bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of misclassification on covariate‐adaptive randomized clinical trials
Authors: Wang Tong , Ma Wei
Published: May 2020

Covariate‐adaptive randomization (CAR) is widely used in clinical trials to balance treatment allocation over covariates. Over the past decade, significant progress has been made on the theoretical properties of covariate‐adaptive design and associated inference. However, most results are established under the assumption that the covariates are correctly measured. In practice, measurement error is inevitable, resulting in misclassification for discrete covariates. When covariate misclassification is present in a clinical trial conducted using CAR, the impact is twofold: it impairs the intended covariate balance, and raises concerns over the validity of test procedures. In this paper, we consider the impact of misclassification on covariate‐adaptive randomized trials from the perspectives of both design and inference. We derive the asymptotic normality, and thereby the convergence rate, of the imbalance of the true covariates for a general family of covariate‐adaptive randomization methods, and show that a superior covariate balance can still be attained compared to complete randomization. We also show that the two sample t‐test is conservative, with a reduced Type I error, but that this can be corrected using a bootstrap method. Moreover, if the misclassified covariates are adjusted in the model used for analysis, the test maintains its nominal Type I error, with an increased power. Our results support the use of covariate‐adaptive randomization in clinical trials, even when the covariates are subject to misclassification.
Exploring the phylogeny of the marattialean ferns
Authors: Lehtonen Samuli , Poczai Péter , Sablok Gaurav , Hyvönen Jaakko , Karger Dirk N. , Flores Jorge
Published: May 2020

The eusporangiate marattialean ferns represent an ancient radiation with a rich fossil record but limited modern diversity in the tropics. The long evolutionary history without close extant relatives has confounded studies of the phylogenetic origin, rooting and timing of marattialean ferns. Here we present new complete plastid genomes of six marattialean species and compiled a plastid genome dataset representing all of the currently accepted marattialean genera. We further supplemented this dataset by compiling a large dataset of mitochondrial genes and a phenotypic data matrix covering both extant and extinct representatives of the lineage. Our phylogenomic and total‐evidence analyses corroborated the postulated position of marattialean ferns as the sister to leptosporangiate ferns, and the position of Danaea as the sister to the remaining extant marattialean genera. However, our results provide new evidence that Christensenia is sister to Marattia and that M. cicutifolia actually belongs to Eupodium. The apparently highly reduced rate of molecular evolution in marattialean ferns provides a challenge for dating the key phylogenetic events with molecular clock approaches. We instead applied a parsimony‐based total‐evidence dating approach, which suggested a Triassic age for the extant crown group. The modern distribution can best be explained as mainly resulting from vicariance following the breakup of Pangaea and Gondwana. We resolved the fossil genera Marattiopsis, Danaeopsis and Qasimia as members of the monophyletic family Marattiaceae, and the Carboniferous genera Sydneia and Radstockia as the monophyletic sister of all other marattialean ferns.
Developmental changes in neural letter‐selectivity: A 1‐year follow‐up of beginning readers
Authors: van de Walle de Ghelcke Alice , Rossion Bruno , Schiltz Christine , Lochy Aliette
Published: May 2020

The developmental course of neural tuning to visual letter strings is unclear. Here we tested 39 children longitudinally, at the beginning of grade 1 (6.45 ± 0.33 years old) and 1 year after, with fast periodic visual stimulation in electroencephalography to assess the evolution of selective neural responses to letter strings and their relationship with emerging reading abilities. At both grades, frequency‐tagged letter strings were discriminated from pseudofont strings (i.e. letter‐selectivity) over the left occipito‐temporal cortex, with effects observed at the individual level in 62% of children. However, visual words were not discriminated from pseudowords (lexical access) at either grade. Following 1 year of schooling, letter‐selective responses showed a specific increase in amplitude, a more complex pattern of harmonics, and were located more anteriorly over the left occipito‐temporal cortex. Remarkably, at both grades, neural responses were highly significant at the individual level and correlated with individual reading scores. The amplitude increase in letter‐selective responses between grades was not found for discrimination responses of familiar keyboard symbols from pseudosymbols, and was not related to a general increase in visual stimulation responses. These findings demonstrate a rapid onset of left hemispheric letter selectivity, with 1 year of reading instruction resulting in increased emerging reading abilities and a clear quantitative and qualitative evolution within left hemispheric neural circuits for reading.
Role of 3‐dimensional transesophageal echocardiography in guiding transcatheter mitral valve replacement
Authors: Faza Nadeen N. , Little Stephen H.
Published: May 2020

Background

Transcatheter mitral valve replacement technologies have been developed to treat a wide range of mitral valve pathologies including primary and secondary mitral regurgitation, mitral stenosis, in addition to degenerative bioprosthetic valves and failed annuloplasty rings.

Objective

Transesophageal echocardiography, particularly with use of 3‐dimensional imaging is key in successfully guiding these interventions. In this review, we highlight the key role of 3D transesophageal echocardiography in guiding TMVR, including valve‐in‐native valve, valve‐in‐prosthetic valve, valve‐in‐prosthetic ring, and valve‐in‐mitral annular calcification interventions.
Manipulation of insect gut microbiota towards the improvement of Bactrocera oleae artificial rearing
Authors: Koskinioti Panagiota , Ras Erica , Augustinos Antonios A. , Beukeboom Leo W. , Mathiopoulos Kostas D. , Caceres Carlos , Bourtzis Kostas
Published: May 2020

Bactrocera oleae (Rossi) (Diptera: Tephritidae) is the main pest of olive trees (Olea europaea L.), causing major damages in olive crops. Improvement of mass rearing is a prerequisite for the successful development of large‐scale sterile insect technique (SIT) applications. This can be achieved through the enrichment of artificial diets with gut bacteria isolates. We assessed the efficiency of three gut bacteria previously isolated from Ceratitis capitata (Wiedemann), and four isolated from B. oleae, as larval diet additives in both live and inactivated/dead forms. Our results showed that dead Enterobacter sp. AA26 increased pupal weight, whereas both live and dead cells increased pupal and adult production and reduced immature developmental time, indicating that its bacterial cells serve as a direct nutrient source. Live Providencia sp. AA31 improved pupal and adult production, enhanced male survival under stress conditions, and delayed immature development. Dead Providencia sp. AA31, however, did not affect production rates, indicating that live bacteria can colonize the insect gut and biosynthesize nutrients essential for larval development. Live and dead Bacillus sp. 139 increased pupal weight, accelerated immature development, and increased adult survival under stress. Moreover, live Bacillus sp. 139 improved adult production, indicating that Bacillus cells are a direct source of nutrients. Dead Serratia sp. 49 increased pupal and adult production and decreased male survival under stress conditions whereas live cells decreased insect production, indicating that the live strain is entomopathogenic, but its dead cells can be utilized as nutrient source. Klebsiella oxytoca, Enterobacter sp. 23, and Providencia sp. 22 decreased pupal and subsequent adult production and were harmful for B. oleae. Our findings indicate that dead Enterobacter sp. AA26 is the most promising bacterial isolate for the improvement of B. oleae mass rearing in support of future SIT or related population suppression programs.
Lessons learned from 40 novel PIGA patients and a review of the literature
Authors: Bayat Allan , Knaus Alexej , Pendziwiat Manuela , Afenjar Alexandra , Barakat Tahsin Stefan , Bosch Friedrich , Callewaert Bert , Calvas Patrick , Ceulemans Berten , Chassaing Nicolas , Depienne Christel , Endziniene Milda , Ferreira Carlos R. , Moura de Souza Carolina Fischinger , Freihuber Cécile , Ganesan Shiva , Gataullina Svetlana , Guerrini Renzo , Guerrot Anne‐Marie , Hansen Lars , Jezela‐Stanek Aleksandra , Karsenty Caroline , Kievit Anneke , Kooy Frank R. , Korff Christian M. , Kragh Hansen Johanne , Larsen Martin , Layet Valérie , Lesca Gaetan , McBride Kim L. , Meuwissen Marije , Mignot Cyril , Montomoli Martino , Moore Hannah , Naudion Sophie , Nava Caroline , Nougues Marie‐Christine , Parrini Elena , Pastore Matthew , Schelhaas Jurgen H. , Skinner Steven , Szczałuba Krzysztoł , Thomas Ashley , Thomassen Mads , Tranebjærg Lisbeth , van Slegtenhorst Marjon , Wolfe Lynne A. , Lal Dennis , Gardella Elena , Bomme Ousager Lilian , Brünger Tobias , Helbig Ingo , Krawitz Peter , Møller Rikke S.
Published: May 2020

Objective

To define the phenotypic spectrum of phosphatidylinositol glycan class A protein (PIGA)‐related congenital disorder of glycosylation (PIGA‐CDG) and evaluate genotype‐phenotype correlations.

Methods

Our cohort encompasses 40 affected males with a pathogenic PIGA variant. We performed a detailed phenotypic assessment, and in addition, we reviewed the available clinical data of 36 previously published cases and assessed the variant pathogenicity using bioinformatical approaches.

Results

Most individuals had hypotonia, moderate to profound global developmental delay, and intractable seizures. We found that PIGA‐CDG spans from a pure neurological phenotype at the mild end to a Fryns syndrome–like phenotype. We found a high frequency of cardiac anomalies including structural anomalies and cardiomyopathy, and a high frequency of spontaneous death, especially in childhood. Comparative bioinformatical analysis of common variants, found in the healthy population, and pathogenic variants, identified in affected individuals, revealed a profound physiochemical dissimilarity of the substituted amino acids in variant constrained regions of the protein.

Significance

Our comprehensive analysis of the largest cohort of published and novel PIGA patients broadens the spectrum of PIGA‐CDG. Our genotype‐phenotype correlation facilitates the estimation on pathogenicity of variants with unknown clinical significance and prognosis for individuals with pathogenic variants in PIGA.
Cannabidiol efficacy and clobazam status: A systematic review and meta‐analysis
Authors: Lattanzi Simona , Trinka Eugen , Striano Pasquale , Zaccara Gaetano , Del Giovane Cinzia , Nardone Raffaele , Silvestrini Mauro , Brigo Francesco
Published: May 2020

Objective

To evaluate the potential impact of concomitant clobazam (CLB) use on the efficacy of cannabidiol (CBD) treatment in patients with Dravet syndrome and Lennox‐Gastaut syndrome using meta‐analytical techniques.

Methods

We searched for randomized, placebo‐controlled, single‐ or double‐blinded trials. The proportion of patients who achieved ≥50% reduction from baseline in seizure frequency during the treatment period was assessed according to CLB status. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated.

Results

Four trials were included and enrolled 714 participants, 429 for the add‐on CBD group and 285 for the add‐on placebo group. Among CBD‐treated patients, 240 (55.9%) were taking concomitant CLB (CLB‐On) and 189 (44.1%) were not taking concomitant CLB (CLB‐Off); in placebo‐treated patients, 158 (55.4%) were CLB‐On and 127 (44.6%) CLB‐Off. The percentages of patients who had at least 50% reduction in seizure frequency during the treatment period were 29.1% in the CBD arm and 15.7% in the placebo group among CLB‐Off patients (RR = 1.80, 95% CI = 1.12‐2.90, P = .015). Among CBL‐On patients, the ≥50% reduction in seizure frequency was found in 52.9% and 27.8% in the CBD and placebo groups, respectively (RR = 1.85, 95% CI = 1.40‐2.44, P < .001).

Significance

CBD was associated with a higher rate of seizure response in comparison to placebo when added to the existing antiepileptic regimen both in patients taking and in those not taking concomitant CLB. The lack of randomization for CLB status and the limited sample size need to be considered in the interpretation of the findings.
Urbanization reduces gene flow but not genetic diversity of stream salamander populations in the New York City metropolitan area
Authors: Fusco Nicole A. , Pehek Ellen , Munshi‐South Jason
Published: May 2020

Natural landscape heterogeneity and barriers resulting from urbanization can reduce genetic connectivity between populations. The evolutionary, demographic, and ecological effects of reduced connectivity may lead to population isolation and ultimately extinction. Alteration to the terrestrial and aquatic environment caused by urban influence can affect gene flow, specifically for stream salamanders who depend on both landscapes for survival and reproduction. To examine how urbanization affects a relatively common stream salamander species, we compared genetic connectivity of Eurycea bislineata (northern two‐lined salamander) populations within and between streams in an urban, suburban, and rural habitat around the New York City (NYC) metropolitan area. We report reduced genetic connectivity between streams within the urban landscape found to correspond with potential barriers to gene flow, that is, areas with more dense urbanization (roadways, industrial buildings, and residential housing). The suburban populations also exhibited areas of reduced connectivity correlated with areas of greater human land use and greater connectivity within a preserve protected from development. Connectivity was relatively high among neighboring rural streams, but a major roadway corresponded with genetic breaks even though the habitat contained more connected green space overall. Despite greater human disturbance across the landscape, urban and suburban salamander populations maintained comparable levels of genetic diversity to their rural counterparts. Yet small effective population size in the urban habitats yielded a high probability of loss of heterozygosity due to genetic drift in the future. In conclusion, urbanization impacted connectivity among stream salamander populations where its continual influence may eventually hinder population persistence for this native species in urban habitats.
The knowledge, attitudes and behaviours of Syrian refugee women towards family planning: Sample of Hatay
Authors: Gümüş Şekerci Yasemin , Aydın Yıldırım Tuğba
Published: May 2020

Objective

This study was conducted with the aim of determining the fertility characteristics of Syrian refugee women and their knowledge, attitudes and behaviours with regard to family planning.

Design and Sample

The research was designed as a descriptive and cross‐sectional type of study. The study group consisted of 389 refugee women in the 15‐ to 49‐year age group who had migrated from Syria to Hatay.

Measure

Study data were collected between October 2018 and January 2019 using forms containing questions on participants' sociodemographic characteristics, and their knowledge, attitudes and behaviour regarding family planning. Data analysis was performed with the use of frequency, percentage, mean, median, standard deviation values and the chi‐square test.

Results

Most of the participants reported that they used a family planning method, 47.9% that they preferred traditional methods, 15.2% that the method used was supported by their husbands. Most of the participants had mistaken beliefs about pregnancy and family planning methods.

Participants' information on modern family planning methods was affected by their age, income level and social security status; their knowledge of traditional family planning methods was affected by their income level, their family structure and their use of a traditional method. Women's use of family planning was affected by their age, income level and their knowledge of modern and traditional methods.

Conclusions

Determination of the knowledge, attitudes and practice of refugee women regarding family planning and establishing the influential factors will enable nurses to make a contribution to the future provision of specific and culturally sensitive care to sick and healthy refugee women.
Book Review: Harpaz, Yossi (2019) Citizenship 2.0: Dual Nationality as a Global Asset. Princeton University Press, Princeton, New Jersey, 216pp.
Authors: Lāce Agnese
Published: May 2020

Harpaz sets out to analyse the strategic acquisition of a second citizenship as one of the examples for the growing legitimacy and prevalence of dual citizenship. He seeks an answer on how the nature of the institution of citizenship changes with wider acceptance of dual citizenship, but, instead of looking at it from the perspective of the lawmakers, Harpaz offers a perspective of the individual, based on extensive fieldwork in three countries – Serbia, Mexico and Israel.
Modeling bluffing behavior in signaling security games
Authors: Chen Ling , Li Mingchu , Liu Jia
Published: May 2020

In some security domains, the defender holds more private information than the attacker, such as the authenticity of resources. A mock camera can be adopted by the defender to deter potential attackers while the attacker may see it as a real one. This provides an opportunity for a defender with fake resources to bluff, as if all resources she owns are real. We model the bluffing behavior as a signaling game where the attacker is uncertain whether the defender is strong (all resources are real) or weak (fake resources disguised as real resources). We propose a mixed integer cubic programming formulation to solve for the solution concept based on perfect Bayesian equilibrium. We compare our bluffing security game model with a model without signaling. The experiments indicate that our model outperforms the no‐signaling model in terms of the defender's utility.
Human migration networks and policy interventions: bringing population distributions in line with system optimization
Authors: Nagurney Anna , Daniele Patrizia , Cappello Giorgia
Published: May 2020

In this paper, we demonstrate that, through policy interventions, in the form of subsidies, a system‐optimum for a multiclass human migration network can be achieved, despite the migrants, who can be refugees, behaving in a user‐optimized manner. The formulation and analysis are conducted using variational inequality theory. The policy intervention allows governmental decision‐makers to moderate the flow of migrants while enhancing societal welfare. An algorithm is proposed and applied to compute the solutions to a series of numerical examples, with changes in initial populations and utility functions, inspired by a pandemic, followed by a natural disaster.
Consultation, Consent, and the Silencing of Indigenous Communities
Authors: Townsend Leo , Townsend Dina Lupin
Published: May 2020

Over the past few decades, Indigenous communities have successfully campaigned for greater inclusion in decision‐making processes that directly affect their lands and livelihoods. As a result, two important participatory rights for Indigenous peoples have now been widely recognized: the right to consultation and the right to free, prior and informed consent (FPIC). Although these participatory rights are meant to empower the speech of these communities—to give them a proper say in the decisions that most affect them—we argue that the way these rights have been implemented and interpreted sometimes has the opposite effect, of denying them a say or ‘silencing’ them. In support of this conclusion we draw on feminist speech act theory to identify practices of locutionary, illocutionary, and perlocutionary group silencing that arise in the context of consultation with Indigenous communities.
Focal adhesion kinase is activated by microtubule‐depolymerizing agents and regulates membrane blebbing in human endothelial cells
Authors: Zheng Yan‐Bo , Gong Jian‐Hua , Zhen Yong‐Su
Published: May 2020

Microtubule‐depolymerizing agents can selectively disrupt tumor vessels via inducing endothelial membrane blebbing. However, the mechanism regulating blebbing is largely unknown. IMB5046 is a newly discovered microtubule‐depolymerizing agent. Here, the functions of focal adhesion kinase (FAK) during IMB5046‐induced blebbing and the relevant mechanism are studied. We found that IMB5046 induced membrane blebbing and reassembly of focal adhesions in human vascular endothelial cells. Both FAK inhibitor and knock‐down expression of FAK inhibited IMB5046‐induced blebbing. Mechanism study revealed that IMB5046 induced the activation of FAK via GEF‐H1/ Rho/ ROCK/ MLC2 pathway. cRGD peptide, a ligand of integrin, also blocked IMB5046‐induced blebbing. After activation, FAK further promoted the phosphorylation of MLC2. This positive feedback loop caused more intensive actomyosin contraction and continuous membrane blebbing. FAK inhibitor blocked membrane blebbing via inhibiting actomyosin contraction, and stimulated stress fibre formation via promoting the phosphorylation of HSP27. Conclusively, these results demonstrate that FAK is a molecular switch controlling endothelial blebbing and stress fibre formation. Our study provides a new molecular mechanism for microtubule‐depolymerizing agents to be used as vascular disrupting agents.
Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide‐induced sepsis
Authors: Nie Mu‐Wen , Han Ye‐Chen , Shen Zhu‐Jun , Xie Hong‐Zhi
Published: May 2020

Sepsis is the most common cause of death in intensive care units. This study investigated the circular RNA (circRNA) and mRNA expression profiles and functional networks of the aortic tissue in sepsis. We established a lipopolysaccharide (LPS)‐induced rat sepsis model. High‐throughput sequencing was performed on the aorta tissue to identify differentially expressed (DE) circRNAs and mRNAs, which were validated by real‐time quantitative polymerase chain reaction (RT‐qPCR). Bioinformatic analysis was carried out and coding and non‐coding co‐expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed to investigate the mechanisms. In total, 373 up‐regulated and 428 down‐regulated circRNAs and 2063 up‐regulated and 2903 down‐regulated mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of mRNAs showed that the down‐regulated genes were mainly enriched in the process of energy generation. CNC and ceRNA regulatory networks were constructed with seven DE circRNAs. The results of functional enrichment analysis of CNC target genes revealed the important role of circRNAs in inflammatory response. The ceRNA network also highlighted the significant enrichment in calcium signalling pathway. Significant alterations in circRNAs and mRNAs were observed in the aortic tissue of septic rats. In addition, CNC and ceRNA networks were established.
Mapping the danger to life in flash flood events adopting a mechanics based methodology and planning evacuation routes
Authors: Musolino Giovanni , Ahmadian Reza , Xia Junqiang , Falconer Roger A.
Published: May 2020

Extreme flood events are becoming more frequent and challenging due to climate change. Key objectives of this study are to evaluate different criteria used in assessing the hazard to people during flood events and, once determined, the most suitable method is then used to assess the hazard and the safest route(s) for evacuation during a flood event and for a particular case study. The results of the application of two criteria are analysed in terms of the flood hazard assessment with the two criteria being based on a widely used empirical approach and a mechanics based approach. Both criteria are used to assess the flood hazard to people during an extreme flash flood, which occurred on 16th August 2004 in Boscastle (UK). Results obtained for this study have highlighted that the mechanics based criteria are preferable in identifying the ideal escape routes, when considering the flood characteristics and the corresponding response of a human body. The main novelty of this study lies in linking the flood hazard rating with the human body characteristics, when determining the safest route and with a revised formula being developed, which includes the effects of ground slope in the application to a real case study.
Association of serum autotaxin levels with liver fibrosis in patients pretreatment and posttreatment with chronic hepatitis C
Authors: Takemura Kazuya , Takizawa Etsuko , Tamori Akihiro , Nakamae Mika , Kubota Hiroshi , Uchida‐Kobayashi Sawako , Enomoto Masaru , Kawada Norifumi , Hino Masayuki
Published: May 2020

Background and Aim

The evaluation of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection is important as it is a risk factor for hepatocellular carcinoma. In the recent years, autotaxin (ATX) has been established as a new noninvasive biomarker to predict liver fibrosis. However, antiviral treatment has been reported to decrease serum ATX, but it is unclear whether posttreatment ATX levels reflect liver fibrosis. In the present study, the correlation between ATX and liver fibrosis in pretreatment and posttreatment patients with HCV infection was analyzed.

Methods

A total of 199 samples from 136 patients with HCV infection who had undergone hepatic biopsy before and/or after antiviral treatment at Osaka City University Hospital were used. Posttreatment patients included 38 interferon‐treated patients and 80 interferon‐free direct‐acting antiviral‐treated patients; all patients achieved a sustained virological response (SVR). Serum ATX levels were determined by enzyme immunoassay with an AIA‐2000 analyzer.

Results

Serum ATX levels were largely correlated with liver fibrosis stage in patients with HCV infection before and after antiviral treatment. The measured values decreased even in similar liver fibrosis stages after treatment. The area under the receiver operating characteristic curve for the ability of ATX to diagnose above F2 stage before treatment was 0.81 (both male and female) and that after achieving SVR, it was 0.71 (male) and 0.72 (female).

Conclusions

Serum ATX levels were correlated with histological liver fibrosis stage after achieving SVR. However, separate cutoff values before and after antiviral therapy should be established.
Associations between lncRNA‐related polymorphisms and hepatocellular carcinoma risk: A two‐stage case–control study
Authors: Li Yue , He Hui‐Chan , Zhou Da‐Lei , Liu Qing , Zhang Xiao , Yang Xin‐Hua , Ye Zu‐lu , Peng Jun‐Ling , Tang Tao , Su Xuan , He Cai‐Yun
Published: May 2020

Background and Aim

Single‐nucleotide polymorphisms (SNPs) in long non‐coding RNAs (lncRNAs) are potential biomarkers for cancer risk, but their association with hepatocellular carcinoma (HCC) is unclear. We examined the association of lncRNA‐related SNPs with HCC susceptibility and explored the optimal genetic models for SNPs.

Methods

Five candidate SNPs linked with digestive tumors were first genotyped in a screening population of 700 HCC and 2800 control cases. The association between each SNP and HCC risk was estimated by multivariate logistic regression adjusted by sex and age and recorded as odds ratio (OR) with 95% confidence interval. Significant associations were further tested in a validation population with 1140 HCC and 5115 control cases. Finally, the most appropriate genetic models for HCC‐associated SNPs were identified using pairwise allele differences; the overall gene effects of each SNP were further evaluated based on optimal genetic models.

Results

Three candidate SNPs, rs7315438, rs6983267, and rs10795668, showed statistical connections with HCC risk in the discovery stage. Among these, rs7315438 remained steadily significant in the validation stage; rs7315438 and rs10795668 both reached statistical threshold in the combined analysis of both stages. SNP rs7315438 (TC vs TT/CC, OR = 1.410, P < 0.001) was associated with increased risk of HCC in a complete overdominant model, whereas rs10795668 (AG vs AA/GG, OR = 0.892, P = 0.035) exerted a protective effect on HCC risk in a complete overdominant model.

Conclusions

Long non‐coding RNA‐related SNPs rs7315438 and rs10795668 are potential biomarkers for HCC susceptibility, especially when evaluated based on their optimal genetic models.
Nitrous Oxide Use During Labor: Satisfaction, Adverse Effects, and Predictors of Conversion to Neuraxial Analgesia
Authors: Nodine Priscilla M. , Collins Michelle R. , Wood Cristina L. , Anderson Jessica L. , Orlando Barbara S. , McNair Bryan K. , Mayer David C. , Stein Deborah J.
Published: May 2020

Introduction

Women desire safe and effective choices for pain management during labor. Currently, neuraxial and opioid analgesia are the most common methods used in the United States. The purpose of this study was to investigate demographic characteristics, safety, and satisfaction in a cohort of parturients who used inhaled nitrous oxide (N2O) analgesia and to determine predictors of conversion from N2O to neuraxial analgesia.

Methods

This was a prospective chart review study. Individuals aged at least 18 years who used inhaled N2O during the first or second stage of labor between March 1, 2016, and July 23, 2017, on the labor and delivery unit of one academic medical center (N = 463) and their neonates were included. Data describing maternal and neonatal factors are reported. Logistic regression and chi‐square tests were used to model the effects of oxytocin augmentation, labor induction, parity, prior cesarean birth, pre‐N2O cervical dilatation, and post‐N2O cervical dilatation on the odds of conversion from N2O to neuraxial analgesia.

Results

In this cohort, 31% who chose N2O for analgesia did not convert to any other analgesic method. Significant positive predictors for conversion from N2O to neuraxial analgesia included labor induction (odds ratio [OR], 2.9; 95% CI, 1.7‐5.0), oxytocin augmentation (OR, 3.1; 95% CI, 1.6‐6.0), and labor after cesarean (OR, 6.4; 95% CI, 2.5‐16.5). Multiparity (OR, 0.4; 95% CI, 0.2‐0.6) and post‐N2O cervical dilatation (OR, 0.8; 95% CI, 0.7‐0.9) were negative predictors. Adverse effects related to N2O use during labor were rare (8%) and were not a significant reason for conversion to neuraxial analgesia. Parturients had moderately high satisfaction with N2O for pain management (11‐point scale, mean [SD], 7.4 [2.9]). Five‐minute Apgar scores were 7 or greater in 97.8% of the newborns.

Discussion

Understanding predictors of conversion from inhaled N2O to neuraxial analgesia may assist perinatal care providers in their discussions with women about analgesia options during labor. N2O is a useful, safe option for labor analgesia in the United States.
Microvesicles derived from squamous cell carcinoma induce cell death, autophagy, and invasion of benign myoepithelial cells
Authors: Martinez Elizabeth Ferreira , de Araújo Vera Cavalcanti , Navarini Natalia Festugatto , de Souza Isabela Fernandes , Rena Gabriel Bernardo , Demasi Ana Paula Dias , de Paula Eneida , Teixeira Lucas Novaes
Published: May 2020

Background

There has been great interest recently in the mechanisms of cell‐to‐cell communication through microvesicles (MV). These structures are produced by many different cell types and can modulate cellular activity by induction of epigenetic alterations. These vesicles may promote tumor mass increase either by stimulating cell proliferation via growth factors or by inhibiting apoptosis, which reinforces the role of such vesicles as important modulators of tumor progression.

Methods

The present in vitro study aimed to characterize MV derived from malignant neoplastic epithelial cell cultures (EP) and their effect on the expression of apoptosis/autophagy and invasion related genes of benign myoepithelial (Myo) cell cultures.

Results

The results revealed round structures with a mean size of 153.6 (±0.2) nm, with typical MV morphology. CD63 quantification indicated that EP cell culture at 70%‐80% confluence secreted 3.088 × 108 MV/mL. Overall, Myo exposed to MVs derived from EP showed both up‐ and downregulation of tumorigenesis promoting genes. MVs from EP cells promoted cell death of Myo cells and positively modulate BAX, SURVIVIN, LC3B, MMP‐2, and MMP‐9 expression. Furthermore, an increasing of MMP‐2 and MMP‐9 secretion by Myo was observed after MV exposure.

Conclusions

These findings suggest that MVs from EP modulate autophagy of Myo cells, which may, in part, explain the disappearance of these cells in in situ areas of invasive carcinoma ex‐pleomorphic adenoma. Additionally, the overexpression of MMPs contributes to the development of an invasive phenotype of Myo cells, which could favor the dissolution of the basement membrane during tumorigenesis process.
Convergent evolution of tree hydraulic traits in Amazonian habitats: implications for community assemblage and vulnerability to drought
Authors: Fontes Clarissa G. , Fine Paul V. A. , Wittmann Florian , Bittencourt Paulo R. L. , Piedade Maria Teresa Fernandez , Higuchi Niro , Chambers Jeffrey Q. , Dawson Todd E.
Published: May 2020

Amazonian droughts are increasing in frequency and severity. However, little is known about how this may influence species‐specific vulnerability to drought across different ecosystem types.

We measured 16 functional traits for 16 congeneric species from six families and eight genera restricted to floodplain, swamp, white‐sand or plateau forests of Central Amazonia. We investigated whether habitat distributions can be explained by species hydraulic strategies, and if habitat specialists differ in their vulnerability to embolism that would make water transport difficult during drought periods.

We found strong functional differences among species. Nonflooded species had higher wood specific gravity and lower stomatal density, whereas flooded species had wider vessels, and higher leaf and xylem hydraulic conductivity. The P50 values (water potential at 50% loss of hydraulic conductivity) of nonflooded species were significantly more negative than flooded species. However, we found no differences in hydraulic safety margin among species, suggesting that all trees may be equally likely to experience hydraulic failure during severe droughts.

Water availability imposes a strong selection leading to differentiation of plant hydraulic strategies among species and may underlie patterns of adaptive radiation in many tropical tree genera. Our results have important implications for modeling species distribution and resilience under future climate scenarios.
When and where soil is important to modify the carbon and water economy of leaves
Authors: Paillassa Jennifer , Wright Ian J. , Prentice I. Colin , Pepin Steeve , Smith Nicholas G. , Ethier Gilbert , Westerband Andrea C. , Lamarque Laurent J. , Wang Han , Cornwell Will K. , Maire Vincent
Published: May 2020

Photosynthetic ‘least‐cost’ theory posits that the optimal trait combination for a given environment is that where the summed costs of photosynthetic water and nutrient acquisition/use are minimised. The effects of soil water and nutrient availability on photosynthesis should be stronger as climate‐related costs for both resources increase.

Two independent datasets of photosynthetic traits, Globamax (1509 species, 288 sites) and Glob13C (3645 species, 594 sites), were used to quantify biophysical and biochemical limitations of photosynthesis and the key variable Ci/Ca (CO2 drawdown during photosynthesis). Climate and soil variables were associated with both datasets.

The biochemical photosynthetic capacity was higher on alkaline soils. This effect was strongest at more arid sites, where water unit‐costs are presumably higher. Higher values of soil silt and depth increased Ci/Ca, likely by providing greater H2O supply, alleviating biophysical photosynthetic limitation when soil water is scarce.

Climate is important in controlling the optimal balance of H2O and N costs for photosynthesis, but soil properties change these costs, both directly and indirectly. In total, soil properties modify the climate‐demand driven predictions of Ci/Ca by up to 30% at a global scale.
Connecting with New Partners in COVID‐19 Response
Authors: Grizzle David , Goodin Amy , Robinson Scott E.
Published: May 2020

The COVID‐19 crisis has called for the mobilization of diverse resources and coordination through administrative networks. This mobilization has brought to light the challenges involved in the recruitment and retention of diverse administrative networks. This Viewpoint essay reviews the importance and difficulties of maintaining diverse administrative networks. The review is followed by concrete strategies for building and maintaining diverse networks in Norman, Oklahoma. The lessons emphasize the role of active and imaginative recruitment and a realistic assessment of the challenges facing members of the network that can interfere with their participation.
Central nervous system infections in renal transplant recipients
Authors: Basic‐Jukic Nikolina , Juric Ivana , Furic‐Cunko Vesna , Kastelan Zeljko
Published: May 2020

Background

The aim of this study is to determine the incidence, etiology, clinical characteristics, and outcomes of renal transplant recipients diagnosed and treated for central nervous system (CNS) infection at our institution.

Methods

We analyzed data from all renal transplant recipients between January 2007 and December 2019 that were diagnosed and treated for CNS infections at our institution.

Results

Of 1374 patients who received renal allografts, 13 were diagnosed with CNS infections (9 males), with a mean age of 53.5 years. Patients were diagnosed with CNS infections between 2 months and 11 years after the transplantation. Causative agents included JC virus, Streptococcus pneumoniae, Cryptococcus neoformans, Herpes zoster virus, Mycobacterium tuberculosis, Listeria monocytogenes, and West Nile virus. One patient had concomitant Nocardia and Neisseria infection. Immunosuppression was reduced in all patients. The patient with JC encephalitis and the patient with concomitant Neisseria and Nocardia meningitis died. One patient was returned to dialysis. Other patients recovered with differing levels of neurologic sequelae.

Conclusion

Central nervous system infections in renal transplant recipients are rare. However, they are associated with significant morbidity and mortality. A high level of awareness is needed: neurological symptoms may be nonspecific and caused by non‐infectious conditions related to the underlying disease, or side‐effects of immunosuppressive drugs.
Political metaphor in world Englishes
Authors: Musolff Andreas
Published: May 2020

One of the key‐metaphor complexes in conceptualizing national identity is that of the nation as a body or a person, especially in English‐speaking cultures, as evidenced in the lexicalization of phrases such asbody politic, head of state). It has a long conceptual history and still figures prominently in present‐day political discourse, both in Inner Circle English‐speaking countries and internationally. It thus seems to show considerable semantic stability; however, it is still an open question whether theuseofbody‐orperson‐based metaphors in international English means that recipients in different culturesunderstandthese metaphors uniformly. This paper discusses empirical evidence from an international interpretation survey that shows substantial variation in conceptualization of the nation as a body, with five main conceptual scenarios (nation as body, nation's territory as body, nation as body part, nation as part of egoandnation as person).
The status and functions of English in contemporary Lebanon
Authors: Banat Hadi
Published: May 2020

This paper is a descriptive case study of the status and functions of English in contemporary Lebanon. It consults archival research (primary and secondary sources), firsthand observations, and governmental artifacts for data collection purposes. I use such data to portray the spread of English in various domains of use and build an evidence‐based argument about the relationship between policy making/implementation and its effects on local users for practicing agency in promoting the status of English. The paper includes a sociohistorical overview of the Lebanese context and discusses findings in relation to the uses of English, the role of educational institutions in enforcing language policies, and users’ interactions with language policy and planning. The sociolinguistic profiling of English in Lebanon facilitates a unique analysis of a multifaceted argument in favor of linguistic pragmatism over linguistic colonialism for institutionalizing the uses and functions of English in an Arabic speaking country.
Samoan English: An emerging variety in the South Pacific
Authors: Biewer Carolin
Published: May 2020

While much has been published on Outer Circle varieties of English in Asia and Africa, Outer Circle Englishes in the South Pacific (SPE) are still relatively unknown. This paper focuses on Samoan English, a newly emerging variety in Samoa, an island state in Polynesia. The paper discusses the role of English in Samoa's past and present and describes major structural features of Samoan English in terms of its phonology, lexicon and grammar. Local discourse and pragmatic strategies will also be touched upon. The study is based on recordings of Samoan speakers made during a field trip and a newspaper corpus of 300,000 words from the Samoa Observer, a local newspaper. The study demonstrates that we can indeed speak of Samoan English as a variety in the making and that it is useful to consider SPE to gain a better understanding of the evolution and nature of Outer Circle Englishes in general.
Shimura varieties at level and Galois representations
Authors: Caraiani Ana , Gulotta Daniel R. , Hsu Chi-Yun , Johansson Christian , Mocz Lucia , Reinecke Emanuel , Shih Sheng-Chi
Published: May 2020

We show that the compactly supported cohomology of certain $\text{U}(n,n)$- or $\text{Sp}(2n)$-Shimura varieties with $\unicode[STIX]{x1D6E4}_{1}(p^{\infty })$-level vanishes above the middle degree. The only assumption is that we work over a CM field $F$ in which the prime $p$ splits completely. We also give an application to Galois representations for torsion in the cohomology of the locally symmetric spaces for $\text{GL}_{n}/F$. More precisely, we use the vanishing result for Shimura varieties to eliminate the nilpotent ideal in the construction of these Galois representations. This strengthens recent results of Scholze [On torsion in the cohomology of locally symmetric varieties, Ann. of Math. (2) 182 (2015), 945–1066; MR 3418533] and Newton–Thorne [Torsion Galois representations over CM fields and Hecke algebras in the derived category, Forum Math. Sigma 4 (2016), e21; MR 3528275].
Thickness dependence of infrared lattice absorption and excitonic absorption in ZnO layers on Si and SiO2 grown by atomic layer deposition
Authors: Samarasingha Nuwanjula S. , Zollner Stefan , Pal Dipayan , Singh Rinki , Chattopadhyay Sudeshna
Published: May 2020

Using spectroscopic ellipsometry from the midinfrared (0.03 eV) to the deep ultraviolet (6.5 eV), the authors determined the thickness dependence of the dielectric function for ZnO thin layers (5–50 nm) on Si and quartz in comparison to bulk ZnO. They observed a small blueshift of the band gap (∼80 meV) in thin ZnO layers due to quantum confinement, which is consistent with a simple effective mass theory in an infinite potential well. There is a drastic reduction in the excitonic effects near the bandgap, especially for thin ZnO on Si, which not only affects the excitonic absorption peak but also lowers the high-frequency dielectric constant by up to 40%. No significant change of the phonon parameters (except an increased broadening) in thin ZnO layers was found.
Sensitivity to binaural temporal-envelope beats with single-sided deafness and a cochlear implant as a measure of tonotopic match (L)
Authors: Dirks Coral E. , Nelson Peggy B. , Winn Matthew B. , Oxenham Andrew J.
Published: May 2020

For cochlear-implant users with near-normal contralateral hearing, a mismatch between the frequency-to-place mapping in the two ears could produce a suboptimal performance. This study assesses tonotopic matches via binaural interactions. Dynamic interaural time-difference sensitivity was measured using bandpass-filtered pulse trains at different rates in the acoustic and implanted ear, creating binaural envelope beats. Sensitivity to beats should peak when the same tonotopic region is stimulated in both ears. All nine participants detected dynamic interaural timing differences and demonstrated some frequency selectivity. This method provides a guide to frequency-to-place mapping without compensation for inherent latency differences between the acoustic and implanted ears.
Skeletal Muscle Composition and Glucose Levels in Children Who Are Overweight and Obese
Authors: Herda Trent J. , Gallagher Philip M. , Miller Jonathan D. , Bubak Matthew P. , Parra Mandy E.
Published: May 2020

Background: Skeletal muscle is overlooked in the realm of insulin resistance in children who are overweight and obese despite the fact that it accounts for the most glucose disposal. Objectives: Therefore, this study examined fasted glucose levels and muscle cross-sectional area and echo intensity (EI) via ultrasound images of the first dorsal interosseous, vastus lateralis, and rectus femoris in children who are normal weight and overweight and obese aged 8–10 years. Methods: In total, 13 males (age = 9.0 [0.7] y) and 7 females (age = 9.0 [0.8] y) volunteered for this study. Independent samples t tests and effect sizes (ESs) were used to examine potential differences in skeletal muscle composition and glucose concentrations. Results: There were no significant differences between groups for glucose concentration (P = .07, ES = 0.86); however, the children who were overweight and obese had significantly greater EI (P < .01, ES = 0.98–1.63) for the first dorsal interosseous, vastus lateralis, and rectus femoris and lower cross-sectional area when normalized to EI when collapsed across muscles (P < .04, ES = 0.92). Glucose concentrations correlated with EI and cross-sectional area/EI for the vastus lateralis (r = .514 to −.593) and rectus femoris (r = .551 to −.513), but not the first dorsal interosseous. Discussion: There is evidence that adiposity-related pathways leading to insulin resistance and skeletal muscle degradation are active in young children who are overweight and obese.