bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed Administration of Recombinant Plasma Gelsolin Improves Survival in a Murine Model of Penicillin-Susceptible and Penicillin-Resistant Pneumococcal Pneumonia
Authors: Yang Zhiping , Bedugnis Alice , Levinson Susan , Dinubile Mark , Stossel Thomas , Lu Quan , Kobzik Lester 
Published: July 2019

Abstract
Therapy to enhance host immune defenses may improve outcomes in serious infections, especially for antibiotic-resistant pathogens. Recombinant human plasma gelsolin (rhu-pGSN), a normally circulating protein, has beneficial effects in diverse preclinical models of inflammation and injury. We evaluated delayed therapy (24–48 hours after challenge) with rhu-pGSN in a mouse model of pneumococcal pneumonia. rhu-pGSN without antibiotics increased survival and reduced morbidity and weight loss after infection with either penicillin-susceptible or penicillin-resistant pneumococci (serotypes 3 and 14, respectively). rhu-pGSN improves outcomes in a highly lethal pneumococcal pneumonia model when given after a clinically relevant delay, even in the setting of antimicrobial resistance.
Specific Vaginal Bacteria Are Associated With an Increased Risk of Trichomonas vaginalis Acquisition in Women
Authors: Jarrett Olamide D , Srinivasan Sujatha , Richardson Barbra A , Fiedler Tina , Wallis Jacqueline M , Kinuthia John , Jaoko Walter , Mandaliya Kishor , Fredricks David N , McClelland R Scott 
Published: July 2019

AbstractBackgroundWhile bacterial vaginosis has been associated with an increased risk of Trichomonas vaginalis (TV) acquisition, it is unknown whether other characteristics of the vaginal microbiota, including the presence of key bacterial species, influence a woman’s risk of TV acquisition.MethodsThe vaginal microbiota before 25 unique episodes of TV infection involving 18 women was compared to that of 50 controls who remained uninfected. TV was detected by transcription-mediated amplification. Vaginal microbiota were quantified using broad-range polymerase chain reaction analysis and taxon-specific quantitative PCR of the 16S ribosomal RNA gene.ResultsTV acquisition was significantly associated with the presence of Prevotella amnii (risk ratio [RR], 2.21; 95% confidence interval [CI], 1.12–4.38; P = .02) and Sneathia sanguinegens (RR, 2.58; 95% CI, 1.00–6.62; P = .049). When adjusted for menstrual phase, the association between P. amnii and TV acquisition remained similar (adjusted RR, 2.11; 95% CI, 1.03–4.33; P = .04), but the association between S. sanguinegens and TV acquisition was attenuated (adjusted RR, 2.31; 95% CI, .86–6.23; P = .10).ConclusionsKey vaginal bacterial species may contribute to the susceptibility to TV acquisition. Understanding how these bacterial species increase a woman’s risk of TV acquisition could help to guide the development of novel strategies to reduce women’s risk of TV infection.
Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015–2017
Authors: Soeters Heidi M , Diallo Alpha Oumar , Bicaba Brice W , Kadadé Goumbi , Dembélé Assétou Y , Acyl Mahamat A , Nikiema Christelle , Sadji Adodo Yao , Poy Alain N , Lingani Clement , Tall Haoua , Sakandé Souleymane , Tarbangdo Félix , Aké Flavien , Mbaeyi Sarah A , Moïsi Jennifer , Paye Marietou F , Sanogo Yibayiri Osee , Vuong Jeni T , Wang Xin , Ronveaux Olivier , Novak; Ryan T ,   MenAfriNet Consortium
Published: July 2019

Abstract

Background
The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo. We describe bacterial meningitis epidemiology in these 5 countries in 2015–2017.

Methods
Case-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae cases were confirmed and N. meningitidis/H. influenzae were serogrouped/serotyped by real-time polymerase chain reaction, culture, or latex agglutination. We calculated annual incidence in participating districts in each country in cases/100 000 population.

Results
From 2015–2017, 18 262 suspected meningitis cases were reported; 92% had a CSF specimen available, of which 26% were confirmed as N. meningitidis (n = 2433; 56%), S. pneumoniae (n = 1758; 40%), or H. influenzae (n = 180; 4%). Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3. N. meningitidis incidence was 1.5 in Burkina Faso, 2.7 in Chad, 0.4 in Mali, 14.7 in Niger, and 12.5 in Togo. Several outbreaks occurred: NmC in Niger in 2015–2017, NmC in Mali in 2016, and NmW in Togo in 2016–2017. Of N. meningitidis cases, 53% were NmC, 30% NmW, and 13% NmX. Five NmA cases were reported (Burkina Faso, 2015). NmX increased from 0.6% of N. meningitidis cases in 2015 to 27% in 2017.

Conclusions
Although bacterial meningitis epidemiology varied widely by country, NmC and NmW caused several outbreaks, NmX increased although was not associated with outbreaks, and overall NmA incidence remained low. An effective low-cost multivalent meningococcal conjugate vaccine could help further control meningococcal meningitis in the region.
Effect of Age on Relative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries Aged ≥65 Years
Authors: Lu Yun , Chillarige Yoganand , Izurieta Hector S , Wei Yuqin , Xu Wenjie , Lu Michael , Sung Heng-Ming , Lindaas Arnstein , Wernecke Michael , Macurdy Thomas , Kelman Jeffrey , Forshee Richard A 
Published: July 2019

AbstractBackgroundStudies have found that the high-dose influenza vaccine has a higher relative vaccine effectiveness (RVE) versus standard-dose vaccines in some seasons. We evaluated the effect of age on the RVE of high-dose versus standard-dose influenza vaccines among Medicare beneficiaries.MethodsA 6-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries aged ≥65 years was performed. Poisson regression was used to evaluate the effect of age on the RVE of high-dose versus standard-dose influenza vaccines in preventing influenza-related hospitalizations.ResultsThe study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza-related hospital encounters (ie, influenza-related inpatient stays and emergency department visits) in the 2012–2013 (RVE, 23.1%; 95% confidence interval [CI], 17.6%–28.3%), 2013–2014 (RVE, 15.3%; 95% CI, 7.8%–22.3%), 2014–2015 (RVE, 8.9%; 95% CI, 5.6%–12.1%), and 2016–2017 (RVE, 12.6%; 95% CI, 6.3%–18.4%) seasons and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines across all seasons for people aged ≥85 years. Similar trends were observed for influenza-related inpatient stays.ConclusionsThe RVE of high-dose versus standard-dose influenza vaccines increases with age.
Glucocorticoids and “Stress” Are Not Synonymous
Authors: MacDougall-Shackleton S A , Bonier F , Romero L M , Moore I T 
Published: July 2019

SynopsisReference to glucocorticoids as “stress hormones” has been growing in prevalence in the literature, including in comparative and environmental endocrinology. Although glucocorticoids are elevated in response to a variety of stressors in vertebrate animals, the primary functions of glucocorticoids are not responding to stressors and they are only one component of complex suite of physiological and behavioral responses to stressors. Thus, the use of the short-hand phrase “stress hormone” can be misleading. Further, simply measuring glucocorticoids is not equivalent to measuring a stress response, nor is manipulating glucocorticoids equivalent to exposing an animal to a stressor. In this commentary we highlight the problems with using functional names for hormones, and of treating cortisol or corticosterone as synonymous with stress. We provide recommendations to add clarity to the presentation of research on this topic, and to avoid conflation of glucocorticoids with stressors and the stress response in the design of experiments.
Separate Universe simulations with IllustrisTNG: baryonic effects on power spectrum responses and higher-order statistics
Authors: Barreira Alexandre , Nelson Dylan , Pillepich Annalisa , Springel Volker , Schmidt Fabian , Pakmor Ruediger , Hernquist Lars , Vogelsberger Mark 
Published: July 2019

Abstract
We measure power spectrum response functions in the presence of baryonic physical processes using separate universe simulations with the IllustrisTNG galaxy formation model. The response functions describe how the small-scale power spectrum reacts to long-wavelength perturbations and they can be efficiently measured with the separate universe technique by absorbing the effects of the long modes into a modified cosmology. Specifically, we focus on the total first-order matter power spectrum response to an isotropic density fluctuation R1(k, z), which is fully determined by the logarithmic derivative of the non-linear matter power spectrum dlnPm(k, z)/dlnk and the growth-only response function G1(k, z). We find that G1(k, z) is not affected by the baryonic physical processes in the simulations at redshifts z < 3 and on all scales probed (k ≲ 15 h Mpc−1; i.e. length scales $\gtrsim 0.4\, {\rm Mpc}\,h^{-1}$). In practice, this implies that the power spectrum fully specifies the baryonic dependence of its response function. Assuming an idealized lensing survey set-up, we evaluate numerically the baryonic impact on the squeezed-lensing bispectrum and the lensing supersample power spectrum covariance, which are given in terms of responses. Our results show that these higher-order lensing statistics can display varying levels of sensitivity to baryonic effects compared to the power spectrum, with the squeezed bispectrum being the least sensitive. We also show that ignoring baryonic effects on lensing covariances slightly overestimates the error budget (and is therefore conservative from the point of view of parameter error bars) and likely has negligible impact on parameter biases in inference analyses.
Extraction of globular clusters members with Gaia DR2 astrometry
Authors: Fierro Iván H Bustos , Calderón J H 
Published: July 2019

Abstract
In this work we present a method to identify possible members of globular clusters using data from Gaia DR2. The method consists of two stages: the first one based on a clustering algorithm, and the second one based on the analysis of the projected spatial distribution of stars with different proper motions. In order to confirm that the clusters members extracted by the method correspond to actual globular clusters, the spatial distribution, the vector point diagram of the proper motions and the colour-magnitude diagrams are analysed. We apply the developed method to eight clusters: NGC 1261, NGC 3201, NGC 6139, NGC 6205, NGC 6362, NGC 6397, NGC 6712 and Palomar 13; we show the number of members extracted, the mean proper motions derived from them and finally we compare our results with other authors. In order to analyse the efficiency of the extraction method we perform an estimation of the completeness and the degree of contamination of the extracted members.
Propagation of star formation at sub-kiloparsec scales
Authors: Gusev A S , Shimanovskaya E V 
Published: July 2019

ABSTRACT
We study the propagation of star formation based on the investigation of the separation of young star clusters from H ii regions nearest to them. The relation between the separation and U − B colour index (or age) of a star cluster was found. The average age of star clusters increases with the separation as the 1.0–1.2 power in the separation range from 40 to 200 pc and as the 0.4–0.9 power in the range of 100–500 pc in the galaxies with symmetric morphology. The galaxies with distorted asymmetric disc structure show more complex and steeper (power >1.2 at separations from 40 to 500 pc) dependence between the age and the separation. Our results confirm the findings of previous studies on the dominant role of turbulence in propagation of the star formation process on spatial scales up to 500 pc and on time-scales up to 300 Myr. On a smaller scale (≤100 pc), other physical processes, such as stellar winds and supernova explosions, play an important role along with turbulence. On the scale of stellar associations (100–200 pc and smaller), the velocity of star formation propagation is almost constant and it has a typical value of a few km s−1.
Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations
Authors: Bueren-Calabuig Juan A , G. Bage Marcus , Cowling Victoria H , Pisliakov Andrei V 
Published: July 2019

Abstract
The RNA guanine-N7 methyltransferase (RNMT) in complex with RNMT-activating miniprotein (RAM) catalyses the formation of a N7-methylated guanosine cap structure on the 5′ end of nascent RNA polymerase II transcripts. The mRNA cap protects the primary transcript from exonucleases and recruits cap-binding complexes that mediate RNA processing, export and translation. By using microsecond standard and accelerated molecular dynamics simulations, we provide for the first time a detailed molecular mechanism of allosteric regulation of RNMT by RAM. We show that RAM selects the RNMT active site conformations that are optimal for binding of substrates (AdoMet and the cap), thus enhancing their affinity. Furthermore, our results strongly suggest the likely scenario in which the cap binding promotes the subsequent AdoMet binding, consistent with the previously suggested cooperative binding model. By employing the network community analyses, we revealed the underlying long-range allosteric networks and paths that are crucial for allosteric regulation by RAM. Our findings complement and explain previous experimental data on RNMT activity. Moreover, this study provides the most complete description of the cap and AdoMet binding poses and interactions within the enzyme’s active site. This information is critical for the drug discovery efforts that consider RNMT as a promising anti-cancer target.
Biomarkers and smart intracranial devices for the diagnosis, treatment, and monitoring of high-grade gliomas: a review of the literature and future prospects
Authors: Hafeez Umbreen , Cher Lawrence M 
Published: July 2019

Abstract
Glioblastoma (GBM) is the most common primary brain neoplasm with median overall survival (OS) around 15 months. There is a dearth of effective monitoring strategies for patients with high-grade gliomas. Relying on magnetic resonance images of brain has its challenges, and repeated brain biopsies add significant morbidity. Hence, it is imperative to establish a less invasive way to diagnose, monitor, and guide management of patients with high-grade gliomas. Currently, multiple biomarkers are in various phases of development and include tissue, serum, cerebrospinal fluid (CSF), and imaging biomarkers. Here we review and summarize the potential biomarkers found in blood and CSF, including extracellular macromolecules, extracellular vesicles, circulating tumor cells, immune cells, endothelial cells, and endothelial progenitor cells. The ability to detect tumor-specific biomarkers in blood and CSF will potentially not only reduce the need for repeated brain biopsies but also provide valuable information about the heterogeneity of tumor, response to current treatment, and identify disease resistance. This review also details the status and potential scope of brain tumor-related cranial devices and implants including Ommaya reservoir, microelectromechanical systems-based depot device, Alzet mini-osmotic pump, Metronomic Biofeedback Pump (MBP), ipsum G1 implant, ultra-thin needle implant, and putative devices. An ideal smart cranial implant will overcome the blood-brain barrier, deliver various drugs, provide access to brain tissue, and potentially measure and monitor levels of various biomarkers.
Sumoylation of BRI1-EMS-SUPPRESSOR 1 (BES1) by the SUMO E3 Ligase SIZ1 Negatively Regulates Brassinosteroids Signaling in Arabidopsis thaliana
Authors: Zhang Li’e , Han Qing , Xiong Jiawei , Zheng Ting , Han Jifu , Zhou Huanbin , Lin Honghui , Yin Yanhai , Zhang Dawei 
Published: July 2019

AbstractBrassinosteroids (BRs), a group of plant steroid hormones, participate in the regulation of plant growth and developmental processes. BR functions through the BES1/BZR1 family of transcription factors, however, the regulation of the BES1 activity by post-translational modifications remains largely unknown. Here, we present evidence that the SUMO E3 ligase SIZ1 negatively regulates BR signaling pathway. T-DNA insertion mutant siz1-2 shows BL (Brassinolide, the most active BR) hypersensitivity and BRZ (Brassinazole, a BR biosynthesis inhibitor) insensitivity during hypocotyl elongation. In addition, expression of BES1-dependent BR-response genes is hyper-regulated in siz1-2 seedlings. The siz1-2bes1-D double mutant exhibits longer hypocotyl than bes1-D. Moreover, SIZ1 physically interacts with BES1 in vivo and in vitro and mediates the sumoylation of BES1. A K302R substitution in BES1 blocks its sumoylation mediated by SIZ1 in plants, indicating that K302 is the principal site for SUMO conjugation. Consistently, we find that sumoylation inhibits BES1 protein stability and activity. Taken together, our data show that the sumoylation of BES1 via SIZ1 negatively regulates the BR signaling pathway.
Identification and Characterization of Stress-Responsive TAS3-Derived TasiRNAs in Melon
Authors: Cervera-Seco Luis , Marques Marï¿½a Carmen , Sanz-Carbonell Alejandro , Marquez-Molins Joan , Carbonell Alberto , Darï¿½s Josï¿½-Antonio , Gomez Gustavo 
Published: July 2019

AbstractSmall interfering RNAs (siRNA) are key regulators of gene expression that play essential roles in diverse biological processes. Trans-acting siRNAs (tasiRNAs) are a class of plant-endogenous siRNAs that lead the cleavage of nonidentical transcripts. TasiRNAs are usually involved in fine-tuning development. However, increasing evidence supports that tasiRNAs may be involved in stress response. Melon is a crop of great economic importance extensively cultivated in semiarid regions frequently exposed to changing environmental conditions that limit its productivity. However, knowledge of the precise role of siRNAs in general, and of tasiRNAs in particular, in regulating the response to adverse environmental conditions is limited. Here, we provide the first comprehensive analysis of computationally inferred melon-tasiRNAs responsive to two biotic (viroid-infection) and abiotic (cold treatment) stress conditions. We identify two TAS3-loci encoding to length (TAS3-L) and short (TAS3-S) transcripts. The TAS candidates predicted from small RNA-sequencing data were characterized according to their chromosome localization and expression pattern in response to stress. The functional activity of cmTAS genes was validated by transcript quantification and degradome assays of the tasiRNA precursors and their predicted targets. Finally, the functionality of a representative cmTAS3-derived tasiRNA (TAS3-S) was confirmed by transient assays showing the cleavage of ARF target transcripts.
Evolving a lipase for hydrolysis of natural triglycerides along with enhanced tolerance towards a protease and surfactants
Authors: Alfaro-Chávez Ana L , Liu Jian-Wei , Stevenson Bradley J , Goldman Adrian , Ollis David L 
Published: July 2019

Abstract
In the accompanying paper, we described evolving a lipase to the point where variants were soluble, stable and capable of degrading C8 TAG and C8 esters. These variants were tested for their ability to survive in an environment that might be encountered in a washing machine. Unfortunately, they were inactivated both by treatment with a protease used in laundry detergents and by very low concentrations of sodium dodecyl sulfate (SDS). In addition, all the variants had very low levels of activity with triglycerides with long aliphatic chains and with naturally occurring oils, like olive oil. Directed evolution was used to select variants with enhanced properties. In the first 10 rounds of evolution, the primary screen was selected for variants capable of hydrolyzing olive oil whereas the secondary screen was selected for enhanced tolerance towards a protease and SDS. In the final six rounds of evolution, the primary and secondary screens identified variants that retained activity after treatment with SDS. Sixteen cycles of evolution gave variants with greatly enhanced lipolytic activity on substrates that had both long (C16 and C18) as well as short (C3 and C8) chains. We found variants that were stable for more than 3 hours in protease concentrations that rapidly degrade the wild-type enzyme. Enhanced tolerance towards SDS was found in variants that could break down naturally occurring lipid and resist protease attack. The amino acid changes that gave enhanced properties were concentrated in the cap domain responsible for substrate binding.
Financial Illiteracy and Pension Contributions: A Field Experiment on Compound Interest in China
Authors: Song Changcheng 
Published: July 2019

Abstract
I conduct a field experiment to study the relationship between peoples’ misunderstanding of compound interest and their pension contributions in rural China. I find that explaining the concept of compound interest to subjects increased pension contributions by roughly 40%. The treatment effect is larger for those who underestimate compound interest than for those who overestimate compound interest. Moreover, financial education enables households to partially correct their misunderstanding of compound interest. I structurally estimate the level of misunderstanding of compound interest and conduct a counterfactual welfare analysis: lifetime utility increases by about 10% if subjects’ misunderstanding of compound interest is eliminated.
Long-term efficacy and safety of phrenic nerve stimulation for the treatment of central sleep apnea
Authors: Fox Henrik , Oldenburg Olaf , Javaheri Shahrokh , Ponikowski Piotr , Augostini Ralph , Goldberg Lee R , Stellbrink Christoph , Mckane Scott , Meyer Timothy E , Abraham William T , Costanzo Maria Rosa 
Published: July 2019

Abstract

Study Objective
To evaluate long-term efficacy and safety of phrenic nerve stimulation (PNS) in patients with moderate-to-severe central sleep apnea (CSA) through 3 years of therapy.

Methods
Patients in the remedē System Pivotal Trial were observed every 3 months after implant until US Food and Drug Administration approval. At the time of approval and study closure, all patients completed 24 months of follow-up; 33 patients had not reached the 36-month visit. Sleep metrics (polysomnography) and echocardiographic parameters are reported at baseline, 12, 18, and 24 months, in addition to available 36-month sleep results from polygraphy. Safety was assessed through 36 months; however, analysis focused through 24 months and available 36-month results are provided.

Results
Patients were assessed at 24 (n = 109) and 36 (n = 60) months. Baseline characteristics included mean age 64 years, 91% male, and mean apnea–hypopnea index 47 events per hour. Sleep metrics (apnea–hypopnea index (AHI), central apnea index, arousal index, oxygen desaturation index, rapid eye movement sleep) remained improved through 24 and 36 months with continuous use of PNS therapy. At least 60% of patients in the treatment group achieved at least 50% reduction in AHI through 24 months. Serious adverse events (SAEs) related to the remedē System implant procedure, device, or therapy through 24 months were reported by 10% of patients, no unanticipated adverse device effects or deaths, and all events resolved. No additional related SAEs were reported between 24 and 36 months.

Conclusion
These data suggest beneficial effects of long-term PNS in patients with CSA appear to sustain through 36 months with no new safety concerns.

Trial Registration
NCT01816776.