bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imbalance of synaptic actin dynamics as a key to fragile X syndrome?
Authors: Michaelsen‐Preusse Kristin , Feuge Jonas , Korte Martin 
Published: January 2018

AbstractOur experiences and memories define who we are, and evidence has accumulated that memory formation is dependent on functional and structural adaptations of synaptic structures in our brain. Especially dendritic spines, the postsynaptic compartments of synapses show a strong structure‐to‐function relationship and a high degree of structural plasticity. Although the molecular mechanisms are not completely understood, it is known that these modifications are highly dependent on the actin cytoskeleton, the major cytoskeletal component of the spine. Given the crucial involvement of actin in these mechanisms, dysregulations of spine actin dynamics (reflected by alterations in dendritic spine morphology) can be found in a variety of neurological disorders ranging from schizophrenia to several forms of autism spectrum disorders such as fragile X syndrome (FXS). FXS is caused by a single mutation leading to an inactivation of the X‐linked fragile X mental retardation 1 gene and loss of its gene product, the RNA‐binding protein fragile X mental retardation protein 1 (FMRP), which normally can be found both pre‐ and postsynaptically. FMRP is involved in mRNA transport as well as regulation of local translation at the synapse, and although hundreds of FMRP‐target mRNAs could be identified only a very few interactions between FMRP and actin‐regulating proteins have been reported and validated. In this review we give an overview of recent work by our lab and others providing evidence that dysregulated actin dynamics might indeed be at the very base of a deeper understanding of neurological disorders ranging from cognitive impairment to the autism spectrum.
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Bayesian Network Learning for Data-Driven Design
Authors: Hu Zhen , Mahadevan Sankaran 
Published: January 2018

Abstract
Bayesian networks (BNs) are being studied in recent years for system diagnosis, reliability analysis, and design of complex engineered systems. In several practical applications, BNs need to be learned from available data before being used for design or other purposes. Current BN learning algorithms are mainly developed for networks with only discrete variables. Engineering design problems often consist of both discrete and continuous variables. This paper develops a framework to handle continuous variables in BN learning by integrating learning algorithms of discrete BNs with Gaussian mixture models (GMMs). We first make the topology learning more robust by optimizing the number of Gaussian components in the univariate GMMs currently available in the literature. Based on the BN topology learning, a new multivariate Gaussian mixture (MGM) strategy is developed to improve the accuracy of conditional probability learning in the BN. A method is proposed to address this difficulty of MGM modeling with data of mixed discrete and continuous variables by mapping the data for discrete variables into data for a standard normal variable. The proposed framework is capable of learning BNs without discretizing the continuous variables or making assumptions about their conditional probability densities (CPDs). The applications of the learned BN to uncertainty quantification and model calibration are also investigated. The results of a mathematical example and an engineering application example demonstrate the effectiveness of the proposed framework.
Multiple Environmental Factors Influence the Importance of the Phosphodiesterase DipA upon Pseudomonas aeruginosa Swarming
Authors: Mattingly Anne E. , Kamatkar Nachiket G. , Morales-Soto Nydia , Borlee Bradley R. , Shrout Joshua D. 
Published: January 2018

ABSTRACTPseudomonas aeruginosaexhibits flagellum-mediated swimming in liquid and swarming on hydrated surfaces under diverse nutrient conditions. Prior studies have implicated a phosphodiesterase, DipA, in regulating these flagellum-mediated motilities, but collectively, the necessity for DipA was unclear. In this study, we find that the medium composition conditionally constrains the influence of DipA on flagellar motility. We show that DipA exhibits more influence on minimal medium supplemented with glutamate or glucose, where flagellar motility was negated for thedipAmutant. Conversely, adipA-deficient mutant exhibits flagellar motility when growing with LB Lennox broth and minimal medium supplemented with Casamino Acids. Swarming under these rich medium conditions occurs under elevated levels of c-di-GMP. We also demonstrate that the influence of DipA upon swimming often differs from that upon swarming, and we conclude that a direct comparison of the motility phenotypes is generally valid only when characterizing motility assay results from the same medium composition. Our results are consistent with the explanation that DipA is one of several phosphodiesterases responding to the nutrient environment sensed byP. aeruginosa. On minimal medium with glutamate or glucose, DipA is dominant; however, on rich medium, the necessity of DipA is fully negated.IMPORTANCEMotile and ubiquitous bacteria such asPseudomonas aeruginosacan quickly colonize surfaces and form biofilms in numerous environments such as water distribution systems, soil, and the human lung. To effectively disrupt bacterial colonization, it is imperative to understand how bacteria regulate motility in these different growth environments. Here, we show that the phosphodiesterase DipA is not required for flagellar motility under all nutrient conditions. Thus, the maintenance of intracellular c-di-GMP levels to promote flagellar motility or biofilm development must be conditionally regulated by differing phosphodiesterases in variation with select nutrient cues.
Practical Guidance for Clinical Microbiology Laboratories: Mycobacteria
Authors: Forbes Betty A. , Hall Geraldine S. , Miller Melissa B. , Novak Susan M. , Rowlinson Marie-Claire , Salfinger Max , Somoskövi Akos , Warshauer David M. , Wilson Michael L. 
Published: January 2018

SUMMARY
Mycobacteria are the causative organisms for diseases such as tuberculosis (TB), leprosy, Buruli ulcer, and pulmonary nontuberculous mycobacterial disease, to name the most important ones. In 2015, globally, almost 10 million people developed TB, and almost half a million patients suffered from its multidrug-resistant form. In 2016, a total of 9,287 new TB cases were reported in the United States. In 2015, there were 174,608 new case of leprosy worldwide. India, Brazil, and Indonesia reported the most leprosy cases. In 2015, the World Health Organization reported 2,037 new cases of Buruli ulcer, with most cases being reported in Africa. Pulmonary nontuberculous mycobacterial disease is an emerging public health challenge. The U.S. National Institutes of Health reported an increase from 20 to 47 cases/100,000 persons (or 8.2% per year) of pulmonary nontuberculous mycobacterial disease among adults aged 65 years or older throughout the United States, with 181,037 national annual cases estimated in 2014. This review describes contemporary methods for the laboratory diagnosis of mycobacterial diseases. Furthermore, the review considers the ever-changing health care delivery system and stresses the laboratory's need to adjust and embrace molecular technologies to provide shorter turnaround times and a higher quality of care for the patients who we serve.
Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene
mcr-1
in CRE in a Hospital in Henan, China
Authors: Li Yi , Sun Qiao-ling , Shen Yingbo , Zhang Yangjunna , Yang Jun-wen , Shu Ling-bin , Zhou Hong-wei , Wang Yang , Wang Bing , Zhang Rong , Wang Shaolin , Shen Zhangqi 
Published: January 2018

ABSTRACT

The global spread of carbapenem-resistant
Enterobacteriaceae
(CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene
mcr-1
among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249
Enterobacteriaceae
isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant
Klebsiella pneumoniae
and carbapenem-resistant
Escherichia coli
were the two most common CRE species, with
Klebsiella pneumoniae
carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% (
n
= 589) of the
K. pneumoniae
isolates from the intensive care unit were carbapenem resistant. Furthermore,
bla
NDM-5
and
mcr-1
were found to coexist in one
E. coli
isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by
K. pneumoniae
in the studied hospital.
Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies
In Vitro
and
In Vivo
Authors: Wang Xue-Feng , Liu Qiang , Wang Yu-Hong , Wang Shuai , Chen Jie , Lin Yue-Zhi , Ma Jian , Zhou Jian-Hua , Wang Xiaojun 
Published: January 2018

ABSTRACT

The equine infectious anemia virus (EIAV) attenuated vaccine was developed by long-term passaging of a field-isolated virulent strain in cross-species hosts, followed by successive cultivation in cells
in vitro
. To explore the molecular mechanism underlying the evolution of the EIAV attenuated vaccine, a systematic study focusing on long-terminal-repeat (LTR) variation in numerous virus strains ranging from virulent EIAV to attenuated EIAV was performed over time both
in vitro
and
in vivo
. Two hypervariable regions were identified within the U3 region in the enhancer region (EHR) and the negative regulatory element (NRE) and within the R region in the transcription start site (TSS) and the Tat-activating region (TAR). Among these sites, variation in the U3 region resulted in the formation of additional transcription factor binding sites; this variation of the
in vitro
-adapted strains was consistent with the loss of pathogenicity. Notably, the same LTR variation pattern was observed both
in vitro
and
in vivo
. Generally, the LTR variation in both the attenuated virus and the virulent strain fluctuated over time
in vivo
. Interestingly, the attenuated-virus-specific LTR variation was also detected in horses infected with the virulent strain, supporting the hypothesis that the evolution of an attenuated virus might have involved branching from EIAV quasispecies. This hypothesis was verified by phylogenetic analysis. The present systematic study examining the molecular evolution of attenuated EIAV from EIAV quasispecies may provide an informative model reflecting the evolution of similar lentiviruses.

IMPORTANCE
The attenuated EIAV vaccine was the first lentiviral vaccine used to successfully control for equine infectious anemia in China. This vaccine provides an important reference for studying the relationship between EIAV gene variation and changes in biological characteristics. Importantly, the vaccine provides a model for the investigation of lentiviral quasispecies evolution. This study followed the “natural” development of the attenuated EIAV vaccine by use of a systematic analysis of LTR evolution
in vitro
and
in vivo
. The results revealed that the increase in LTR variation with passaging was accompanied by a decrease in virulence, which indicated that LTR variability might parallel the attenuation of virulence. Interestingly, the attenuated-virus-specific LTR variation was also detected in virulent-strain-infected horses, a finding consistent with those of previous investigations of
gp90
and
S2
evolution. Therefore, we present a hypothesis that the evolution of the attenuated virus may involve branching from EIAV quasispecies present
in vivo
.
Computerised decision to reduce inappropriate medication in the elderly: a systematic review with meta-analysis protocol
Authors: Monteiro Luís , Maricoto Tiago , Solha Isabel S , Monteiro-Soares Matilde , Martins Carlos 
Published: January 2018

IntroductionLife expectancy continues to increase in developed countries. Elderly people are more likely to consume more medications and become vulnerable to age-related changes in drugs’ pharmacokinetics and pharmacodynamics. Recent studies have identified opportunities and barriers for deprescribing potentially inappropriate medications. It has already been demonstrated that computerised decision support systems can reduce physician orders for unnecessary tests. We will systematically review the available literature to understand if computerised decision support is effective in reducing the use of potentially inappropriate medications, thus having an impact on health outcomes.Methods and analysisA systematic review will be conducted using MEDLINE, CENTRAL, EMBASE and Web of Science databases, as well as the grey literature assessing the effectiveness of computer decision support interventions in deprescribing inappropriate medication, with an impact on health outcomes in the elderly. The search will be performed during January and February 2018. Two reviewers will conduct articles’ screening, selection and data extraction, independently and blind to each other. Eligible sources will be selected after discussing non-conformities. All extracted data from the included articles will be assessed based on studies’ participants, design and setting, methodological quality, bias and any other potential sources of heterogeneity. This review will be conducted and reported in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement of quality for reporting systematic reviews and meta-analyses.Ethics and disseminationAs a systematic review, this research is exempt from ethical approval. We intend to publish the full article in a related peer-reviewed journal and present it at international conferences.PROSPEROregistration numberCRD42017067021.
Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population
Authors: Doorakkers Eva , Lagergren Jesper , Engstrand Lars , Brusselaers Nele 
Published: January 2018

ObjectiveGastric infection with Helicobacter pylori is a strong risk factor for non-cardia gastric adenocarcinoma. The aim of this study was to assess whether the risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma decreases after eradication treatment for H. pylori in a Western population.DesignThis was a nationwide, population-based cohort study in Sweden in 2005–2012. Data from the Swedish Prescribed Drug Registry provided information on H. pylori eradication treatment, whereas information concerning newly developed gastric adenocarcinoma was retrieved from the Swedish Cancer Registry. The risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in individuals who had received H. pylori eradication treatment was compared with the background population of the corresponding age, sex and calendar year distribution, yielding standardised incidence ratios (SIRs) with 95% CIs.ResultsDuring the follow-up of 95 176 individuals who had received eradication treatment (351 018 person-years at risk), 75 (0.1%) developed gastric adenocarcinoma and 69 (0.1%) developed non-cardia gastric adenocarcinoma. The risk of gastric adenocarcinoma decreased over time after eradication treatment to levels below that of the corresponding background population. The SIRs were 8.65 (95% CI 6.37 to 11.46) for 1–3 years, 2.02 (95% CI 1.25 to 3.09) for 3–5 years and 0.31 (95% CI 0.11 to 0.67) for 5–7.5 years after eradication treatment. When restricted to non-cardia adenocarcinoma, the corresponding SIRs were 10.74 (95% CI 7.77 to 14.46), 2.67 (95% CI 1.63 to 4.13) and 0.43 (95% CI 0.16 to 0.93).ConclusionEradication treatment for H. pylori seems to counteract the development of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in this Western population.
Body mass index status and peripheral airway obstruction in school-age children: a population-based cohort study
Authors: Ekström Sandra , Hallberg Jenny , Kull Inger , Protudjer Jennifer L P , Thunqvist Per , Bottai Matteo , Gustafsson Per Magnus , Bergström Anna , Melén Erik 
Published: January 2018

BackgroundFew large prospective studies have investigated the impact of body mass index (BMI) on lung function during childhood.MethodsUsing data collected between 2002 and 2013, we analysed associations between BMI status and lung function (assessed by spirometry) from 8 to 16 years, as well as cross-sectional associations with small airway function (impulse oscillometry) at 16 years in the BAMSE cohort (n=2889). At 16 years, cross-sectional associations with local and systemic inflammation were investigated by analysing FENO, blood eosinophils and neutrophils.ResultsOverweight and obesity at 8 years were associated with higher FVC, but lower FEV1/FVC ratio at 8 and 16 years. In boys, but not girls, obesity at 8 years was associated with a further reduction in FEV1/FVC between 8 and 16 years. In cross-sectional analyses, overweight and obesity were associated with higher frequency dependence of resistance (R5–20) and larger area under the reactance curve (AX0.5) at 16 years. Increased blood neutrophil counts were seen in overweight and obese girls, but not in boys. No association was found between BMI status and FENO. Persistent, but not transient, overweight/obesity between 8 and 16 years was associated with higher R5–20and AX0.5and lower FEV1/FVC (−2.8% (95% CI −4.1 to −1.2) in girls and −2.7% (95% CI −4.4 to −1.1) in boys) at 16 years, compared with persistent normal weight.ConclusionIn childhood and adolescence, overweight and obesity, particularly persistent overweight, were associated with evidence of airway obstruction, including the small airways.
Overt Increase of Oxidative Stress and DNA Damage in Murine and Human Colitis and Colitis-Associated Neoplasia
Authors: Frick Adrian , Khare Vineeta , Paul Gregor , Lang Michaela , Ferk Franziska , Knasmüller Siegfried , Beer Andrea , Oberhuber Georg , Gasche Christoph 
Published: January 2018

Abstract
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated-cancer (CAC); however, the underlying processes of disease progression are not completely understood. Here, the molecular processes of inflammation-driven colon carcinogenesis were investigated using IL10-deficient mice (IL10 KO). IL10 KO mice were euthanized after development of colitis and dysplasia. IHC was performed for markers of colitis-induced DNA damage (CIDD): oxidative DNA lesions (8-oxoG), double-strand breaks (DSB; γH2AX). and DSB repair. MSI, LOH (Trp53, Apc), and global methylation (CIMP) were assessed on microdissected tissue. Comet assay for DNA damage, immunofluorescence, and immunoblotting were performed on intestinal organoids from wild-type (WT) and IL10 KO mice. Sequential biopsies and surgical specimens from IBD and CAC patients were used for IHC analysis. Severity of inflammation correlated with number of dysplasia. 8-oxoG and γH2AX-positive cells were significantly increased in inflamed and dysplastic areas along with activation of DSB repair. The amount of positively stained cells strongly correlated with degree of inflammation (8-oxoG: R = 0.923; γH2AX: R = 0.858). Neither CIMP, MSI nor LOH was observed. Enhanced DSBs in IL10 KO organoids were confirmed by comet assay and increased expression of γH2AX. Human clinical specimens exhibited significantly higher γH2AX and 8-oxoG in IBD, dysplasia, and CAC compared with normal mucosa. These data indicate that inflammation-driven colon carcinogenesis in IL10 KO mice and IBD patients is associated with oxidative DNA damage and overt presence of DSB. Mol Cancer Res; 16(4); 634–42. ©2018 AACR.
“Reformas estimulam ou evitam revoluções? Os dízimos da Capitania da Bahia e a Conjuração Baiana de 1798"
Authors: Valim Patricia 
Published: January 2018

O presente artigo analisa o impacto das reformas de d. Rodrigo de Sousa Coutinho na capitania da Bahia, no final do século XVIII, para um grupo de poderosos, qualificados por Luís dos Santos Vilhena de “corporação dos enteados”,. Esse potentado integrou a Conjuração Baiana de 1798, estimulado pela contenda sobre a arrematação dos dízimos na capitania, que ameaçou sua participação no leilão público. A partir da deflagração do movimento de 1798, a coroa portuguesa empreendeu soluções de compromisso com esse grupo de poderosos ao tempo em que evitou qualquer possibilidade de ruptura do sistema de dominação colonial.
Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome
Authors: Frencken Jos F. , Donker Dirk W. , Spitoni Cristian , Koster-Brouwer Marlies E. , Soliman Ivo W. , Ong David S.Y. , Horn Janneke , van der Poll Tom , van Klei Wilton A. , Bonten Marc J.M. , Cremer Olaf L. , de Beer Friso M. , Bos Lieuwe D.J. , Glas Gerie J. , van Hooijdonk Roosmarijn T.M. , Schouten Laura R.A. , Straat Marleen , Witteveen Esther , Wieske Luuk , van Vught Lonneke A. , Wiewel Maryse , Hoogendijk Arie J. , Huson Mischa A. , Scicluna Brendon , Schultz Marcus J. , Klein Klouwenberg Peter M.C. , van de Groep Kirsten , Verboom Diana 
Published: January 2018

Background:
Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes.

Methods and Results:
We enrolled consecutive patients with sepsis in 2 Dutch intensive care units between 2011 and 2013. Subjects with a clinically apparent cause of troponin release were excluded. High-sensitivity cardiac troponin I (hs-cTnI) concentration in plasma was measured daily during the first 4 intensive care unit days, and multivariable Cox regression analysis was used to model its association with 1-year mortality while adjusting for confounding. In addition, we studied cardiovascular morbidity occurring during the first year after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%) were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673 (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4 days. Cox regression analysis revealed that high hs-cTnI concentrations were associated with increased death rates during the first 14 days (adjusted hazard ratio, 1.72; 95% confidence interval, 1.14–2.59 and hazard ratio, 1.70; 95% confidence interval, 1.10–2.62 for hs-cTnI concentrations of 100–500 and >500 ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were associated with the development of cardiovascular disease among 200 hospital survivors who were analyzed for this end point (adjusted subdistribution hazard ratio, 1.25; 95% confidence interval, 1.04–1.50).

Conclusions:
Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early—but not late—mortality, as well as postdischarge cardiovascular morbidity.