bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Mouse and Human Cochlea at Single Cell Resolution
Authors: Yu Kevin Shengyang , Frumm Stacey M. , Park Jason S. , Lee Katharine , Wong Daniel M. , Byrnes Lauren , Knox Sarah M. , Sneddon Julie B. , Tward Aaron D.
Published: August 2019

Hearing loss is a common and disabling condition, yet our understanding of the physiologic workings of the inner ear has been limited by longstanding difficulty characterizing the function and characteristics of the many diverse, fragile, and rare cell types in the cochlea. Using single-cell RNA-sequencing and a novel clustering algorithm, CellFindR, we created a developmental map of the mouse and human cochlea, identifying multiple previously undescribed cell types, progenitor populations, and predicted lineage relationships. We additionally associated the expression of known hearing loss genes to the cell types and developmental timepoints in which they are expressed. This work will serve as a resource for understanding the molecular basis of hearing and designing therapeutic approaches for hearing restoration.
Assessment of a western blot signal for the Bcnt/Cfdp1, a tentative component of Srcap chromatin remodeling complex; trial to overcome off-target problems
Authors: Iwashita Shintaro , Suzuki Takehiro , Kiriyama Yoshimitsu , Dohmae Naoshi , Ohka Yoshiharu , Song Si-Young , Nakashima Kentaro
Published: August 2019

The BCNT (Bucentaur) protein family is characterized by a conserved amino acid sequence at the C-terminus (BCNT-C domain) and plays an essential role in gene expression and chromosomal maintenance in fungi, fly, and chicken. The mammalian Bucentaur/Craniofacial developmental protein 1 (Bcnt/Cfdp1) is also a tentative component of the Srcap (SNF2-Related CBP Activator Protein) chromatin remodeling complex, but little is known about its properties, partly because there are few suitable antibodies to detect the endogenous protein. We used multiple anti-Bcnt/Cfdp1 antibodies against unrelated immunogens derived from BCNT-C domain and mouse-specific N-terminal peptide. To assign western blot signals and evaluate these antibodies, we utilized a stem cell line from mutant embryos of mouse Bcnt/Cfdp1, whose mRNA expression levels were reduced to 75% of the parental cells. In western blotting of these mutant and parental cell extracts with the anti-Bcnt/Cfdp1 antibodies, mouse Bcnt/Cfdp1 was detected as a doublet of approximately 45 kDa. LC-MS/MS analysis of the corresponding doublet for the Flag-tagged mouse Bcnt/Cfdp1 constitutively expressed in T-REx 293 cell (a HEK293 derivative) exhibited that the upper band was much more phosphorylated than the lower band and that there was preferential Ser phosphorylation in the WESF motif in the BCNT-C domain. Western blot with these validated antibodies indicated a preferential expression of Bcnt/Cfdp1 in the early stages of brain development in mouse and rat, which is consistent with the expression of Bcnt/Cfdp1 mRNA. This article describes the evaluation of anti-Bcnt/Cfdp1 antibodies, including a scheme to prepare a potential negative control for western blot, and discusses immune-cross reactions with off-target proteins, particularly immunoreaction probabilities.
A universal reporter cell line for bioactivity evaluation of engineered cytokine products
Authors: Mock Jacqueline , Pellegrino Christian , Neri Dario
Published: August 2019

Engineered cytokine products represent a growing class of therapeutic proteins which need to be tested for biological activity at various stages of pharmaceutical development. In most cases, dedicated biological assays are established for different products, in a process that can be time-consuming and cumbersome. Here we describe the development and implementation of a universal cell-based reporter system for various classes of immunomodulatory proteins. The novel system capitalizes on the fact that the signaling of various types of pro-inflammatory agents (e.g., cytokines, chemokines, Toll-like receptor agonists) may involve transcriptional activation by NF-κB. Using viral transduction, we generated stably-transformed cell lines of B or T lymphocyte origin and compared the new reporter cell lines with conventional bioassays. The experimental findings with various interleukins and with members of the TNF superfamily revealed that the newly-developed “universal” bioassay method yielded bioactivity data which were comparable to the ones obtained with dedicated conventional methods. The engineered cell lines with reporters for NF-κB were tested with several antibody-cytokine fusions and may be generally useful for the characterization of novel immunomodulatory products. The newly developed methodology also revealed a mechanism for cytokine potentiation, based on the antibody-mediated clustering of TNF superfamily members on tumor-associated extracellular matrix components.
Social network analysis and the implications for Pontocaspian biodiversity conservation in Romania and Ukraine: A comparative study
Authors: Gogaladze Aleksandre , Raes Niels , Biesmeijer Koos , Ionescu Camelia , Pavel Bianca , Son Mikhail O. , Gozak Natalia , Anistratenko Vitaliy , Wesselingh Frank P.
Published: August 2019

Romania and Ukraine share the Black Sea coastline, the Danube Delta and associated habitats, which harbor the unique Pontocaspian biodiversity. Pontocaspian biota represents endemic aquatic taxa adapted to the brackish (anomalohaline) conditions, which evolved in the Caspian and Black Sea basins. Currently, this biota is diminishing both in the numbers of species and their abundance because of human activities. Consequently, its future persistence strongly depends on the adequacy of conservation measures. Romania and Ukraine have a common responsibility to effectively address the conservation of this biota. The socio-political and legal conservation frameworks, however, differ in the two countries - Romania is a member of the European Union (EU), thus complying with the EU environmental policy, whereas Ukraine is an EU-associated country. This may result in differences in the social network structure of stakeholder institutions with different implications for Pontocaspian biodiversity conservation. Here, we study the structure and implications of the social network of stakeholder organizations involved in conservation of Pontocaspian biodiversity in Romania, and compare it to Ukraine. We apply a mix of qualitative and quantitative social network analysis methods to combine the content and context of the interactions with relational measures. We show that the social networks of stakeholder organizations in Romania and Ukraine are very different. Structurally, in Romanian network there is a room for improvement through e.g. more involvement of governmental and non-governmental organizations and increased motivation of central stakeholders to initiate conservation action, whereas Ukrainian network is close to optimal. Regardless, both networks translate into sub-optimal conservation action and the road to optimal conservation is different. We end with sketching implications and recommendations for improved national and cross-border conservation efforts.
A Bayesian framework for the detection of diffusive heterogeneity
Authors: Cass Julie A. , Williams C. David , Theriot Julie
Published: August 2019

Cells are crowded and spatially heterogeneous, complicating the transport of organelles, proteins and other substrates. One aspect of this complex physical environment, the mobility of passively transported substrates, can be quantitatively characterized by the diffusion coefficient: a descriptor of how rapidly substrates will diffuse in the cell, dependent on their size and effective local viscosity. The spatial dependence of diffusivity is challenging to quantitatively characterize, because temporally and spatially finite observations offer limited information about a spatially varying stochastic process. We present a Bayesian framework that estimates diffusion coefficients from single particle trajectories, and predicts our ability to distinguish differences in diffusion coefficient estimates, conditional on how much they differ and the amount of data collected. This framework is packaged into a public software repository, including a tutorial Jupyter notebook demonstrating implementation of our method for diffusivity estimation, analysis of sources of uncertainty estimation, and visualization of all results. This estimation and uncertainty analysis allows our framework to be used as a guide in experimental design of diffusivity assays.
Short-term effects of GPS collars on the activity, behavior, and adrenal response of scimitar-horned oryx (Oryx dammah)
Authors: Stabach Jared A. , Cunningham Stephanie A. , Connette Grant , Mota Joel L. , Reed Dolores , Byron Michael , Songer Melissa , Wacher Tim , Mertes Katherine , Brown Janine L. , Comizzoli Pierre , Newby John , Monfort Steven , Leimgruber Peter
Published: August 2019

GPS collars have revolutionized the field of animal ecology, providing detailed information on animal movement and the habitats necessary for species survival. GPS collars also have the potential to cause adverse effects ranging from mild irritation to severe tissue damage, reduced fitness, and death. The impact of GPS collars on the behavior, stress, or activity, however, have rarely been tested on study species prior to release. The objective of our study was to provide a comprehensive assessment of the short-term effects of GPS collars fitted on scimitar-horned oryx (Oryx dammah), an extinct-in-the-wild antelope once widely distributed across Sahelian grasslands in North Africa. We conducted behavioral observations, assessed fecal glucocorticoid metabolites (FGM), and evaluated high-resolution data from tri-axial accelerometers. Using a series of non-standard regression models, we illustrate clear but short-term effects to animals fitted with GPS collars. Behavioral observations highlighted a significant increase in the amount of headshaking from pre-treatment levels, returning below baseline levels during the post-treatment period (>3 days post-collaring). Similarly, FGM concentrations (i.e., stress hormones) increased after GPS collars were fitted on animals but returned to pre-collaring levels within 5 days of collaring. Lastly, tri-axial accelerometers, collecting data at eight positions per second, indicated a > 480 percent increase in the amount of hourly headshaking immediately after collaring. This post-collaring increase in headshaking was estimated to decline in magnitude within 4 hours after GPS collar fitting. These effects constitute a handling and/or habituation response (model dependent), with animals showing short-term responses in activity, behavior, and stress that dissipated within several hours to several days of being fitted with GPS collars. Importantly, none of our analyses indicated any long-term effects that would have more pressing animal welfare concerns.
Integrated single-cell transcriptomics and chromatin accessibility analysis reveals novel regulators of mammary epithelial cell identity
Authors: Pervolarakis Nicholas , Nguyen Quy H. , Gutierrez Guadalupe , Sun Peng , Jhutty Darisha , Zheng Grace XY , Nemec Corey M , Dai Xing , Watanabe Kazuhide , Kessenbrock Kai
Published: August 2019

The mammary epithelial cell (MEC) system is a bi-layered ductal epithelial network consisting of luminal and basal cells, which is maintained by a lineage of stem and progenitor cell populations. Here, we used integrated single-cell transcriptomics and chromatin accessibility analysis to reconstruct the cell types of the mouse MEC system and their underlying gene regulatory features in an unbiased manner. We define previously unrealized differentiation states within the secretory type of luminal cells, which can be divided into distinct clusters of progenitor and mature secretory cells. By integrating single-cell transcriptomics and chromatin accessibility landscapes, we identified novel cis- and trans-regulatory elements that are differentially activated in the specific epithelial cell types and our newly defined luminal differentiation states. Our work provides an unprecedented resource to reveal novel cis/trans regulatory elements associated with MEC identity and differentiation that will serve as a valuable reference to determine how the chromatin accessibility landscape changes during breast cancer.
DropSynth 2.0: high-fidelity multiplexed gene synthesis in emulsions
Authors: Sidore Angus M. , Plesa Calin , Samson Joyce A. , Kosuri Sriram
Published: August 2019

Multiplexed assays allow functional testing of large synthetic libraries of genetic elements, but are limited by the designability, length, fidelity and scale of the input DNA. Here we improve DropSynth, a low-cost, multiplexed method which builds gene libraries by compartmentalizing and assembling microarray-derived oligos in vortexed emulsions. By optimizing enzyme choice, adding enzymatic error correction, and increasing scale, we show that DropSynth can build thousands of gene-length fragments at >20% fidelity.
Structural insights into stressosome assembly
Authors: Kwon Eunju , Pathak Deepak , Kim Han-ul , Dahal Pawan , Ha Sung Chul , Lee Seung Sik , Jeong Hyeongseop , Jeoung Dooil , Chang Hyeun Wook , Jung Hyun Suk , Kim Dong Young
Published: August 2019

The stressosome transduces environmental stress signals to SigB to upregulate SigB-dependent transcription, which is required for bacterial viability. The stressosome core is composed of RsbS and at least one of the RsbR paralogs. A previous cryo-electron microscopy (cryo-EM) structure of the RsbRA–RsbS complex determined under a D2 symmetry restraint showed that the stressosome core forms a pseudo-icosahedron consisting of 60 STAS domains of RsbRA and RsbS. However, it is still unclear how RsbS and one of the RsbR paralogs assemble into the stressosome. Here, an assembly model of the stressosome is presented based on the crystal structure of the RsbS icosahedron and cryo-EM structures of the RsbRA–RsbS complex determined under diverse symmetry restraints (nonsymmetric C1, dihedral D2 and icosahedral I envelopes). 60 monomers of the crystal structure of RsbS fitted well into the I-restrained cryo-EM structure determined at 4.1 Å resolution, even though the STAS domains in the I envelope were averaged. This indicates that RsbS and RsbRA share a highly conserved STAS fold. 22 protrusions observed in the C1 envelope, corresponding to dimers of the RsbRA N-domain, allowed the STAS domains of RsbRA and RsbS to be distinguished in the stressosome core. Based on these, the model of the stressosome core was reconstructed. The mutation of RsbRA residues at the binding interface in the model (R189A/Q191A) significantly reduced the interaction between RsbRA and RsbS. These results suggest that nonconserved residues in the conserved STAS folds between RsbS and RsbR paralogs determine stressosome assembly.
Feature intersection for agent-based customer churn prediction
Authors: N. Sandhya , Samuel Philip , Chacko Mariamma
Published: August 2019

Purpose

Telecommunication has a decisive role in the development of technology in the current era. The number of mobile users with multiple SIM cards is increasing every second. Hence, telecommunication is a significant area in which big data technologies are needed. Competition among the telecommunication companies is high due to customer churn. Customer retention in telecom companies is one of the major problems. The paper aims to discuss this issue.

Design/methodology/approach

The authors recommend an Intersection-Randomized Algorithm (IRA) using MapReduce functions to avoid data duplication in the mobile user call data of telecommunication service providers. The authors use the agent-based model (ABM) to predict the complex mobile user behaviour to prevent customer churn with a particular telecommunication service provider.

Findings

The agent-based model increases the prediction accuracy due to the dynamic nature of agents. ABM suggests rules based on mobile user variable features using multiple agents.

Research limitations/implications

The authors have not considered the microscopic behaviour of the customer churn based on complex user behaviour.

Practical implications

This paper shows the effectiveness of the IRA along with the agent-based model to predict the mobile user churn behaviour. The advantage of this proposed model is as follows: the user churn prediction system is straightforward, cost-effective, flexible and distributed with good business profit.

Originality/value

This paper shows the customer churn prediction of complex human behaviour in an effective and flexible manner in a distributed environment using Intersection-Randomized MapReduce Algorithm using agent-based model.
Identification of operational demand in law enforcement agencies
Authors: Basilio Marcio Pereira , Pereira Valdecy , Brum Gabrielle
Published: August 2019

Purpose

The purpose of this paper is to develop a methodology for knowledge discovery in emergency response service databases based on police occurrence reports, generating information to help law enforcement agencies plan actions to investigate and combat criminal activities.

Design/methodology/approach

The developed model employs a methodology for knowledge discovery involving text mining techniques and uses latent Dirichlet allocation (LDA) with collapsed Gibbs sampling to obtain topics related to crime.

Findings

The method used in this study enabled identification of the most common crimes that occurred in the period from 1 January to 31 December of 2016. An analysis of the identified topics reaffirmed that crimes do not occur in a linear manner in a given locality. In this study, 40 per cent of the crimes identified in integrated public safety area 5, or AISP 5 (the historic centre of the city of RJ), had no correlation with AISP 19 (Copacabana – RJ), and 33 per cent of the crimes in AISP 19 were not identified in AISP 5.

Research limitations/implications

The collected data represent the social dynamics of neighbourhoods in the central and southern zones of the city of Rio de Janeiro during the specific period from January 2013 to December 2016. This limitation implies that the results cannot be generalised to areas with different characteristics.

Practical implications

The developed methodology contributes in a complementary manner to the identification of criminal practices and their characteristics based on police occurrence reports stored in emergency response databases. The generated knowledge enables law enforcement experts to assess, reformulate and construct differentiated strategies for combating crimes in a given locality.

Social implications

The production of knowledge from the emergency service database contributes to the government integrating information with other databases, thus enabling the improvement of strategies to combat local crime. The proposed model contributes to research on big data, on the innovation aspect and on decision support, for it breaks with a paradigm of analysis of criminal information.

Originality/value

The originality of the study lies in the integration of text mining techniques and LDA to detect crimes in a given locality on the basis of the criminal occurrence reports stored in emergency response service databases.
A systematic literature review on Wikidata
Authors: Mora-Cantallops Marçal , Sánchez-Alonso Salvador , García-Barriocanal Elena
Published: August 2019

Purpose

The purpose of this paper is to review the current status of research on Wikidata and, in particular, of articles that either describe applications of Wikidata or provide empirical evidence, in order to uncover the topics of interest, the fields that are benefiting from its applications and which researchers and institutions are leading the work.

Design/methodology/approach

A systematic literature review is conducted to identify and review how Wikidata is being dealt with in academic research articles and the applications that are proposed. A rigorous and systematic process is implemented, aiming not only to summarize existing studies and research on the topic, but also to include an element of analytical criticism and a perspective on gaps and future research.

Findings

Despite Wikidata’s potential and the notable rise in research activity, the field is still in the early stages of study. Most research is published in conferences, highlighting such immaturity, and provides little empirical evidence of real use cases. Only a few disciplines currently benefit from Wikidata’s applications and do so with a significant gap between research and practice. Studies are dominated by European researchers, mirroring Wikidata’s content distribution and limiting its Worldwide applications.

Originality/value

The results collect and summarize existing Wikidata research articles published in the major international journals and conferences, delivering a meticulous summary of all the available empirical research on the topic which is representative of the state of the art at this time, complemented by a discussion of identified gaps and future work.
Social enterprise marketing: review of literature and future research agenda
Authors: Bandyopadhyay Chinmoy , Ray Subhasis
Published: August 2019

Purpose

The purpose of this paper is to review existing literature on marketing in social enterprises (SEs). It identifies major trends and issues and highlights gaps in the existing knowledge base on social enterprise marketing (SEM).

Design/methodology/approach

Relevant articles on SEM were searched, following the PRISMA framework, in online databases using keywords and phrases like “marketing in social enterprises,” “marketing strategy/practice in social enterprises,” “social enterprise marketing” and “business practices in social enterprises.” After screening and checking for eligibility, 47 significant articles published in 21 peer-reviewed journals during 1995–2018 were selected for review.

Findings

The findings suggest that marketing in SEs has different issues and challenges when compared to marketing practices adopted by conventional business organizations. They are forced to address the varied expectations of the stakeholders in a resource-constrained situation, which creates problems for them. The review also highlights the fact that resource constraints, legacy mindset, and lack of marketing skills limit the impact of marketing practices in SEs. To address these issues, many social entrepreneurs survive through cost-effective marketing techniques.

Originality/value

To the authors’ knowledge, this is the first effort to identify and analyze extant literature in SEM. The resultant themes and research gaps highlight the current status of SEM literature. The paper can help SEs to understand and plan their marketing activities for better impact and profitability. Future research can draw on the findings of this review.
CSR through social media: examining the intervening factors
Authors: S. Sreejesh , Sarkar Juhi Gahlot , Sarkar Abhigyan
Published: August 2019

Purpose

The purpose of this paper is to examine the casual role of consumers’ perceptions of brands’ corporate social responsibility (CSR) motives (self-serving vs society-serving) in influencing consumer–brand relationships. Further, the authors explore the roles of brand initiated CSR activities (e.g. CSR co-creation), social media characteristics (e.g. media richness) and consumer’s community identification in shaping the effect of perceived CSR motive on consumer–brand relationship.

Design/methodology/approach

A 2 (CSR motives: self-oriented vs society-oriented) × 2 (CSR co-creation: yes vs no) × 2 (media richness: high vs low) between-subjects experimental design is employed.

Findings

The results elucidate that when consumers perceive that CSR is for self-serving (vs society-serving) motive, allowing consumers to co-create CSR in a high media-rich virtual platform enhances consumer–brand relationship quality. In addition, the results also support that the interactions of perceived CSR motives, co-creation and media richness enhance consumer–brand relationship through the mediation of community identification.

Originality/value

The current study draws implications for effective CSR co-creation through rich social media platforms, so as to enhance consumer–brand relationship quality via creating community identification.
An intensive study on the AC impedance mechanism of (AgPO3)1-x(Ag2SO4)x ionic glass systems under various conditions
Authors: Alkhazali Atif , Etier Morad , Aljarrah Mohammad , Alsukker Akram , Salman Fathy
Published: August 2019

Purpose

The purpose of this study is to investigate the effect of the considerable Ag2SO4 content on the electrical and dielectric properties of (AgPO3)1−x(Ag2SO4)x ion glass system as well as to extract thermodynamic parameters.

Design/methodology/approach

Glass samples of (AgPO3)1-x(Ag2SO4)x with different mole ratios of Ag2SO4 [x = 0.00, 0.10,0.15,0.20 and 0.25] have been synthesized and used. X-ray diffraction and differential thermal analysis were used to investigate structural and thermal properties, and then the electrical characterizations of the bulk glasses were performed in different frequency and temperature range.

Findings

For different ratios of Ag2SO4 on AgPO3, the bulk conductivity is enhanced with increasing the amount of Ag2SO4 until the composition of x = 0.20, after which the conductivity decreases. The general behavior of both ε’ and ε” decreases with increasing frequency and increases with increasing temperature. Complex impedance analysis studied by Z‘−Z’ and Cole–Cole plot at different temperatures revealed that bulk resistance decreases with temperature.

Originality/value

The calculated values of activation free energy, enthalpy and entropy change for different compositions of (AgPO3)1-x(Ag2SO4)x showed an increase in activation energy and enthalpy when Ag2SO4 ratio is increased in (AgPO3)1-x(Ag2SO4)x composition up to 20%, and then there is a decrease in their values at x = 25%, which may be explained based on non-bridging oxygen.
Development and motion control of spatial serial robotic manipulator under varying disturbances
Authors: Epenetus Alex Barre , CS Meera , Mohan Santhakumar , Gupta Mukul Kumar
Published: August 2019

Purpose

Key challenges in evaluating the performance of a robotic manipulator are disturbances that rise internally and externally. Effects of non-linear disturbances like varying payload and joint friction can adversely affect the tracking performance in a robotic manipulator. This paper aims to discuss motion control of a three-link spatial manipulator using a computed torque observer-based control technique.

Design/methodology/approach

The overall motion control problem consists of derivation of kinematic and dynamic model of the manipulator followed by the control design to achieve desired manipulator response. In this study, the manipulator is subjected to uncertain varying load disturbances. The proposed motion controller compensates the effect of the disturbances and guarantees the convergence of tracking error to steady state value.

Findings

One major advantage of using observer-based control is positioning accuracy with robustness to parameter uncertainty and fast dynamics response. The performance of the proposed control technique is validated through real-time experiments conducted on the manipulator. The experiment results confirm the superior performance of the control system in achieving perfect tracking.

Originality/value

This paper demonstrates an observer-based control technique over a serial spatial manipulator which can be applied different robotic configurations under the effect of varying disturbances.
Demographic plasticity facilitates ecological and economic resilience in a commercially important reef fish
Authors: Taylor Brett M. , Choat John Howard , DeMartini Edward E. , Hoey Andrew S. , Marshell Alyssa , Priest Mark A. , Rhodes Kevin L. , Meekan Mark G.
Published: August 2019

Variation in life‐history characteristics is evident within and across animal populations. Such variation is mediated by environmental gradients and reflects metabolic constraints or trade‐offs that enhance reproductive outputs. While generalizations of life‐history relationships across species provide a framework for predicting vulnerability to overexploitation, deciphering patterns of intraspecific variation may also enable recognition of peculiar features of populations that facilitate ecological resilience.

This study combines age‐based biological data from geographically disparate populations of bluespine unicornfish (Naso unicornis)—the most commercially valuable reef‐associated species in the insular Indo‐Pacific—to explore the magnitude and drivers of variation in life span and examine the mechanisms enabling peculiar mortality schedules.

Longevity and mortality schedules were investigated across eleven locations encompassing a range of latitudes and exploitation levels. The presence of different growth types was examined using back‐calculated growth histories from otoliths. Growth‐type‐dependent mortality (mortality rates associated with particular growth trajectories) was corroborated using population models that incorporated size‐dependent competition.

We found a threefold geographic variation in life span that was strongly linked to temperature, but not to anthropogenic pressure or ocean productivity. All populations consistently displayed a two‐phase mortality schedule, with higher than expected natural mortality rates in earlier stages of post‐settlement life. Reconstructed growth histories and population models demonstrated that variable growth types within populations can yield this peculiar biphasic mortality schedule, where fast growers enjoy early reproductive outputs at the expense of greater mortality, and benefits for slow growers derive from extended reproductive outputs over a greater number of annual cycles. This promotes population resilience because individuals can take advantage of cycles of environmental change operating at both short‐ and long‐term scales.

Our results highlight a prevailing, fundamental misperception when comparing the life histories of long‐lived tropical ectotherms: the seemingly incongruent combination of extended life spans with high mortality rates was enabled by coexistence of variable growth types in a population. Thus, a demographic profile incorporating contrasting growth and mortality strategies obscures the demographic effects of harvest across space or time in N. unicornis and possibly other ectotherms with the combination of longevity and asymptotic growth.
Testing the benefits of conservation set‐asides for improved habitat connectivity in tropical agricultural landscapes
Authors: Scriven Sarah A. , Carlson Kimberly M. , Hodgson Jenny A. , McClean Colin J. , Heilmayr Robert , Lucey Jennifer M. , Hill Jane K.
Published: August 2019

Habitat connectivity is important for tropical biodiversity conservation. Expansion of commodity crops, such as oil palm, fragments natural habitat areas, and strategies are needed to improve habitat connectivity in agricultural landscapes. The Roundtable on Sustainable Palm Oil (RSPO) voluntary certification system requires that growers identify and conserve forest patches identified as High Conservation Value Areas (HCVAs) before oil palm plantations can be certified as sustainable. We assessed the potential benefits of these conservation set‐asides for forest connectivity.

We mapped HCVAs and quantified their forest cover in 2015. To assess their contribution to forest connectivity, we modelled range expansion of forest‐dependent populations with five dispersal abilities spanning those representative of poor dispersers (e.g. flightless insects) to more mobile species (e.g. large birds or bats) across 70 plantation landscapes in Borneo.

Because only 21% of HCVA area was forested in 2015, these conservation set‐asides currently provide few connectivity benefits. Compared to a scenario where HCVAs contain no forest (i.e. a no‐RSPO scenario), current HCVAs improved connectivity by ~3% across all dispersal abilities. However, if HCVAs were fully reforested, then overall landscape connectivity could improve by ~16%. Reforestation of HCVAs had the greatest benefit for poor to intermediate dispersers (0.5–3 km per generation), generating landscapes that were up to 2.7 times better connected than landscapes without HCVAs. By contrast, connectivity benefits of HCVAs were low for highly mobile populations under current and reforestation scenarios, because range expansion of these populations was generally successful regardless of the amount of forest cover.

Synthesis and applications. The Roundtable on Sustainable Palm Oil (RSPO) requires that High Conservation Value Areas (HCVAs) be set aside to conserve biodiversity, but HCVAs currently provide few connectivity benefits because they contain relatively little forest. However, reforested HCVAs have the potential to improve landscape connectivity for some forest species (e.g. winged insects), and we recommend active management by plantation companies to improve forest quality of degraded HCVAs (e.g. by enrichment planting). Future revisions to the RSPO's Principles and Criteria should also ensure that large (i.e. with a core area >2 km2) HCVAs are reconnected to continuous tracts of forest to maximize their connectivity benefits.
Galanin receptors activation modulates myocardial metabolic and antioxidant responses to ischaemia/reperfusion stress
Authors: Studneva Irina , Serebryakova Larisa , Veselova Oksana , Pal'keeva Marina , Molokoedov Alexander , Ovchinnikov Michael , Konovalova Galina , Lankin Vadim , Sidorova Maria , Pisarenko Oleg
Published: August 2019

The mechanisms of protective action of the neuropeptide galanin and its N‐terminal fragments against myocardial ischaemia/reperfusion (I/R) injury remain obscure. The aim of this work was to study effects of a novel peptide agonist of galanin receptors [βAla14, His15]‐galanin (2‐15) (G1) and the full‐length galanin (G2) on energy and antioxidant status of the heart with acute infarction. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1H‐NMR spectroscopy and MALDI‐TOF mass spectrometry. Experiments were performed on anaesthetized open‐chest rats subjected to myocardial regional ischaemia and reperfusion. Intravenous (iv) administration of optimal doses of peptides G1 and G2 (1.0 and 0.5 mg/kg, respectively, at the onset of reperfusion significantly reduced infarct size (on average by 40% compared with control) and the plasma activity of creatine kinase‐MB (CK‐MB) and lactate dehydrogenase (LDH). These effects were associated with augmented preservation of aerobic energy metabolism, increased activity of Cu,Zn superoxide dismutase (Cu,Zn‐SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) and decreased lipid peroxidation in the area at risk (AAR) at the end of reperfusion. Peptide G1 showed more efficient recovery of the majority of metabolic and antioxidant parameters. The results provide evidence that the galaninergic system can be considered a promising target to reduce energy dysregulation and oxidative damage in myocardial I/R injury.
Suppression of the proliferation and invasion of breast cancer cells by ST7L occurs through inhibition of activation of Wnt/GSK‐3β/β‐catenin signalling
Authors: Wang Hua , Sun Lei , Jiang Jue , Yu Shanshan , Zhou Qi
Published: August 2019

Emerging evidence has indicated that suppression of tumorigenicity 7‐like (ST7L) is a tumour suppressor in multiple types of cancers. However, the functional involvement of ST7L has not been studied in breast cancer. In the present study, we aimed to investigate the potential biological function of ST7L in breast cancer. Herein, we found that ST7L expression was frequently downregulated in breast cancer cell lines. Functional assays revealed that ST7L overexpression significantly inhibited the proliferation and invasion of breast cancer cells, while ST7L silencing showed opposite effect. Notably, ST7L was found to decrease glycogen synthase kinase (GSK)‐3β phosphorylation and downregulate active β‐catenin protein expression, thereby leading to repression of β‐catenin transcriptional activity. Activation of Wnt/β‐catenin signalling by treatment of GSK‐3β inhibitor significantly abrogated ST7L‐mediated antitumour effect. Additionally, ST7L overexpression blunted the tumorigenicity of breast cancer cells in vivo in xenograft mice. Taken together, our results demonstrate that ST7L exerts antitumor function in breast cancer associated with the suppression of Wnt/β‐catenin signalling, suggesting ST7L as a potential therapeutic target for breast cancer.
Free Expression, Pre‐Crime and Counter‐Terrorism Legislation
Authors: Stoughton Corey
Published: August 2019

This article examines the Counter‐Terrorism and Border Security Act 2019 and how this new piece of legislation undermines fundamental human rights, including those protected in the Universal Declaration of Human Rights (UDHR). It considers in particular how the new act criminalises behaviour with a wide sweep, to include behaviour that is not in itself criminal, but might be indicative of future criminal intent. As a result, the act restricts the right to freedom of speech and to liberty in a manner that is neither necessary nor proportionate.
Novel application of approaches to predicting medication adherence using medical claims data
Authors: Zullig Leah L. , Jazowski Shelley A. , Wang Tracy Y. , Hellkamp Anne , Wojdyla Daniel , Thomas Laine , Egbuonu‐Davis Lisa , Beal Anne , Bosworth Hayden B.
Published: August 2019

Objective

To compare predictive analytic approaches to characterize medication nonadherence and determine under which circumstances each method may be best applied.

Data Sources/Study Setting

Medicare Parts A, B, and D claims from 2007 to 2013.

Study Design

We evaluated three statistical techniques to predict statin adherence (proportion of days covered [PDC ≥ 80 percent]) in the year following discharge: standard logistic regression with backward selection of covariates, least absolute shrinkage and selection operator (LASSO), and random forest. We used the C‐index to assess model discrimination and decile plots comparing predicted values to observed event rates to evaluate model performance.

Data Extraction

We identified 11 969 beneficiaries with an acute myocardial infarction (MI)‐related admission from 2007 to 2012, who filled a statin prescription at, or shortly after, discharge.

Principal Findings

In all models, prior statin use was the most important predictor of future adherence (OR = 3.65, 95% CI: 3.34‐3.98; OR = 3.55). Although the LASSO regression model selected nearly 90 percent of all candidate predictors, all three analytic approaches had moderate discrimination (C‐index ranging from 0.664 to 0.673).

Conclusions

Although none of the models emerged as clearly superior, predictive analytics could proactively determine which patients are at risk of nonadherence, thus allowing for timely engagement in adherence‐improving interventions.
Analysis of 2,4‐Dinitrophenol in Postmortem Blood and Urine by Gas Chromatography–Mass Spectrometry: Method Development and Validation and Report of Three Fatalities in the United States
Authors: Geraldo de Campos Eduardo , Fogarty Melissa , Spinosa De Martinis Bruno , Kerr Logan Barry
Published: August 2019

2,4‐dinitrophenol (2,4‐DNP) is a compound used in the early 1900s as a weight‐loss drug but later prohibited due to its severe adverse effects, including death. It has however been attracting interest, due to its weight‐loss properties, and appears to be re‐emerging in forensic casework. As 2,4‐DNP is available for use in industry and as a pesticide and easily accessible online, the dissemination of this drug can be fast. The compound exerts its effects through inhibition of ATP synthesis, and corresponding thermogenic energy loss which can be fatal. A method for qualitative and quantitative analysis of 2,4‐DNP in blood and urine specimens using GC‐MS with hydrogen as carrier gas is described. The method was validated and displayed acceptable performance parameters with linearity (R2 higher than 0.998), inter‐assay imprecision (lower than 10.6%), intra‐assay imprecision (lower than 10.7%), and extraction efficiency (92.1%). Stability of 2,4‐DNP in blood and urine was studied, and the drug was stable up to 30 days refrigeration or frozen. Six cases in United States suspected to be related to 2,4‐DNP were analyzed. Three cases were found to be positive for 2,4‐DNP. Concentrations of 2,4‐DNP were in the range of 61.6–220 mg/L in urine and <3–114 mg/L in blood. Based on our findings, we suggest that medical examiners and forensic toxicologists be aware of the reappearance of 2,4‐DNP, including this compound as a target in death investigations related to weight‐loss drugs.
Initiating buprenorphine treatment for opioid use disorder during short‐term in‐patient ‘detoxification’: a randomized clinical trial
Authors: Stein Michael , Herman Debra , Conti Micah , Anderson Bradley , Bailey Genie
Published: August 2019

Background and Aims

The effectiveness of linking people from short‐term in‐patient managed withdrawal programs (‘detoxification’) to long‐term, primary care‐based buprenorphine is unknown. We tested whether buprenorphine initiation during an opioid withdrawal program and linkage to office‐based buprenorphine (LINK) after discharge would increase engagement with office‐based buprenorphine and decrease illicit opioid use during the ensuing 6 months compared with standard withdrawal management (WM).

Design

Single‐site randomized controlled trial.

Setting

Short‐term in‐patient detoxification program in Massachusetts, USA.

Participants

People with opioid use disorder (n = 115) who averaged 32.4 years of age, 68.2% male, 79.1% white, using illicit opioids on 27.3 of the last 30 days, were randomly assigned to WM (n = 59) versus LINK (n = 56).

Intervention and comparator

Intervention was buprenorphine induction, in‐patient dose stabilization and post‐discharge transition to maintenance buprenorphine at an affiliated primary care clinic (LINK). Comparator was 5‐day buprenorphine managed withdrawal protocol (WM).

Measurements

Mean 30‐day rate of use of illicit opioids (primary aim) and prescribed buprenorphine (secondary aim) at 1, 3 and 6 months.

Findings

Compared with WM, participants in the LINK condition had lower illicit opioid use rates at days 12 [b = −6.81, 95% confidence interval (CI) = –9.69; −3.92, P < 0.001], 35 (b = −8.55, 95% CI – 11.63; −5.47, P < 0.001), 95 (b = −7.34, 95% CI = –10.59; −4.11, P < 0.001) and 185 (b = −3.52, 95% CI = –7.07; 0.27, P = 0.052). The LINK arm had higher prescription buprenorphine use rates (P < 0.001) at all assessments.

Conclusions

Among people with opioid use disorder, initiation of, and linkage to, office‐based buprenorphine treatment post‐discharge reduced illicit opioid use and increased days of buprenorphine treatment for up to 6 months post‐discharge compared with an in‐patient detoxification protocol.
The adequacy of Victoria's protected areas for conserving its forest‐dependent fauna
Authors: Taylor Chris , Lindenmayer David B.
Published: August 2019

Networks of protected areas are a key component of efforts to conserve biodiversity. However, there are concerns about an uncritical focus on the percentage area of reserves without an assessment of how well formal reserves are actually protecting biodiversity. In response, we completed a spatial analysis of the formal reserve system in the Australian state of Victoria. We quantified how well the reserve system captured a crude surrogate for vegetation communities (viz: Ecological Vegetation Classes) as well as distribution models for an array of threatened forest‐dependent species. We found evidence of a high degree of overlap between areas subject to intensive forestry (clearcutting) operations and the modelled distribution of a suite of forest‐dependent species. A key outcome of our study was that areas around sites subject to past logging as well as new areas proposed for logging under the Timber Release Plan in Victoria had significantly higher values for threatened forest‐dependent species (as determined by habitat distribution models) than areas that had not been logged. We found significant differences in the spatial characteristics of the dedicated reserve systems and informal protected area networks, with the latter featuring much of its area close to a tenure boundary where logging occurs. Our empirical analyses demonstrating the impacts of ongoing logging operations on areas with high environmental suitability for threatened species have important implications. In particular, the current reserve system is inadequate for a suite of forest‐dependent taxa, including critically endangered Leadbeater's Possum (Gymnobelideus leadbeateri) and the vulnerable Greater Glider (Petauroides volans). This suggests a high degree of conflict between areas of high value for conservation and areas targeted for wood production.
Synoptic reporting in Mohs micrographic surgery
Authors: Cabrera Samantha , Smith Saxon , Ryman William
Published: August 2019

There is currently no standardised reporting format for Mohs surgery with its operation reports mostly written in a narrative form making them prone to unintentional errors and omission of necessary data. Synoptic histology reporting is used to describe excised skin cancers such as melanomas and, more recently, squamous cell and basal cell carcinomas. Since Mohs surgery is utilised as the gold standard treatment for locally invasive squamous and basal cell carcinomas, we propose the use of our model of synoptic reporting to ensure the completeness and consistency of Mohs surgery operation reports.
Rural palliative care to support dying at home can be realised; experiences of family members and nurses with a new model of care
Authors: Spelten Evelien , Timmis Jenny , Heald Simone , Duijts Saskia F. A.
Published: August 2019

Objective

While 60%‐70% of people would prefer to die at home, only 14% do so. Families in a rural environment feel particularly unsupported in fulfilling this last wish of their loved one, which reflects the general shortage of health care workforce and resource allocation to institutions. The aim of this study was to describe the experience of families and nurses with extended rural palliative care to support dying at home.

Design

Semistructured interviews were conducted with family members and nurses. Process data were included to describe the frequency and nature of contacts. The results were analysed using descriptive analysis.

Settings

A rural town in Northern Victoria, Australia (Australian Statistical Geography Standard‐Remoteness Area).

Participants

Ten family members and four nurses were interviewed.

Main outcome measures

Experience with the extended palliative care service and with the dying at home process.

Results

All patients in the project died at home. The families were very positive about the extended palliative care; it increased their familiarity with dying, and had a positive impact on bereavement. The nurses were equally positive, but also commented on the need to debrief and on the heavy emotional toll the work takes.

Conclusions

Rural care support for dying at home can be realised. This study has demonstrated the positive impact of an end‐of‐life service, while at the same time pointing to concerns of the nursing staff on the suitability of the model of care. Health care workers and communities alike need to be educated and have conversations on end‐of‐life care.