bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder
Authors: Lobentanzer Sebastian , Hanin Geula , Klein Jochen , Soreq Hermona
Published: April 2019

RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male- and female-originated cell lines, and connectomics of transcription factor- and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies disease-affected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases.
Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers
Authors: Noushmehr H , Sabedot TS , Malta TM , Nelson K , Snyder J , Wells M , deCarvalho A , Mukherjee A , Chitale D , Mosella M , Asmaro K , Robin A , Rosenblum M , Mikkelsen T , Rock J , Poisson LM , Lee I , Walbert T , Kalkanis S , Castro AV
Published: April 2019

Genome-wide DNA methylation profiling has shown that epigenetic abnormalities are biologically important in glioma and can be used to classify these tumors into distinct prognostic groups. Thus far, DNA profiling has required surgically resected glioma tissue; however, gliomas release tumoral material into biofluids, such as blood and cerebrospinal fluid, providing an opportunity for a minimally invasive testing. While prior studies have shown that genetic and epigenetic markers can be detected in blood or cerebrospinal fluid (e.g., liquid biopsy [LB]), there has been low sensitivity for tumor-specific markers. We hypothesize that the low sensitivity is due to the targeted assay methods. Therefore, we profiled the genome-wide CpG methylation levels in DNA of tumor tissue and cell-free DNA in serum of glioma patients, to identify non-invasive epigenetic LB (eLB) markers in the serum that reflect the characteristics of the tumor tissue. From the epigenetic profiles of serum from patients diagnosed with glioma (N=15IDHmutant and N=7IDHwildtype) and with epilepsy (N=3), we defined glioma-specific andIDH-specific eLB signatures (Glioma-eLB andIDH-eLB, respectively). The epigenetic profiles of the matched tissue demonstrate that these eLB signatures reflected the signature of the tumor. Through cross-validation we show that Glioma-eLB can accurately predict a patient’s glioma from those with other neoplasias (N=6 Colon; N=14 Pituitary; N=3 Breast; N=4 Lung), non-neoplastic immunological conditions (N=22 sepsis; N=9 pancreatic islet transplantation), and from healthy individuals (sensitivity: 98%; specificity: 99%). Finally,IDH-eLB includes promoter methylated markers associated with genes known to be involved in glioma tumorigenesis (PVT1andCXCR6). The application of the non-invasive eLB signature discovered in this study has the potential to complement the standard of care for patients harboring glioma.
Unequal interactions between alcohol and nicotine co-consumption: Suppression and enhancement of concurrent drug intake
Authors: DeBaker Margot C , Moen Janna K , Robinson Jenna M , Wickman Kevin , Lee Anna M
Published: April 2019

Rationale

Alcohol and nicotine addiction are prevalent conditions that co-occur. Despite the prevalence of co-use, factors that influence the suppression and enhancement of concurrent alcohol and nicotine intake are largely unknown.

Objectives

Our goals were to assess how nicotine abstinence and availability influenced concurrent alcohol consumption, and to determine the impact of quinine adulteration of alcohol on aversion resistant alcohol consumption and concurrent nicotine consumption.

Methods

Male and female C57BL/6J mice voluntarily consumed unsweetened alcohol, nicotine and water in a chronic 3-bottle choice procedure. In Experiment 1, nicotine access was removed for 1 week and re-introduced the following week, while the alcohol and water bottles remained available at all times. In Experiment 2, quinine (100-1000 μM) was added to the 20% alcohol bottle, while the nicotine and water bottles remained unaltered.

Results

In Experiment 1, we found that alcohol consumption and preference were unaffected by the presence or absence of nicotine access in both male and female mice. In Experiment 2a, we found that quinine temporarily suppressed alcohol intake and enhanced concurrent nicotine, but not water, preference in both male and female mice. In Experiment 2b, chronic quinine suppression of alcohol intake increased nicotine consumption and preference in female mice without affecting water preference, whereas it increased water and nicotine preference in male mice.

Conclusions

Quinine suppression of alcohol consumption enhanced the preference for concurrent nicotine preference in male and female mice, suggesting that mice compensate for the quinine adulteration of alcohol by increasing their nicotine preference.
Whole genome phylogenies reflect long-tailed distributions of recombination rates in many bacterial species
Authors: Sakoparnig Thomas , Field Chris , van Nimwegen Erik
Published: April 2019

Although homologous recombination is accepted to be common in bacteria, so far it has been challenging to accurately quantify its impact on genome evolution within bacterial species. We here introduce methods that use the statistics of single-nucleotide polymorphism (SNP) splits in the core genome alignment of a set of strains to show that, for many bacterial species, recombination dominates genome evolution. Each genomic locus has been overwritten so many times by recombination that it is impossible to reconstruct the clonal phylogeny and, instead of a consensus phylogeny, the phylogeny typically changes many thousands of times along the core genome alignment.

We also show how SNP splits can be used to quantify the relative rates with which different subsets of strains have recombined in the past. We find that virtually every strain has a unique pattern of frequencies with which its lineages have recombined with those of other strains, and that the relative rates with which different subsets of strains share SNPs follow long-tailed distributions. Our findings show that bacterial populations are neither clonal nor freely recombining, but structured such that recombination rates between different lineages vary along a continuum spanning several orders of magnitude, with a unique pattern of rates for each lineage. Thus, rather than reflecting clonal ancestry, whole genome phylogenies reflect these long-tailed distributions of recombination rates.
YAP controls cell migration and invasion through a Rho-GTPase switch
Authors: Shah Sagar R. , Ren Chunxiao , Tippens Nathaniel D. , Park JinSeok , Mohyeldin Ahmed , Wang Shuyan , Vela Guillermo , Martinez-Gutierrez Juan C. , Margolis Seth S. , Schmidt Susanne , Xia Shuli , Quiñones-Hinojosa Alfredo , Levchenko Andre
Published: April 2019

Delineating the mechanisms controlling the invasive spread of non-diseased and transformed cells is central to understanding diverse processes including cancer progression. Here, we found that Yes-associated protein (YAP), a central transcriptional regulator implicated in controlling organ and body size, modulated a Rho-GTPase switch that drives cellular migration by transactivating the Rac1-GEF protein TRIO through direct modulation of its intronic enhancer. Additionally, YAP and TRIO may promote invasive behavior through putative crosstalk with STAT3 signaling, a potential downstream target. Although we found this YAP-dependent infiltrative program in many cell types, it was particularly enhanced in a patient-specific manner in the most common malignant brain tumor, glioblastoma (GBM), where hyperactivation of the YAP, TRIO, and STAT3 signatures also conferred poor clinical outcome. Our analysis suggests that the YAP-TRIO-Rho-GTPase signaling network identified in this study is a ubiquitous regulator of invasive cell spread in both physiological and pathological contexts.
Dynamic chromosome rearrangements of the white-spotted bamboo shark shed light on cartilaginous fish diversification mechanisms
Authors: Zhang Yaolei , Gao Haoyang , Li Hanbo , Guo Jiao , Wang Meiniang , Xu Qiwu , Wang Jiahao , Lv Meiqi , Guo Xinyu , Liu Qun , Wei Likun , Ren Han , Xi Yang , Guo Yang , Zhao Qian , Pan Shanshan , Liu Chuxin , Sang Liping , Ding Xiaoyan , Wang Chen , Xiang Haitao , Song Yue , Liu Yujie , Liu Shanshan , Jiang Yuan , Shao Changwei , Shi Jiahai , Liu Shiping , Sabir Jamal S. M. , Sabir Mumdooh J. , Khan Muhummadh , Hajrah Nahid H. , Lee Simon Ming-Yuen , Xu Xun , Yang Huanming , Wang Jian , Fan Guangyi , Yang Naibo , Liu Xin
Published: April 2019

Cartilaginous fishes have a very high phenotypical diversity, a phenomenon for which the mechanisms have been largely unexplored. Here, we report the genome of the white-spotted bamboo shark as the first chromosome-level genome assembly of cartilaginous fish. Using this genome, we illustrated a dynamic chromosome rearrangement process in the bamboo shark, which resulted in the formation of 13 chromosomes, all of which were sparsely distributed with conserved genes and fast-evolving. We found the fast-evolving chromosomes to be enriched in immune-related genes with two chromosomes harboring the major genes for developing the single-chain antibody. We also found chromosome rearrangements to have resulted in the loss of two genes (p2rx3andp2rx5) which we also showed were involved in cartilage development using a CRISPR/Cas9 approach in zebrafish. Our study highlighted the significance of chromosome rearrangements in the phenotypical evolution of cartilaginous fishes, providing clues to inform further studies on mechanisms for fish diversification.
Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine
Authors: Yesylevskyy Semen , Rivel Timothée , Ramseyer Christophe
Published: April 2019

In this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown that permeability of the membranes increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results show that the membrane curvature is an important factor which should be considered during evaluation of drug translocation.

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tRNA dissociation from EF-Tu after GTP hydrolysis and Pirelease: primary steps and antibiotic inhibition
Authors: Warias Malte , Grubmüller Helmut , Bock Lars V.
Published: April 2019

In each round of ribosomal translation, the translational GTPase EF-Tu delivers a tRNA to the ribosome. After successful decoding, EF-Tu hydrolyses GTP, which triggers a conformational change that ultimately results in the release of the tRNA from EF-Tu. To identify the primary steps of these conformational changes and how they are prevented by the antibiotic kirromycin, we employed all-atom explicit-solvent Molecular Dynamics simulations of the full ribosome-EF-Tu complex. Our results suggest that after GTP hydrolysis and Pi release, the loss of interactions between the nucleotide and the switch 1 loop of EF-Tu allows domain D1 of EF-Tu to rotate relative to domains D2 and D3 and leads to an increased flexibility of the switch 1 loop. This rotation induces a closing of the D1-D3 interface and an opening of the D1-D2 interface. We propose that the opening of the D1-D2 interface, which binds the CCA-tail of the tRNA, weakens the crucial EF-Tu-tRNA interactions which lowers tRNA binding affinity, representing the first step of tRNA release. Kirromycin binds within the D1-D3 interface, sterically blocking its closure, but does not prevent hydrolysis. The resulting increased flexibility of switch 1 explains why it is not resolved in kirromycin-bound structures.
Ventriculo-arterial uncoupling is associated with VO2dependency in cardiac surgical patients
Authors: Guinot Pierre-Grégoire , Nguyen Maxime , Huette Pierre , Abou-Arab Osama , Bouhemad Belaid , Longrois Dan
Published: April 2019

Background

The clinical relevance of V-A (un)coupling in critically ill patients is under investigation. In this study we measured the association between V-A coupling and oxygen consumption (VO2) response in patients with acute circulatory instability following cardiac surgery.

Methods and results

Sixty-one cardio-thoracic ICU patients who received fluid challenge or norepinephrine infusion were included. Arterial pressure, cardiac output (CO), heart rate (HR), arterial (EA), and ventricular elastances (EV), total indexed peripheral resistance (TPRi) were assessed before and after hemodynamic interventions. VO2responders were defined as VO2increase > 15 %. V-A coupling was evaluated by the ratio EA/EV.Left ventricle stroke work (SW) to pressure volume area (PVA) ratio was calculated. In the overall population, 24 patients (39%) were VO2responders and 48 patients were uncoupled (i.e., EA/EVratio > 1.3): 1.9 (1.6-2.4). Most of the uncoupled patients were classified as VO2responders (28 of 31 patients, p=0.031). Changes in VO2were correlated with those of TPRi, EA, EA/EVand CO. EA/EVratio predicted VO2increase with an AUC of 0.76 [95 % CI: 0.62-0.87]; p=0.001. In multivariate and principal component analyses, EA/EVand SW/PVA ratios were independently associated (P < 0.05) with VO2response following interventions.

Conclusions

VO2responders were characterized by baseline V-A uncoupling due to high EAand low EV. Baseline EA/EVand SW/PVA ratios were associated with VO2changes independently of the hemodynamic intervention used. These results further underline the pathophysiological significance of V-A uncoupling in patients with hemodynamic instability.
Large-scale Lassa fever outbreaks in Nigeria: quantifying the association between disease reproduction number and local rainfall
Authors: Zhao Shi , Musa Salihu S. , Fu Hao , He Daihai , Qin Jing
Published: April 2019

Background

Lassa fever (LF) is increasingly recognized as an important rodent-borne viral hemorrhagic fever presenting a severe public health threat to sub-Saharan West Africa. In 2018, LF caused an unprecedented outbreak in Nigeria, and the situation was worse in 2019. This work aims to study the epidemiological features of outbreaks in different Nigerian regions and quantify the association between reproduction number (R) and local rainfall by using modeling analysis.

Methods

We quantify the infectivity of LF by the reproduction numbers estimated from four different growth models: the Richards, three-parameter logistic, Gompertz, and Weibull growth models. LF surveillance data are used to fit the growth models and estimate theRs and epidemic turning points (τ) in different regions at different time periods. Cochran’s Q test is further applied to test the spatial heterogeneity of the LF epidemics. A linear random-effect regression model is adopted to quantify the association betweenRand local rainfall with various lag terms.

Findings

Our estimatedRs for 2017-18 (1.33 with 95% CI: [1.29, 1.37]) and 2018-19 (1.29 with 95% CI: [1.27, 1.32]) are significantly higher than those for 2016-17 (1.23 with 95% CI: [1.22, 1.24]). We report spatial heterogeneity in theRs for outbreaks in different Nigerian regions. For the association between rainfall andR, we find that a one unit (mm) increase in average rainfall over the past 7 months could cause a 0.62% (95% CI: [0.20%, 1.05%]) rise inR.

Conclusion

There is significant spatial heterogeneity in the LF epidemics in different Nigerian regions. We report clear evidence of rainfall impacts on LF outbreaks in Nigeria and quantify the impact.
Internationalization of Bosnian black coffee brand: bringing the traditional coffee experience to the world
Authors: Kadić-Maglajlić Selma , Arslanagic-Kalajdzic Maja
Published: April 2019

Learning outcomes

The teaching objectives of the case study are to provide students with an understanding of how strategic marketing tools are applied in an international marketing context and how brands, especially brands that come from emerging markets, are introduced and managed within modern versus traditional trade (e.g. ethnic shops).

Case overview/synopsis

This case illustrates the challenges and opportunities related to the introduction of a brand to a new market wherein the product (traditional coffee), although part of a very well-developed product category (coffee), may have been new to consumers in the new market. The brand itself, Zlatna džezva, is a flagship brand in its home country (Bosnia and Herzegovina) within a developing market. However, both the brand and the traditional coffee experience are relatively unknown to other markets. The case study focuses on Vispak’s CEO and CMO who are contemplating their next business move in the new market. Finally, the Dutch market and consumers are presented to facilitate the process of segmentation, targeting and positioning for students. The case study concludes with a task and dilemma for managers of the company.

Complexity academic level

This case could be used in a variety of undergraduate level classes, depending on what the instructor wishes to emphasize. The authors use the case for following courses: principles of marketing, marketing management and international marketing. In all courses, the case is allowing students to obtain the greater overview of the scope of the strategic marketing decision-making. Before starting with case analysis, students should have some familiarity with central marketing issues and concepts, specifically related to analysis of environment, segmentation-targeting-positioning, product and brand management.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS: 8: Marketing.
Frontline employee authenticity and its influence upon adaptive selling outcomes
Authors: Yoo Jaewon , Arnold Todd
Published: April 2019

Purpose

Frontline employee authenticity has been investigated in relation to both potentially positive and negative outcomes, but largely from the employee perspective. The current paper aims to investigate frontline authenticity in a sales/service context from the customer perspective, specifically examining the influence of adaptive selling in relation to a customer’s perception of salesperson authenticity. Effects on customer’s perceptions of final benefits and value are examined.

Design/methodology/approach

Survey data collected from customers of an insurance firm in South Korea were used to investigate the proposed model. Customer perceptions of salesperson adaptive selling, authenticity, key benefits delivered and organizational value provision were all captured.

Findings

The results suggest that authenticity does indeed positively influence perceptions of beneficial outcomes related to a transaction with a salesperson. These benefits then fully mediate the linkage from adaptive selling to a customer’s perceived value, gained from the salesperson’s organization.

Research limitations/implications

The collection of data from only the customer’s perspective is both a strength and a weakness. Although all of the key variables investigated are important to evaluate via the lens of the customer, such a data collection always introduces the potential problem of common method bias.

Practical implications

Managers should be aware of the importance of a salesperson behaving in an authentic manner. Although many frontline contexts have desired and scripted narratives for interacting with customers, deriving key benefits through the customers’ eyes may come more strongly by allowing the frontline employee to act naturally.

Originality/value

Authenticity has been investigated in managerial and brand contexts, but an understanding of its importance in a frontline context is in its early stages. Similarly, the importance of understanding conditions that moderate the effectiveness of adaptive selling is consistent with calls in the literature.
The responsibilities of the project owner in benefits realization
Authors: Zwikael Ofer , Meredith Jack R. , Smyrk John
Published: April 2019

Purpose

Recent research has proposed the position of a project owner as the individual accountable for realizing target benefits. However, there is a lack of understanding in the literature of this role – in particular, the specific responsibilities of the project owner that can enhance benefits realization and operations performance. The paper aims to discuss this issue.

Design/methodology/approach

The paper identifies these responsibilities in practice through two studies – a qualitative study, which includes interviews with senior executives who fund projects, and an in-depth longitudinal case study, which describes a company that continuously realizes the benefits from its projects.

Findings

The results suggest that a project owner should have 22 key responsibilities across four project phases and that an operations manager is often the most suitable candidate to fulfill this role in operations improvement projects. When performing these project responsibilities effectively, operations managers enhance benefits realization and operations improvement. Finally, the paper proposes five hypotheses for future research.

Originality/value

Based on agency theory, the paper increases our knowledge of the role of the project owner in practice. This new knowledge can enhance the realization of target benefits from projects and ensure a smooth transition from the project to the operations environment.
An automated quantitative content analysis process for humanitarian logistics research
Authors: Kunz Nathan
Published: April 2019

Purpose

Access to high-quality data is a challenge for humanitarian logistics researchers. However, humanitarian organizations publish large quantities of documents for various stakeholders. Researchers can use these as secondary data, but interpreting big volumes of text is time consuming. The purpose of this paper is to present an automated quantitative content analysis (AQCA) approach that allows researchers to analyze such documents quickly and reliably.

Design/methodology/approach

Content analysis is a method to facilitate a systematic description of documents. This paper builds on an existing content analysis method, to which it adds automated steps for processing large quantities of documents. It also presents different measures for quantifying the content of documents.

Findings

The AQCA approach has been applied successfully in four papers. For example, it can identify the main theme in a document, categorize documents along different dimensions, or compare the use of a theme in different documents. This paper also identifies several limitations of content analysis in the field of humanitarian logistics research and suggests ways to mitigate them.

Research limitations/implications

The AQCA approach does not provide an exhaustive qualitative analysis of documents. Instead, it aims to analyze documents quickly and reliably to extract the contents’ quantifiable aspects.

Originality/value

Although content analysis has been used in humanitarian logistics research before, no paper has yet proposed an automated, step-by-step approach that researchers can use. It also is the first study to discuss specific limitations of content analysis in the context of humanitarian logistics.
Preparation and characterisation of modified VAc-VeoVa10 latex
Authors: Gong Yilu , Shao Tantan , Wang Xiuming , Zhang Xin , Sun Zhijuan , Chen Lijun
Published: April 2019

Purpose

Fluorine and silicon materials have received the keen attention of many researchers because of their water repellency and low surface free energy. The purpose this study was to prepare vinyl acetate (VAc)-vinyl ester of neodecanoic acid (VeoVa 10) copolymer latex modified with fluorine and silicone monomer, which is emulsified with the novel surfactants of disodium laureth sulfosuccinate (MES) and octylphenol polyoxyethylene ether (OP-10).

Design/methodology/approach

A series of modified latices containing fluorine-silicon have been prepared by semi-continuous seeded emulsion polymerisation of mixed monomers of VAc, VeoVa10, hexafluorobutylmethacrylate (HFMA) and vinyltriethoxysilane (VTES) and emulsified by novel surfactants of MES and OP-10.

Findings

The optimum conditions for preparing the modified latex is as follows: the amount of the surfactant was 4.0 Wt.% and the mass ratio of the anionic and nonionic surfactant was 3:1; the dosage of initiator was 0.4 Wt.% and the mass ratio of the main monomer was 3:1; and the amounts of VTES and HFMA were 2.0 and 6.0 Wt.%, respectively. In comparison with the conventional latex, the hydrophobicity of latex film was improved further.

Originality/value

The modified p (VAC-VeoVa) latex is prepared via semi-continuous seeded emulsion polymerisation, which is emulsified with the novel mixed surfactants of MES and OP-10. There are two main innovations. One is that the novel p (VAC-VeoVa) latex containing fluorine-silicon is prepared successfully. The other is that the emulsifier is composed of the novel mixed surfactants of MES and OP-10.
Medicaid Accountable Care Organizations in Four States: Implementation and Early Impacts
Authors: RUTLEDGE REGINA I. , ROMAIRE MELISSA A. , HERSEY CATHERINE L. , PARISH WILLIAM J. , KISSAM STEPHANIE M. , LLOYD JENNIFER T.
Published: April 2019

Policy Points

Maine, Massachusetts, Minnesota, and Vermont leveraged State Innovation Model awards to implement Medicaid accountable care organizations (ACOs). Flexibility in model design, ability to build on existing reforms, provision of technical assistance to providers, and access to feedback data all facilitated ACO development. Challenges included sustainability of transformation efforts and the integration of health care and social service providers.

Early estimates showed promising improvements in hospital‐related utilization and Vermont was able to reduce or slow the growth of Medicaid costs.

These states are sustaining Medicaid ACOs owing in part to provider support and early successes in generating shared savings. The states are modifying their ACOs to include greater accountability and financial risk.

Context

As state Medicaid programs consider alternative payment models (APMs), many are choosing accountable care organizations (ACOs) as a way to improve health outcomes, coordinate care, and reduce expenditures. Four states (Maine, Massachusetts, Minnesota, and Vermont) leveraged State Innovation Model awards to create or expand Medicaid ACOs.

Methods

We used a mixed‐methods design to assess achievements and challenges with ACO implementation and the impact of Medicaid ACOs on health care utilization, quality, and expenditures in three states. We integrated findings from key informant interviews, focus groups, document review, and difference‐in‐difference analyses using data from Medicaid claims and an all‐payer claims database.

Findings

States built their Medicaid ACOs on existing health care reforms and infrastructure. Facilitators of implementation included allowing flexibility in design and implementation, targeting technical assistance, and making clinical, cost, and use data readily available to providers. Barriers included provider concerns about their ability to influence patient behavior, sustainability of provider practice transformation efforts when shared savings are reinvested into the health system and not shared with participating clinicians, and limited integration between health care and social service providers. Medicaid ACOs were associated with some improvements in use, quality, and expenditures, including statistically significant reductions in emergency department visits. Only Vermont's ACO demonstrated slower growth in total Medicaid expenditures.

Conclusions

Four states demonstrated that adoption of ACOs for Medicaid beneficiaries was both possible and, for three states, associated with some improvements in care. States revised these models over time to address stakeholder concerns, increase provider participation, and enable some providers to accept financial risk for Medicaid patients. Lessons learned from these early efforts can inform the design and implementation of APMs in other Medicaid programs.
Crop and Livestock Diversity Cultivating Gastronomic Potential, Illustrated by Sensory Profiles of Landraces
Authors: Westling Magnus , Leino Matti W. , Nilsen Asgeir , Wennström Stefan , Öström Åsa
Published: April 2019

Landraces, that is, crop and livestock not improved by formal breeding, are scarce in the industrialized world and are mainly maintained ex situ for breeding purposes. The natural biodiversity of these landraces may contribute to securing food production that can adapt to a changing climate, crop pathogens, diseases, and other agricultural challenges. In addition, landraces might also possess unique quality traits. Our aim is to take the idea of crop and livestock diversity further by connecting flavor differences of different landraces and varieties, with gastronomic applications. Do landraces provide a creative possibility of using distinct sensory characteristics to create new dishes and food products and/or to optimize recipes by finding the right variety for existing dishes and food products? This study suggests that apple, pea, pear, and poultry landraces, apart from being valuable in terms of biodiversity in sustainable food systems, also possess unique and distinct gastronomic potential. For example, citrus odors in apples, nutty taste in gray peas, astringent taste in pears, and high odor intensity of stable in poultry is of culinary relevance when working with apple juice, plant‐based alternatives to meat, poached pears, and roasted rooster, respectively. To fully explore, and take advantage of, the gastronomic potential landraces possess, additional studies are needed in order to find suitable cooking methods and development of recipes.

Practical Application

Seeking to increase market interest for landraces, highlighting gastronomic values could stimulate higher demand and, in turn, contribute to larger and more resilient populations preserved in situ. Specifically, the paper is of use to (I) crop and livestock producers and food companies who wish to provide products with greater sensory variation, (II) individuals, companies, and organizations with the aim to increase landrace demand and/or preservation, and (III) breeders and genetic engineers managing genetic traits of landraces and other varieties.
Nicotine Produces a High‐Approach, Low‐Avoidance Phenotype in Response to Alcohol‐Associated Cues in Male Rats
Authors: Loney Gregory C. , Angelyn Hailley , Cleary Liam M. , Meyer Paul J.
Published: April 2019

Background

Nicotine and alcohol use are highly comorbid. Modulation of drug‐paired extrinsic and intrinsic cues likely plays a role in this interaction, as cues can acquire motivational properties and augment drug seeking. The motivational properties of cues can be measured through Pavlovian conditioning paradigms, in which cues either elicit approach following pairing with the reinforcing properties of alcohol or elicit avoidance following pairing with the aversive consequences of alcohol. The present experiments tested whether nicotine would enhance the incentive properties of an appetitive ethanol (EtOH) cue and diminish the avoidance of an aversive EtOH cue in Pavlovian paradigms.

Methods

In experiment 1, male Long‐Evans rats with or without prior chronic intermittent access to EtOH were administered nicotine or saline injections prior to Pavlovian conditioned approach (PavCA) sessions, during which conditioned approach to the cue (“sign‐tracking”) or the EtOH delivery location (“goal‐tracking”) was measured. In experiment 2, male Long‐Evans rats were administered nicotine or saline injections prior to pairing a flavor cue with increasing doses of EtOH (i.p.) in an adaptation of the conditioned taste avoidance (CTA) paradigm.

Results

Results from PavCA indicate that, regardless of EtOH exposure, nicotine enhanced responding elicited by EtOH‐paired cues with no effect on a similar cue not explicitly paired with EtOH. Furthermore, nicotine reduced sensitivity to EtOH‐induced CTA, as indicated by a rightward shift in the dose–response curve of passively administered EtOH. The ED50, or the dose of EtOH that produced a 50% reduction in intake relative to baseline, was significantly higher in nicotine‐treated rats compared to saline‐treated rats.

Conclusions

We conclude that nicotine increases the approach and diminishes the avoidance elicited by Pavlovian cues paired, respectively, with the reinforcing and aversive properties of EtOH consumption in male rats. As such, nicotine may enhance alcoholism liability by engendering an attentional bias toward cues that predict the reinforcing outcomes of drinking.
Short and sporadic injecting cessation episodes as predictors of incident hepatitis C virus infection: findings from a cohort study of people who inject drugs in Montréal, Canada
Authors: Fortier Emmanuel , Artenie Andreea Adelina , Zang Geng , Jutras‐Aswad Didier , Roy Élise , Grebely Jason , Bruneau Julie
Published: April 2019

Background and Aims

For most people who inject drugs (PWID), drug injecting follows a dynamic process characterized by transitions in and out of injecting. The objective of this investigation was to examine injecting cessation episodes of 1–3‐month duration as predictors of hepatitis C virus (HCV) acquisition.

Design

Cohort study.

Setting

Montréal, Canada.

Participants

A total of 372 HCV‐uninfected (HCV RNA‐negative, HCV antibody‐positive or ‐negative) PWID (mean age = 39.3 years, 82% male, 45% HCV antibody‐positive) enrolled between March 2011 and June 2016.

Measurements

At 3‐month intervals, participants completed an interviewer‐administered questionnaire and were tested for HCV particles (HCV RNA). At each visit, participants indicated whether they injected in each of the past 3 months (defined as three consecutive 30‐day periods). Injecting cessation patterns were evaluated on a categorical scale: persistent injecting (no injecting cessation in the past 3 months), sporadic injecting cessation (injecting cessation in 1 of 3 or 2 of 3 months) and short injecting cessation (injecting cessation in 3 of 3 months). Their association with HCV infection risk was examined using Cox regression analyses with time‐dependent covariates, including age, gender, incarceration, opioid agonist treatment and other addiction treatments.

Findings

At baseline, 61, 26 and 13% of participants reported persistent injecting, sporadic injecting cessation and short injecting cessation, respectively. HCV incidence was 7.5 per 100 person‐years [95% confidence interval (CI) = 5.9–9.5; 916 person‐years of follow‐up]. In adjusted Cox models, sporadic injecting cessation and short injecting cessation were associated with lower risks of incident HCV infection compared to persistent injecting (adjusted hazard ratios = 0.56, 95% CI = 0.30–1.04 and 0.24, 95% CI = 0.09–0.61), respectively.

Conclusion

Short and sporadic injecting cessation episodes were common among a cohort of people who inject drugs in Montréal, Canada. Injecting cessation episodes appear to be protective against hepatitis C virus acquisition, particularly when maintained for at least 3 months.
Generalist trophic ecology in a changing habitat: The case of the four‐striped mouse in a woody‐encroached savannah
Authors: Lloyd Kyle J. , Vetter Susanne
Published: April 2019

Trophic generalists tolerate greater habitat change than specialists; however, few studies explore how generalist trophic ecology is affected. We established how the trophic ecology of an extreme generalist, Rhabdomys pumilio, changed in relation to a directionally changing woody‐encroached savannah in Eastern Cape, South Africa by investigating (a) foraging behaviour, (b) trophic niche and (c) feedback effects. (a) Giving‐up densities showed that R. pumilio preferred foraging in subcanopy microhabitat during the night as a result of lower thermoregulatory costs, but had similar preferences for sub‐ and intercanopy microhabitats during the day. (b) An isotope analysis revealed that the dietary composition and trophic niche occupied by R. pumilio differed among tree canopy cover levels (0%, 30% and 80%), which appeared to be related to changes in C4 grass material and invertebrate availability. (c) Artificial seed patches suggested that R. pumilio was a potentially important postdispersal seed predator of the woody‐encroaching species, Vachellia karroo. Thus, an increase in tree canopy cover altered the trophic niche of R. pumilio by reducing foraging costs at night and providing alternative food resources in terms of availability and source. These findings demonstrate how an extreme generalist adapted to human‐induced habitat change through changes in its trophic ecology.
Doctors’ rural practice self‐efficacy is associated with current and intended small rural locations of practice
Authors: Bentley Megan , Dummond Nadine , Isaac Vivian , Hodge Heidi , Walters Lucie
Published: April 2019

Objective

Key factors which positively influence recruitment and retention of doctors to rural practice include rural background and positive rural training experience. Despite this knowledge, there is no well‐established conceptual framework to explain how these factors influence intention. The aim of this study was to consider rural practice self‐efficacy and its influence on rural career choice by doctors. Questions relating to self‐efficacy were formulated using Bandura's four proposed sources of self‐efficacy, which include mastery experiences, vicarious experience, social persuasion and emotional and physical response to experiences.

Design

Cross‐sectional study.

Setting and participants

Medical school graduates from Flinders University, who completed a rural year as a part of the clinical component of the course between 1997 and 2015.

Main outcome measures

Rural self‐efficacy; current and intended location of practice in small rural communities (<25 000 people).

Result

It was found that 28.5% of participants were currently working in communities of <25 000 people. Levels of intent for future small town rural practice were consistent across career stages after internship. Higher rural practice self‐efficacy scores were found in doctors working in smaller towns (<25 000) and small communities (<10 000). Higher self‐efficacy was also associated with rural background, more senior career status, earlier speciality decision time and smaller expectation‐experience gap.

Conclusion

An independent association exists between rural self‐efficacy and intention to remain or return to small rural practice. The article offers rural clinical schools the opportunity to consider how they can influence future rural career outcomes.
Exposure‐response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components
Authors: Bastida Carla , Soy Dolors , Ruiz‐Esquide Virginia , Sanmartí Raimon , Huitema Alwin D.R.
Published: April 2019

Aims

Tocilizumab has a direct effect on inflammatory markers. Therefore, composite measures for disease activity assessment in rheumatoid arthritis (RA) using these inflammatory markers may not be suitable for tocilizumab treatment. We used a modelling approach to describe the tocilizumab exposure‐response relationship and to investigate the different dynamics of the individual components of the routinely used continuous composite measures.

Methods

Pharmacokinetic (PK), clinical and laboratory data were obtained from a prospective, observational, single‐centre study involving 35 subjects with RA treated with intravenous tocilizumab. A population PK/pharmacodynamic analysis was performed using nonlinear mixed effects models.

Results

The population for model development comprised 1086, 1083 and 1082 observations calculated with the disease activity score based on 28 joint (DAS28) and the simplified and clinical disease activity scores (SDAI, CDAI). The tocilizumab exposure‐response relationship was described with an indirect‐response model. Two main groups of individual components were identified based on their different dynamics under tocilizumab treatment: (i) tender and swollen joint counts and patient and evaluator global assessment showed a slower decrease of their baseline value (half‐life: 4.6 weeks, RSE: 24%) and the need for higher serum drug concentration (EC50: 4.60 μg/mL, RSE: 103%, IIV: 359%) than (ii) C‐reactive protein and erythrocyte sedimentation rate (half‐life: 2.3 weeks, RSE 19%; EC50: 0.878 μg/mL, RSE: 41%, IIV: 238%).

Conclusion

Our study confirms a different dynamics of the individual components of the most frequently used continuous composite measures under tocilizumab treatment which should be taken into account to avoid misassessment of disease activity.
Feeling like a burden to others and the wish to hasten death in patients with advanced illness: A systematic review
Authors: Rodríguez‐Prat Andrea , Balaguer Albert , Crespo Iris , Monforte‐Royo Cristina
Published: April 2019

Studies that have explored the wish to hasten death (WTHD) in patients with advanced illness have found that the feeling of being a burden may trigger WTHD. Research suggests that both the feeling and the wish are indicators of multidimensional suffering whose meaning may depend on the patient's biographical background. Therefore, we carried out a systematic review and meta‐ethnography. Fourteen qualitative studies, reported in 16 articles, met the inclusion criteria. The analysis identified two themes: the personal and social dimensions that could help to explain the feeling of being a burden in these patients. These dimensions reveal how this feeling is linked to physical, psychological/emotional, existential and social factors. The feeling of being a burden cannot be understood without considering patients’ personal interpretation of their dependency or care needs, and hence it is also necessary to understand their biographical background. Such an understanding is crucial to inform clinical policies based on the moral duty to provide all patients with humane care.
Patient and public involvement: Two sides of the same coin or different coins altogether?
Authors: McCoy Matthew S. , Warsh Jonathan , Rand Leah , Parker Michael , Sheehan Mark
Published: April 2019

Patient and public involvement (PPI) has gained widespread support in health research and health policy circles, but there is little consensus on the precise meaning or justifications of PPI. We argue that an important step towards clarifying the meaning and justification for PPI is to split apart the familiar acronym and draw a distinction between patient and public involvement. Specifically, we argue that patient involvement should refer to the practice of involving individuals in health research or policy on the basis of their experience with a particular condition, while public involvement should refer to the practice of involving individuals in health policy or research based on their status as members of a relevant population. Analyzing cases from the UK, Australia, and the USA, we show how our proposed distinction can deliver much needed clarity to conversations on PPI, while guiding the development and evaluation of future PPI‐based policies.
Pathophysiology of atopic dermatitis
Authors: Grobe William , Bieber Thomas , Novak Natalija
Published: April 2019

Only few diseases have been studied as extensively and on as many different levels in recent years as atopic dermatitis (AD). One of the reasons why AD is the focus of interest is that it is one of the most common chronic inflammatory skin diseases, affecting up to 30 % of children and 1–10 % of adults. Numerous complex alterations both on the genetic level as well as on the level of innate and adaptive immunity have been identified and form the basis for the characterization of different patient groups and the development of novel diagnostic and therapeutic approaches. Despite the complex pathophysiological and immunological differences, which are closely related to disease stage and severity, as well as the heterogeneity of individual trigger factors, treatment of AD – in particular that of moderate‐to‐severe AD – was long limited to merely symptomatic and relatively nonspecific immunosuppressive approaches. Since the approval of the first biologic for the treatment of moderate‐to‐severe adult AD (commercially available in Germany since late 2017), there has been some movement in the field of AD management.

The present review highlights recent pathophysiologic insights. Advances in research allow for better characterization of certain patient subgroups and different disease manifestations. In addition, they form the basis of current and future developments in the field of precision medicine in AD.
Elimination of oncogenic cells that regulate epithelial homeostasis in Drosophila
Authors: Ohsawa Shizue
Published: April 2019

Normal epithelial tissues often put anti‐tumorigenic pressure on newly emerged oncogenic cells through cell–cell communications. In Drosophila epithelium, clones of oncogenic cells mutant for evolutionarily conserved apico‐basal polarity genes such as scribble (scrib) and discs large (dlg) are actively eliminated when surrounded by normal cells. It has been reported that c‐Jun N‐terminal kinase (JNK) signaling in polarity‐deficient cells is crucial for their cell death. However, the mechanism by which normal epithelial tissues exert anti‐tumorigenic effects on polarity‐deficient cells had been elusive. Here, I describe our genetic studies in Drosophila epithelium especially focused on the role of surrounding normal epithelial cells in response to the emergence of polarity‐deficient cells. Furthermore, I also describe recent studies regarding the mechanism by which polarity‐deficient cells are extruded from the tissue, and discuss future perspectives on the study of cell–cell communications in epithelial homeostasis.
Morphometric MRI findings challenge the concept of the “unaffected” hemisphere in Rasmussen encephalitis
Authors: David Bastian , Prillwitz Conrad C. , Hoppe Christian , Sassen Robert , Hörsch Sophia , Weber Bernd , Hattingen Elke , Elger Christian E. , Rüber Theodor
Published: April 2019

Rasmussen encephalitis (RE) is an immune‐mediated brain disease with progressive unihemispheric atrophy. Although it is regarded as a strictly one‐sided pathology, volumetric magnetic resonance imaging (MRI) studies have revealed atrophy in the so‐called unaffected hemisphere. In contrast to previous studies, we hypothesized that the contralesional hemisphere would show increased gray matter volume in response to the ipsilesional atrophy. We assessed the gray matter volume differences among 21 patients with chronic, late‐stage RE and 89 age‐ and gender‐matched healthy controls using voxel‐based morphometry. In addition, 11 patients with more than one scan were tested longitudinally. Compared to controls, the contralesional hemisphere of the patients revealed a higher cortical volume but a lower subcortical gray matter volume (all P < 0.001, unpaired t test). Progressive gray matter volume losses in bilateral subcortical gray matter structures were observed (P < 0.05, paired t test). The comparatively higher cortical volume in the contralesional hemisphere can be interpreted as a result of compensatory structural remodeling in response to atrophy of the ipsilesional hemisphere. Contralesional subcortical gray matter volume loss may be due to the pathology or its treatment. Because MRI provides the best marker for determining the progression of RE, an accurate description of its MRI features is clinically relevant.