgenic durum wheat displayed much greater DON-to-D3G conversion ability and a considerable decrease of total DON+D3G content in flour extracts. The transgenic bread wheat exhibited a UGT dose–dependent efficacy of DON detoxification. In addition, we showed, for the first time, that DON detoxification limits FCR caused by F. culmorum. FCR symptoms were reduced throughout the experiment by nearly 50% in seedlings of transgenic plants constitutively expressing HvUGT13248. Our results demonstrate that limiting the effect of the virulence factor DON via in planta glycosylation restrains FHB and FCR development. Therefore, ability for DON detoxification can be a trait of interest for wheat breeding targeting FHB and FCR resistance.
Soybean Sudden Death Syndrome Causal Agent Fusarium brasiliense Present in Michigan
Authors: Wang Jie , Sang Hyunkyu , Jacobs Janette L. , Oudman Kjersten A. , Hanson Linda E. , Chilvers Martin I.
Published: November 2018

Sudden death syndrome (SDS), caused by members of Fusarium solani species complex (FSSC) clade 2, is a major and economically important disease in soybean worldwide. The primary causal agent of SDS isolated to date in North America has been F. virguliforme. In 2014 and 2016, SDS symptoms were found in two soybean fields located on the same farm in Michigan. Seventy Fusarium strains were isolated from roots of the SDS-symptomatic soybeans in two fields. Phylogenetic analysis of partial sequences of elongation factor-1α, the nuclear ribosomal DNA intergenic spacer region, and the RNA polymerase II beta subunit revealed that the primary FSSC species isolated was F. brasiliense (58 and 36% in each field) and the remaining Fusarium strains were identified as F. cuneirostrum, F. phaseoli, an undescribed Fusarium sp. from FSSC clade 2, and strains in FSSC clade 5 and FSSC clade 11. Molecular identification was supported with morphological analysis and a pathogenicity assay. The soybean seedling pathogenicity assay indicated that F. brasiliense was capable of causing typical foliar SDS symptoms. Both root rot and foliar disease severity were variable by strain, just as they are in F. virguliforme. Both FSSC 5 and FSSC 11 strains were also capable of causing root rot, but SDS foliar symptoms were not detected. To our knowledge, this is the first report of F. brasiliense causing SDS in soybean in the United States and the first report of F. cuneirostrum, F. phaseoli, an as-yet-unnamed Fusarium sp., and strains in FSSC clade 5 and FSSC clade 11 associated with or causing root rot of soybean in Michigan.
Phylogeography and Molecular Species Delimitation of Pratylenchus capsici n. sp., a New Root-Lesion Nematode in Israel on Pepper (Capsicum annuum)
Authors: Qing Xue , Bert Wim , Gamliel Abraham , Bucki Patricia , Duvrinin Svetlana , Alon Tamar , Braun Miyara Sigal
Published: November 2018

Root-lesion nematodes of the genus Pratylenchus parasitize the roots of numerous plants and can cause severe damage and yield loss. Here, we report on a new species, Pratylenchus capsici n. sp., from the Arava rift, Israel, which was characterized by integrative methods, including detailed morphology, molecular phylogeny, population genetics, and phylogeography. This species is widely spread across the Arava rift, causing significant infection in pepper (Capsicum annuum) roots and inhibiting plant growth. Both morphological and molecular species delimitation support the recovered species as a new species. We found high cytochrome oxidase subunit I haplotype diversity, and phylogeography analysis suggests that contemporary gene flow is prevented among different agricultural farms, while population dispersal from weeds (Chenopodium album and Sonchus oleraceus) to pepper occurs on a relatively small scale. Our results suggest that weeds are an important reservoir for the dispersal of P. capsici n. sp., either as the original nematode source or at least in maintaining the population between growing seasons.
Do postoperative drain volumes correlate with intraoperative blood loss and postoperative transfusion requirements in posterior spinal fusion for adolescent idiopathic scoliosis?
Authors: Choi Daniel E. , Vives Michael J. , Shah Harsh , Zhao Caixia , Patel Anuradha , Sabharwal Sanjeev
Published: November 2018

Most studies have excluded postoperative drain volumes in analyzing blood loss associated with scoliosis surgery. We sought to analyze patient and surgical factors that influenced postoperative drain outputs. A retrospective review was conducted on 50 consecutive patients who had undergone posterior spinal fusion with pedicle screw instrumentation and subfascial drain placement over a 6-year period at a single institution for adolescent idiopathic scoliosis. Postoperative drain volumes were correlated to patient factors, surgical variables, and change in postoperative hemoglobin values. The association between drain output volumes and the need for allogeneic blood transfusion was also analyzed using univariate and multivariate analysis. Total postoperative drain volume positively correlated with Cell Saver volume (r=0.28, P=0.049), units of packed red blood cells transfused intraoperatively (r=0.31, P=0.03), and a number of Ponte osteotomies (r=0.43, P=0.002). On the basis of multiple linear regression analysis, only the number of osteotomies performed was associated with increasing total drain volume (R
2=0.25, P=0.003). Total drain output did not correlate with postoperative change in hemoglobin (P=0.85), the need for postoperative blood transfusion (P=0.22), or the total volume of blood transfused perioperatively (P=0.06). Patients with large intraoperative blood loss or multiple osteotomies are more likely to have higher postoperative drain volumes. Drain volume alone, however, should not be used as a trigger for recommending a postoperative blood transfusion.
Knowledge and Opinion of Obstetrician-Gynecologists and Midwives Regarding Complementary and Alternative Medicine in Spain
Authors: López-Garrido Beatriz , Gil-Pita Roberto , Francisco-Rey Cristina , Zapico-Goñi Álvaro , Tena-Gómez Daniel
Published: November 2018

The objective of this article is to present the results from a cross-sectional survey carried out to assess and compare knowledge, attitudes, and beliefs of the obstetrician-gynecologists and midwives, regarding a set of complementary and alternative therapies in the area of the Corredor del Henares in Spain. The results show a high percentage of acceptance regarding complementary and alternative therapies in the field of obstetrics and gynecology, and more than half of the Spanish professionals of reproductive health would like to learn more about these therapies.
Complete heart block in systemic sclerosis
Authors: Wang Qinghai , Shang Yinghui , Li Shicheng , Wu Yanxiang , Wang Chenyu , Yan Xiaowei
Published: November 2018

Rationale:

Complete heart block (CHB) is a common clinical manifestation. Systemic sclerosis (SSc) is a rare etiology of CHB that has not received enough attention. Whether pacemaker implantation is required remains inconclusive, especially when patients have no symptoms or mild symptoms of CHB.

Patient concerns:

In this study, we report the case of a 48-year-old Chinese male who suffers from SSc and CHB.

Diagnose:

The patient was previously diagnosed with left anterior hemiblock (LAHB) and right bundle block with normal heart function. CHB was observed on a regular follow-up electrocardiogram (ECG) examination 1 month before his hospitalization.

Interventions:

A permanent dual chamber pacemaker was implanted.

Outcomes:

The patient responded well to pacemaker implantation treatment, and his exertional dyspnea disappeared.

Lessons:

The occurrence of heart block associated with SSc often appears concealed. The case highlights the importance of regular follow-up of a patient with SSc. Pacemaker implantation might be unavoidable if CHB is secondary to SSc, even if it is asymptomatic.
Modified quadruple therapy versus bismuth-containing quadruple therapy in first-line treatment of Helicobacter pylori infection in Korea; rationale and design of an open-label, multicenter, randomized controlled trial
Authors: Lim Hyun , Bang Chang Seok , Shin Woon Geon , Choi Jae Ho , Soh Jae Seung , Kang Ho Suk , Yang Young Joo , Hong Ji Taek , Shin Suk Pyo , Suk Ki Tae , Lee Jae Jun , Baik Gwang Ho , Kim Dong Joon
Published: November 2018

Background:

Clarithromycin-containing triple regimen for eradication of Helicobacter pylori is no longer acceptable in Korea due to high clarithromycin resistance. Concomitant therapy or bismuth-containing quadruple therapy is recommended as an alternative regimen. A recent study in Korea has shown that modified quadruple therapy has comparable efficacy and safety to concomitant therapy as a first-line regimen. However, there has been no comparative study of modified quadruple therapy with bismuth-containing quadruple therapy. The aim of this study is to compare the efficacy and safety of modified quadruple therapy with those of bismuth-containing quadruple therapy as a first-line regimen and to present the phenotypic and genotypic antibiotic resistance profile of H pylori.

Methods:

This study is an open-label, multicenter, randomized controlled trial. We are recruiting subjects endoscopically diagnosed with H pylori infection from 2 hospitals in Korea. Subjects will be randomly allocated either to modified quadruple therapy (proton-pump inhibitor bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid daily) or bismuth-containing quadruple therapy (proton-pump inhibitor bid, tetracycline 500 mg qid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid daily) for 14 days. The rate of eradication success and adverse events will be checked at least 4 weeks after the treatment. Antibiotic resistance will be established using both a bacterial culture with agar dilutions and DNA sequencing of the clarithromycin resistance point mutations in the 23S rRNA gene of H pylori.

Conclusion:

The results of this study will provide solid evidence for determining the optimal treatment regimen for first-line H pylori eradication in Korea.
Psychiatric risk geneNT5C2regulates protein translation in human neural progenitor cells
Authors: Duarte Rodrigo R.R. , Bachtel Nathaniel D. , Côtel Marie-Caroline , Lee Sang H. , Selvackadunco Sashika , Watson Iain A. , Hovsepian Gary A. , Troakes Claire , Breen Gerome D. , Nixon Douglas F. , Murray Robin M. , Bray Nicholas J. , Eleftherianos Ioannis , Vernon Anthony C. , Powell Timothy R. , Srivastava Deepak P.
Published: November 2018

Genome-wide significant variants associated with combined risk for major psychiatric disorders on chromosome 10q24 affect the expression of the cytosolic 5’-nucleotidase II (NT5C2, cN-II) in population controls, implicating it as a psychiatric susceptibility gene. Risk alleles are associated with reduced expression of this gene in the developing and adult brain, but the resulting neurobiological risk mechanisms remain elusive. In this study, we provide further evidence for the association ofNT5C2with psychiatric disorders, and use a functional genetics approach to gain a deeper understanding of the function of this risk gene in the nervous system.NT5C2expression was significantly reduced in thepost-mortembrain of schizophrenia and bipolar disorder patients, and its protein predominately expressed in neurons within the adult brain. Using human neural progenitor cells (hNPCs), we found thatNT5C2expression peaked at the neural progenitor state, where the encoded protein was ubiquitously distributed through the cell.NT5C2knockdown in hNPCs elicited transcriptomic changes associated with protein translation, that were accompanied by regulation of adenosine monophosphate-activated protein kinase (AMPK) signalling and ribosomal protein S6 (rpS6) activity. To identify the effect of reduced neuronalNT5C2expression at a systems level, we knockdown its homologue,CG32549, inDrosophila melanogasterCNS. This elicited impaired climbing behaviour in the model organism. Collectively, our data implicateNT5C2expression in risk for psychiatric disorders and inDrosophila melanogastermotility, and further suggest that risk is mediated via regulation of AMPK signalling and protein translation during early neurodevelopment.
Ensembles from ordered and disordered proteins reveal similar structural constraints during evolution
Authors: Marchetti Julia , Monzon Alexander Miguel , Tosatto Silvio C.E. , Parisi Gustavo , Fornasari María Silvina
Published: November 2018

Inter-residue contacts determine the structural properties for each conformer in the ensembles describing the native state of proteins. Structural constraints during evolution could then provide biologically relevant information about the conformational ensembles and their relationship with protein function. Here, we studied the proportion of sites evolving under structural constraints in two very different types of ensembles, those coming from ordered or disordered proteins. Using a structurally constrained model of protein evolution we found that both types of ensembles show comparable, near 40%, number of positions evolving under structural constraints. Among these sites, ~68% are in disordered regions and ~57% of them show long-range inter-residue contacts. Also, we found that disordered ensembles are redundant in reference to their structurally constrained evolutionary information and could be described on average with ~11 conformers. Despite the different complexity of the studied ensembles and proteins, the similar constraints reveal a comparable level of selective pressure to maintain their biological functions. These results highlight the importance of the evolutionary information to recover meaningful biological information to further characterize conformational ensembles.
From spatio-temporal morphogenetic gradients to rhythmic patterning at the shoot apex
Authors: Galvan-Ampudia Carlos S. , Cerutti Guillaume , Legrand Jonathan , Azais Romain , Brunoud Géraldine , Moussu Steven , Wenzl Christian , Lohmann Jan U. , Godin Christophe , Vernoux Teva
Published: November 2018

Rhythmic patterning is central to the development of eukaryotes, particularly in plant shoot post-embryonic development. The plant hormone auxin drives rhythmic patterning at the shoot apical meristem, but the spatio-temporal dynamics of the auxin gradients is unknown. We used quantitative imaging to demonstrate that auxin provides high-definition graded information not only in space but also in time. We provide evidence that developing organs are auxin-emitting centers that could self-organize spatio-temporal auxin gradients through a transport network converging on the meristem center. We further show that a memory of the exposition of cells to auxin allows to differentiate temporally sites of organ initiation, providing a remarkable example of how the dynamic redistribution of a morphogenetic regulator can be used to create rhythmicity.
Biliary microbiota and bile acids composition in cholelithiasis
Authors: Petrov Vyacheslav A. , Fernández-Peralbo María A. , Derks Rico , Knyazeva Elena M. , Merzlikin Nikolay V. , Sazonov Alexey E. , Mayboroda Oleg A. , Saltykova Irina V.
Published: November 2018

Background

A functional interplay between BAs and microbial composition in gut is a well-documented phenomenon. In bile this phenomenon is far less studied and with this report we describe the interactions between the BAs and microbiota in this complex biological matrix.

Methodology

Thirty-seven gallstone disease patients of which twenty-one withOpisthorchis felineusinfection were enrolled in the study. The bile samples were obtained during laparoscopic cholecystectomy for gallstone disease operative treatment. Common bile acids composition were measured by LC-MS/MS using a column in reverse phase. For all patients gallbladder microbiota was previously analyzed with 16S rRNA gene sequencing on Illumina MiSeq platform. The associations between bile acids composition and microbiota were analysed.

Principal findings

Bile acids signature andO. felineusinfection status exerts influence on beta-diversity of bile microbial community. Direct correlations were found between taurocholic acid, taurochenodeoxycholic acid concentrations and alpha-diversity of bile microbiota. Taurocholic acid and taurochenodeoxycholic acid both shows positive associations with the presence of Chitinophagaceae family,MicrobacteriumandLutibacteriumgenera andPrevotella intermedia. Also direct associations were identified for taurocholic acid concentration and the presence of Actinomycetales and Bacteroidales orders,Lautropiagenus,Jeotgalicoccus psychrophilusandHaemophilus parainfluenzaeas well as for taurochenodeoxycholic acid and Acetobacteraceae family and Sphingomonas genus. There were no differences in bile acids concentrations between O.felineusinfected and non-infected patients.

Conclusions/Significance

Associations between diversity, taxonomic profile of bile microbiota and bile acids levels were evidenced in patients with cholelithiasis. Increase of taurochenodeoxycholic acid and taurocholic acid concentration correlates with bile microbiota alpha-diversity and appearance of opportunistic pathogens. Alteration of bile acids signature could cause shifts in bile microbial community structure.
Proton disorder in a short intramolecular hydrogen bond investigated by single-crystal neutron diffraction at 2.5 and 170 K
Authors: Truong Khai-Nghi , Meven Martin , Englert Ulli
Published: November 2018

The substituted acetylacetone 3-[2-(pyridin-4-yl)ethyl]pentane-2,4-dione, C12H15NO2, (1), with an ethylene bridge between the acetylacetone moiety and the heteroaromatic ring, represents an attractive linker for mixed-metal coordination polymers. In the crystal, (1) adopts an antiperiplanar conformation with respect to the C—C bond in the central ethylene group and almost coplanar acetylacetone and pyridyl groups. The ditopic molecule exists as the enol tautomer, with proton disorder in the short intramolecular hydrogen bond. Single-crystal neutron diffraction at 2.5 K indicated site occupancies of 0.602 (17) and 0.398 (17). The geometry of the acetylacetone moiety is in agreement with such a site preference of the bridging hydrogen: the O atom associated with the preferred H-atom site subtends the longer [1.305 (2) Å] and the more carbonyl-like O atom the shorter [1.288 (2) Å] C—O bond. Based on structure-factor calculations for the alternative H-atom sites, reflections particularly sensitive for proton distribution were identified and measured in a second neutron data collection at 170 K. At this temperature, 546 independent neutron intensities were used to refine positional and isotropic displacement parameters for a structure model in which parameters for C and O atoms were constrained to those obtained by single-crystal X-ray diffraction at the same temperature. The site occupancies for the disordered proton do not significantly differ from those at 2.5 K.
Packing polymorphism in the structure oftrans-aqua[N,N′-bis(salicylidene)ethane-1,2-diamine-κ4O,N,N′,O′]chloridomanganese(III) monohydrate
Authors: Reyes Perea Juan Alberto , Bernès Sylvain , Quintero Téllez Ma Guadalupe
Published: November 2018

The crystal structure of the title complex (systematic name:trans-aquachlorido{2,2′[ethane-1,2-diylbis(nitrilomethylidyne)]diphenolato-κ4O,N,N′,O′}manganese(III) monohydrate), [Mn(C16H14N2O2)Cl(H2O)]·H2O has been reported previously in the space groupP21/n[Panjaet al.(2003).Polyhedron,22, 1191–1198]. We obtained the same hydrated complex through an alternative synthesis, and crystallized a new polymorph, in the space groupP21. The molecular conformation of the complex is virtually unmodified, but the absence of the glide plane in the new polymorph halves the unit-cell parameterc, affording a non-centrosymmetric crystal structure withZ= 2, while the previously reported crystal is centrosymmetric withZ= 4. Both phases represent a case of packing polymorphism, similar to other dimorphic crystal structures retrieved from the Cambridge Structural Database.
MNC involvement in social innovations: the issue of knowledge, networks and power
Authors: Holmström Lind Christine , Kang Olivia , Ljung Anna , Forsgren Mats
Published: November 2018

Purpose

This paper aims to develop a conceptual framework and presents a number of propositions relating to why and how multinational companies (MNCs) engage in social innovations. The central focus is on the role of MNC knowledge, networks and power for their involvement in social innovations.

Design/methodology/approach

The authors combine literature on social innovations, business innovations and MNC literature, and present a number of propositions dealing with the link between MNC knowledge, networks and power-relations and their potential involvement in social innovations.

Findings

The authors emphasize that when social innovations are embraced by MNCs, the way that these corporations use their knowledge, networks and existing power-relations needs to be adapted to the new conditions present in the social innovation arena.

Research limitations/implications

The main limitation of this work is that the propositions are based on anecdotal evidence and that they are restricted to literature revolving around a few theoretical concepts (knowledge, networks, power). Against this, the authors suggest that to address the call for more empirical work on MNCs engagement in social innovation, these concepts could be used as a starting point in future empirical investigations.

Originality/value

The paper brings together and outlines a theoretical framework based on three theoretical approaches to the MNC as suggested by the literature: the knowledge-based MNC, differentiated MNC and political MNC. Based on these three perspectives, the key contribution of this paper is to develop a broader understanding of why and how MNCs engage in social innovation and the potential underlying liabilities for this involvement.
Retail blues in black and white: an emerging market context
Authors: Pandey Pallavi , Singh Saumya , Pathak Pramod
Published: November 2018

Purpose

Research investigating turnover intention among frontline employees in the Indian retail industry is scarce. The purpose of this paper is to explore factors affecting withdrawal cognitions among front-end retail employees in India.

Design/methodology/approach

Semi-structured interviews were conducted to explore the factors responsible for developing turnover intentions among the front-end employees. Data were analyzed using the ground theory approach.

Findings

Qualitative investigation revealed nine factors (abusive supervision, favoritism, perceived job image, insufficient pay, work exhaustion, perceived unethical climate, organization culture shock, staff shortage and job dissatisfaction) are responsible for developing turnover intention among front-end employees in the Indian retail industry.

Originality/value

The study uncovers antecedents of turnover intention among front-end employees in the relatively neglected Indian retail sector through a qualitative technique. Theoretical contributions, managerial implications, limitations and direction for future research are discussed.
The effect of IT ambidexterity and cloud computing absorptive capacity on competitive advantage
Authors: Chang Younghoon , Wong Siew Fan , Eze Uchenna , Lee Hwansoo
Published: November 2018

Purpose

Founded on the concept of organizational ambidexterity and the competing value model, the purpose of this paper is to develop an information technology (IT) ambidexterity framework to underscore the importance of a balanced and harmonious IT environment in enterprise cloud adoption.

Design/methodology/approach

With survey responses from 165 IT executives in a managerial position who are in charge of cloud computing implementation, partial least square method is used to test the research model.

Findings

Cloud absorptive capacity plays an important role for firms to secure a competitive advantage. The synergy of the two capabilities (flexibility and control), which have conflicting characteristics, contributes to the enhancement of cloud absorptive capacity and leads to a firm’s knowledge accumulation and performance.

Research limitations/implications

This study is the very first attempt that empirically establishes the relationship between a firm’s competitiveness and cloud computing absorptive capacity. This study provides a comprehensive framework that integrates ambidexterity theory with the competing value framework (CVF) with extending the concept of absorptive capacity that is bounded within an organizational perspective into a cloud computing context.

Practical implications

Firms should treat cloud computing as a strategic consideration to secure a competitive advantage in the contemporary business environment. For a firm’s performance, a dual governance structure, that encompasses flexibility and control, is required to achieve competitive advantage from cloud computing adoption.

Originality/value

To facilitate organizational effort in achieving a harmonious cloud environment, the authors propose a comprehensive ambidexterity framework integrating the CVF approach. This framework maps IT ambidexterity onto the CVF. As CVF considers internal and external factors that ambidexterity theory does not cover, integrating two theories can provide more comprehensive implications and discussions regarding cloud computing adoption.
Strategic corporate responsibility: a theory review and synthesis
Authors: Heikkurinen Pasi
Published: November 2018

Purpose

This article examines how responsibility and strategy can and should be connected in a business organization.

Design/methodology/approach

The article offers a review of the field by mapping previous studies according to their strategy and responsibility orientations and, consequently, identifies the classic perspective, as well as the major deficiencies and prevailing research gaps in the literature.

Findings

The article contributes to the field of strategic corporate responsibility by reframing the field with a contender perspective that challenges the classic view of strategy and responsibility amalgamation. Together, the classic and the contender perspectives are synthesized to form an integrative perspective that is more holistic than those currently available.

Originality/value

The article ends by calling for a reimagining of the relationship between corporate responsibility and strategy to find promising future research avenues and effective business practices suitable to meet the challenges of the twenty-first century.