bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double‐blind, placebo‐controlled, crossover study
Authors: Cheng Jocelyn Y. , Filippov Gleb , Moline Margaret , Zammit Gary K. , Bsharat Mohammad , Hall Nancy 
Published: March 2020

AbstractLemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. Some current pharmacologic treatments for insomnia cause respiratory depression, a serious safety concern, particularly for individuals with obstructive sleep apnea (OSA). This phase 1, randomized, double‐blind, placebo‐controlled, two‐period crossover study examined respiratory safety parameters in individuals with mild OSA following treatment with lemborexant. Participants (n = 39) were randomized to one of two treatment sequences, including placebo and lemborexant 10 mg. Each treatment period lasted 8 days and was separated by a washout of at least 14 days. Following single or multiple doses, there were no significant differences in mean apnea–hypopnea index for lemborexant 10 mg versus placebo (least squares mean [LSM] difference [95% confidence interval {CI}]: day 1, −0.03 [−2.22, 2.17]; day 8, −0.06 [−1.95, 1.83]) or peripheral capillary oxygen saturation during sleep (LSM difference [95% CI]: day 1, 0.07 [−0.31, 0.46]; day 8, 0.25 [−0.11, 0.61]). There were no significant differences versus placebo for the percentage of total sleep time during which peripheral capillary oxygen saturation was <80% (LSM difference [95% CI]: day 1, 0.002 [−0.019, 0.023]; day 8, 0.006 [−0.015, 0.026]), <85% (LSM difference [95% CI]: day 1, 0.067 [−0.124, 0.258]; day 8, 0.056 [−0.117, 0.228]) or <90% (LSM difference [95% CI]: day 1, 0.312 [−0.558, 1.181]; day 8, 0.088 [−0.431, 0.607]). The incidence of treatment‐emergent adverse events was low and similar for lemborexant and placebo. Lemborexant demonstrated respiratory safety in this study population and was well tolerated.
New hepatitis C diagnoses in Ontario, Canada are associated with the local prescription patterns of a controlled‐release opioid
Authors: Meyer Matthew , Bondy Lise , Koivu Sharon , Koval John , Scarffe Andrew D. , Silverman Michael S. 
Published: March 2020

AbstractIncreases in acute hepatitis C virus (HCV) incidence may be a result of the rising prevalence of injection drug use and the opioid epidemic. Among persons who inject drugs, sharing of needles/syringes is less common and leads to a smaller proportion of incident cases than does sharing of injection drug preparation equipment. In Canada and Europe, hydromorphone controlled release has been associated with frequent reuse and sharing of IDPE. Drug excipients within HCR have been shown to preserve virus survival within IDPE. We hypothesized that regional differences in HCV incidence would mirror regional differences in HCR prescribing. We reviewed HCV incidence data across Ontario, Canada for 2016. Opioid prescribing patterns in each Health Unit were reviewed. Multivariable Poisson regression analyses were performed to test the strength of hydromorphone controlled release dispensing patterns in explaining HCV incidence compared to all opioids. Less vehicle access, lack of education, lower income, less population density, higher white race/ethnicity and more opioid substitution therapy recipients remained significant positive predictors of hepatitis C incidence in the Ontario model. Higher hydromorphone controlled release dispensing rate was a stronger predictor of HCV incidence than all opioid prescriptions (standardized risk ratio = 1.17, P < .0001 vs sRR = 1.11, P = .02). When hydromorphone controlled release was excluded from the opioid prescription variable, dispensing patterns of all other opioids no longer remained a significant predictor (sRR = 1.042, P = .34). The observed relationship between HCV incidence and hydromorphone controlled release dispensing suggests that the type of opioid prescribed locally may contribute to variations in HCV incidence. These data add support to evidence that hydromorphone controlled release use is contributing to HCV spread in Ontario.
Measuring hepatitis C virus elimination as a public health threat: Beyond global targets
Authors: van Santen Daniela K. , Sacks‐Davis Rachel , Doyle Joseph S. , Scott Nick , Prins Maria , Hellard Margaret 
Published: March 2020

AbstractAn increasing number of countries are committing to meet the World Health Organization (WHO) targets to eliminate hepatitis C virus (HCV) as a public health threat by 2030. These include service coverage targets (90% diagnosed and 80% of diagnosed patients treated) and impact targets (80% and 65% reductions in incidence and mortality, respectively, compared to 2015 levels). Currently, a dozen countries are on track to reach 2030 WHO HCV targets. However, while striving for the WHO targets is important, it should be recognized that progress on impact targets is derived from mathematical models projecting decreases in incidence and mortality on a global scale. Despite HCV treatment access in many counties for a number of years, limited empirical data are available to evaluate progress towards elimination. In some countries, substantial incidence and mortality reductions based on reaching the WHO service coverage targets may be unachievable. For example, in countries with ageing hepatitis C–infected populations, even if they have a quality hepatitis C response, high hepatitis C–related morbidity at baseline may not be reversible even with increased HCV treatment uptake and diagnosis. Finally, WHO targets are not necessarily easily or reliably measurable. Measuring relative impact targets requires high‐quality data at baseline (ie 2015) and longitudinal data to assess temporal trends. In this commentary, we propose alternative additional measures to track progress on reducing the HCV burden, offer examples where the WHO targets may not be informative or achievable, and potential practical solutions.
Implications of biological information digitization: Access and benefit sharing of plant genetic resources
Authors: Smyth Stuart J. , Macall Diego M. , Phillips Peter W. B. , de Beer Jeremy 
Published: March 2020

AbstractThe decoupling of biological information from its material source has changed debates about global access and benefit sharing (ABS) of genetic resources. What does the digitization of biological information imply for genetic resources of proven and potential value? What implications does digital sequence information (DSI) have for individuals and groups, who have invested time and effort in augmenting and refining valuable characteristics in genetic resources? Stakeholders discussing this issue in various international fora unanimously acknowledge there are currently more questions than answers. Online digital publicly accessible resources represent a transformative technological shift, resulting in intellectual property governance gaps. This article provides interdisciplinary perspectives on options available to governments to continue advancing the goals of ABS, when physical access to genetic resources is no longer needed because DSI is readily accessible. It envisions four governance scenarios.
Selective and non‐selective bottlenecks as drivers of the evolution of hypermutable bacterial loci
Authors: De Ste Croix Megan , Holmes Jonathan , Wanford Joseph J. , Moxon E. Richard , Oggioni Marco R. , Bayliss Christopher D. 
Published: March 2020

AbstractBottlenecks reduce the size of the gene pool within populations of all life forms with implications for their subsequent survival. Here, we examine the effects of bottlenecks on bacterial commensal‐pathogens during transmission between, and dissemination within, hosts. By reducing genetic diversity, bottlenecks may alter individual or population‐wide adaptive potential. A diverse range of hypermutable mechanisms have evolved in infectious agents that allow for rapid generation of genetic diversity in specific genomic loci as opposed to the variability arising from increased genome‐wide mutation rates. These localised hypermutable mechanisms include multi‐gene phase variation (PV) of outer membrane components, multi‐allele PV of restriction systems and recombination‐driven antigenic variation. We review selected experimental and theoretical (mathematical) models pertaining to the hypothesis that localised hypermutation (LH) compensates for fitness losses caused by bottlenecks and discuss whether bottlenecks have driven the evolution of hypermutable loci.
Galactosylated wall teichoic acid, but not lipoteichoic acid, retains InlB on the surface of serovar 4b Listeria monocytogenes
Authors: Sumrall Eric T. , Schefer Christopher R. E. , Rismondo Jeanine , Schneider Stephan R. , Boulos Samy , Gründling Angelika , Loessner Martin J. , Shen Yang 
Published: March 2020

AbstractListeria monocytogenes is a Gram‐positive, intracellular pathogen harboring the surface‐associated virulence factor InlB, which enables entry into certain host cells. Structurally diverse wall teichoic acids (WTAs), which can also be differentially glycosylated, determine the antigenic basis of the various Listeria serovars. WTAs have many physiological functions; they can serve as receptors for bacteriophages, and provide a substrate for binding of surface proteins such as InlB. In contrast, the membrane‐anchored lipoteichoic acids (LTAs) do not show significant variation and do not contribute to serovar determination. It was previously demonstrated that surface‐associated InlB non‐covalently adheres to both WTA and LTA, mediating its retention on the cell wall. Here, we demonstrate that in a highly virulent serovar 4b strain, two genes gtlB and gttB are responsible for galactosylation of LTA and WTA respectively. We evaluated the InlB surface retention in mutants lacking each of these two genes, and found that only galactosylated WTA is required for InlB surface presentation and function, cellular invasiveness and phage adsorption, while galactosylated LTA plays no role thereof. Our findings demonstrate that a simple pathogen‐defining serovar antigen, that mediates bacteriophage susceptibility, is necessary and sufficient to sustain the function of an important virulence factor.
Advances in bacterial transcriptome understanding: From overlapping transcription to the excludon concept
Authors: Toledo‐Arana Alejandro , Lasa Iñigo 
Published: March 2020

AbstractIn the last decade, the implementation of high‐throughput methods for RNA profiling has uncovered that a large part of the bacterial genome is transcribed well beyond the boundaries of known genes. Therefore, the transcriptional space of a gene very often invades the space of a neighbouring gene, creating large regions of overlapping transcription. The biological significance of these findings was initially regarded with scepticism. However, mounting evidence suggests that overlapping transcription between neighbouring genes conforms to regulatory purposes and provides new strategies for coordinating bacterial gene expression. In this MicroReview, considering the discoveries made in a pioneering transcriptome analysis performed on Listeria monocytogenes as a starting point, we discuss the progress in understanding the biological meaning of overlapping transcription that has given rise to the excludon concept. We also discuss new conditional transcriptional termination events that create antisense RNAs depending on the metabolite concentrations and new genomic arrangements, known as noncontiguous operons, which contain an interspersed gene that is transcribed in the opposite direction to the rest of the operon.
Transcriptional regulation of NIN expression by IPN2 is required for root nodule symbiosis in Lotus japonicus
Authors: Xiao Aifang , Yu Haixiang , Fan Yuqian , Kang Heng , Ren Yaping , Huang Xiaoqin , Gao Xiumei , Wang Chao , Zhang Zhongming , Zhu Hui , Cao Yangrong 
Published: March 2020

Summary

Expression of Nodule Inception (NIN) is essential for initiation of legume–rhizobial symbiosis. An existing model regarding the regulation of NIN expression involves two GRAS transcription factors – NSP1 (Nodulation Signaling Pathway 1) and NSP2. NSP2 forms a complex with NSP1 to directly bind to NIN promoter. However, rhizobial treatment‐induced NIN expression could still be detected in the nsp1 mutant plants, suggesting that other proteins must be involved in the regulation of NIN expression.

A combination of molecular, biochemical and genetic analyses was used to investigate the molecular basis of IPN2 in regulating root development and NIN expression in Lotus japonicus.

In this study, we identified that IPN2 is a close homolog of Arabidopsis APL (ALTERED PHLOEM DEVELOPMENT) with essential function in root development. However, Lotus IPN2 has a different expression pattern compared with the Arabidopsis APL gene. IPN2 binds to the IPN2‐responsive cis element (IPN2‐RE) of NIN promoter and activates NIN expression. IPN2, NSP1 and NSP2 form a protein complex to directly target NIN promoter and activate NIN expression in the legume–rhizobial symbiosis.

Our data refine the regulatory model of NIN expression that NSP2 works together with NSP1 and IPN2 to activate the NIN gene allowing nodulation in L. japonicus.
Targeting bile acid metabolism in obesity reduction: A systematic review and meta‐analysis
Authors: So Stephanie Sik Yu , Yeung Chris Ho Ching , Schooling C. Mary , El‐Nezami Hani 
Published: March 2020

SummaryA systematic review and meta‐analysis was conducted of studies that address the association of bile acid (BA) with obesity and of studies on the effects of treatment in patients with obesity on BA metabolism, assessed from systemic BA, fibroblast growth factor 19 (FGF19), 7α‐hydroxy‐4‐cholesten‐3‐one (C4) level, and faecal BA. We searched PubMed, Embase, and the Cochrane Library from inception to 1 August 2019 using the keywords obesity, obese, body mass index, and overweight with bile acid, FGF19, FXR, and TGR5. Two reviewers independently searched, selected, and assessed the quality of studies. Data were analysed using either fixed or random effect models with inverse variance weighting. Of 3771 articles, 33 papers were relevant for the association of BA with obesity of which 22 were included in the meta‐analysis, and 50 papers were relevant for the effect of obesity interventions on BA of which 20 were included in the meta‐analysis. Circulating fasting total BA was not associated with obesity. FGF19 was inversely and faecal BA excretion was positively associated with obesity. Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy (SG) modulated BA metabolism, ie, increased BA and FGF19. Our results indicate that BA metabolism is altered in obesity. Certain bariatric surgeries including RYGB and SG modulate BA, whether these underlie the beneficial effect of the treatment should be investigated.
The DroughtBox: A new tool for phenotyping residual branch conductance and its temperature dependence during drought
Authors: Billon Lise M. , Blackman Chris J. , Cochard Hervé , Badel Eric , Hitmi Adnane , Cartailler Julien , Souchal Romain , Torres‐Ruiz José M. 
Published: March 2020

AbstractXylem hydraulic failure is a major driver of tree death during drought. However, to better understand mortality risk in trees, especially during hot‐drought events, more information is required on both rates of residual water‐loss from small branches (gres) after stomatal closure, as well as the phase transition temperature (Tp), beyond which gres significantly increases. Here, we describe and test a novel low‐cost tool, the DroughtBox, for phenotyping gres and Tp across species. The system consists of a programmable climatically controlled chamber in which branches dehydrate and changes in the mass recorded. Test measurements show that the DroughtBox maintains stable temperature and relative humidity across a range of set points, a prerequisite for getting accurate gres and Tp values. Among a study group of four conifer and one angiosperm species, we observed a range of gres (0.44–1.64 mmol H2O m−2 s−1) and Tp (39.4–43.8°C) values. Furthermore, the measured time to hydraulic failure varied between two conifers species and was shortened in both species following a heatwave event. The DroughtBox is a reliable and customizable tool for phenotyping gres and Tp, as well as for testing models of time to hydraulic failure that will improve our ability to assess climate change impacts on plants.
RNA‐Seq analysis revealed the molecular mechanisms of photobiomodulation effect on human fibroblasts
Authors: Li Wenqi , Hu Xiaojian , Lu Xi , Liu Jie , Chen Zeqing , Zhou Xiaoli , Liu Muqing , Liu Shangfeng 
Published: March 2020

AbstractBackgroundThe photobiomodulation (PBM) effect has been applied to various clinical therapy for a long time. However, the mechanism related to the PBM effect in terms of wavelengths has been lack of in‐depth study, except that ultraviolet radiation has attracted much attention due to its strong cell‐killing effect.PurposeTo clarify the principle behind PBM and the main mechanism of improvement.MethodsTo carry on this study, we created light equipment using three LED chips, which emit 390 nm ultraviolet radiation, 415 nm blue light and 660 nm red light, respectively. We choose human fibroblasts (HF) to be irradiated by three different wavelengths for PBM test. In this study, we used cell counting kit (CCK‐8) test to show the cell proliferation roughly and reported on a systematic RNA sequencing (RNA‐seq) analysis at transcriptional expression levels from HF, which accepted PBM of different wavelengths of light.ResultsWe found that 415 nm blue light inhibited cell proliferation and 660 nm red light stimulated cell proliferation while 390 nm ultraviolet radiation has little influence on cell proliferation. Furthermore, RNA‐seq results showed that CSF1R, PPP3CC, ITGAL, ITGAM, IL2RB, and several other differentially expressed genes (DEGs) are involved in the cell proliferation. Relative DEGs values for matrix metalloproteinases (MMPs) gene family have shown a great difference in blue and red light radiation especially on MMP25, MMP9, MMP21, and MMP13.ConclusionTaken together, the results provide a valuable resource to describe the variation of HFs under PBM of different light at gene level.
Adjusting ADJUST: Optimizing the ADJUST algorithm for pediatric data using geodesic nets
Authors: Leach Stephanie C. , Morales Santiago , Bowers Maureen E. , Buzzell George A. , Debnath Ranjan , Beall Daniel , Fox Nathan A. 
Published: March 2020

AbstractA major challenge for electroencephalograph (EEG) studies on pediatric populations is that large amounts of data are lost due to artifacts (e.g., movement and blinks). Independent component analysis (ICA) can separate artifactual and neural activity, allowing researchers to remove such artifactual activity and retain a greater percentage of EEG data for analyses. However, manual identification of artifactual components is time‐consuming and requires subjective judgment. Automated algorithms, like ADJUST and ICLabel, have been validated on adults, but to our knowledge, no such algorithms have been optimized for pediatric data. Therefore, in an attempt to automate artifact selection for pediatric data collected with geodesic nets, we modified ADJUST's algorithm. Our “adjusted‐ADJUST” algorithm was compared to the “original‐ADJUST” algorithm and ICLabel in adults, children, and infants on three different performance measures: respective classification agreement with expert coders, the number of trials retained following artifact removal, and the reliability of the EEG signal after preprocessing with each algorithm. Overall, the adjusted‐ADJUST algorithm performed better than the original‐ADJUST algorithm and no ICA correction with adult and pediatric data. Moreover, in some measures, it performed better than ICLabel for pediatric data. These results indicate that optimizing existing algorithms improves artifact classification and retains more trials, potentially facilitating EEG studies with pediatric populations. Adjusted‐ADJUST is freely available under the terms of the GNU General Public License at: https://github.com/ChildDevLab/MADE-EEG-preprocessing-pipeline/tree/master/adjusted_adjust_scripts.
Carbohydrates do not accelerate force recovery after glycogen‐depleting followed by high‐intensity exercise in humans
Authors: Cheng Arthur J. , Chaillou Thomas , Kamandulis Sigitas , Subocius Andrejus , Westerblad Håkan , Brazaitis Marius , Venckunas Tomas 
Published: March 2020

AbstractProlonged low‐frequency force depression (PLFFD) induced by fatiguing exercise is characterized by a persistent depression in submaximal contractile force during the recovery period. Muscle glycogen depletion is known to limit physical performance during prolonged low‐ and moderate‐intensity exercise, and accelerating glycogen resynthesis with post‐exercise carbohydrate intake can facilitate recovery and improve repeated bout exercise performance. Short‐term, high‐intensity exercise, however, can cause PLFFD without any marked decrease in glycogen. Here, we studied whether recovery from PLFFD was accelerated by carbohydrate ingestion after 60 minutes of moderate‐intensity glycogen‐depleting cycling exercise followed by six 30‐seconds all‐out cycling sprints. We used a randomized crossover study design where nine recreationally active males drank a beverage containing either carbohydrate or placebo after exercise. Blood glucose and muscle glycogen concentrations were determined at baseline, immediately post‐exercise, and during the 3‐hours recovery period. Transcutaneous electrical stimulation of the quadriceps muscle was performed to determine the extent of PLFFD by eliciting low‐frequency (20 Hz) and high‐frequency (100 Hz) stimulations. Muscle glycogen was severely depleted after exercise, with a significantly higher rate of muscle glycogen resynthesis during the 3‐hours recovery period in the carbohydrate than in the placebo trials (13.7 and 5.4 mmol glucosyl units/kg wet weight/h, respectively). Torque at 20 Hz was significantly more depressed than 100 Hz torque during the recovery period in both conditions, and the extent of PLFFD (20/100 Hz ratio) was not different between the two trials. In conclusion, carbohydrate supplementation enhances glycogen resynthesis after glycogen‐depleting exercise but does not improve force recovery when the exercise also involves all‐out cycling sprints.