bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of error-prone long-read whole-genome shotgun sequencing on characterizing reference microbiomes
Authors: Hu Yu , Fang Li , Nicholson Christopher , Wang Kai
Published: March 2020

Long-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length, and are therefore particularly relevant for microbiome studies. However, due to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (~99%) and completeness (~99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R=0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results demonstrate the feasibility to characterize complete microbial genomes and populations from error-prone Nanopore sequencing data, but also highlight necessary bioinformatics improvements for future metagenomics tool development.
The Evolution of Human Cancer Gene Duplications across Mammals
Authors: Tollis Marc , Schneider-Utaka Aika K. , Maley Carlo C.
Published: March 2020

Cancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species’ cancer gene copy number and it’s longevity, but not body size, contrary to predictions from Peto’s Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.
Fronto-striatal projections regulate approach-avoidance conflict
Authors: Loewke Adrienne C. , Minerva Adelaide R. , Nelson Alexandra B. , Kreitzer Anatol C. , Gunaydin Lisa A.
Published: March 2020

The dorsomedial prefrontal cortex (dmPFC) has been linked to approach-avoidance behavior and decision-making under conflict, key neural computations thought to be altered in anxiety disorders. However, the heterogeneity of efferent prefrontal projections has obscured identification of the specific top-down neural pathways regulating these anxiety-related behaviors. While the dmPFC-amygdala circuit has long been implicated in controlling reflexive fear responses, recent work suggests that this circuit is less important for avoidance behavior. We hypothesized that dmPFC neurons projecting to the dorsomedial striatum (DMS) represent a subset of prefrontal neurons that robustly encode and drive approach-avoidance behavior. Using fiber photometry recording during the elevated zero maze (EZM) task, we show heightened neural activity in prefrontal and fronto-striatal projection neurons, but not fronto-amydalar projection neurons, during exploration of the anxiogenic open arms of the maze. Additionally, through pathway-specific optogenetics we demonstrate that this fronto-striatal projection preferentially excites postsynaptic D1 receptor-expressing medium spiny neurons in the DMS and bidirectionally controls avoidance behavior. We conclude that this striatal-projecting subpopulation of prefrontal neurons regulates approach-avoidance conflict, supporting a model for prefrontal control of defensive behavior in which the dmPFC-amygdala projection controls reflexive fear behavior and the dmPFC-striatum projection controls anxious avoidance behavior. Our findings identify this fronto-striatal circuit as a valuable therapeutic target for developing interventions to alleviate excessive avoidance behavior in anxiety disorders.
Effects of transcranial direct current stimulation on brain networks related to creative thinking
Authors: Koizumi Koji , Ueda Kazutaka , Li Ziyang , Nakao Masayuki
Published: March 2020

Human creative thinking is unique and capable of generating novel and valuable ideas. Recent research has clarified the contribution of different brain networks (default mode network, DN; executive control network; salience network) to creative thinking. However, the effects of brain stimulation on brain networks during creative thinking and on creative performance have not been clarified. The present study was designed to examine the changes in functional connectivity (FC) and effective connectivity (EC) of the large-scale brain network, and the ensuing changes in creative performance, induced by transcranial direct current stimulation (tDCS). Fourteen healthy male students underwent two tDCS sessions, one with actual stimulation and one with sham stimulation, on two separate days. Participants underwent tDCS (anode over the left dorsolateral prefrontal cortex, DLPFC; cathode over the right inferior parietal lobule, IPL) for 20 minutes. Before and after the tDCS session, electroencephalography signals were acquired from 32 electrodes over the whole head during the creative thinking task. On FC analysis, the delta band FC between the posterior cingulate cortex and IPL significantly increased only after real stimulation. We also found that the change of flexibility score was significantly correlated with the change in (i) delta band FC between mPFC and left lateral temporal cortex (LTC) and (ii) alpha band FC between IPL and right LTC. On EC analysis, decreased flow within the DN (from left LTC to right IPL) was observed. Our results reveal that tDCS could affect brain networks, particularly the DN, during creative thinking and modulate key FC in the generation of flexible creative ideas.
Art marketing as an emerging area in an emerging market
Authors: Gürşen Aylin Ecem
Published: March 2020

Purpose

In this study, art is considered as a product subjected to marketing activities. In this context, this study aims to present a conceptual framework covering the research areas related to art marketing, the relation of art product with brand and consumer and how internet technologies can transform the art market. Finally, the situation of art marketing and its progressing process in a developing country and its potential horizons was discussed.

Design/methodology/approach

This study uses a literature review to present a conceptual framework about art marketing activities and their potential horizons in an emerging country.

Findings

Globalization, digitalization, democratization of access to art products, art becoming a subject for marketing, open up new horizons for western markets as well as for developing countries. Developing countries constitute a new market segment for the art market. Addressing the changes and the transformations in art market in terms of these markets will provide important opportunities for marketing researchers and practitioners.

Originality/value

This study elaborates the art marketing concept in a developing country. The marketing of art is a subject studied and elaborated mostly in western countries. It is thought that this study is differentiated in terms of addressing these dynamics from a developing country point of view.
Through the lens of choreographic process
Authors: deLahunta Scott , Vincent Jordan Beth
Published: March 2020

Purpose

This article aims to bring together and demonstrate overlaps in three different areas of reflexive research concerned variously with audiences for contemporary dance. These are: 1) artists reflecting on their own creative process and engaging other researchers in doing so, generating new insights and language as a result; 2) humanities-based dance studies and a small number of dance scholars reflecting on this “process turn” in dance; and 3) the field of empirical audience studies, drawing on a single study specifically interested in access to creative process. The goal is to propose how these areas might coexist and mutually inform each other.

Design/methodology/approach

The approach develops a three-fold framework where the multiple definitions and examples of reflexive research in dance-making processes coexist. It draws systematically on a detailed example of one self-reflective study conducted by a dance company into creative process, on new scholarly writing on the “process turn” in dance research and written analysis of a unique audience research project as well as related literature.

Findings

In conclusion, the article suggests that in whatever combination of different research approaches, empirical evidence is increasingly important. This risks tipping the balance towards a more utilitarian understanding, particularly in the area of audience studies. It is possible to counterbalance this with approaches from artists and scholars interested in understanding arrived at through reflexive study of creative practice.

Originality/value

The original contribution is to bring these three areas together for the first time to expose difference and overlaps and suggest that challenges of understanding (in a non-utilitarian form) could be mitigated through more systematic dialogue between them, such as presented here.
Analysis of memristor-based differentiating circuit
Authors: Kirilov Stoyan , Zaykov Ivan
Published: March 2020

Purpose

The purpose of this paper is to propose a detailed analysis of a memristor-based differentiating circuit with buffering amplifier, a capacitor and a memristor.

Design/methodology/approach

The analyzed circuit is based on a resistor–capacitor differentiating scheme together with a buffering operational amplifier. In the proposed circuit, the resistor is replaced by a memristor element.

Findings

The considered circuit and its classical analog are investigated using a rectangular pulse sequence as input signal. A comparison between the derived results is made. An advantage of the proposed memristor circuit is the shortened duration, i.e. higher localization, of the output pulses of rectangular input pulses to be derived.

Originality/value

Differentiating circuits are important modules in radio-electronics. Because of their widespread usage, it is of higher interest that their new potential schematic realizations are analyzed. For the computer simulations, a previously proposed modified nonlinear memristor model is used. Several of the best and widely used basic memristor models are applied as well.
Free upgrades with costly consequences
Authors: Polyakova Alexandra , Estes Zachary , Ordanini Andrea
Published: March 2020

Purpose

Companies often provide preferential treatment, such as free upgrades, to customers. The present study aims to identify a costly consequence of such preferential treatment (i.e. opportunistic behavior) and reveal which type of customer is most likely to engage in that negative behavior (i.e. new customers).

Design/methodology/approach

Across two experimental studies, the authors test whether preferential treatment increases customers’ entitlement, which in turn increases their propensity to behave opportunistically. Moderated mediation analysis further tests whether that mediated effect is moderated by customers’ prior relationship with the company.

Findings

Preferential treatment increases feelings of entitlement, which consequently triggers customers’ opportunistic behaviors. New customers are more likely to feel entitled after preferential treatment than repeat customers, and hence new customers are more likely to behave opportunistically. Preferential treatment also increases customers’ suspicion of the company’s motives, but suspicion was unrelated to opportunistic behavior.

Research limitations/implications

Future research may focus on other marketplace situations that trigger entitlement and explore whether multiple occurrences of preferential treatment provide different effects on consumers.

Practical implications

Present findings demonstrate that preferential treatment can evoke opportunistic behaviors among customers. The authors suggest that preferential treatment should be provided to customers who previously invested in their relationship with a company (i.e. repeat customers) rather than new customers.

Originality/value

Prior research has focused more on the ways companies prioritize their repeat customers than how they surprise their new customers. The present research instead examines preferential treatment based on customers’ relationship with a firm (i.e. both repeat and new customers) and demonstrates behavioral and contextual effects of entitlement.
Stress in paramedics: relationships with coping strategies and personality traits
Authors: Duschek Stefan , Bair Angela , Haux Sarah , Garrido Alba , Janka Amelie
Published: March 2020

Purpose

Though working in the ambulance service implies persistent confrontation with human suffering and exposure to significant work-related stressors, previous research revealed comparatively low self-reported stress in paramedics. This study investigated stress, personality traits, sensation seeking and resilience in paramedics. Moreover, the impact of psychological variables on individual differences in paramedics' stress burden was explored.

Design/methodology/approach

A convenience sample of 395 paramedics and 397 professionals from other disciplines completed the Perceived Stress Questionnaire, Stress Coping Style Questionnaire, Big Five Inventory, Sensation Seeking Scale and Resilience Scale. Multivariate group comparison and regression analysis were performed.

Findings

Compared to other professionals, paramedics reported lower stress burden, more positive and less negative coping strategies, lower neuroticism and higher extraversion, conscientiousness, openness, agreeableness, adventure seeking and resilience. In the regression analysis conducted on paramedics, positive coping, resilience, extraversion and conscientiousness negatively predicted perceived stress; negative coping and neuroticism were positive predictors.

Research limitations/implications

The cross-sectional design of the study limits the interpretability of the data.

Practical implications

Training in stress management and resilience should be core elements in the education of paramedics.

Originality/value

The findings confirm the notion of reduced stress burden and increased resilience in paramedics. Regarding personality traits, a pattern of emotional stability, conscientiousness, extraversion, prosocial attitudes and propensity to exciting experiences might characterize this group. Moreover, the use of adaptive coping strategies, high levels of resilience, extraversion and conscientiousness and low neuroticism are associated with lower stress burden in paramedics.
The “power few” of missing persons’ cases
Authors: Huey Laura , Ferguson Lorna , Kowalski Larissa
Published: March 2020

Purpose

The purpose of this paper is to test the “power few” concept in relation to missing persons and the locations from which they are reported missing.

Design/methodology/approach

Data on missing persons’ cases (n = 26,835) were extracted from the record management system of a municipal Canadian police service and used to create data sets of all of the reports associated with select repeat missing adults (n = 1943) and repeat missing youth (n = 6,576). From these sources, the five locations from which repeat missing adults and youth were most commonly reported missing were identified (“power few” locations). The overall frequency of reports generated by these locations was then assessed by examining all reports of both missing and repeat missing cases, and demographic and incident factors were also examined.

Findings

This study uncovers ten addresses (five for adults; five for youths) in the City from which this data was derived that account for 45 percent of all adults and 52 percent of all youth missing person reports. Even more striking, the study data suggest that targeting these top five locations for adults and youths could reduce the volume of repeat missing cases by 71 percent for adults and 68.6 percent for youths. In relation to the demographic characteristics of the study’s sample of adults and youths who repeatedly go missing, the authors find that female youth are two-thirds more likely to go missing than male youth. Additionally, the authors find that Aboriginal adults and youths are disproportionately represented among the repeat missing. Concerning the incident factors related to going missing repeatedly, the authors find that the repeat rate for going missing is 63.2 percent and that both adults and youths go missing 3–10 times on average.

Practical implications

The study results suggest that, just as crime concentrates in particular spaces among specific offenders, repeat missing cases also concentrate in particular spaces and among particular people. In thinking about repeat missing persons, the present research offers support for viewing these concerns as a behavior setting issue – that is, as a combination of demographic factors of individuals, as well as factors associated with particular types of places. Targeting “power few” locations for prevention efforts, as well as those most at risk within these spaces, may yield positive results.

Originality/value

Very little research has been conducted on missing persons and, more specifically, on how to more effectively target police initiatives to reduce case volumes. Further, this is the first paper to successfully apply the concept of the “power few” to missing persons’ cases.
Hidden danger
Authors: Violanti John M. , Fekedulegn Desta , Shi Mingming , Andrew Michael E.
Published: March 2020

Purpose

Law enforcement is a dangerous profession not only due to assaults, accidents and homicides but also due to health risks. This study examined trends in the national frequency and rate of law enforcement job-related illness deaths in the United States over a 22-year period (1997–2018).

Design/methodology/approach

Data were obtained from the National Law Enforcement Officers Memorial Fund (NLEOMF) on death frequencies related to health issues at work. Death rates were based on the total number of police officers in the United States [rate = (frequency/population at risk) × 100,000]. Trends were examined using standardized regression.

Findings

A total of 646 deaths were attributed to job-related illness. There was a significant upward trend in overall job-related illness deaths (frequency analyses: β = 0.88, p < 0.0001; rate analyses: β = 0.82, p ≤ 0.0001) mainly driven by a significant increase in 911 cancer deaths (frequency analyses: β = 0.88, p < 0.0001; rate analyses: β = 0.88, p ≤ 0.0001). Nearly 82 percent of circulatory deaths were from a heart attack, with an average death age of 46.5 years.

Research limitations/implications

Deaths were not included if they failed to meet medical requirements of the NLEOMF. The data are descriptive, do not estimate risk and should be interpreted cautiously.

Practical implications

Police wellness programs may help to reduce the danger of deaths associated with job-related illness.

Originality/value

This is among the first studies to examine frequency and rate of police health–related deaths due to job exposures.
Use of blockchain in designing smart city
Authors: Dewan Surbhi , Singh Latika
Published: March 2020

Purpose

A blockchain is a shared distributed ledger technology that stores the information of every transaction in the network. The blockchain has emerged with a huge diversity of applications not only in the economic but in the non-economical domain as well. Blockchain technology promises to provide a wide range of solutions to the problems faced during implementation of smart cities. It has the potential to build smart contracts more secure, thus eliminating the need for centralized authority.

Design/methodology/approach

This paper presents a proof-of-concept for a use case that uses an Ethereum platform to build a blockchain network to buy, sell or rent a property.

Findings

The findings of this study provide an opportunity to create novel decentralized scalable solutions to develop smart cities by enabling paperless transactions. There are enormous opportunities in this distributed ledger technology which will bring a revolutionary change in upcoming years.

Originality/value

The concept of blockchain along with smart contracts can be used as a promising technology for sharing services which is a common requirement in smart cities. All the blockchain transactions are stored in decentralized shared database. The transaction recorded in decentralized system is immutable, it cannot be altered and hence chance of forgery is negligible.
Improving physician research training: understanding the student perspective
Authors: Knapke Jacqueline , Haynes Erin N. , Vaughn Lisa M.
Published: March 2020

Purpose

Using a mixed-methods approach, this study evaluated a Master of Science program in Clinical and Translational Research (MSCTR) geared toward training physicians in research methodology. The purpose of this study is to allow trainees to articulate their expectations, needs and experiences in the MSCTR and to develop novel training methods and/or curriculum modifications to improve physician-scholar training.

Design/methodology/approach

The mixed-method study design with qualitative emphasis included interviews, participant journal entries and a survey. Interview and journal entry data were analyzed using a modified seven-stage hermeneutic analysis and survey data were analyzed using descriptive statistics.

Findings

Findings suggest three major areas for improvement, namely, curriculum, mentorship/relationships and instructional methods. Concluding recommendations to address these three areas include: make ongoing curriculum updates to provide a sequential pathway but also allow for flexibility, improve statistical training, invest in online courses and create a more structured mentorship program.

Originality/value

Extant research, though minimal, has evaluated clinical research training programs in terms of alumni productivity. However, this is the first study of its kind to examine a clinical research training program primarily qualitatively and from the perspective of its students and alumni.
Effectiveness of harvest strategies in achieving multiple management objectives in a multispecies fishery
Authors: Pascoe Sean , Hutton Trevor , Hoshino Eriko , Sporcic Miriana , Yamasaki Satoshi , Kompas Tom
Published: March 2020

Fisheries management is characterised by multiple objectives, some of which may be complementary, while others may require trade‐offs between outcomes. Balancing these objectives is made more complex in the case of multispecies and multigear fisheries. In this paper, we develop a bioeconomic model that captures the key elements of such a fishery to test a range of potential harvest strategies to provide insights into how economic target reference points could lead to both desirable and undesirable management outcomes (e.g. discards). The model is developed as a long‐run optimisation model to identify target reference points to achieve multispecies maximum economic yield, and a dynamic recursive optimisation model, which includes more realistic representation of fishers’ behaviour, such as discards and trading of under‐caught species quotas. The potential economic, social and ecological impacts are evaluated using data envelopment analysis (DEA). The results suggest that the use of proxy target reference points can result in short‐term economic benefits at the cost of slower stock recovery and higher discarding. Limiting the number of species subject to quota controls may also prove beneficial in multispecies fisheries, while ensuring quota markets are efficient is likely to produce benefits irrespective of the harvest strategy adopted.
Amino acids effects on heterocyclic amines formation and physicochemical properties in pan‐fried beef patties
Authors: Linghu Ziyi , Karim Faris , Taghvaei Mostafa , Albashabsheh Zaher , Houser Terry A. , Smith J. Scott
Published: March 2020

The effects of surface application of amino acids on the formation of heterocyclic amines (HCAs) and meat quality properties were evaluated in pan‐fried beef patties (230 °C/15 min). Tryptophan, lysine, leucine, and proline at three concentrations, 0.05%, 0.20%, and 0.50% (w/w), were tested. The meat crusts were analyzed for HCA content using liquid chromatography‐tandem mass spectrometry. Results showed that surface application of all tested amino acids significantly reduced total HCA content (P < 0.05), and the interaction of amino acid type and concentration significantly affected (P < 0.05) both individual and total HCA formation. Tryptophan at 0.50% reduced total HCAs the most (0.92 ng/g, 93% inhibition), followed by 0.50% lysine (1.94 ng/g, 84% inhibition), while leucine (3.95 ng/g, 64% inhibition) and proline (4.71 ng/g, 56% inhibition) were less effective at 0.50%. In addition, applying amino acids to meat surface significantly influenced (P < 0.05) pH and surface color change of beef crusts; particularly, lysine at 0.20% and 0.50% increased pH and a* (redness) but reduced b* (yellowness), while tryptophan and leucine at 0.50% increased L* (whiteness). No significant effect was observed on cooking loss. Adding amino acids at 0.50% affected (P < 0.05) formation of aldehydes and pyrazines (as the key flavor compounds of fried beef). Overall, the results of this study suggested that adding amino acids to ground beef patties could effectively mitigate mutagenic HCA formation during cooking.
Effects of Group‐Based Exercise on Flourishing and Stigma Consciousness among Older Adults: Findings from a Randomised Controlled Trial
Authors: Ruissen Geralyn R. , Liu Yan , Schmader Toni , Lubans David R. , Harden Samantha M. , Wolf Svenja A. , Rhodes Ryan E. , Dunlop William L. , Puterman Eli , Zumbo Bruno D. , Beauchamp Mark R.
Published: March 2020

Background

To examine the extent to which group‐based exercise programs, informed by self‐categorisation theory, result in improvements in psychological flourishing and reductions in age‐ and gender‐related stigma consciousness among older adults.

Methods

In the study, older adults (N = 485, ≥ 65 years) were randomised to similar age same gender (SASG), similar age mixed gender (SAMG), or “standard” mixed age mixed gender (MAMG) group‐based exercise programs. Flourishing and stigma consciousness were assessed on six occasions during the 24‐week intervention and represented secondary trial outcomes. Multilevel growth models examined the effects of the interventions on flourishing and stigma consciousness over time.

Results

Participants in the SASG and SAMG conditions demonstrated, on average, higher levels of flourishing, relative to the MAMG condition, over the course of the 24 weeks (p < .05). Additionally, participants demonstrated lower levels of age‐ and gender‐related stigma consciousness in both the SASG and SAMG conditions relative to the MAMG condition (p < .05). No time by group interaction effects were observed for either flourishing or stigma consciousness.

Conclusions

The results provide some support for the utility of group exercise programs, informed by self‐categorisation theory, to enhance psychological flourishing and reduce stigma consciousness among older adults.
A joint modeling approach for analyzing marker data in the presence of a terminal event
Authors: Zhou Jie , Chen Xin , Song Xinyuan , Sun Liuquan
Published: March 2020

In many medical studies, markers are contingent on recurrent events and the cumulative markers are usually of interest. However, the recurrent event process is often interrupted by a dependent terminal event, such as death. In this article, we propose a joint modeling approach for analyzing marker data with informative recurrent and terminal events. This approach introduces a shared frailty to specify the explicit dependence structure among the markers, the recurrent, and terminal events. Estimation procedures are developed for the model parameters and the degree of dependence, and a prediction of the covariate‐specific cumulative markers is provided. The finite sample performance of the proposed estimators is examined through simulation studies. An application to a medical cost study of chronic heart failure patients from the University of Virginia Health System is illustrated.
Type of disability, gender, and age affect school satisfaction: Findings from the UK Millennium Cohort Study
Authors: Arciuli Joanne , Emerson Eric
Published: March 2020

Background

Self‐reported school satisfaction is an important indicator of child and adolescent well‐being. Few studies have examined how disability, gender, and age affect school satisfaction.

Aim

We sought to determine whether the interaction between disability and gender with regard to self‐reported school satisfaction might be specific to particular types of disability and particular ages.

Methods

We undertook secondary analysis of Waves 5 and 6 of the UK’s Millennium Cohort Study (MCS), a nationally representative sample of children born 2000–2002. MCS is the fourth in the series of British birth cohort studies.

Result

At 11 years of age (n = 12,207), school satisfaction was significantly higher for girls and those without disabilities. By contrast, at 14 (n = 10,933), school satisfaction was significantly higher for boys and those without disabilities. Subsequent analyses of gender moderation of the association between disability and school satisfaction revealed a significant interaction between gender and disabilities associated with mental health and with dexterity, respectively, at 14 years but not at age 11.

Conclusion

These findings will inform future research endeavours, policy, and practice in psychology, education, and other areas associated with child development and disability.
Benchmarking analysis of deleterious SNP prediction tools on CYP2D6 enzyme
Authors: Ferreira Karla Cristina do Vale , Fialho Leonardo Ferreira , Franco Octávio Luiz , de Alencar Sérgio Amorim , Porto William Farias
Published: March 2020

The cytochrome P450 family is composed of hemeproteins involved in the metabolic transformation of endogenous and exogenous substances. The CYP2D6 enzyme is responsible for the metabolism of ~25% of clinically used drugs and is mainly expressed in the liver. The CYP2D6 gene is known to have a large number of single nucleotide polymorphisms (SNPs). Nevertheless, these variations could modify the CYP2D6 enzyme's function, resulting in poor metabolizing or ultra‐extensive metabolizing phenotypes, when metabolism is slower or accelerated, respectively. Currently, there are several computational tools for predicting functional changes caused by genetic variations. Here, we evaluated the predictive power of 20 web servers using a data set of 37 CYP2D6 missense SNPs (2 neutral and 35 deleterious) previously reported in literature with enzymatic assays with the purified protein. The results suggest that the most appropriate tools for CYP2D6 SNP prediction are SDM and PoPMuSiC, which could aid in the classification of novel missense SNPs in this gene, providing the identification of mutations potentially associated with drug metabolism and pointing new directions for precise medicine.
Writing resistance together
Authors: Ahonen Pasi , Blomberg Annika , Doerr Katherine , Einola Katja , Elkina Anna , Gao Grace , Hambleton Jennifer , Helin Jenny , Huopalainen Astrid , Johannsen Bjørn Friis , Johansson Janet , Jääskeläinen Pauliina , Kaasila‐Pakanen Anna‐Liisa , Kivinen Nina , Mandalaki Emmanouela , Meriläinen Susan , Pullen Alison , Salmela Tarja , Satama Suvi , Tienari Janne , Wickström Alice , Zhang Ling Eleanor
Published: March 2020

This piece of writing is a joint initiative by the participants in the Gender, Work and Organization writing workshop organized in Helsinki, Finland, in June 2019. This is a particular form of writing differently. We engage in collective writing and embody what it means to write resistance to established academic practices and conventions together. This is a form of emancipatory initiative where we care for each other as writers and as human beings. There are many author voices and we aim to keep the text open and dialogical. As such, this piece of writing is about suppressed thoughts and feelings that our collective picket line allows us to express. In order to maintain the open‐ended nature of the text, and perhaps also to retain some ‘dirtiness’ that is essential to writing, the article has not been language checked throughout by a native speaker of English.
Environmental drivers of taxonomic and functional diversity of ant communities in a tropical mountain
Authors: Castro Flávio Siqueira de , Da Silva Pedro Giovâni , Solar Ricardo , Fernandes Geraldo Wilson , Neves Frederico de Siqueira
Published: March 2020

We investigated the patterns of taxonomic (TD) and functional (FD) α and β‐diversities of ants in a mountainous landscape along three dimensions, namely one temporal (seasonal) and two spatial dimensions: between habitats – grassland and forest habitats (horizontal), and among elevation bands (vertical). In addition, we tested the effects of environmental variables (mean elevation and temperature, and normalised difference vegetation index – NDVI) on taxonomic and functional α‐ and β‐diversities.

β diversities among the two spatial dimensions are the main components of TD. Conversely, FD is almost entirely composed by the α‐diversity component, with a very low contribution of β‐diversity.

Regarding environmental drivers, the decrease in temperature caused by increased elevations and seasonal variations had a negative effect on taxonomic α‐diversity. There were no effects of environmental variables on ant functional α‐diversity.

Despite the high turnover of ant species occurring along spatial dimensions, the communities were functionally redundant. The changes in species richness and composition patterns in this mountain were strongly influenced by variables correlated with elevation and habitat structure.

Species composition changed across all dimensions, but the core traits and functions remained unchanged. Differences observed in the composition of ant communities over relatively short geographic distances highlight the importance to conserve the entire mountain, ensuring the maintenance of the ant diversity and associated ecosystem functions.
Insufficient CD100 shedding contributes to suppression of CD8+ T‐cell activity in non‐small cell lung cancer
Authors: Wang Hong‐Min , Zhang Xiao‐Hong , Ye Li‐Qun , Zhang Kai , Yang Ning‐Ning , Geng Shen , Chen Jing , Zhao Shun‐Xin , Yang Kang‐Li , Fan Fei‐Fei
Published: March 2020

CD100 is an immune semaphorin constitutively expressed on T‐cells. Matrix metalloproteinase (MMP) is an important mediator of membrane‐bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T‐cell function in non‐small cell lung cancer (NSCLC). sCD100 and MMP‐14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung‐resident CD8+ T‐cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP‐14 on mCD100 shedding for the regulation of non‐cytolytic and cytolytic functions of CD8+ T‐cells were also analysed in direct and indirect contact co‐culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8+ T‐cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8+ T‐cells compared with the non‐tumour site. Recombinant CD100 stimulation enhanced non‐cytolytic and cytolytic functions of CD8+ T‐cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8+ T‐cell activity. NSCLC patients had lower MMP‐14 in the serum and in BALF from the tumour site. Recombinant MMP‐14 mediated mCD100 shedding from CD8+ T‐cell membrane, and led to promotion of CD8+ T‐cell response in NSCLC patients. Overall, decreased MMP‐14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung‐resident CD8+ T‐cell activity in NSCLC.
Understanding factors influencing venous leg ulcer guideline implementation in Australian primary care
Authors: Weller Carolina D. , Richards Catelyn , Turnour Louise , Team Victoria
Published: March 2020

The aim of this study was to gain a better understanding of the venous leg ulcer (VLU) management in primary health care settings located in Melbourne metropolitan and rural Victoria, Australia. We explored health professionals' perspective on the use of the Australian and New Zealand Venous Leg Ulcer Clinical Practice Guideline (VLU CPG) to identify the main challenges of VLU CPG uptake in clinical practice. We conducted semi‐structured interviews with 15 general practitioners (GPs) and 20 practice nurses (PNs), including two Aboriginal health nurses. The Theoretical Domains Framework guided data collection and analysis. Data were analysed using a theory‐driven analysis. We found a lack of awareness of the VLU CPGs, which resulted in suboptimal knowledge and limited adherence to evidence‐based recommendations. Environmental factors, such as busy nature of clinical environment and absence of handheld Doppler ultrasound, as well as social and professional identity factors, such as reliance on previous experience and colleague's advice, influenced the uptake of the VLU CPGs in primary care. Findings of this study will inform development of interventions to increase the uptake of the VLU CPG in primary care settings and to reduce the evidence‐practice gap in VLU management by health professionals.
Glucocorticoid‐transactivated TSC22D3 attenuates hypoxia‐ and diabetes‐induced Müller glial galectin‐1 expression via HIF‐1α destabilization
Authors: Kanda Atsuhiro , Hirose Ikuyo , Noda Kousuke , Murata Miyuki , Ishida Susumu
Published: March 2020

Galectin‐1/LGALS1, a newly recognized angiogenic factor, contributes to the pathogenesis of diabetic retinopathy (DR). Recently, we demonstrated that glucocorticoids suppressed an interleukin‐1β‐driven inflammatory pathway for galectin‐1 expression in vitro and in vivo. Here, we show glucocorticoid‐mediated inhibitory mechanism against hypoxia‐inducible factor (HIF)‐1α‐involved galectin‐1 expression in human Müller glial cells and the retina of diabetic mice. Hypoxia‐induced increases in galectin‐1/LGALS1 expression and promoter activity were attenuated by dexamethasone and triamcinolone acetonide in vitro. Glucocorticoid application to hypoxia‐stimulated cells decreased HIF‐1α protein, but not mRNA, together with its DNA‐binding activity, while transactivating TSC22 domain family member (TSC22D)3 mRNA and protein expression. Co‐immunoprecipitation revealed that glucocorticoid‐transactivated TSC22D3 interacted with HIF‐1α, leading to degradation of hypoxia‐stabilized HIF‐1α via the ubiquitin‐proteasome pathway. Silencing TSC22D3 reversed glucocorticoid‐mediated ubiquitination of HIF‐1α and subsequent down‐regulation of HIF‐1α and galectin‐1/LGALS1 levels. Glucocorticoid treatment to mice significantly alleviated diabetes‐induced retinal HIF‐1α and galectin‐1/Lgals1 levels, while increasing TSC22D3 expression. Fibrovascular tissues from patients with proliferative DR demonstrated co‐localization of galectin‐1 and HIF‐1α in glial cells partially positive for TSC22D3. These results indicate that glucocorticoid‐transactivated TSC22D3 attenuates hypoxia‐ and diabetes‐induced retinal glial galectin‐1/LGALS1 expression via HIF‐1α destabilization, highlighting therapeutic implications for DR in the era of anti‐vascular endothelial growth factor treatment.
Endogenous ethanol produced by intestinal bacteria induces mitochondrial dysfunction in non‐alcoholic fatty liver disease
Authors: Chen Xiao , Zhang Zheng , Li Huan , Zhao Jiangtao , Wei Xiao , Lin Weishi , Zhao Xiangna , Jiang Aimin , Yuan Jing
Published: March 2020

Background and Aim

A causal relationship between changes of the gut microbiome and non‐alcoholic fatty liver disease (NAFLD) remains unclear. We demonstrated that endogenous ethanol (EnEth) produced by intestinal microbiota is likely a causative agent of NAFLD.

Methods

Two mutants with different alcohol‐producing abilities, namely, W14‐adh and W14Δadh, were constructed using the clinical high alcohol‐producing (HiAlc) Klebsiella pneumoniae strain W14 as a parent. Damage to hepatocytes caused by bacteria with different alcohol‐producing capacities was evaluated (EtOH group as positive control). The ultrastructural changes of mitochondria were assessed via transmission electron microscopy (TEM). Hepatic levels of mitochondrial reactive oxygen species (ROS), DNA damage, and adenosine triphosphate were examined.

Results

The results illustrated that steatosis was most severe in the W14‐adh group, followed by the W14 group, whereas the W14Δadh group had few fatty droplets. TEM and examination of related protein expression revealed that the mitochondrial integrity of HepG2 hepatocytes was considerably damaged in the EtOH and bacteria treatment groups. The impaired mitochondrial function in HepG2 hepatocytes was evidenced by reduced adenosine triphosphate content and increased mitochondrial ROS accumulation and DNA damage in the EtOH and bacteria treatment groups, especially the W14‐adh group. Meanwhile, liver injury and mitochondrial damage were observed in the hepatocytes of mice. The livers of mice in the W14‐adh group, which had the highest ethanol production, exhibited the most serious damage, similar to that in the EtOH group.

Conclusions

EnEth produced by HiAlc bacteria induces mitochondrial dysfunction in NAFLD.
Oxytocin release deficit and social cognition in craniopharyngioma patients
Authors: Brandi Marie‐Luise , Gebert Dorothea , Kopczak Anna , Auer Matthias K. , Schilbach Leonhard
Published: March 2020

Oxytocin is a neuropeptide known to affect social behaviour and cognition. Craniopharyngioma patients are considered to have an oxytocin‐release‐deficit caused by a rare tumour affecting the pituitary and/or the hypothalamus relevant for oxytocin production and release. To assess social behaviour and socio‐cognitive abilities in this patient group, we tested 13 patients and 23 healthy controls on self‐report questionnaires and an eye‐tracking paradigm including fast facial emotion recognition. Additionally, saliva oxytocin levels acquired before and after a physical stress induction were available from a previous study, representing the reactivity of the oxytocin system. The data revealed three major results. First, patients with an oxytocin‐release‐deficit scored higher on self‐reported autistic traits and reduced levels of hedonia for social encounters, although they showed no impairments in attributing mental states. Second, patients showed more difficulties in the fast emotion recognition task. Third, although automatic gaze behaviour during emotion recognition did not differ between groups, gaze behaviour was related to the reactivity of the oxytocin system across all participants. Taken together, these findings demonstrate the importance of investigating the reactivity of the oxytocin system and its relationship with social cognition. Our findings suggest that reduced emotional processing abilities may represent a pathological feature in a group of craniopharyngioma patients, indicating that this patient group might benefit from specific treatments within the social domain.
Health‐Related Quality of Life and Use of Hospital Services by Patients with Heart Failure and Their Family Caregivers: A Multicenter Case‐Control Study
Authors: Timonet‐Andreu Eva , Morales‐Asencio José Miguel , Alcalá Gutierrez Purificación , Cruzado Alvarez Concepcion , López‐Moyano Gracia , Mora Banderas Ana , López‐Leiva Inmaculada , Canca‐Sanchez José Carlos
Published: March 2020

Background

Heart failure (HF) causes high rates of hospital admissions. It is known that disease progression impacts the health‐related quality of life (HRQoL) of both patients and caregivers, yet to date, this finding is based on cross‐sectional studies with limited samples.

Objectives

The study aim is to analyze the relationship between HF patients’ use of hospital services (a proxy for disease progression) and the HRQoL of their family caregivers.

Methods

This work is a multicenter nested case‐control study on a population of patients admitted to hospitals in southern Spain due to heart failure. The sample comprised 530 patient‐caregiver dyads. Hospital admission data were retrospectively collected for the 5 years prior to inclusion in the study. Bivariate analyses and multivariate logistic regression were used to determine associations between patient deterioration and caregivers’ quality of life.

Results

Patients’ use of hospital services was associated with worsened quality of life for family caregivers, with an overall OR of 1.48 (95% CI: 1.23‐1.79). A positive correlation was found between patients’ perceptions of their physical health and the perceived mental health of caregivers (r = 0.127, p = 0.004) and between the perceived mental health of both (r = 0.291; p <0.0001).

Conclusions

Greater use of hospital services by patients with HF is an independent predictor of deterioration of family caregivers’ HRQoL. The physical and mental components of patients’ and their family caregivers’ HRQoL interact and influence each other. Additional factors, such as the nature and intensity of care provided, also determine the worsening of a family caregiver’s HRQoL.

Clinical Relevance

These results can be used to identify family caregivers of people with heart failure at risk of suffering a deterioration in their health‐related quality of life. Increased use of hospital services is an independent predictor of the deterioration of the family caregivers’ health‐related quality of life. Since clinical nurses are the main provider who gives support and education to family caregivers, they should be alert to this situation and individualize interventions to prevent this deterioration.