bluuebunny/crossref_metadata_2025 huggingface dataset:
Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations
Authors: Laamarti Meriem , Alouane Tarek , Kartti Souad , Chemao-Elfihri M.W. , Hakmi Mohammed , Essabbar Abdelomunim , Laamarti Mohamed , Hlali Haitam , Allam Loubna , El Hafidi Naima , El Jaoudi Rachid , Allali Imane , Marchoudi Nabila , Fekkak Jamal , Benrahma Houda , Nejjari Chakib , Amzazi Saaid , Belyamani Lahcen , Ibrahimi Azeddine
Published: May 2020

In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variant sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed certain genotypes specific to the geographic location. We also found co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2.

On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets

We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.
Synthesis of the novel transporter YdhC, is regulated by the YdhB transcription factor controlling adenosine and adenine uptake
Authors: Rodionova Irina A. , Gao Ye , Sastry Anand , Yoo Reo , Rodionov Dmitry A. , Saier Milton H. , Palsson Bernhard Ø.
Published: May 2020

The YdhB transcriptional factor, re-named here AdnB, homologous to the allantoin regulator, AllS, was shown to regulateydhCgene expression inEscherichia coli, which is divergently transcribed fromadnB,and this gene arrangement is conserved in many Protreobacteria. The predicted consensus DNA binding sequence for YdhB is also conserved in Entrobacterial genomes. RNA-seq data confirmed the activation predicted due to the binding of AdnB as shown by Chip-Exo results. Fluorescent polarization experiments revealed binding of YdhB to the predicted binding site upstream ofydhCin the presence of 0.35 mM adenine, but not in its absence. TheE. coliMG1655, strain lacking theydhBgene, showed a lower level ofydhCmRNA in cells grown in M9-glucose supplemented with 2 mM adenosine. Adenosine and adenine are products of purine metabolism and provide sources of ammonium for many organisms. They are utilized under nitrogen starvation conditions as single nitrogen sources. Deletion of either theydhCor theydhBgene leads to a substantially decreased growth rate forE. coliin minimal M9 medium with glycerol as the carbon source and adenosine or adenine as the single nitrogen source. TheydhCmutant showed increased resistance to Paromomycine, Sulfathiazole and Sulfamethohazole using Biolog plates. We provide evidence that YdhB, (a novel LysR family regulator) activates expression of theydhCgene, encoding a novel adenosine/adenine transporter inE. coli. The YdhB binding consensus for different groups of Enterobacteria was predicted.
Pricing policies of a dynamic green supply chain with strategies of retail service
Authors: Chen Shan , Zhou Fuli , Su Jiafu , Li Longxiao , Yang Biyu , He Yandong
Published: May 2020

Purpose

The paper investigates firms' optimal pricing policies and green strategies in a dynamic green supply chain with consideration of different retail service strategies. The purpose of the paper is to address the following research questions: (1) What are the optimal pricing policies and green strategies of the dynamic decentralized supply chain with the competitive or supportive retail service? (2) How does the dynamic consumer's perception of green product affect these equilibrium solutions?

Design/methodology/approach

The paper establishes the dynamic game models and then derives a firm's instantaneous and steady-state feedback equilibrium solutions in three scenarios as follows: (1) the integrated supply chain; (2) the decentralized supply chain with competitive retail service and (3) the decentralized supply chain with supportive retail service. Finally, we conduct numerical analyses to compare the firm's instantaneous and steady-state equilibrium solutions and profit in the three scenarios.

Findings

The theoretical and numerical analysis results suggest that the supportive retail service is less inefficient than the competitive retail service in the decentralized supply chain and that the types of retail service have no influence on the green strategy. Moreover, a firm's myopia leads to lowering the greenness degree, retail service level and severe price competition, resulting in economic losses. Consumers’ initial perception of greenness degree determines whether the retailer should adopt the skimming pricing strategy or penetration pricing strategy. Furthermore, only when consumers’ perception of greenness degree is higher than a threshold, will the manufacturer produce green product with positive greenness degree.

Originality/value

This is one of few studies on the effect of different types of retail service on horizontal competition in green supply chain. The extension of the static study by adopting differential game approaches provides researchers with a deeper understanding of the application of retail service in green supply chain.
Design techniques for cogging torque reduction in a fractional-slot PMBLDC motor
Authors: Petkovska Lidija , Lefley Paul , Cvetkovski Goga Vladimir
Published: May 2020

Purpose

This paper presents the design techniques applied to a novel fractional-slot 6/4 pole permanent magnet brushless direct current (PMBLDC) motor, for cogging torque reduction. The notable feature of this motor is the simplicity of the design and low production cost. The purpose of this paper is to reduce the peak cogging torque of the motor. The focus is put on the stator topology tuning, and a new design for the stator poles is proposed. By determining the optimum stator pole arc length and the best pole shoe thickness, the cogging torque is significantly reduced. This new optimised motor design has been analysed in detail. The validation of the results is documented with respective figures and charts.

Design/methodology/approach

At the beginning, the design data for the 6/4 pole PMBLDC motor with concentrated three phase windings and asymmetric stator pole arcs is presented. In the study, this motor is taken as a reference model (A0,T0). A full performance finite element analysis of the reference motor has been carried out, and the weak points in the motor design have been identified. By simple design techniques, tuning the stator pole geometry, a two-stage design optimisation for cogging torque minimisation has been performed and the solution array has been derived. The optimised model is selected and proposed (Aopt,Topt). The comparative analysis of the reference and optimised motors show the advantages of the proposed novel design and prove the methodology.

Findings

The results of the work demonstrate how simple design techniques can minimise the peak of the cogging torque profile, while maintaining the specified electromagnetic torque value. The sensitivity of the cogging torque profile because of changes of the stator pole design inside the prescribed constraints is apparent. The stator poles of the reference motor have an arc length of 85° and pole shoe thickness of 6 mm. The newly shaped stator poles have an arc length of 78.5° and pole shoe thickness 4.8 mm. The peak-cogging torque has been reduced from 0.158 Nm to a respectable value of 0.066 Nm. However, to reduce electromagnetic torque ripple and pulsations, further investigations are required.

Originality/value

The paper presents an approach to cogging torque reduction for a 6/4 PMBLDC motor. A two-step original design procedure is introduced and an optimised stator pole geometry is defined. The minimised cogging torque has been demonstrated with improved usage of the active materials. This work could serve as a good basis for further optimisation of the motor design.
Navigating barriers faced by women in leadership positions in the US construction industry: a retrospective on women’s continued struggle in a male-dominated industry
Authors: Lekchiri Siham , Kamm Jesse D.
Published: May 2020

Purpose

This investigation examined the challenges faced by women in leadership positions in the US construction industry. The overall purpose of this study was to gain a better understanding of the challenges, and identify suitable practices, strategies and suggestions to support the employment and retention of women in the US construction industry.

Design/methodology/approach

Using a qualitative approach, the authors distributed a survey to the target audience composed of women leaders in the US construction industry, and 14 participants completed the survey.

Findings

The outcomes of the study revealed the following challenges: negative perceptions of women in the industry manifested through discrimination and hostility; a stressful work environment that does not promote a good work-life balance; and a lack of role models that impacts women’s retention and career development in the construction industry.

Originality/value

This study discusses possible strategies and recommendations for women in construction to rise through the ranks of power within the industry.
Gender and the #MeToo effect in Spanish professional football organizations: an exploratory qualitative approach
Authors: Klavenes Henriette , Orea-Giner Alicia , García-Muiña Fernando E. , Fuentes-Moraleda Laura
Published: May 2020

Purpose

The purpose of this paper is to examine the effects of the #MeToo movement in the work environment of professional football organizations in Spain. It also explores the current situation of the professional career of women working in this industry to know if the opportunities are equal for men and women to reach management or executive positions.

Design/methodology/approach

From a gender approach and considering gender as a social structure (Risman, 2004), the authors are going to analyse men and women’s professional careers in football organizations from a three-dimensional gender perspective (individual, interactional and institutional). The objective is twofold: to know the effect of the #MeToo movement in these organizations; and also to know the opinion of both men and women of these organizations concerning gender influence for women’s career progression. The methodology implemented in this investigation is qualitative; 24 in-depth interviews (12 men and 12 women) have been carried out with professionals from different executive positions in both football clubs and organizations.

Findings

The gender approach improves current knowledge about women’s roles in the football industry. The exploratory analysis of the results shows that although the #MeToo phenomenon is relatively known it has had an indirect impact in Spanish football, where its consequences have not been as visible as in other sectors.

Originality/value

The paper provides an exploratory approach by analysing the effects of the #MeToo movement in the football sector, an area where almost no previous research has been done. Also, it presents the main factors that influence women’s professional careers in this sector and the significance of the recent #MeToo phenomenon in the football industry.
“Stuck in the middle” first-line healthcare managers’ responsibilities and needs of support when applying Lean
Authors: Kahm Therese , Ingelsson Pernilla
Published: May 2020

Purpose

The purpose of this paper is to present the supportive conditions that the first-line health-care managers claim that they need from their own managers and what they experience as their own roles and responsibilities in relation to their coworkers when applying Lean principles and practices.

Design/methodology/approach

A survey with a Web-based questionnaire was designed and used in a Swedish health-care organization two years after the initiation of Lean to investigate the managers’ views on their role, conditions and ability to create change according to Lean. The result from two of the questions will be presented where one focuses on the relationship to the first-line managers’ own manager and the second on the relationship to their coworkers.

Findings

The results show that to initiate improvement, work based on Lean first-line managers ask for own managers who are assured about Lean, include them in discussions and ask for follow-ups and results about Lean. Concerning first-line managers’ relation to their coworkers they experience themselves as responsible for leading toward creating a culture where problems and mistakes are viewed as possibilities to improve, for encouraging that new work procedures are tested and for creating commitment and inspiration in relation to their coworkers.

Originality/value

The questions can be used separately or as part of an entire questionnaire before and along the Lean process to highlight organizational issues such as shared responsibility and supportive relations when developing health care.
Corporate diversification and firms' value in emerging economy: the role of growth opportunity
Authors: Setianto Rahmat Heru
Published: May 2020

Purpose

This paper examines empirically how growth opportunities determine the relationship between corporate diversification and firm's value in an emerging economy.

Design/methodology/approach

This study employs annual data of Indonesian manufacturing firm's spanning five years. To test the potential nonlinear relationship between diversification and value, nonlinear regression model is employed. Baron and Kenny’s (1986) procedure is also employed to test the mediation role of the growth opportunities in the relation between diversification strategy and firm's value. This study also performs further robustness analysis on mediating role of growth opportunities on the relationship between diversification strategy and corporate value using path analysis approach.

Findings

The analyses reveal the U-shaped diversification and value relationship; this result suggests that the effect of diversification on value will vary across firms, the negative effect of diversification strategy on firm's value may reverse at higher levels of diversification. Further analysis indicates that such relationship is fully mediated by firm's growth opportunities.

Practical implications

Given the results, firms that are considering implementing diversification strategy should seek the optimal level of diversification to gain diversification premium. Furthermore, the manager should observe the best opportunities available for the firm before undertaking the diversification strategies.

Originality/value

This paper contributes to the existing literature on diversification strategy by extending the insight of this research area of a large emerging economy, on which prior studies have not reached conclusive results.
A small open economy DSGE model with workers' remittances
Authors: Rehman Muhammad , Khan Sajawal , Hayat Zafar , Balli Faruk
Published: May 2020

Purpose

In this paper, the authors develop and estimate a small open economy dynamic stochastic general equilibrium (DSGE) model with an enriched micro-founded specification to account for foreign remittances, an important source that helps bridge the trade gap in many developing and emerging market economies.

Design/methodology/approach

Although the authors’ specification provides a general frame for the analysis of the role of workers' remittances, they motivate and calibrate the model with specific focus on Pakistan, where most of the trade deficit is met through the remittance channel.

Findings

The results indicate that a negative shock to workers' remittances hampers real growth via decreased consumption and imported investment goods, while it builds pressure on exchange rate and hence worsens current account balance. These results indicate that too much dependence on workers' remittances to help meet foreign exchange deficits may potentially leave the economy in doldrums in case sizable negative shocks occur to the flow of foreign remittances.

Originality/value

The authors develop and estimate a small open economy DSGE model with an enriched micro-founded specification to account for foreign remittances, an important source that helps bridge the trade gap in many developing and emerging market economies.
The big data regime shift in real estate
Authors: DeLisle James R. , Never Brent , Grissom Terry V.
Published: May 2020

Purpose

The paper explores the emergence of the “big data regime” and the disruption that it is causing for the real estate industry. The paper defines big data and illustrates how an inductive, big data approach can help improve decision-making.

Design/methodology/approach

The paper demonstrates how big data can support inductive reasoning that can lead to enhanced real estate decisions. To help readers understand the dynamics and drivers of the big data regime shift, an extensive list of hyperlinks is included.

Findings

The paper concludes that it is possible to blend traditional and non-traditional data into a unified data environment to support enhanced decision-making. Through the application of design thinking, the paper illustrates how socially responsible development can be targeted to under-served urban areas and helps serve residents and the communities in which they live.

Research limitations/implications

The paper demonstrates how big data can be harnessed to support decision-making using a hypothetical project. The paper does not present advanced analytics but focuses aggregating disparate longitudinal data that could support such analysis in future research.

Practical implications

The paper focuses on the US market, but the methodology can be extended to other markets where big data is increasingly available.

Social implications

The paper illustrates how big data analytics can be used to help serve the needs of marginalized residents and tenants, as well as blighted areas.

Originality/value

This paper documents the big data movement and demonstrates how non-traditional data can support decision-making.
Nancy Dixon: empowering the learning organization through psychological safety
Authors: Sidani Yusuf , Reese Simon
Published: May 2020

Purpose

This paper aims to provide an overview of the development of learning organization concepts from the perspective of Nancy Dixon, who has been at the forefront of the learning organization discussion since the 1980s.

Design/methodology/approach

Through a conversation with Dixon, and a scan of some of her works, this paper discusses several topics pertaining to the evolution of the learning organization debate, from Dixon’s perspective.

Findings

Dixon’s understanding of learning organizations was influenced by concepts related to action learning where people in organizations learn through meeting and talking about their problems. What distinguishes her understanding from others in that it is built more on the perspective of psychological safety, as inspired by Amy Edmonson's work.

Originality/value

Dixon acknowledges that her work has had more impact on the practitioner side. Dixon maintains that learning organizations are more egalitarian and move away from hierarchy. There are ethical underpinnings to this understanding as, with psychological safety, people are willing to speak up in those situations when their voices are needed to be heard.
Acquired agminated melanocytic nevus in the acral area is a potential mimicker of acral lentiginous melanoma: A three‐case series report and published work review
Authors: Ogawa Kohei , Fujimoto Masakazu , Takai Toshihiro , Mitsui Yasuhiro , Iwasa Kentaro , Ohsita Akifumi , Komori Satoshi , Asai Jun , Azukizawa Hiroaki , Miyagawa Fumi , Yurugi Satoshi , Kuwahara Masamitsu , Sasaki Chikako , Ando Junji , Asada Hideo
Published: May 2020

Agminated nevus refers to a clustered group of melanocytic nevi confined to a localized area of the body. It rarely involves acral skin, but recognition of acquired agminated nevus (AAN) in the acral area is clinically important because it may mimic acral lentiginous melanoma (ALM). However, acral AAN has only been described in a few case reports and its clinical characteristics remain unclear. We report three additional cases of acral AAN to further analyze the differential points between ALM. Clinical images, including those of dermoscopy, of three cases of acral AAN were reviewed. The lesions were located on the sole or lateral border of the foot. All acral AAN were flat and large in size (>20 mm in greatest dimension), and associated with asymmetry and irregular border. However, no parallel ridge pattern suggesting ALM was observed on dermoscopy. In two patients, the lesions on the sole were totally resected; microscopic evaluation of these two lesions confirmed junctional nests of banal melanocytes. AAN lesions on the sole with chronic mechanical pressure are slightly larger and more diffuse; thus, they may be more likely to be overdiagnosed as malignancy upon inspection than those in the non‐acral area. Understanding the concept of the disease and careful dermoscopic evaluation leads to an accurate diagnosis.
Predicting meiofauna abundance to define preservation and impact zones in a deep‐sea mining context using random forest modelling
Authors: Uhlenkott Katja , Vink Annemiek , Kuhn Thomas , Martínez Arbizu Pedro
Published: May 2020

There is a strong economic interest in commercial deep‐sea mining of polymetallic nodules and therefore a need to define suitable preservation zones in the abyssal plain of the Clarion Clipperton Fracture Zone (CCZ). However, besides ship‐based multibeam data, only sparse continuous environmental information is available over large geographic scales.

We test the potential of modelling meiofauna abundance and diversity on high taxonomic level on large geographic scale using a random forest approach. Ship‐based multibeam bathymetry and backscatter signal are the only sources for 11 predictor variables, as well as the modelled abundance of polymetallic nodules on the seafloor. Continuous meiofauna predictions have been combined with all available environmental variables and classified into classes representing abyssal habitats using k‐means clustering.

Results show that ship‐based, multibeam‐derived predictors can be used to calculate predictive models for meiofauna distribution on a large geographic scale. Predicted distribution varies between the different meiofauna response variables.

To evaluate predictions, random forest regressions were additionally computed with 1,000 replicates, integrating varying numbers of sampling positions and parallel samples per site. Higher numbers of parallel samples are especially useful to smoothen the influence of the remarkable variability of meiofauna distribution on a small scale. However, a high number of sampling positions is even more important, integrating a greater amount of natural variability of environmental conditions into the model.

Synthesis and applications. Polymetallic nodule exploration contractors are required to define potential mining and preservation zones within their licence area. The biodiversity and the environment of preservation zones should be representative of the sites that will be impacted by mining. Our predicted distributions of meiofauna and the derived habitat maps are an essential first step to enable the identification of areas with similar ecological conditions. In this way, it is possible to define preservation zones not only based on expert opinion and environmental proxies but also integrating evidence from the distribution of benthic communities.
Epigenetic biosensors for bacteriophage detection and phage receptor discrimination
Authors: Olivenza David R. , Casadesús Josep , Ansaldi Mireille
Published: May 2020

Environmental monitoring of bacteria using phage‐based biosensors has been widely developed for many different species. However, there are only a few available methods to detect specific bacteriophages in raw environmental samples. In this work, we developed a simple and efficient assay to rapidly monitor the phage content of a given sample. The assay is based on the bistable expression of the Salmonella enterica opvAB operon. Under regular growth conditions, opvAB is only expressed by a small fraction of the bacterial subpopulation. In the OpvABON subpopulation, synthesis of the OpvA and OpvB products shortens the O‐antigen and confers resistance to phages that use LPS as a receptor. As a consequence, the OpvABON subpopulation is selected in the presence of such phages. Using an opvAB::gfp fusion, we could monitor LPS‐binding phages in various media, including raw water samples. To enlarge our phage‐biosensor panoply, we also developed biosensors able to detect LPS, as well as protein‐binding coliphages. Moreover, the combination of these tools allowed to identify the bacterial receptor triggering phage infection. The epigenetic opvAB::gfp biosensor thus comes in different flavours to detect a wide range of bacteriophages and identify the type of receptor they recognize.
Vibrio–bivalve interactions in health and disease
Authors: Destoumieux‐Garzón Delphine , Canesi Laura , Oyanedel Daniel , Travers Marie‐Agnès , Charrière Guillaume M. , Pruzzo Carla , Vezzulli Luigi
Published: May 2020

In the marine environment, bivalve mollusks constitute habitats for bacteria of the Vibrionaceae family. Vibrios belong to the microbiota of healthy oysters and mussels, which have the ability to concentrate bacteria in their tissues and body fluids, including the hemolymph. Remarkably, these important aquaculture species respond differently to infectious diseases. While oysters are the subject of recurrent mass mortalities at different life stages, mussels appear rather resistant to infections. Thus, Vibrio species are associated with the main diseases affecting the worldwide oyster production. Here, we review the current knowledge on Vibrio–bivalve interaction in oysters (Crassostrea sp.) and mussels (Mytilus sp.). We discuss the transient versus stable associations of vibrios with their bivalve hosts as well as technical issues limiting the monitoring of these bacteria in bivalve health and disease. Based on the current knowledge of oyster/mussel immunity and their interactions with Vibrio species pathogenic for oyster, we discuss how differences in immune effectors could contribute to the higher resistance of mussels to infections. Finally, we review the multiple strategies evolved by pathogenic vibrios to circumvent the potent immune defences of bivalves and how key virulence mechanisms could have been positively or negatively selected in the marine environment through interactions with predators.
Strategies and novel technologies to control Campylobacter in the poultry chain: A review
Authors: Soro Arturo B. , Whyte Paul , Bolton Declan J. , Tiwari Brijesh K.
Published: May 2020

Campylobacteriosis is one of the most common bacterial infections worldwide causing economic costs. The high prevalence of Campylobacter spp. in poultry meat is a result of several contamination and cross‐contamination sources through the production chain. Moreover, survival mechanisms, such as biofilm formation, viable but nonculturable state, and antimicrobial resistance, enable its persistence during food processing. Therefore, mitigation strategies are necessary in order to avoid and/or inactivate Campylobacter at farm, abattoir, industry, and retail level. In this review, a number of potential strategies and novel technologies that could reduce the prevalence of Campylobacter in poultry meat have been identified and evaluated to provide a useful overview. At farm level for instance, biosecurity, bacteriocins, probiotics, feed and water additives, bacteriophages, and vaccination could potentially reduce colonization in chicken flocks. However, current technologies used in the chicken slaughter and processing industry may be less effective against this foodborne pathogen. Novel technologies and strategies such as cold plasma, ultraviolet light, high‐intensity light pulses, pulsed electric fields, antimicrobials, and modified atmosphere packaging are discussed in this review for reducing Campylobacter contamination. Although these measures have achieved promising results, most have not been integrated within processing operations due to a lack of knowledge or an unwillingness to implement these into existing processing systems. Furthermore, a combination of existing and novel strategies might be required to decrease the prevalence of this pathogen in poultry meat and enhance food safety. Therefore, further research will be essential to assess the effectiveness of all these strategies.
MicroRNA‐374b mediates the initiation of non‐small cell lung cancer by regulating ITGB1 and p53 expressions
Authors: Zhao Meng , Tong Chuntang , Hao Zerui , Zhao Ruixing , Wang Liming
Published: May 2020

Background

Previous studies have shown that microRNAs (miRNAs) play important roles in the pathogenesis of human cancers. This study aims to clarify the role of miR‐374b in non‐small cell lung cancer (NSCLC).

Methods

In this study, RT‐qPCR and western blot analysis were used to measure mRNA and protein expression. The regulatory mechanism of miR‐374b/ITGB1 was investigated by dual‐luciferase reporter, CCK‐8, and transwell assays.

Results

MiR‐374b expression was reduced in NSCLC tissues and associated with lymph node metastasis, tumor stage and prognosis in NSCLC patients. Functionally, overexpression of miR‐374b inhibited cell viability and metastasis in NSCLC. In addition, miR‐374b blocked EMT and promoted p53 expression in NSCLC. MiR‐374b was found to directly target ITGB1. Furthermore, upregulation of ITGB1 weakened the antitumor effect of miR‐374b in NSCLC.

Conclusions

MiR‐374b inhibits the tumorigenesis of NSCLC by downregulating ITGB1 and upregulating p53.
Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment‐Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial of Varenicline
Authors: Miranda Robert , O’Malley Stephanie S. , Treloar Padovano Hayley , Wu Ran , Falk Daniel E. , Ryan Megan L. , Fertig Joanne B. , Chun Thomas H. , Muvvala Srinivas B. , Litten Raye Z.
Published: May 2020

Background

The alcohol cue reactivity paradigm is increasingly used to screen medications for the treatment of alcohol use disorder (AUD) and other substance use disorders. Yet, its prospective association with craving and naturalistic drinking outcomes in clinical trials remains unknown. This study embedded repeated human laboratory assessments of alcohol cue reactivity within the context of a randomized controlled trial to examine the effects of varenicline tartrate (Chantix®), a partial agonist of α4β2 nicotinic acetylcholine receptors, on alcohol craving among treatment‐seeking heavy drinkers with AUD. Our main objectives were to test whether varenicline, as compared to placebo, blunts alcohol cue–elicited craving and test whether alcohol cue reactivity observed in the human laboratory predicts subsequent alcohol craving and use during the remainder of the trial.

Design and Methods

This double‐blind, randomized, 2‐site study compared the effects of varenicline (up to 2 mg/d) and placebo on responses to in vivo alcohol cue and affective picture cue exposure in the human laboratory. Forty‐seven volunteers (18 females, 29 males), ages 23 to 67 years (M = 43.7, SD = 11.5), were recruited from the community via advertisements to participate in a clinical trial designed to study the effects of varenicline on alcohol use. Participants were randomized to either varenicline or placebo for 6 weeks.

Results

Varenicline did not attenuate cue‐induced alcohol craving relative to placebo, but craving captured during the cue reactivity paradigm significantly predicted subsequent alcohol use in real‐world settings during the clinical trial. Higher craving predicted heavier alcohol use.

Conclusions

Our results are among the first to show alcohol cue–induced craving captured during a human laboratory paradigm predicts drinking outcomes in the context of a clinical trial.
A neural mechanism of the relationship between impulsivity and emotion dysregulation in patients with Internet gaming disorder
Authors: Shin Yu‐Bin , Kim Hyunji , Kim Soo‐Jeong , Kim Jae‐Jin
Published: May 2020

Impulsivity and emotion dysregulation have been known to be risk factors for Internet gaming disorder (IGD), but their underlying neural mechanisms are not yet fully understood. Given that the prefrontal cortex has a key role in higher order cognition and addiction, the present study aimed to investigate emotional influences on response inhibition in situations with different cognitive demands. A total of 41 young male adults (20 with and 21 without IGD) were scanned while performing two versions of an emotional go/no‐go task with demands on low and high working memory load. Patients with IGD showed a failure in response inhibition and increased activation of widespread brain regions, including prefrontal, motor‐sensory, parietal, occipital, insula, and striatal regions across tasks. Among these regions, involvement of the dorsolateral prefrontal cortex and ventral striatum was observed only during the task with high demands on working memory. Moreover, it was also only during the high‐load task that interaction between response inhibition and emotional states was observed in the dorsomedial prefrontal cortex, with observations revealing that its alteration in patients with IGD was associated with number of hours spent on Internet gaming. Our findings highlight a failure of response inhibition and dysfunction within the inhibitory control network. The special significance of our study is that dysfunctional dorsomedial prefrontal cortex may mediate abnormal emotional influences on response inhibition in patients with IGD.
A Comparative Case Study of Public Pre‐K Teachers’ Enactment of Parent Involvement Policy
Authors: Wilinski Bethany , Vellanki Vivek
Published: May 2020

This article employs the comparative case study (CCS) approach to examine how four public pre‐kindergarten (pre‐K) teachers in Michigan enacted a state‐mandated parent involvement policy. Using CCS, we trace policy enactment from the policy text, through mid‐level administrators, and into the classroom context. We demonstrate how teachers used strategic knowledge to develop hybrid parent involvement practices that satisfied program requirements while prioritizing the needs of families in their classrooms.
Acral lentiginous melanoma: Clinicopathologic and survival differences according to tumour location
Authors: Howard Matthew , Xie Charles , Wee Edmund , Wolfe Rory , McLean Catriona , Kelly John W. , Pan Yan
Published: May 2020

Background/Objectives

Acral lentiginous melanoma (ALM) is a melanoma subtype associated with atypical locations on the hands and feet and advanced disease at diagnosis. There is a limited understanding of whether the survival is similar for nail, non‐nail, lower limb and upper limb ALM patients. We therefore explored clinicopathologic characteristics and melanoma‐specific survival of ALM patients according to tumour location.

Methods

A prospectively collected cohort study was performed of all primary invasive cutaneous acral lentiginous melanomas with known thickness and tumour location reviewed at a tertiary referral centre over 21 years.

Results

A total of 101 ALM patients were reviewed from 1994 until 2016. The majority of cases (82/101) occurred on the feet. Hand ALMs were thicker and more likely to be ulcerated than feet ALMs (P = 0.05 and 0.02, respectively); however, survival was not statistically different between these two groups (univariate HR 0.48 P = 0.11, 95% CI, 0.20–1.17; multivariate HR 0.67 P = 0.40, 95% CI, 0.27–1.69, respectively). Non‐nail ALM patients had longer survival when compared to nail ALM on univariate analysis (HR 0.40, 95% CI, 0.17 to 0.90) which was accounted for by Breslow thickness and ulceration (multivariate HR 0.56, 95% CI, 0.24 to 1.34).

Conclusions

The reduced melanoma‐specific survival in nail ALM patients was likely due to their greater thickness and ulceration. Although hand ALMs are thicker and more frequently ulcerated, this is likely due to the higher proportion of nail ALMs present in this location.
Effectiveness of Connected Legislators
Authors: Battaglini Marco , Sciabolazza Valerio Leone , Patacchini Eleonora
Published: May 2020

Important work has been done to measure legislative effectiveness in the U.S. Congress and to explain the individual characteristics that drive it. Much less attention, however, has been devoted to study the extent to which legislative effectiveness depends on the legislators' social connections. We address this issue with a new model of legislative effectiveness that formalizes the role of social connections, and we test its predictions using the network of cosponsorship links in the 109th–113th Congresses. We propose a new empirical strategy that addresses network endogeneity by implementing a two‐step Heckman correction based on an original instrument: the legislators' alumni connections. We find that social connections are a significant determinant of legislative effectiveness. We also study the influence of legislators' characteristics in shaping the network effects. In doing so, we provide new insights into how social connectedness interacts with factors such as seniority, partisanship, and legislative leadership in determining legislators' effectiveness.
Fatal anaphylaxis in Italy: Analysis of cause‐of‐death national data, 2004‐2016
Authors: Bilò Maria Beatrice , Corsi Alice , Martini Matteo , Penza Elena , Grippo Francesco , Bignardi Donatella
Published: May 2020

Background

Epidemiological data on fatal anaphylaxis are underestimated worldwide. Few Italian data do exist. The aims of the study are to determine the anaphylaxis mortality rate in Italy and its associations with demographic characteristics (gender, age, and geographical distribution), and to investigate which are the most common triggers of fatal anaphylaxis.

Material and methods

This is a descriptive study analyzing data reported to the National Register of Causes of Death database and managed by the Italian National Institute of Statistics for the years 2004‐2016. An analytical method was developed to identify all the ICD‐10 codes related to anaphylaxis deaths, which were divided into two classes: “Definite anaphylaxis deaths” and “Possible anaphylaxis deaths.”

Results

From 2004 through 2016, 392 definite anaphylaxis deaths and 220 possible anaphylaxis deaths were recorded. The average mortality rate for definite anaphylaxis, from 2004 to 2016, was 0.51 per million population per year. Definite fatal anaphylaxis was mostly due to the use of medications (73.7%), followed by unspecified causes (20.7%) and hymenoptera stings (5.6%). Concerning possible anaphylaxis deaths, the most common cause was venom‐stinging insect (51.4%). We did not find any data on food fatal anaphylaxis. Unspecified anaphylaxis accounted for 21%‐28% of all cases, underlining the difficulty in accurately ascertaining the causes of fatal anaphylaxis and therefore in assigning the proper ICD‐10 code.

Conclusion

This is the first study of anaphylaxis‐related mortality coming from an official database of the whole Italian population. However, the actual number of deaths by anaphylaxis, and their related triggers, is probably underreported, mostly due to limitations of the current recording system, and to a poor allergy education. Corrective actions should be undertaken for the benefit of the Health System.
Clinician perception of long‐term survival at the point of critical care discharge: a prospective cohort study
Authors: Morton B. , Penston V. , McHale P. , Hungerford D. , Dempsey G.
Published: May 2020

Critical care survivors suffer persistent morbidity and increased risk of mortality as compared with the general population. Nevertheless, there are no standardised tools to identify at‐risk patients. Our aim was to establish whether the Sabadell score, a simple tool applied by the treating clinician upon critical care discharge, was independently associated with 5‐year mortality through a prospective observational cohort study of adults admitted to a general critical care unit. The Sabadell score, which is a measure of clinician‐assigned survival perception, was applied to all patients from September 2011 to December 2017. The primary outcome was 5‐year mortality, assessed using a multivariable flexible parametric survival analysis adjusted for baseline characteristics and clinically relevant covariates. We studied 5954 patients with a minimum of 18 months follow‐up. Mean (SD) age was 59.5 (17.0) years and 3397 (57.1%) patients were men. We categorised 2287 (38.4%) patients as Sadabell 0; 2854 (47.9%) as Sadabell 1; 629 (10.5%) as Sadabell 2; and 183 (3.1%) as Sadabell 3. Adjusted hazard ratios for mortality were 2.1 (95%CI 1.9–2.4); 4.0 (95%CI 3.4–4.6); and 21.0 (95%CI 17.2–25.7), respectively. Sabadell 3 patients had 99.9%, 99.5%, 98.5% and 87.4% mortality at 5 years for patients in the age brackets ≥ 80, 60–79, 40–59 and 16–39 years, respectively. Sabadell 2 patients had 71.0%, 52.7%, 44.8% and 23.7% 5‐year mortality for these same age categories. The Sabadell score was independently associated with 5‐year survival after critical care discharge. These findings can be used to guide provision of increased support for patients after critical care discharge and/or informed discussions with patients and relatives about dying to ascertain their future wishes.
Outcomes after hepatic encephalopathy in population‐based cohorts of patients with cirrhosis
Authors: Tapper Elliot B. , Aberasturi Devin , Zhao Zhe , Hsu Chia‐Yang , Parikh Neehar D.
Published: May 2020

Background

Hepatic encephalopathy is a devastating complication of cirrhosis.

Aim

To describe the outcomes after developing hepatic encephalopathy among contemporary, aging patients.

Methods

We examined data for a 20% random sample of United States Medicare enrolees with cirrhosis and Part D prescription coverage from 2008 to 2014. Among 49 164 persons with hepatic encephalopathy, we evaluated the associations with transplant‐free survival using Cox proportional hazard models with time‐varying covariates (hazard ratios, HR) and incidence rate ratios (IRR) for healthcare utilisation measured in hospital‐days and 30‐day readmissions per person‐year. We validated our findings in an external cohort of 2184 privately insured patients with complete laboratory values.

Results

Hepatic encephalopathy was associated with median survivals of 0.95 and 2.5 years for those ≥65 or <65 years old and 1.1 versus 3.9 years for those with and without ascites. Non‐alcoholic fatty‐liver disease posed the highest adjusted risk of death among aetiologies, HR 1.07 95% CI (1.02, 1.12). Both gastroenterology consultation and rifaximin utilisation were associated with lower mortality, respective adjusted‐HR 0.73 95% CI (0.67, 0.80) and 0.40 95% CI (0.39, 0.42). Thirty‐day readmissions were fewer for patients seen by gastroenterologists (0.71 95% CI [0.57‐0.88]) and taking rifaximin (0.18 95% CI [0.08‐0.40]). Lactulose alone was associated with fewer hospital‐days, IRR 0.31 95% CI (0.30‐0.32), than rifaximin alone, 0.49 95% CI (0.45‐0.53), but the optimal therapy combination was lactulose/rifaximin, IRR 0.28 95% CI (0.27‐0.30). These findings were validated in the privately insured cohort adjusting for model for endstage liver disease‐sodium score and serum albumin.

Conclusions

Hepatic encephalopathy remains morbid and associated with poor outcomes among contemporary patients. Gastroenterology consultation and combination lactulose‐rifaximin are both associated with improved outcomes. These data inform the development of care coordination efforts for subjects with cirrhosis.
Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
Authors: Bangma Amber , Voskuil Michiel D. , Uniken Venema Werna T. C. , Brugge Harm , Hu Shixian , Lanting Pauline , Franke Lude , Dijkstra Gerard , Festen Eleonora A. M. , Weersma Rinse K.
Published: May 2020

Background

High inter‐individual variability in therapeutic response to drugs used in the management of Inflammatory Bowel Disease (IBD) leads to high morbidity and high costs. Genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis and immunogenicity of Tumour Necrosis Factor alpha (TNFα) antagonists have been identified, but uptake of pre‐treatment pharmacogenetic testing into clinical guidelines has been slow.

Aim

To explore the efficacy of a pharmacogenetic passport for IBD that includes multiple pharmacogenetic predictors of response.

Methods

Patients with IBD exposed to thiopurines and/or TNFα antagonists were retrospectively evaluated for the presence of thiopurine toxicity and/or immunogenicity of TNFα antagonists. All patients were genotyped using both whole‐exome sequencing and the Illumina Global Screening Array. An in‐house‐developed computational pipeline translated genetic data into an IBD pharmacogenetic passport that predicted risks for thiopurine toxicity and immunogenicity of TNFα antagonists per patient. Using pharmacogenetic‐guided treatment guidelines, we calculated clinical efficacy estimates for pharmacogenetic testing for IBD.

Results

Among 710 patients with IBD exposed to thiopurines and/or TNFα antagonists, 150 adverse drug responses occurred and our pharmacogenetic passport would have predicted 54 (36%) of these. Using a pharmacogenetic passport for IBD that includes genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis, and immunogenicity of TNFα antagonists, 24 patients need to be genotyped to prevent one of these adverse drug responses.

Conclusions

This study highlights the clinical efficacy of a pharmacogenetic passport for IBD. Implementation of such a pharmacogenetic passport into clinical management of IBD may contribute to a reduction in adverse drug responses.