bluuebunny/crossref_metadata_2025 huggingface dataset:
The Power of Association Studies to Detect the Contribution of Candidate Genetic Loci to Variation in Complex Traits
Authors: Long Anthony D. , Langley Charles H.
Published: November 2021

The statistical power of five association study test statistics (two haplotype-based tests, two marker-based tests, and the Transmission Disequilibrium Test–Q5) to detect single nucleotide polymorphism (SNP)/phenotype associations in a linkage–disequilibrium-based candidate gene scan employing a number of SNPs is examined. Power is estimated as a function of realistic parameters expected to affect the likelihood of detecting a significant association: the number of SNPs examined, the scaled recombination size of the region examined, the proportion of variance in the trait attributable to a hidden causative polymorphism within the region, and the number of individuals or families examined. For the different combinations of parameter values, power is estimated from a large number of realizations of a simulated coalescent describing a single random mating population with mutation, random genetic drift, and recombination. This explicit population genetics model results in a distribution of DNA marker heterozygosities and linkage disequilibria that are likely to resemble those expected in actual population samples. The study concludes that (1) marker-based permutation tests are more powerful than simple haplotype-based tests, (2) there is sufficient power to detect the presence of causative polymorphisms of small effect if on the order of 500 individuals are sampled, (3) greater power is achieved by increasing the sample size than by increasing the number of polymorphisms, (4) association studies are generally more powerful than transmission disequilibrium-based tests, and (5) for the range of parameters considered association studies have a low repeatability unless sample sizes are on the order of 500 individuals. Estimates of 4Nc for a number of gene regions and human populations will be of use in determining the density of SNPs that are likely to be required for successful association studies.
Candidate Regulatory Sequence Elements for Cell Cycle-Dependent Transcription in Saccharomyces cerevisiae
Authors: Wolfsberg Tyra G. , Gabrielian Andrei E. , Campbell Michael J. , Cho Raymond J. , Spouge John L. , Landsman David
Published: November 2021

Recent developments in genome-wide transcript monitoring have led to a rapid accumulation of data from gene expression studies. Such projects highlight the need for methods to predict the molecular basis of transcriptional coregulation. A microarray project identified the 420 yeast transcripts whose synthesis displays cell cycle-dependent periodicity. We present here a statistical technique we developed to identify the sequence elements that may be responsible for this cell cycle regulation. Because most gene regulatory sites contain a short string of highly conserved nucleotides, any such strings that are involved in gene regulation will occur frequently in the upstream regions of the genes that they regulate, and rarely in the upstream regions of other genes. Our strategy therefore utilizes statistical procedures to identify short oligomers, five or six nucleotides in length, that are over-represented in upstream regions of genes whose expression peaks at the same phase of the cell cycle. We report, with a high level of confidence, that 9 hexamers and 12 pentamers are over-represented in the upstream regions of genes whose expression peaks at the early G1, late G1, S, G2, or M phase of the cell cycle. Some of these sequence elements show a preference for a particular orientation, and others, through a separate statistical test, for a particular position upstream of the ATG start codon. The finding that the majority of the statistically significant sequence elements are located in late G1 upstream regions correlates with other experiments that identified the late G1/early S boundary as a vital cell cycle control point. Our results highlight the importance of MCB, an element implicated previously in late G1/early S gene regulation, as most of the late G1 oligomers contain the MCB sequence or variations thereof. It is striking that most MCB-like sequences localize to a specific region upstream of the ATG start codon. Additional sequences that we have identified may be important for regulation at other phases of the cell cycle.

[A companion website to this manuscript is available fromhttp://www.ncbi.nlm.nih.gov/CBBresearch/Landsman/Cell_cycle_data]
Deformation of polyiodides in Cs2I8 crystals at high pressure
Authors: Poreba Tomasz , Garbarino Gaston , Comboni Davide , Mezouar Mohamed
Published: November 2021

Dicaesium octaiodide is composed of layers of zigzag polyiodide units (I8
2−) intercalated with caesium cations. Each I8
2− unit is built of two triiodides bridged with one diiodine molecules. This system was subjected to compression up to 5.9 GPa under hydrostatic conditions. Pressure alters the supramolecular architecture around I8
2−, leading to bending of the triiodide units away from their energetically preferred geometry (D
∞h). Short I2...I3
− contacts compress significantly, reaching lengths typical for the covalently bonded polyiodides. Unlike in reported structures at ambient conditions, pressure-induced catenation proceeds without symmetrization of the polyiodides, pointing to a different electron-transfer mechanism. The structure is shown to be half as compressible [B0 = 12.9 (4) GPa] than the similar CsI3 structure. The high bulk modulus is associated with higher I—I connectivity and a more compact cationic net, than in CsI3. The small discontinuity in the compressibility trend around 3 GPa suggests formation of more covalent I—I bonds. The potential sources of this discontinuity and its implication on the electronic properties of Cs2I8 are discussed.
Crystal structure of a TbIII–CuII glycinehydroxamate 15-metallacrown-5 sulfate complex
Authors: Pavlishchuk Anna V. , Vasylenko Inna V. , Zeller Matthias , Addison Anthony W.
Published: November 2021

The core of the title complex, bis[hexaaquahemiaquapentakis(μ3-glycinehydroxamato)sulfatopentacopper(II)terbium(III)] sulfate hexahydrate, [TbCu5(SO4)(GlyHA)5(H2O)6.5]2(SO4)·6H2O (1), which belongs to the 15-metallacrown-5 family, consists of five glycinehydroxamate dianions (GlyHA2−; C2H4N2O2) and five copper(II) ions linked together forming a metallamacrocyclic moiety. The terbium(III) ion is connected to the centre of the metallamacrocycle through five hydroxamate oxygen atoms. The coordination environment of the Tb3+ ion is completed to an octacoordination level by oxygen atoms of a bidentate sulfate and an apically coordinated water molecule, while the copper(II) atoms are square-planar, penta- or hexacoordinate due to the apical coordination of water molecules. Continuous shape calculations indicate that the coordination polyhedron of the Tb3+ ion in 1 is best described as square antiprismatic. The positive charge of each pair of [TbCu5(GlyHA)5(H2O)6.5(SO4)]2
2+ fragments is compensated by a non-coordinated sulfate anion, which is located on an inversion center with 1:1 disordered oxygen atoms. Complex 1 is isomorphous with the previously reported compounds [LnCu5(GlyHA)5(SO4)(H2O)6.5]2(SO4), where Ln
III = Pr, Nd, Sm, Eu, Gd, Dy and Ho.
(E)-5-(4-Chlorobenzylidene)-1-phenyl-4,5,6,7-tetrahydro-1H-indazol-4-one: crystal structure and Hirshfeld surface analysis
Authors: Meenatchi C. Selva , Athimoolam S. , Suresh J. , Rubina S. Raja , Kumar R. Ranjith , Bhandari S. R.
Published: November 2021

In the title compound, C20H15ClN2O, the non-aromatic six-membered ring adopts a distorted envelope conformation with methylene-C atom nearest to the five-membered ring being the flap atom. The dihedral angle between the phenyl and chlorobenzene rings is 74.5 (1)°. The heterocyclic ring forms dihedral angles of 37.9 (1) and 64.3 (1)° with the phenyl and chlorobenzene rings, respectively. In the crystal, weak C—H...O interactions feature predominantly within the three-dimensional architecture. The intermolecular interactions are further analysed with the calculation of the Hirshfeld surfaces highlighting the prominent role of C—H...O interactions, along with H...H (36.8%) and C...H/H...C (26.5%) contacts.
Impacts of COVID-19 on patterns of meat and seafood consumption: evidence from Australia
Authors: Rolfe John , Rajapaksa Darshana , De Valck Jeremy , Star Megan
Published: November 2021

Purpose

In 2020, mechanisms to limit the chain of transmission of coronavirus disease 2019 (COVID-19) in Australia led to widespread restrictions on population mobility and business operations. Such conditions provide a natural experiment that may help to provide insights into consumer behaviour and future trends in food consumption. The overall objective of this study is to explore the possible impacts of COVID-19 on meat consumption patterns in Australia, both in the short and medium term, and to explore whether there have been impacts on the underlying drivers for consumption.

Design/methodology/approach

The research reported in this paper analyses the impacts of COVID-19 on meat and seafood consumption in Australia, drawing on a national random survey of 1,200 participants in June 2020. Survey data on past and current consumption rates are compared to respondent estimates of their future consumption behaviour, and ordered probit models are used to identify whether consumption changes can be explained by socio-demographic, attitudinal or economic factors.

Findings

Two potential scenarios were evaluated to explore future consumption trends. The first “acceleration” scenario is that the restrictions would encourage people to speed up existing declines in meat consumption, perhaps taking more account of credence factors such as health, animal welfare and environmental issues. The second “transformation” scenario is that people will change consumption patterns, perhaps moving more towards home-cooked meals and increased consumption. Slightly stronger support was found for the transformation scenario, indicating that consumption rates for most meats and seafood will be stable or increase over the next five years.

Originality/value

This study capitalises on changed social and economic settings generated by COVID-19 to test the effects on consumption of meat (chicken, beef, pork, lamb) and seafood at a national level. Ordered probit models are applied to evaluate participant data on their future intentions for meat consumption to test two scenarios, finding stronger support for the “transformative” scenario than the “accelerate” scenario.
International mobile marketing: a satisfactory concept for companies and users in times of pandemic
Authors: Florido-Benítez Lázaro
Published: November 2021

Purpose

This study’s purpose is to analyze the international mobile marketing (IMK) in order to stage the importance of this tool in the internationalization of companies. Our understanding of mobile marketing is constantly evolving, due to its high business penetration in a world globalized by technologies.

Design/methodology/approach

A review of the relevant literature on IMK, companies and customers is undertaken to understand the link between them. The paper begins by explaining the coronavirus disease 2019 is accelerating the change of the rules of the game in traditional and online commerce around the world. Furthermore, this study uses secondary data from organisation for economic co-operation and development (OECD), Sensor Tower, mobile marketing association (MMA), App Annie, among others, to support research results.

Findings

The results have shown that IMK has opened a melting pot of opportunities for companies and consumers in this period of pandemic; the potential of this tool is being redefined, in order to identify, anticipate and satisfy customers requirement profitably and efficiently. This study aims to provide an assessment of new concept of IMK and how this tool has to be integrated into the firm’s digital marketing strategies.

Originality/value

The study contributes to make better future decisions in the international digital expansion of companies by company executives and marketing experts. This paper provides a comprehensive framework intended to guide research efforts focusing on digital marketing as well as to aid practitioners in their quest to achieve IMK success.
Determining response time factors of emergency medical services during the COVID-19 pandemic
Authors: Mulyono Nur Budi , Pambudi Noorhan Firdaus , Ahmad Lukni Burhanuddin , Adhiutama Akbar
Published: November 2021

Purpose

The lack of studies about the response time of emergency medical service during the coronavirus disease 2019 (COVID-19) pandemic in a dense city of a developing country has triggered this study to explore the factors contributing to a high response time of ambulance service to reach patients in need. An evaluation of contributing factors to the response time is necessary to guide decision-makers in keeping a high service level of emergency medical service.

Design/methodology/approach

This research employed an agent-based modeling approach with input parameters from interviews with emergency medical service staff in Bandung city, Indonesia. The agent-based model is established to evaluate the relevant contribution of the factors to response time reduction using several scenarios.

Findings

According to agent-based simulation, four factors contribute to the response time: the process of preparing crew and ambulance during the pandemic, coverage area, traffic density and crew responsiveness. Among these factors, the preparation process during the pandemic and coverage area significantly contributed to the response time, while the traffic density and crew responsiveness were less significant. The preparation process is closely related to the safety procedure in handling patients during the COVID-19 pandemic and normal time. The recommended coverage area for maintaining a low response time is 5 km, equivalent to six local subdistricts.

Research limitations/implications

This study has explored the factors contributing to emergency medical response time. The insignificant contribution of the traffic density showed that citizens, in general, have high awareness and compliance to traffic priority regulation, so crew responsiveness in handling ambulances is an irrelevant factor. This study might have different contributing factors for less dense population areas and focuses on public emergency medical services provided by the local government.

Practical implications

The local government must provide additional funding to cover additional investment for ambulance, crew and administration for the new emergency service deployment point. Exercising an efficient process in ambulance and crew preparation is mandatory for each emergency deployment point.

Originality/value

This study evaluates the contributing factors of emergency medical response time in the pandemic and normal situation by qualitative analysis and agent-based simulation. The performance comparison in terms of medical response time before and after COVID-19 through agent-based simulation is valuable for decision-makers to reduce the impact of COVID-19.
An IoT-based agriculture maintenance using pervasive computing with machine learning technique
Authors: Kailasam Swathi , Achanta Sampath Dakshina Murthy , Rama Koteswara Rao P. , Vatambeti Ramesh , Kayam Saikumar
Published: November 2021

Purpose

In cultivation, early harvest offers farmers an opportunity to increase production while decreasing the chances of lower crop production rates, ensuring that the economy remains balanced. The significant reason is to predict the disease in plants and distinguish the type of syndrome with the help of segmentation and random forest optimization classification. In this investigation, the accurate prior phase of crop imagery has been collected from different datasets like cropscience, yesmodes and nelsonwisc . In the current study, the real-time earlier state of crop images has been gathered from numerous data sources similar to crop_science, yes_modes, nelson_wisc dataset.

Design/methodology/approach

In this research work, random forest machine learning-based persuasive plants healthcare computing is provided. If proper ecological care is not applied to early harvesting, it can cause diseases in plants, decrease the cropping rate and less production. Until now different methods have been developed for crop analysis at an earlier stage, but it is necessary to implement methods to advanced techniques. So, the detection of plant diseases with the help of threshold segmentation and random forest classification has been involved in this investigation. This implemented design is verified on Python 3.7.8 software for simulation analysis.

Findings

In this work, different methods are developed for crops at an earlier stage, but more methods are needed to implement methods with prior stage crop harvesting. Because of this, a disease-finding system has been implemented. The methodologies like “Threshold segmentation” and RFO classifier lends 97.8% identification precision with 99.3% real optimistic rate, and 59.823 peak signal-to-noise (PSNR), 0.99894 structure similarity index (SSIM), 0.00812 machine squared error (MSE) values are attained.

Originality/value

The implemented machine learning design is outperformance methodology, and they are proving good application detection rate.
Disruptions in sourcing and distribution practices of supply chains due to COVID-19 pandemic: a sustainability paradigm
Authors: Sharma Vishal , Singh Amrinder , Rai Siddharth Shankar
Published: November 2021

Purpose

The present research paper is an attempt to study how COVID-19 can affect the global sourcing practices of various supply chain intermediaries across the demand chain. This study aims to explore and is an attempt to understand the overall impact of COVID-19 on the sustainable operations of the firm such as sourcing, procurement, economic performance, social responsibility, consumption and distributions.

Design/methodology/approach

This study uses a quantitative technique using data collected from 708 respondents. Structural equation modeling (SEM) has been applied to test the proposed model and hypothesis.

Findings

The findings of the study suggest that sourcing practices, distribution and sustainability considerations of manufacturers, suppliers, distributors and retailers are affected by COVID-19 to a great extent but the pandemic has also led to making supply chain intermediaries understand the changing dynamics of the business scenario which can help them in their own strategic and business evolution.

Research limitations/implications

The current disruptions throughout global delivery chains caused by COVID-19 affect badly, the already poor-performing supply chains. Hence, the present study provides fresh insight on how organizations can limit the ill effects of COVID-19 by safeguarding some of their key sustainable operations in a post-pandemic business scenario.

Originality/value

The present study takes into consideration how core supply functions such as sourcing, distribution and manufacturing and various sustainable operations are disrupted by pandemic and its after-effects. This knowledge base can help business organizations to mitigate such problems/disruptions in the future.
The impact of mental health information overload on community education programs to enhance mental health-care seeking
Authors: Bink Andrea B. , Corrigan Patrick
Published: November 2021

Purpose

Education programs seek to increase the public’s mental health literacy so they are better able to, among other things, help others engage in care when in need. This task may be diminished when such programs overwhelm participants with too much information. In addition, participants might arrive to the program with information overload related to the covered health topic. Information overload about health topics has been shown to influence attitudes and behavioral intentions. The overall purpose of the current study was to examine the relationship between mental health information overload, topic interest, and care seeking recommendations.

Design/methodology/approach

The current study tested a path suggesting high mental health information overload diminishes interest in learning about mental health, which in turn reduces recommendations to others to seek appropriate help when in need. Participants completed online measures of mental health information overload, topic interest and recommendations for care seeking. The data set analyzed represents valid responses from 221 participants. Structural equation modeling was completed to confirm the path model hypothesized for this study.

Findings

Structural equation modeling showed satisfactory fit and significant betas for the hypothesized path.

Originality/value

This study adds to the emerging literature on the impact of health information overload and is the first to the best of the authors’ knowledge to measure mental health information overload. Program developers should consider information overload in the ongoing development of public mental health education programs.
Personal goals in consumers' adoption of mHealth services
Authors: Schuster Lisa , Parkinson Joy
Published: November 2021

Purpose

mHealth services are effective and cost efficient, yet wide-scale adoption of these services by consumers has yet to be achieved, constraining their public health benefit. Further investigation of non-technological determinants of mHealth adoption is needed; specifically, the role of consumers' goals has received scant attention and forms the research focus.

Design/methodology/approach

Study 1 comprised 20 interviews with participants who possess a health goal, with the data analysed using an abductive reasoning approach. Study 2 was a 15-min online survey (n = 653), with the data analysed using multi-group structural equation modelling.

Findings

Study 1 identified several antecedents to the desirability and feasibility of consumers' health goals, which influence their desire to use mHealth services. Study 2 shows significant differences in the determinants of mHealth service acceptance depending on whether consumers set concrete as opposed to abstract goals, but social acceptance of mHealth services of these services is important for both groups.

Practical implications

The findings suggest emphasising the importance of health goals to achieving other consumer goals (e.g. work or travel goals), the efficacy of mHealth services relative to other service alternatives for achieving those health goals, and the social acceptance of mHealth services to increase their uptake.

Originality/value

This study is the first to use construal-level theory to improve understanding of the role of consumers' goals in the adoption of mHealth services. By identifying the antecedents to goal desirability and feasibility, it also broadens the model of goal-directed behaviour.
The profile of the Portuguese regarding the perception of financial literacy
Authors: Santos Eulália Maria Mota , Tavares Vasco Capela , Ratten Vanessa , Tavares Fernando Oliveira
Published: November 2021

Purpose

The purpose of this study is to identify the profile of the Portuguese regarding the perception of financial literacy.

Design/methodology/approach

The utilized methodology is based on a questionnaire survey that assesses the perception of financial literacy. The sample is composed of 830 Portuguese individuals over 18 years old.

Findings

The results show that the financial literacy scale presents a tri-factor structure with adequate validity and reliability levels. The three obtained factors are designated 1-2-year financial planning and goals, long-term saving and taste for numeric calculations.

Originality/value

The originality in this study is shown in the application of the cluster analysis, which demonstrates the formation of three clusters that present different perceptions of financial literacy, classifying the Portuguese into a cluster of high financial literacy and taste for numeric calculation, a cluster of low financial literacy and a cluster of financial planning and saving but without the taste for numeric calculation.
Evaluation of thermal and physical properties of PMMA/PMVEMA-ES blends as organic coating
Authors: Hisham Shameer , Tajuddin Hairul Anuar , Muhamad Sarih Norazilawati , Zakaria Nur Zarith Diana Diana , Zainal Abidin Zul Hazrin , Abdul Halim Norhana
Published: November 2021

Purpose

In this work, the blends of poly(methyl methacrylate), PMMA and poly(methyl vinyl ether-alt-maleic acid monoethyl ester), PMVEMA-ES are studied as organic coatings to evaluate the impact of intermolecular hydrogen bonding on the physical and thermal characteristics of the prepared coatings.

Design/methodology/approach

PMMA (Mw = 120,000 g mol-1) was chosen as our binder material. Due to the low adhesion property of PMMA on polar substrates, it was blended with PMVEMA-ES, which contains polar –COOH groups, to improve the adhesion and thermal properties of the coatings by forming intermolecular hydrogen bonds. A cross-hatch adhesion test was carried out to evaluate the adhesion strength of different ratios of PMMA/PMVEMA-ES blends as coatings. In addition, changes in the glass-transition temperature, Tg as the composition varies were studied using Differential Scanning Calorimetry, DSC. Then, glossiness and hiding power tests were also conducted to evaluate the physical properties of the prepared coatings.

Findings

Upon a closer look at the DSC results, it was found that blends consisting of 12.5, 25.0 and 87.5 wt. % PMMA were completely compatible due to the presence of only a single Tg in their thermograms. Other blend compositions showed two distinct Tgs, indicating partial compatibility. Furthermore, the addition of PMVEMA-ES caused the Tg of PMMA to shift to lower temperatures, a strong indication of intermolecular hydrogen bonding interactions between the two components. From the cross-hatch adhesion results, the addition of PMVEMA-ES improved the adhesion properties of PMMA coating, except for blends consisting of 62.5 and 75.0 wt. % PMMA possibly due to the partial incompatibility between the two components. These findings were further corroborated with the results of glossiness and hiding power measurements. The superior result was seen for the blend consisting of 12.5 wt. % PMMA with strong adhesion property, high glossiness, compatibility and high translucency.

Practical implications

PMVEMA-ES can potentially be used as an adhesion promoter in PMMA-based coating formulations.

Originality/value

This is the first report on the properties of PMMA/PMVEMA-ES blends as coatings.
Parents’ literacy on mobile advertising aimed at children: a cross - cultural approach
Authors: Robayo-Pinzon Oscar , Rojas-Berrio Sandra , Núñez-Gómez Patricia , Miguélez-Juan Blanca , García-Béjar Ligia
Published: November 2021

Purpose

The use of mobile devices by children and adolescents is increasing significantly; therefore, it is relevant to research the level of advertising literacy (AL) of parents who act as mediators between children and mobile advertising. This study aims to explore the conceptual, moral and attitudinal dimensions of AL and its relationship with different styles of parental control.

Design/methodology/approach

A cross-sectional survey was applied simultaneously to a sample of parents with children between 5 and 16 years old in three Spanish-speaking countries: Mexico, Spain and Colombia. Participants from the three countries were recruited via online social media networks and were asked to fill in an online survey. A questionnaire, which has been adapted from previous literature to suit the mobile advertising context and the population of interest, was designed. Cross-country samples of varying sizes, with a predetermined quota of 200 participants for each country, were used. The total sample consisted of 1,454 participants.

Findings

Four factors of mobile AL were found, which, to a greater extent, correspond to the dimensions of AL proposed in the literature. The following are the dimensions that were identified: cognitive, moral, attitudinal and an emerging factor is known as “children’s perceived mobile AL.” Differences in parents’ perceived knowledge of mobile advertising, parental control styles and AL levels in the three countries were identified. Parents with an authoritative style were identified to have more knowledge than those with an indulgent style. Differences were also identified between countries concerning the amount of exposure that children have to mobile advertising, while no significant differences were found in the moral dimension.

Practical implications

Marketing practitioners and public policymakers must consider that parents differ in some dimensions of AL. Parents also seem to lack adequate knowledge about the advertising tools available to announcers that affect children and adolescents in a mobile communication environment. Therefore, government agencies should consider developing mobile digital media literacy programs for parents.

Originality/value

This paper explores the dimensions of AL applied to the mobile context and identifies the level of parental mobile AL in three Spanish-speaking countries, as well as the differences between these sub-samples concerning parental mobile AL profiles and parental control styles, thus expanding the literature on AL with a cross-cultural approach.
Wolbachia in scale insects: a distinct pattern of infection frequencies and potential transfer routes via ant associates
Authors: Sanaei Ehsan , Lin Yen‐Po , Cook Lyn G. , Engelstädter Jan
Published: November 2021

Wolbachia is one of the most successful endosymbiotic bacteria of arthropods. Known as the ‘master of manipulation’, Wolbachia can induce a wide range of phenotypes in its host that can have far‐reaching ecological and evolutionary consequences and may be exploited for disease and pest control. However, our knowledge of Wolbachia's distribution and the infection rate is unevenly distributed across arthropod groups such as scale insects. We fitted a distribution of within‐species prevalence of Wolbachia to our data and compared it to distributions fitted to an up‐to‐date dataset compiled from surveys across all arthropods. The estimated distribution parameters indicate a Wolbachia infection frequency of 43.6% (at a 10% prevalence threshold) in scale insects. Prevalence of Wolbachia in scale insects follows a distribution similar to exponential decline (most species are predicted to have low prevalence infections), in contrast to the U‐shaped distribution estimated for other taxa (most species have a very low or very high prevalence). We observed no significant associations between Wolbachia infection and scale insect traits. Finally, we screened for Wolbachia in scale insect's ecological associates. We found a positive correlation between Wolbachia infection in scale insects and their ant associates, pointing to a possible route of horizontal transfer of Wolbachia.
Reduction of the resistome risk from cow slurry and manure microbiomes to soil and vegetable microbiomes
Authors: Jauregi Leire , Epelde Lur , González Aitor , Lavín José Luis , Garbisu Carlos
Published: November 2021

In cow farms, the interaction between animal and environmental microbiomes creates hotspots for antibiotic resistance dissemination. A shotgun metagenomic approach was used to survey the resistome risk in five dairy cow farms. To this purpose, 10 environmental compartments were sampled: 3 of them linked to productive cows (fresh slurry, stored slurry, slurry‐amended pasture soil); 6 of them to non‐productive heifers and dry cows (faeces, fresh manure, aged manure, aged manure‐amended orchard soil, vegetables‐lettuces and grazed soil); and, finally, unamended control soil. The resistome risk was assessed using MetaCompare, a computational pipeline which scores the resistome risk according to possible links between antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and human pathogens. The resistome risk decreased from slurry and manure microbiomes to soil and vegetable microbiomes. In total (sum of all the compartments), 18,157 ARGs were detected: 24% related to ansamycins, 21% to multidrugs, 14% to aminoglycosides, 12% to tetracyclines, 9% to β‐lactams, and 9% to macrolide–lincosamide–streptogramin B. All but two of the MGE‐associated ARGs were only found in the animal dejections (not in soil or vegetable samples). Several ARGs with potential as resistome risk markers (based on their presence in hubs of co‐occurrence networks and high dissemination potential) were identified. As a precautionary principle, improved management of livestock dejections is necessary to minimize the risk of antibiotic resistance.
Salivary free light chains and salivary immunoglobulins as potential non‐invasive biomarkers in primary Sjögren's syndrome
Authors: Sandhya Pulukool , Kabeerdoss Jayakanthan , Christudoss Pamela , Arulraj Roy , Mandal Santosh Kumar , Janardana Ramya , Chebbi Pramod Prahlad , Ganesan Maya Pavalasseril , Mahasampath Gowri , Danda Debashish
Published: November 2021

Background

B cells contribute significantly to the pathogenesis of primary Sjögren's syndrome (pSS). Free light chains (FLCs) are generated during the production of immunoglobulins (Igs) and are surrogates of B cell activity. We hypothesized that salivary FLCs and salivary Igs could represent salivary gland inflammation and therefore, serve as biomarkers in pSS.

Methods

Patients >18 years old fulfilling the American College of Rheumatology / European League Against Rheumatism (EULAR) 2016 criteria for pSS and age‐matched healthy and disease controls (sicca non‐pSS, rheumatoid arthritis, systemic lupus erythematosus) were recruited for this cross‐sectional study. FLCs in saliva and serum were measured by immunoturbidimetry. Serum and salivary Igs were measured by nephelometry and enzyme‐linked immunosorbent assay, respectively. Area under the receiver operator characteristic curve was determined. The factors influencing the serum and salivary FLCs in pSS were determined using backward linear regression.

Results

A total of 78 patients with pSS, 76 healthy controls and 62 disease controls were recruited. Median EULAR SS disease activity index (interquartile range) was 1 (3.75). Serum FLCκ and FLCλ, salivary FLCλ, serum and salivary IgG, salivary IgM was significantly higher in the pSS group compared to the controls. Areas under the curve for salivary FLCλ, serum FLCκ, serum and salivary IgG were 0.75, 0.72, 0.78 and 0.77, respectively. Regression analysis showed that salivary FLCκ, salivary FLCλ and salivary IgG were associated with positive salivary gland histopathology. Use of immunosuppressants and glucocorticoids was associated with lower values of salivary parameters.

Conclusion

Salivary FLCλ and salivary IgG were significantly different between pSS and control groups and could be potential non‐invasive biomarkers in pSS. These findings should be confirmed in larger longitudinal studies.
Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion‐aided smoking cessation in African Americans? A moderated mediation analysis
Authors: Chenoweth Meghan J. , Peng Annie R. , Zhu Andy Z. X. , Cox Lisa Sanderson , Nollen Nikki L. , Ahluwalia Jasjit S. , Benowitz Neal L. , Knight Jo , Swardfager Walter , Tyndale Rachel F.
Published: November 2021

Background and Aims

CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion‐aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion‐aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex.

Design and Setting

Secondary analysis of a smoking cessation clinical trial (NCT00666978).

Participants/Cases

African American light smokers (≤ 10 cigarettes/day).

Interventions

Participants were treated with bupropion for 7 weeks.

Measurements

Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased‐function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow‐up (26 weeks).

Findings

Normal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample.

Conclusions

In African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.
Prenatal smoking, alcohol and caffeine exposure and maternal‐reported attention deficit hyperactivity disorder symptoms in childhood: triangulation of evidence using negative control and polygenic risk score analyses
Authors: Haan Elis , Sallis Hannah M. , Zuccolo Luisa , Labrecque Jeremy , Ystrom Eivind , Reichborn‐Kjennerud Ted , Andreassen Ole , Havdahl Alexandra , Munafò Marcus R.
Published: November 2021

Background and aims

Studies have indicated that maternal prenatal substance use may be associated with offspring attention deficit hyperactivity disorder (ADHD) via intrauterine effects. We measured associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms accounting for shared familial factors.

Design

First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner's substance use). The results were meta‐analysed across the cohorts. Secondly, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for smoking, alcohol and coffee consumption were regressed against ADHD symptoms. We triangulated the results across the two approaches to infer causality.

Setting

We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway.

Participants

Phenotype data available for children were: NALSPAC = 5455–7751; NGENR = 1537–3119; NMOBA = 28 053–42 206. Genotype data available for mothers was: NALSPAC = 7074; NMOBA = 14 583.

Measurements

A measure of offspring ADHD symptoms at age 7–8 years was derived by dichotomizing scores from questionnaires and parental self‐reported prenatal substance use was measured at the second pregnancy trimester.

Findings

The pooled estimate for maternal prenatal substance use showed an association with total ADHD symptoms [odds ratio (OR)SMOKING = 1.11, 95% confidence interval (CI) = 1.00–1.23; ORALCOHOL = 1.27, 95% CI = 1.08–1.49; ORCAFFEINE = 1.05, 95% CI = 1.00–1.11], while not for fathers (ORSMOKING = 1.03, 95% CI = 0.95–1.13; ORALCOHOL = 0.83, 95% CI = 0.47–1.48; ORCAFFEINE = 1.02, 95% CI = 0.97–1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD symptoms in MoBa). The PRS analyses were inconclusive for an association in ALSPAC or MoBa.

Conclusions

There appears to be no causal intrauterine effect of maternal prenatal substance use on offspring attention deficit hyperactivity disorder symptoms.
Transitioning to a high volume centre for Whipple pancreaticoduodenectomy in Western Australia: a single centre experience
Authors: Yau Ho‐Cing Victor , Lester Leanne , Johansson Mikael
Published: November 2021

Background

Pancreaticoduodenectomy (PD) is a curative resection for peri‐ampullary tumours associated with high rates of peri‐operative mortality and morbidity. The global trend is towards the establishment of high volume centres to reduce this. Australia faces geographical and population distribution challenges. Western Australia has centralized PD to two centres and we present the results of our institution in transitioning to a high volume centre.

Methods

This was a prospective database of all PDs performed at our institution from 1 January 2005 to 2 April 2020. Mortality outcomes included peri‐operative, 30 day and 90 day mortality. Complications, readmission and reinterventions at 90 days were recorded. The annual volume exceeded 20 from 2015. Outcomes prior to this were compared to characterize the transition to a high volume centre.

Results

One hundred and twenty eight PDs were performed in Period 1 (1 January 2005–31 December 2014) and 170 in the high volume Period 2 (1 January 2015–2 April 2020). There was a non‐statistically significant reduction in 90 day mortality in Period 2 (4.69% versus 1.18%, p = 0.06). There was a reduction in clinically significant post‐operative pancreatic fistulas (31.25% versus 11.76%, p < 0.05), delayed gastric emptying (39.84% versus 22.35%, p < 0.05) and transfusion requirements (56.25% versus 17.65%, p < 0.05). Severe complications (Clavien–Dindo III or greater) were reduced (30.47% versus 18.24%, p < 0.05).

Conclusion

Since establishing a high volume service, there was a reduction in post‐operative complications and 90 day mortality. This is in line with outcomes from international centres and demonstrates the improvements that can be made.
Dexamethasone‐mediated inhibition of Notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells
Authors: Ahmed Helal Mohammed Mohammed , Nimmagadda Subbaiah Chary , Al‐Matary Yahya S. , Fiori Maren , May Tobias , Frank Daria , Patnana Pradeep Kumar , Récher Christian , Schliemann Christoph , Mikesch Jan‐Henrik , Koenig Thorsten , Rosenbauer Frank , Hartmann Wolfgang , Tuckermann Jan , Dührsen Ulrich , Lanying Wei , Dugas Martin , Opalka Bertram , Lenz Georg , Khandanpour Cyrus
Published: November 2021

Acute myeloid leukaemia (AML) is a haematological malignancy characterized by a poor prognosis. Bone marrow mesenchymal stromal cells (BM MSCs) support leukaemic cells in preventing chemotherapy‐induced apoptosis. This encouraged us to investigate leukaemia‐BM niche‐associated signalling and to identify signalling cascades supporting the interaction of leukaemic cells and BM MSC. Our study demonstrated functional differences between MSCs originating from leukaemic (AML MSCs) and healthy donors (HD MSCs). The direct interaction of leukaemic and AML MSCs was indispensable in influencing AML cell proliferation. We further identified an important role for Notch expression and its activation in AML MSCs contributing to the enhanced proliferation of AML cells. Supporting this observation, overexpression of the intracellular Notch domain (Notch ICN) in AML MSCs enhanced AML cells’ proliferation. From a therapeutic point of view, dexamethasone treatment impeded Notch signalling in AML MSCs resulting in reduced AML cell proliferation. Concurrent with our data, Notch inhibitors had only a marginal effect on leukaemic cells alone but strongly influenced Notch signalling in AML MSCs and abrogated their cytoprotective function on AML cells. In vivo, dexamethasone treatment impeded Notch signalling in AML MSCs leading to a reduced number of AML MSCs and improved survival of leukaemic mice. In summary, targeting the interaction of leukaemic cells and AML MSCs using dexamethasone or Notch inhibitors might further improve treatment outcomes in AML patients.
Drought‐induced reductions in plant defenses: Insights from extrafloral nectaries in the Caatinga dry forest
Authors: Câmara Talita , Reis Daniela Queiroz de Assis , Arnan Xavier , de Oliveira Fernanda Maria Pereira , de Arruda Emília Cristina Pereira , Leal Inara Roberta
Published: November 2021

Extrafloral nectaries (EFNs) are anti‐herbivory defense‐related glands. We measured morphological and anatomical EFN traits in Pityrocarpa moniliformis trees along a rainfall gradient in Caatinga dry forest. We observed a reduction in structural EFN traits as rainfall decreased. We conclude that this reduction is a cost‐saving strategy, probably mediated by ants.
Physicochemical properties determining drug detection in skin
Authors: Bittremieux Wout , Advani Rohit S. , Jarmusch Alan K. , Aguirre Shaden , Lu Aileen , Dorrestein Pieter C. , Tsunoda Shirley M.
Published: November 2021

Chemicals, including some systemically administered xenobiotics and their biotransformations, can be detected noninvasively using skin swabs and untargeted metabolomics analysis. We sought to understand the principal drivers that determine whether a drug taken orally or systemically is likely to be observed on the epidermis by using a random forest classifier to predict which drugs would be detected on the skin. A variety of molecular descriptors describing calculated properties of drugs, such as measures of volume, electronegativity, bond energy, and electrotopology, were used to train the classifier. The mean area under the receiver operating characteristic curve was 0.71 for predicting drug detection on the epidermis, and the SHapley Additive exPlanations (SHAP) model interpretation technique was used to determine the most relevant molecular descriptors. Based on the analysis of 2561 US Food and Drug Administration (FDA)‐approved drugs, we predict that therapeutic drug classes, such as nervous system drugs, are more likely to be detected on the skin. Detecting drugs and other chemicals noninvasively on the skin using untargeted metabolomics could be a useful clinical advancement in therapeutic drug monitoring, adherence, and health status.
Co‐existence of BRAF V600E‐mutated malignant melanoma and BRAF V600E‐mutated Langerhans cell histiocytosis: A case report
Authors: Goto Keisuke , Yoshikawa Shusuke , Kiyohara Yoshio , Kukita Yoji , Miura Keiko , Oishi Takuma
Published: November 2021

Langerhans cell histiocytosis (LCH) is a neoplastic condition of Langerhans cells, and can be associated with other neoplasms, especially BRAF‐mutant hematological tumors and papillary thyroid carcinoma. Here we present the first case of co‐existing LCH and low cumulative sun damage (low‐CSD) melanoma, both of which had a BRAF V600E mutation. A 49‐year‐old man had a 45 × 43 × 15 mm semi‐pedunculated, pigmented tumor in his back but had no other systemic symptoms. Histopathology revealed a 2‐mm‐sized incidental focus of LCH within a large lesion of low‐CSD melanoma. Diffuse immunoexpression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was observed in the focus of LCH. Sanger sequencing with microdissection confirmed BRAF V600E mutation in the component of LCH. Interestingly, the advanced melanoma also harbored the same BRAF V600E mutation, although the significance of this tumor combination is still unknown.