bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Inflammatory Bowel Disease
Authors: van Aalst Mariëlle , Garcia Garrido Hannah M , van der Leun Josephine , Meek Bob , van Leeuwen Ester M M , Löwenberg Mark , D’Haens Geert R , Ponsioen Cyriel Y I , Grobusch Martin P , Goorhuis Abraham 
Published: March 2019

Abstract

Background
Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear.

Methods
We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4–8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone &gt;10 mg/day, thiopurines, methotrexate); (2) anti–tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group).

Results
One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1–3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13–.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]).

Conclusions
Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.

Clinical Trials Registration
Dutch trial register #6315.
Isolation of novel quorum-sensing active bacteria from microbial mats in Shark Bay Australia
Authors: Charlesworth James C , Watters Cara , Wong Hon Lun , Visscher Pieter T , Burns Brendan P 
Published: March 2019

ABSTRACT
Quorum sensing is a potent system of genetic control allowing phenotypes to be coordinated across localized communities. In this study, quorum sensing systems in Shark Bay microbial mats were delineated using a targeted approach analyzing whole mat extractions as well as the creation of an isolate library. A library of 165 isolates from different mat types were screened using the AHL biosensor E. coli MT102. Based on sequence identity 30 unique isolates belonging to Proteobacteria, Actinobacteria and Firmicutes were found to activate the AHL biosensor, suggesting AHLs or analogous compounds were potentially present. Several of the isolates have not been shown previously to produce signal molecules, particularly the members of the Actinobacteria and Firmicutes phyla including Virgibacillus, Halobacillius, Microbacterium and Brevibacterium. These active isolates were further screened using thin-layer chromatography (TLC) providing putative identities of AHL molecules present within the mat communities. Nine isolates were capable of producing several spots of varying sizes after TLC separation, suggesting the presence of multiple signalling molecules. This study is the first to delineate AHL-based signalling in the microbial mats of Shark Bay, and suggests quorum sensing may play a role in the ecosphysiological coordination of complex phenotypes across microbial mat communities.
The seagrass holobiont: understanding seagrass-bacteria interactions and their role in seagrass ecosystem functioning
Authors: Tarquinio Flavia , Hyndes Glenn A , Laverock Bonnie , Koenders Annette , Säwström Christin 
Published: March 2019

ABSTRACT
This review shows that the presence of seagrass microbial community is critical for the development of seagrasses; from seed germination, through to phytohormone production and enhanced nutrient availability, and defence against pathogens and saprophytes. The tight seagrass-bacterial relationship highlighted in this review supports the existence of a seagrass holobiont and adds to the growing evidence for the importance of marine eukaryotic microorganisms in sustaining vital ecosystems. Incorporating a micro-scale view on seagrass ecosystems substantially expands our understanding of ecosystem functioning and may have significant implications for future seagrass management and mitigation against human disturbance.
Like a Castor Seed: Jaina Philosophers on the Nature of Liberation
Authors: Bajželj Ana 
Published: March 2019

Abstract
This article examines the nature of the spatial transition of liberated jīvas, a special episode in the life of jīvas that according to Jaina philosophy takes place between the destruction of all karman that binds them to saṃsāra on the one hand and their dwelling in the space of liberated beings on the other. As the place of karmically bound jīvas that are capable of attaining liberation is located far below the space of liberated beings, the disembodied liberated jīvas must travel upwards to reach it. Focused on Umāsvāti’s Tattvārtha-sūtra with four commentaries, the article describes and analyses the discussions and issues that developed around the doctrine of the jīva’s final journey.
BIG TECH BANKING
Authors: de la Mano Miguel , Padilla Jorge 
Published: March 2019

AbstractIn this paper we explore the likely implications of the entry of Big Tech platforms into retail banking and the appropriate response of regulators and policy makers to this new industry development. We find that the entry of Big Tech platforms may transform the banking industry in radical ways: although it may possibly increase competition to the benefit of consumers in the short term, within a few years Big Tech companies may succeed in monopolizing the origination and distribution of loans to consumers and Small and Medium Enterprises (SMEs), forcing traditional banks to become “low cost manufacturers,” which merely fund the loans intermediated by the Big Techs. This situation may harm competition, reduce consumer welfare, and bring about an increase in financial instability in the medium or long term. We analyze alternative policy responses aimed at maximizing the positive impact on consumer welfare of Big Tech entry while limiting the risk of monopolization as well as the potential adverse implications of such entry on market integrity and financial stability.
Material patterning on substrates by manipulation of fluidic behavior
Authors: Li Yitan , Wang Hao , Xu Henglu , Wu Shiting , Li Xuemei , Yu Jiapeng , Huang Chaoyu , Zhang Zeyao , Sun Hao , Han Lu , Li Meihui , Cao Anyuan , Pan Zhenhai , Li Yan 
Published: March 2019

ABSTRACT
Patterned materials on substrates are of great importance for a wide variety of applications. In solution-based approaches to material patterning, fluidic flow is inevitable. Here we demonstrate not only the importance of fluidic behavior but also the methodology of engineering the flow pattern to guide the material crystallization and assembly. We show by both experiment and simulation that substrate heating, which is generally used to accelerate evaporation, produces irregular complex vortexes. Instead, a top-heating–bottom-cooling (THBC) set-up offers an inverse temperature gradient and results in a single Marangoni vortex, which is desired for ordered nanomaterial patterning near the contact line. We then realize the fabrication of large-scale patterns of iodide perovskite crystals on different substrates under THBC conditions. We further demonstrate that harnessing the flow behavior is a general strategy with great feasibility to pattern various functional materials ranging from inorganic, organic, hybrid to biological categories on different substrates, presenting great potential for practical applications.
Variants in the CHRNA5–CHRNA3–CHRNB4 Region of Chromosome 15 Predict Gastrointestinal Adverse Events in the Transdisciplinary Tobacco Use Research Center Smoking Cessation Trial
Authors: Culverhouse Robert C , Chen Li-Shiun , Saccone Nancy L , Ma Yinjiao , Piper Megan E , Baker Timothy B , Bierut Laura J 
Published: March 2019

Abstract

Introduction
Reducing adverse events from pharmacologic treatment is an important goal of precision medicine and identifying genetic predictors of adverse events is a step toward this goal. In 2012, King et al. reported associations between genetic variants and adverse events in a placebo-controlled smoking cessation trial of varenicline and bupropion. Strong associations were found between gastrointestinal adverse events and 11 variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15, a region repeatedly associated with smoking-related phenotypes. Our goal was to replicate, in an independent sample, the impact of variants in the CHRNA5–CHRNA3–CHRNB4 region on gastrointestinal adverse events and to extend the analyses to adherence and smoking cessation.

Methods
The University of Wisconsin Transdisciplinary Tobacco Use Research Center (TTURC) conducted a multiarmed, placebo-controlled smoking cessation trial of bupropion and nicotine replacement therapy that included 985 genotyped European-ancestry participants. We evaluated relationships between our key variables using logistic regression.

Results
Gastrointestinal adverse events were experienced by 31.6% TTURC participants. Each of the CHRNA5–CHRNA3–CHRNB4 associations from the King et al. study was found in TTURC, with the same direction of effect. Neither these variants nor the gastrointestinal adverse events themselves were associated with adherence to medication or successful smoking cessation.

Conclusions
Variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15 are associated with gastrointestinal adverse events in smoking cessation. Additional independent variants in this region strengthen the association. The consistency between the results of these two independent studies supports the conclusion that these findings reflect biological response to the use of smoking cessation medication.

Implications
The fact that our findings from the TTURC smoking cessation trial support the independent findings of King et al. suggest that associations of variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15 with gastrointestinal adverse events while taking medications for smoking cessation reflect biology. However, although adherence to medication was a strong predictor of successful smoking cessation in TTURC, neither adverse events nor the genetic variants associated with them predicted either adherence or successful cessation in this study. Thus, although we should strive to minimize adverse events during treatment, we should not expect that to increase successful smoking cessation substantially.
Antimicrobial Susceptibility of Acinetobacter calcoaceticus–Acinetobacter baumannii Complex and Stenotrophomonas maltophilia Clinical Isolates: Results From the SENTRY Antimicrobial Surveillance Program (1997–2016)
Authors: Gales Ana C , Seifert Harald , Gur Deniz , Castanheira Mariana , Jones Ronald N , Sader Helio S 
Published: March 2019

Abstract

Background
Acinetobacter calcoaceticus–A. baumannii (Acb) complex and Stenotrophomonas maltophilia represent frequent causes of hospital-acquired infections. We evaluated the frequency and resistance rates of Acb complex and S. maltophilia isolates from medical centers enrolled in the SENTRY Program.

Methods
A total of 13 752 Acb complex and 6467 S. maltophilia isolates were forwarded to a monitoring laboratory by 259 participating sites from the Asia-Pacific region, Latin America, Europe, and North America between 1997 and 2016. Confirmation of species identification and antimicrobial susceptibility testing were performed using conventional methods and/or matrix-assisted laser desorption ionization–time of flight mass spectrometry and the broth microdilution method, respectively. Antimicrobial susceptibility results were interpreted by CLSI and EUCAST 2018 criteria.

Results
Acb complex and S. maltophilia were most frequently isolated from patients hospitalized with pneumonia (42.9% and 55.8%, respectively) and bloodstream infections (37.3% and 33.8%, respectively). Colistin and minocycline were the most active agents against Acb complex (colistin MIC50/90, ≤0.5/2 mg/L; 95.9% susceptible) and S. maltophilia (minocycline MIC50/90, ≤1/2 mg/L; 99.5% susceptible) isolates, respectively. Important temporal decreases in susceptibility rates among Acb complex isolates were observed for all antimicrobial agents in all regions. Rates of extensively drug-resistant Acb complex rates were highest in Europe (66.4%), followed by Latin America (61.5%), Asia-Pacific (56.9%), and North America (38.8%). Among S. maltophilia isolates, overall trimethoprim-sulfamethoxazole (TMP-SMX) susceptibility rates decreased from 97.2% in 2001–2004 to 95.7% in 2013–2016, but varied according to the geographic region.

Conclusions
We observed important reductions of susceptibility rates to all antimicrobial agents among Acb complex isolates obtained from all geographic regions. In contrast, resistance rates to TMP-SMX among S. maltophilia isolates remained low and relatively stable during the study period.
Geographic and Temporal Patterns of Antimicrobial Resistance in Pseudomonas aeruginosa Over 20 Years From the SENTRY Antimicrobial Surveillance Program, 1997–2016
Authors: Shortridge Dee , Gales Ana C , Streit Jennifer M , Huband Michael D , Tsakris Athanasios , Jones Ronald N 
Published: March 2019

AbstractBackgroundThe SENTRY Antimicrobial Surveillance Program was established in 1997 and encompasses over 750 000 bacterial isolates from ≥400 medical centers worldwide. Among the pathogens tested, Pseudomonas aeruginosa remains a common cause of multidrug-resistant (MDR) bloodstream infections and pneumonia in hospitalized patients. In the present study, we reviewed geographic and temporal trends in resistant phenotypes of P. aeruginosa over 20 years of the SENTRY Program.MethodsFrom 1997 to 2016, 52 022 clinically significant consecutive isolates were submitted from ≥200 medical centers representing the Asia-Pacific region, Europe, Latin America, and North America. Only 1 isolate per patient per infection episode was submitted. Isolates were identified by standard algorithms and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry. Susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) methods and interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing 2018 criteria at JMI Laboratories.ResultsThe most common infection from which P. aeruginosa was isolated was pneumonia in hospitalized patients (44.6%) followed by bloodstream infection (27.9%), with pneumonia having a slightly higher rate of MDR (27.7%) than bloodstream infections (23.7%). The region with the highest percentage of MDR phenotypes was Latin America (41.1%), followed by Europe (28.4%). The MDR rates were highest in 2005–2008 and have decreased in the most recent period. Colistin was the most active drug tested (99.4% susceptible), followed by amikacin (90.5% susceptible).ConclusionsOver the 20 years of SENTRY Program surveillance, the rate of MDR P. aeruginosa infections has decreased, particularly in Latin America. Whether the trend of decreasing resistance in P. aeruginosa is maintained will be documented in future SENTRY Program and other surveillance reports.
Temporal and Geographic Variation in Antimicrobial Susceptibility and Resistance Patterns of Enterococci: Results From the SENTRY Antimicrobial Surveillance Program, 1997–2016
Authors: Pfaller Michael A , Cormican Martin , Flamm Robert K , Mendes Rodrigo E , Jones Ronald N 
Published: March 2019

Abstract

Background
The SENTRY Antimicrobial Surveillance Program was established in 1997 and presently encompasses more than 750 000 bacterial isolates from over 400 medical centers worldwide. Among these pathogens, enterococci represents a prominent cause of bloodstream (BSIs), intra-abdominal (IAIs), skin and skin structure, and urinary tract infections (UTIs). In the present study, we reviewed geographic and temporal trends in Enterococcus species and resistant phenotypes identified throughout the SENTRY Program.

Methods
From 1997 to 2016, a total of 49 491 clinically significant enterococci isolates (15 species) were submitted from 298 medical centers representing the Asia-Pacific (APAC), European, Latin American (LATAM), and North American (NA) regions. Bacteria were identified by standard algorithms and matrix-assisted laser desorption ionization–time of flight mass spectrometry. Susceptibility (S) testing was performed by reference broth microdilution methods and interpreted using Clinical and Laboratory Standards Institute/US Food and Drug Administration and European Committee on Antimicrobial Susceptibility Testing criteria.

Results
The most common Enterococcus species in all 4 regions were Enterococcus faecalis (64.7%) and E. faecium (EFM; 29.0%). Enterococci accounted for 10.7% of BSIs in NA and was most prominent as a cause of IAIs (24.0%) in APAC and of UTIs (19.8%) in LATAM. A steady decrease in the susceptibility to ampicillin and vancomycin was observed in all regions over the 20-year interval. Vancomycin-resistant enterococci (VRE) accounted for more than 8% of enterococcal isolates in all regions and was most common in NA (21.6%). Among the 7615 VRE isolates detected, 89.1% were the VanA phenotype (91.0% EFM) and 10.9% were VanB. Several newer antimicrobial agents demonstrated promising activity against VRE, including daptomycin (99.6–100.0% S), linezolid (98.0%–99.6% S), oritavancin (92.2%–98.3% S), tedizolid (99.5%–100.0% S), and tigecycline (99.4%–100.0% S).

Conclusions
Enterococci remained a prominent gram-positive pathogen in the SENTRY Program from 1997 through 2016. The overall frequency of VRE was 15.4% and increased over time in all monitored regions. Newly released agents with novel mechanisms of action show promising activity against VRE.
Application of Next-Generation Sequencing for Characterization of Surveillance and Clinical Trial Isolates: Analysis of the Distribution of β-lactamase Resistance Genes and Lineage Background in the United States
Authors: Mendes Rodrigo E , Jones Ronald N , Woosley Leah N , Cattoir Vincent , Castanheira Mariana 
Published: March 2019

AbstractBackgroundSequencing technologies and techniques have seen remarkable transformation and innovation that have significantly affected sequencing capability. Data analyses have replaced sequencing as the main challenge. This paper provides an overview on applying next-generation sequencing (NGS) and analysis and discusses the benefits and challenges. In addition, this document shows results from using NGS and bioinformatics tools to screen for β-lactamase genes and assess the epidemiological structure of Escherichia coli– and Klebsiella pneumoniae–causing bloodstream (BSIs) and urinary tract (UTIs) infections in patients hospitalized in the United States during the SENTRY Antimicrobial Surveillance Program for 2016.MethodsA total of 3525 isolates (2751 E. coli and 774 K. pneumoniae) causing BSIs (n = 892) and UTIs (n = 2633) in hospitalized patients in the United States were included. Isolates were tested for susceptibility by broth microdilution, and those that met a minimum inhibitory concentration (MIC)–based screening criteria had their genomes sequenced and analyzed.ResultsA total of 11.6% and 16.1% of E. coli–causing UTIs and BSIs, respectively, met the MIC-based criteria, whereas 11.0% and 13.7% of K. pneumoniae isolates causing UTIs and BSIs, respectively, met the criteria. Among E. coli, blaCTX-M variants (87.6% overall) prevailed (60.5% of CTX-M group 1 and 26.9% of group 9). A total of 60.3% of K. pneumoniae isolates carried blaCTX-M variants (52.7% and 7.6% of groups 1 and 9, respectively). Two E. coli (0.6%) and 13 K. pneumoniae (12.9%) isolates harbored blaKPC. Among KPC-producing K. pneumoniae (2 from BSIs and 11 from UTIs), 84.6% (11/13) were ST258 (CC258). Seventeen and 38 unique clonal complexes (CCs) were noted in E. coli that caused BSIs and UTIs, respectively, and CC131 (or ST131) was the most common CC among BSI (53.6%) and UTI (58.2%) isolates. Twenty-three and 26 CCs were noted among K. pneumoniae–causing BSIs and UTIs, respectively. CC258 (28.3%) prevailed in UTI pathogens, whereas CC307 (15.0%) was the most common CC among BSI isolates.ConclusionsThis study provides a benchmark for the distribution of β-lactamase genes and the population structure information for the most common Enterobacteriaceae species responsible for BSIs and UTIs in US medical centers during the 2016 SENTRY Program.
Social inclusion in the knowledge economy: unions’ strategies and institutional change in the Austrian and German training systems
Authors: Durazzi Niccolo , Geyer Leonard 
Published: March 2019

AbstractAs skill formation systems are increasingly under pressure from de-industrialization and the rise of knowledge economies, their ability to include the low-skilled has been strained. But what determines how skill formation systems adjust to this challenge? By explaining the divergence of two most-similar systems, those of Austria and Germany, the article highlights the key role of trade unions and of the institutional resources and legacies available to them. Where institutional resources are high and legacies positive, as in Austria, unions were crucial in setting an inclusive pathway of reform of the training system. Where, on the contrary, institutional resources are low and legacies negative, as in Germany, unions’ strategies for inclusion failed, paving the way to a dualizing outcome. The article therefore provides a novel analysis of institutional change in skill formation systems, while also offering broader insights on the relationship between coordinated and egalitarian capitalism in post-industrial knowledge-based economies.
Dosing Time Matters
Authors: Ruben Marc D. , Smith David F. , FitzGerald Garret A. , Hogenesch John B. 
Published: March 2019

AbstractTrainees in medicine are taught to diagnose and administer treatment as needed; time-of-day is rarely considered. Yet accumulating evidence shows that ∼half of human genes and physiologic functions follow daily rhythms. Circadian medicine aims to incorporate knowledge of these rhythms to enhance diagnosis and treatment. Interest in this approach goes back at least six decades, but the path to the clinic has been marked by starts, stops, and ambiguity. How do we move the field forward to impact clinical practice? To gain insight into successful strategies, we studied the results of more than 100 human trials that evaluated time-of-administration of drugs.