bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Organic Matrix and Cations on Bio-Methane Yield with Anthracite Methanogenic Consortium
Authors: Xiao Dong , Wang Enyuan , Zhang Yidong
Published: February 2019

Organic compounds fermentation of coal has been used to generate secondary biogenic gas and enhance gas reservoirs in coalbed. To enhance the bio-degradation process, culture nutrition plays an important role in remediating the nutritional deficiency of the coal seam. The influence of bio-methane yield with organic inputs and cations concentrations was examined. Research of organic matrix influence revealed that the traditional organic material except yeast extract should forbid, and the input of yeast extract should limit at 1.00g/L also. Further, the study demonstrated that the ion concentration of sodium, potassium, magnesium, calcium and ammonia nitrogen also influenced methane and carbon dioxide yields. And the optimize concentrations for Ca2+, K+, Na+, Mg2+ were 5.1, 1.7, 23 and 1.3 mmol/L. The Mg2+ was particularly sensitive in inhibiting CH4 metabolism processes largely for gas-coal methanogenic consortium.
Targeted mutagenesis of the SUMO protease,Overly Tolerant to Salt1in rice through CRISPR/Cas9-mediated genome editing reveals a major role of this SUMO protease in salt tolerance
Authors: Zhang Cunjin , Srivastava Anjil Kumar , Sadanandom Ari
Published: February 2019

SUMO proteases are encoded by a large gene family in rice and are a potential source of specificity within the SUMO system that is responding to different environmental cues. We previously demonstrated a critical role of OsOTS class of SUMO proteases in salt and drought stress in rice by silencing several family members collectively via RNAi methods. However, to date it has not been possible to assign a role to specific family members due to limitations of RNAi mediated off target silencing across several members of the gene family. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease 9 (CRISPR/Cas9) system has emerged as a promising technology for specific gene editing in crop plants. Here, we demonstrate targeted mutagenesis ofOsOTS1in rice using the CRISPR/Cas9 gene editing system in the rice cultivar Kitaake. Guide RNA mediated mutations inOsOTS1was highly efficient with almost 95% of T0transgenics showing the desired effect with no off-target mutations. TheOsOTS1mutations observed in T0generation were heritable in subsequent generations.OsOTS1CRISPR lines show enhanced sensitivity to salt with reduced root and shoot biomass indicating that OsOTS1 has a major role in salt stress tolerance in rice. This unexpected finding indicates that precise and effective genome editing can be used to characterise specificity within the SUMO system in rice.
Deep behavioural phenotyping reveals divergent trajectories of ageing and quantifies health state inC. elegans
Authors: Martineau Céline N. , Baskaner Bora , Seinstra Renée I. , Schafer William R. , Brown André E. X. , Nollen Ellen A. A. , Laurent Patrick
Published: February 2019

Neurodegenerative diseases may be the cause or the consequence of an acceleration of physiological ageing. Evidence for this concept is lacking due to practical limitations of human studies. Here, we compared the processes of physiological and pathological ageing of individualC. elegansover their lifespan. Using multi-parametric phenotyping, trajectories of ageing can be defined within a phenotypic landscape made of a large set of phenotypical features. Rather than an acceleration of ageing, a model for synucleinopathy showed a divergent trajectory of ageing. The pathological progression in individual animals can be predicted from early phenotypes with high accuracy. Despite of similar lifespans, disease-model worms display an early onset of decline in their phenotypic range of ability. This loss of flexibility provides an index of health valid for physiological and pathological contexts. Finally, we demonstrate the power of multi-parametric dataset to describe ageing, to quantify health and to predict specific health risks.
Systemic immune response profiling with SYLARAS implicates a role for CD45R/B220+CD8+T cells in glioblastoma immunology
Authors: Baker Gregory J. , Muhlich Jeremy L. , Palaniappan Sucheendra K. , Moore Jodene K. , Davis Stephanie H. , Santagata Sandro , Sorger Peter K.
Published: February 2019

Accurately profiling systemic immune responses to cancer initiation and progression is necessary for understanding tumor surveillance and, ultimately, improving therapy. Here, we describe the SYLARAS software tool (SYstemicLymphoidArchitectureResponseASsessment) and a data set collected with SYLARAS that describes the frequencies of immune cells in primary and secondary lymphoid organs and in the tumor microenvironment of mice engrafted with a standard syngeneic glioblastoma (GBM) model. The data resource involves profiles of 5 lymphoid tissues in 48 mice and shows that GBM causes wide-spread changes in the local and systemic immune architecture. We perform in-depth analysis of one significant tumor-induced change: depletion of a specialized subset of CD45R/B220+CD8+T cells from the circulation and their accumulation in the tumor mass. Immunoprofiling of tissue microarrays demonstrates the presence of similar cells in human GBM.
The dopamine receptor D5gene shows signs of independent erosion in Toothed and Baleen whales
Authors: Alves Luís Q. , Alves Juliana , Ribeiro Rodrigo , Ruivo Raquel , Castro L. Filipe C.
Published: February 2019

To compare genelociconsidering a phylogenetic framework is a promising approach to uncover the genetic basis of human diseases. Imbalance of dopaminergic systems is suspected to underlie some emerging neurological disorders. The physiological functions of dopamine are transduced via G-protein-coupled receptors, including DRD5which displays a relatively higher affinity towards dopamine. Importantly, DRD5knockout mice are hypertense, a condition emerging from an increase in sympathetic tone. We investigated the evolution of DRD5, a high affinity receptor for dopamine, in mammals. Surprisingly, among 124 investigated mammalian genomes, we found that Cetacea lineages (Mysticeti and Odontoceti) have independently lost this gene, as well as the burrowingChrysochloris asiatica (Cape golden mole).We suggest that DRD5inactivation parallels hypoxia-induced adaptations, such as peripheral vasoconstriction required for deep-diving in Cetacea, in accordance with the convergent evolution of vasoconstrictor genes in hypoxia-exposed animals. Our findings indicate that Cetacea are natural knockouts for DRD5and might offer valuable insights into the mechanisms of some forms of vasoconstriction responses and hypertension in humans.
High sampling effectiveness for non-bee pollinators using vane traps in both open and wooded habitats
Authors: Hall Mark A. , Reboud Eliette L.
Published: February 2019

Non-bee insects are important for pollination, yet few studies have assessed the effectiveness of sampling these taxa using low cost passive techniques, such as coloured vane traps, among different habitat types.

This study sampled 192 sites—108 in wooded and 84 in open habitats within an agricultural region of southern Australia. Pairs of blue and yellow vane traps were placed at each site for a period of seven days during the austral spring.

Overall, 3114 flies (Diptera) from 19 families and 528 wasps (non-bee and non-formicid Hymenoptera) from 16 families were collected during the study. This sampling was representative of the region, with vane traps equally or more likely to collect as many families from both taxa as those reported on the Atlas of Living Australia (ALA) database for the sampling area.

Blue vane taps (BVTs) had greater average richness of both flies and wasps and greater abundance of individuals than yellow vane traps (YVTs). BVTs were particularly favoured by certain fly and wasp families known to pollinate flowers (e.g. Syrphidae, Bombyliidae and Scoliidae), whilst YVTs sampled some less common fly families, such as Acroceridae and Bibionidae that also provide additional ecosystem services to pollination.

Vane traps are an effective passive sampling technique for non-bee pollinators, such as flies and wasps. This study supports the use of vane traps as a component of the sampling protocol for ecological census and population monitoring within multiple habitat types, to effectively sample a more complete pollinator community.
Transcriptomic analysis of human and mouse muscle during hyperinsulinemia demonstrates insulin receptor downregulation as a mechanism for insulin resistance
Authors: Cen Haoning Howard , Botezelli José Diego , Wang Su , Noursadeghi Nilou , Jessen Niels , Timmons James A. , Johnson James D.
Published: February 2019

Hyperinsulinemia is commonly viewed as a compensatory response to insulin resistance, yet studies have suggested that chronically elevated insulin may also drive insulin resistance. The molecular mechanisms underpinning this potentially cyclic process remain poorly defined, especially on a transcriptome-wide level. To study the direct effects of prolonged exposure to excess insulin in muscle cells, we incubated C2C12 myotubes with elevated insulin for 16 hours, followed by 6 hours of serum starvation, and established that acute AKT and ERK signaling were attenuated in this model of in vitro hyperinsulinemia. Global RNA-sequencing of cells both before and after nutrient withdrawal highlighted genes in the insulin signaling, FOXO signaling, and glucose metabolism pathways indicative of ‘hyperinsulinemia’ and ‘starvation’ programs. We observed that hyperinsulinemia led to a substantial reduction in insulin receptor (Insr) gene expression, and subsequently a reduced surface INSR and total INSR protein, both in vitro and in vivo. Transcriptomic meta-analysis in >450 human samples demonstrated that fasting insulin reliably and negatively correlated with insulin receptor (INSR) mRNA in skeletal muscle. Bioinformatic modeling combined with RNAi, identified SIN3A as a negative regulator of Insr mRNA (and JUND, MAX, and MXI as positive regulators of Irs2 mRNA). Together, our analysis identifies novel mechanisms which may explain the cyclic processes underlying hyperinsulinemia-induced insulin resistance in muscle, a process directly relevant to the etiology and disease progression of type 2 diabetes.
ACValidator: a novel assembly-based approach for in silico validation of circular RNAs
Authors: Sekar Shobana , Geiger Philipp , Adkins Jonathan , Serrano Geidy , Beach Thomas G. , Liang Winnie S.
Published: February 2019

Circular RNAs (circRNAs) are evolutionarily conserved RNA species that are formed when exons ‘back-splice’ to each other. Current computational algorithms to detect these back-splicing junctions produce divergent results, and hence there is a need for a method to distinguish true positive circRNAs. To this end, we developed ACValidator (Assembly based CircRNA Validator) for in silico validation of circRNAs. ACValidator extracts reads from a user-defined window on either side of the circRNA junction and assembles them to generate contigs. These contigs are aligned against the circRNA sequence to find contigs spanning the backspliced junction. When evaluated on simulated datasets, ACValidator achieved over 80% sensitivity and specificity on datasets with an average of 10 circRNA-supporting reads and with read lengths of at least 100 bp. In experimental datasets, ACValidator produced higher validation percentages for samples treated with ribonuclease R compared to non-treated samples. Our workflow is applicable to non-polyA-selected RNAseq datasets and can also be used as a candidate selection strategy for experimental validations. All workflow scripts are freely accessible on our github page https://github.com/tgen/ACValidator along with detailed instructions to set up and run ACValidator.

Author summary

Circular RNAs (circRNAs) are a recent addition to the class of non-coding RNAs and are produced when exons ‘back-splice’ and form closed circular loops. Although several computational algorithms have been developed to detect circRNAs from RNA sequencing (RNAseq) data, they produce divergent results. We hence developed the software Assembly based Circular RNA Validator (ACValidator) as an orthogonal strategy to separately validate predicted circRNAs in silico. ACValidator takes as input a sequence alignment mapping (SAM) file and the circRNA coordinate(s) to be validated. Reads surrounding the circRNA junction are extracted from the SAM file and assembled to generate contigs. These contigs are then aligned against the circRNA sequence to identify contigs that span the back-spliced junction. We evaluated our workflow on simulated as well as experimental datasets to demonstrate the utility of our approach. ACValidator is implemented in python and is highly computationally efficient, with a run time of less than 2 minutes for an 8 GB SAM file. This workflow is applicable to non-polyA-selected RNAseq datasets and can also be used as a candidate selection strategy for experimental validations.
New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells
Authors: Bassaganyas Laia , Popa Stephanie J. , Horlbeck Max , Ashok Anupama , Stewart Sarah E. , Butnaru Cristian M. , Brouwers Nathalie , Heydari Kartoosh , Ripoche Jean , Weissman Jonathan , Schekman Randy , Malhotra Vivek , Moreau Kevin , Villeneuve Julien
Published: February 2019

Protein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathways function remains incomplete, and mechanisms involved in their adaptation poorly understood. Here, we present a powerful strategy based on a pooled genome-wide CRISPRi screen that allowed the identification of new factors involved in protein transport. Two newly identified factors, TTC17 and CCDC157, localized along the secretory pathway and were found to interact with resident proteins of ER-Golgi membranes. In addition, we uncovered that upon TTC17 knockdown, the polarized organization of Golgi cisternae was altered, creating glycosylation defects, and that CCDC157 is an important factor for the fusion of transport carriers to the Golgi complex. In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion, and opens stimulating perspectives for the use of our platform in physiological and pathological contexts.
Using machine learning-based lesion behavior mapping to identify anatomical networks of cognitive dysfunction: spatial neglect and attention
Authors: Wiesen Daniel , Sperber Christoph , Yourganov Grigori , Rorden Christopher , Karnath Hans-Otto
Published: February 2019

Previous lesion behavior studies primarily used univariate lesion behavior mapping techniques to map the anatomical basis of spatial neglect after right brain damage. These studies led to inconsistent results and lively controversies. Given these inconsistencies, the idea of a widespread network that might underlie spatial orientation and neglect has been pushed forward. In such case, univariate lesion behavior mapping methods might have been inherently limited in uncover the presumed network in a single study due to limited statistical power. By using multivariate lesion-mapping based on support vector regression, we aimed to validate the network hypothesis directly in a large sample of 203 newly recruited right brain damaged patients. In a single analysis, this method identified a network of parietal, temporal, frontal, and subcortical regions, which also included white matter tracts connecting these regions. The results were compared to univariate analyses of the same patient sample using different combinations of lesion volume correction and statistical thresholding. The comparison revealed clear benefits of multivariate lesion behavior mapping in identifying brain networks.
Bacterial defiance as a form of prodrug failure
Authors: Holt Brandon Alexander , Kwong Gabriel A.
Published: February 2019

Classifying the mechanisms of antibiotic failure has led to the development of new treatment strategies for killing bacteria. Among the currently described mechanisms, which include resistance, persistence and tolerance, we propose bacterial defiance as a form of antibiotic failure specific to prodrugs. As a prototypic model of a bacteria-activated prodrug, we construct cationic antimicrobial peptides (AMP), which are charge neutralized until activated by a bacterial protease. This construct successfully eliminated the vast majority of bacteria populations, while localizing activity to bacterial membranes and maintaining low active drug concentration. However, we observed defiant bacteria populations, which survive in the presence of identical drug concentration and exposure time. Using a multi-rate kinetic feedback model, we show that bacteria switch between susceptibility and defiance under clinically relevant environmental (e.g., hyperthermia) and genetic (e.g., downregulated protease expression) conditions. From this model, we derive a dimensionless quantity (Bacterial Advantage Heuristic, BAH) – representing the balance between bacterial proliferation and prodrug activation – that perfectly classifies bacteria as defiant or susceptible across a broad range of conditions. To apply this concept to other classes of prodrugs, we expand this model to include both linear and nonlinear terms and use general pharmacokinetic parameters (e.g., half-life, EC50, etc.). Taken together, this model reveals an analogous dimensionless quantity (General Advantage Key, GAK), which can applied to prodrugs with different activation mechanisms. We envision that these studies will enable the development of more effective prodrugs to combat antibiotic resistance.
Identification and development of talent in surgery
Authors: Dall Jensen Rune , Ravn Sissel , Krogh Christensen Mette
Published: February 2019

Purpose

Education of the surgeon and development of surgical expertise have been debated for centuries. Today, research in surgical education applies terms and methods from other performance domains such as sport and music. However, there still seems to be a lack of consensus as to how talent may be brought into the discourse about surgical education. Especially, when it comes to identifying and developing trainees who in the future will perform better than the average surgeon.

Design/methodology/approach

This five-step scoping study aims to map existing literature about talent identification, talent development and development of expertise in the domains of surgery, sport and music in the period of 1985-2014.

Findings

A total of 242 studies, divided in the four domains of surgery (69 studies), sport (115 studies), music (34 studies) and cross-disciplinary studies (24 studies) published in the period 1985-2014 were included.

Originality/value

Informed by the performance domains of sports and music and their inclusion of a holistic, ecological approach to research, this study suggests that research in surgical education may benefit from broadening its view on talent by including psychosocial variables and environmental, demographic and structural influencers when considering how surgical talent may be identified and developed.
Performance modeling and assessment of maintenance priorities for steam generation unit of a sugar plant
Authors: Sharma Gaurav , Tewari Puran Chandra
Published: February 2019

Purpose

The purpose of this paper is to deal with the performance modeling and assessment of maintenance priorities for steam generation unit of a sugar plant.

Design/methodology/approach

The unit comprises of four subsystems, i.e., Bagasse elevator, Bagasse carrier, boiler and feed pump. The Chapman–Kolmogorov equations are generated on the basis of transition diagram and further solved recursively to obtain the performance modeling with the help of normalizing condition using the Markov approach.

Findings

Decision matrices are formed with the help of different combinations of failure and repair rates of all subsystems. The performance of steam generation unit is evaluated in terms of availability levels depicted in decision matrices and plots of failure rates and repair rates of various subsystems. The maintenance priorities of various subsystems of steam generation unit are decided on the basis of effect of failure and repair rates of subsystems on the availability of steam generation unit. The key finding is that the boiler subsystem is the most critical subsystem and hence should be kept on top maintenance priority for performance enhancement of the steam generation unit.

Originality/value

The acceptance of both performance modeling and maintenance priorities decision by the management of sugar plant will result in the enhancement of unit availability and reduction of maintenance cost.
Exploring intersectionality and the employment of school leaders
Authors: Fuller Edward , Hollingworth Liz , An Brian P.
Published: February 2019

Purpose

There is growing recognition of the importance of educator diversity. The purpose of this paper is to examine the production, placement and employment of school leaders as assistant principals, principals and school leaders in Texas by the intersection of race/ethnicity and gender over 23 years.

Design/methodology/approach

This is a quantitative study that employs multilevel logistic regression analysis to examine using 25 years of educator employment data from Texas.

Findings

The authors find descriptive evidence of an increase in diversity of school leaders driven by a decreasing percentage of white men educators and an increasing percentage of Latina educators. Important differences, however, emerge when examining assistant principal vs principal positions, particularly with respect to the odds of being hired. The authors find black male and Latino educators are more likely than white male educators to be hired as an assistant principal but are less likely than white male educators to be hired as a principal. Women educators, regardless of race/ethnicity were less likely to be hired as assistant principals or principals relative to white male educators. Women of color had the lowest odds of being hired in any position relative to white male educators. With respect to school leader preparation program accountability, the authors find few program characteristics associated with placement and differences between programs explained very little of the variation in placement rates, bringing into question efforts to hold programs accountable for such outcomes.

Originality/value

A longitudinal examination of racial/ethnic and gender intersectionality over 25 years is a unique contribution to the study of inequitable access to school leadership positions.
Reputation management in cyberspace: evidence from Jordan’s luxury hotel market
Authors: Alrawadieh Zaid , Dincer Mithat Zeki
Published: February 2019

Purpose

Drawing on a sample of 520 negative reviews posted on TripAdvisor against all five-star hotels operating in Petra, Jordan, the purpose of this paper is to evaluate the response of luxury hotels to negative online reviews by considering the Response Rate (RR), the Response Time (RT) and the Response Content (RC).

Design/methodology/approach

A deductive content analysis was used on hotels’ managerial responses. Based on the literature review, a four-construct scheme was identified to guide the analysis including Appreciation; Apology; Explanation; and Incentive. The managerial responses were carefully read and manually coded based on the four-construct scheme. The time between the review posting date and the date of the managerial response was also recorded. Luxury hotel managers were also surveyed to obtain insights into their perceptions and practices with respect to online reputation management.

Findings

The findings call into question luxury hotels’ awareness of the harmful impact of negative online reviews. Specifically, the findings suggest that less than half of the negative reviews received a managerial response, and that more than half of these were standardized and did not refer to the issues raised in the reviews. The low response rate coupled with the hotel managers’ consensus on the importance of answering all online reviews indicates inconsistency between hotel managers’ perceptions and practices with regard to online reputation management.

Originality/value

The paper adds to the ongoing debate on reputation management in the hospitality industry by considering the managerial response to negative online reviews. The paper discusses several managerial implications for hotel managers as well as avenues for future research.
Measuring the burden of multimorbidity among Medicare beneficiaries via condition counts and cumulative duration
Authors: Maciejewski Matthew L. , Hammill Bradley G.
Published: February 2019

Objective

The study's purpose was to describe the cumulative duration of 19 chronic conditions among Medicare fee‐for‐service (FFS) beneficiaries and examine variation in total expenditures explained by cumulative duration and condition counts.

Design, Setting, Study Design, and Data Extraction

In a retrospective cohort of FFS beneficiaries age ≥68, 2015 Medicare enrollment and claims data (N = 20 124 230) were used to identify the presence or absence of 19 diagnosed chronic conditions, and to construct MCC categories (0‐1, 2‐3, 4‐5, 6+) and cumulative duration of each of 19 conditions from the date of first possible occurrence in claims (1/1/1999) to the end of follow‐up (date of death or 12/31/2015). Total Medicare expenditures were estimated using linear models adjusted for demographic characteristics.

Principal Findings

Multimorbidity was common (71.7 percent with 2+ conditions). The mean cumulative duration of all 19 conditions was 23.6 person‐years, which varied greatly by age and number of conditions. Condition counts were more predictive of Medicare expenditures than cumulative duration (R‐squared for continuous measures = 0.461 vs 0.272; R‐squared for quartiles = 0.408 vs 0.266).

Conclusions

The cumulative duration of chronic conditions varied widely for Medicare beneficiaries, especially for those with 6+ conditions, but was less predictive of total expenditures than condition counts.
Forensic Gait Analysis and Recognition: Standards of Evidence Admissibility
Authors: Macoveciuc Ioana , Rando Carolyn J. , Borrion Hervé
Published: February 2019

Gait is one biological characteristic which has attracted strong research interest due to its potential use in human identification. Although almost two decades have passed since a forensic gait expert has testified to the identity of a perpetrator in court, the methods remain insufficiently robust, considering the recent paradigm shift witnessed in the forensic science community regarding quality of evidence. In contrast, technological advancements have taken the lead, and research into automated gait recognition has greatly surpassed forensic gait analysis in terms of the size of acquired datasets and demographic variability of participants, tested variables, and statistical evaluation of results. Despite these advantages, gait recognition presents with different problems which are yet to be resolved. Therefore, courts should treat gait evidence with caution, as they should any other form of evidence originating from disciplines without fully established codes of practice, error rates, and demonstrable applications in forensic scenarios.
Endothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a
Authors: Kim So‐Jin , Shan Peiying , Hwangbo Cheol , Zhang Yi , Min Jin‐Na , Zhang Xuchen , Ardito Taylor , Li Alfred , Peng Tien , Sauler Maor , Lee Patty J.
Published: February 2019

We previously reported that the canonical innate immune receptor toll‐like receptor 4 (TLR4) is critical in maintaining lung integrity. However, the molecular mechanisms via which TLR4 mediates its effect remained unclear. In the present study, we identified distinct contributions of lung endothelial cells (Ec) and epithelial cells TLR4 to pulmonary homeostasis using genetic‐specific, lung‐ and cell‐targeted in vivo methods. Emphysema was significantly prevented via the reconstituting of human TLR4 expression in the lung Ec of TLR4−/− mice. Lung Ec‐silencing of TLR4 in wild‐type mice induced emphysema, highlighting the specific and distinct role of Ec‐expressed TLR4 in maintaining lung integrity. We also identified a previously unrecognized role of TLR4 in preventing expression of p16INK4a, a senescence‐associated gene. Lung Ec‐p16INK4a‐silencing prevented TLR4−/− induced emphysema, revealing a new functional role for p16INK4ain lungs. TLR4 suppressed endogenous p16INK4a expression via HDAC2‐mediated deacetylation of histone H4. These findings suggest a novel role for TLR4 in maintaining of lung homeostasis via epigenetic regulation of senescence‐related gene expression.
Caloric restriction controls stationary phase survival through Protein Kinase A (PKA) and cytosolic pH
Authors: Dolz‐Edo Laura , van der Deen Margaretha , Brul Stanley , Smits Gertien Jacoba
Published: February 2019

Calorie restriction is the only physiological intervention that extends lifespan throughout all kingdoms of life. In the budding yeast Saccharomyces cerevisiae, cytosolic pH (pHc) controls growth and responds to nutrient availability, decreasing upon glucose depletion. We investigated the interactions between glucose availability, pHc and the central nutrient signalling cAMP‐Protein Kinase A (PKA) pathway. Glucose abundance during the growth phase enhanced acidification upon glucose depletion, via modulation of PKA activity. This actively controlled reduction in starvation pHc correlated with reduced stationary phase survival. Whereas changes in PKA activity affected both acidification and survival, targeted manipulation of starvation pHc showed that cytosolic acidification was downstream of PKA and the causal agent of the reduced chronological lifespan. Thus, caloric restriction controls stationary phase survival through PKA and cytosolic pH.
Cryptocurrency, confirmatory bias and news readability – evidence from the largest Chinese cryptocurrency exchange
Authors: Zhang Shuyu , Zhou Xuanyu , Pan Huifeng , Jia Junyi
Published: February 2019

We investigate whether Chinese cryptocurrency investors show confirmatory bias when processing authority‐related news. Authority‐related news is defined as news that is related to government authority (including central bank) policies or talk. By using data from the largest cryptocurrency exchange in China, we find that investors’ response to authority‐related news is negative and significant in general. Moreover, we find that the abnormal trading volume and standard deviation of abnormal trading volume are significantly higher for authority‐related news with higher readability, suggesting investors respond to the more readable authority‐related news with more trading behaviour.
Parenting style associations with sensory threshold and behaviour: a prospective cohort study in term/preterm infants
Authors: Neel Mary Lauren , Slaughter James C. , Stark Ann R. , Maitre Nathalie L.
Published: February 2019

Aim

Early‐life atypical sensory functioning and behavioural profiles are often associated with long‐term developmental problems, especially in former preterm infants. We tested whether parenting style is associated with atypical sensory threshold or behavioural outcomes in preterm and term infants assessed during early childhood.

Methods

We prospectively evaluated parenting style for a cohort of term and preterm infants who had previous assessments of sensory development and behaviour. We used standardised tools to evaluate parenting style, sensory neurological threshold at one year, and internalising and externalising behavioural tendencies at two years. Covariates included gestational age, sex and maternal education.

Results

For the entire cohort (n = 82), children of more permissive parents were 2.7 times more likely to demonstrate abnormal sensory neurological thresholds compared to children of parents with less permissive styles (CI: 1.4–4.9). More permissive parenting scores were also associated with 2.4 times increased internalising (CI: 1.3–4.2) and 3.0 times increased externalising (CI: 1.6–5.6) tendencies. In the preterm group only, higher authoritative parenting scores were associated with fewer behavioural problems.

Conclusion

Permissive parenting is associated with worse infant sensory and behavioural outcomes. Authoritative parenting is associated with fewer behavioural problems in preterm children. Modification of parenting style may improve sensory development and behavioural outcomes.
Constructing Transnational Solidarity: The Role of Campaign Governance
Authors: Sarkar Santanu , Kuruvilla Sarosh
Published: February 2019

Our inductive study of two transnational labour solidarity efforts focuses on the role of campaign governance. Specifically, we study contrasting campaign strategies, tactics and coalition structures in campaigns by two global union federations, UNI Global Union and the IUF, contextualized in terms of how these campaigns unfolded in India. Our contribution consists of two arguments. The first is that a degree of internal consistency amongst different campaign elements is important for success, and the second is that a mode of articulation that allows for local concerns in affiliate countries to find voice in global campaigns is more likely to result in concrete gains at the local level.
Taxometric Analysis of Secure Base Script Knowledge in Middle Childhood Reveals Categorical Latent Structure
Authors: Waters Theodore E.A. , Facompré Christopher R. , Dujardin Adinda , Van De Walle Magali , Verhees Martine , Bodner Najda , Boldt Lea J. , Bosmans Guy
Published: February 2019

Taxometric investigation of scripted attachment representations in lateadolescence and adulthood suggests that variations in secure base script knowledge consist of differences in degree (dimensional latent structure) rather than differences in kind (categorical latent structure). However, the latent structure of secure base script knowledge in younger cohorts has gone unexplored. This study presents a downward extension of prior taxometric work using the middle childhood version of the Attachment Script Assessment in a cross‐sectional sample of 639 normative‐risk children (age 8 to 13 years; M = 10.77, SD = 1.06). Results suggest that secure base script knowledge in middle childhood is categorically distributed. Taxometric curves revealed three distinct taxa, highlighting discontinuity in the latent structure of scripted attachment representations across development.
The impact of a General Practitioner‐led community paediatric allergy clinic: A service evaluation
Authors: El‐Shanawany Isobel R. , Wade Charlotte , Holloway Judith A.
Published: February 2019

Background

The NHS is not meeting the nation's allergy needs. There are insufficient allergy specialists, with variable care across the country. General practitioners (GPs) are lacking in allergy training. London's Whittington Hospital created a GP with Special Interest (GPwSI) community paediatric allergy clinic, running alongside pre‐existing hospital clinics, to address local unmet needs, aiming to provide equity for patients, improve patient experience and decrease secondary care burden.

Objectives

To establish whether improvements have occurred within the service by introducing a GPwSI‐led community paediatric allergy clinic alongside providing GP education and referral pathways. This study asks: (a) Have allergy‐related hospital attendances decreased with the provision of the community service? (b) Are patients seen in the appropriate clinic? (c) What proportion of patients require GPwSI follow‐up? (d) Is there good patient satisfaction? (e) Have allergy clinic waiting times changed?

Methods

Numbers of allergy‐related hospital attendances and waiting times in 2013, 2014 and 2016 were assessed. Data were analysed regarding proportions of patients requiring GPwSI follow‐up or referral from the GPwSI community clinic to hospital. Patient satisfaction was assessed.

Results

Since introducing the GPwSI community service the burden on secondary care has decreased, with reduced hospital attendances for allergy clinic patients, although waiting times have increased. In 2013, 65% of allergy clinic patients attended other hospital services for allergy‐related complaints prior to their first allergy clinic appointment. This was reduced to 27.3% (community) and 36.9% (hospital) in 2014 and maintained in 2016 (27.5% community and 37.5% hospital), P < 0.01. Patient satisfaction in the hospital and community clinics is very high.

Clinical Relevance

This integrated, multidisciplinary Paediatric Allergy Service could provide a model to improve the unmet allergy need both in the UK and beyond. This GPwSI model could also be applied to other chronic diseases in both adults and children, improving care beyond allergy.
Physical exercise and Prader‐Willi syndrome: A systematic review
Authors: Morales Javier S. , Valenzuela Pedro L. , Pareja‐Galeano Helios , Rincón‐Castanedo Cecilia , Rubin Daniela A. , Lucia Alejandro
Published: February 2019

Objective

The aim of this systematic review was to summarize evidence on the acute responses of individuals with Prader‐Willi syndrome (PWS) to physical exercise, and on the effectiveness of long‐term exercise interventions to improve the clinical manifestations of this syndrome.

Design/methods

Relevant articles were identified in the electronic databases PubMed, Medline, CINAHL and SPORTDiscus (from inception to December 2018). Twenty‐two studies including a total of 356 patients with PWS met all inclusion criteria and were included in the review.

Results

Patients with PWS present with a decreased physical performance and impaired cardiorespiratory (maximal oxygen consumption, heart rate recovery after exercise) and hormonal (growth hormone release) responses to exercise. Most long‐term exercise interventions have proven to decrease body mass while improving physical performance. Some benefits have also been reported in biochemical (glucose homeostasis, lipid profile) and biomechanical (gait pattern) variables, although there is controversy regarding the effects on body composition. No exercise‐related adverse events have been reported in patients with PWS.

Conclusion

Physical exercise seems to be safe and effective for improving several phenotypes in PWS, notably physical fitness. However, further research is needed to confirm these results and especially to corroborate whether exercise per se or combined with dietary intervention is an effective coadjuvant treatment for reducing body mass in these patients.
The Effect of Segregated Cities on Ethnoracial Minority Healthcare System Distrust
Authors: Gibbons Joseph
Published: February 2019

Distrust of the health system is a longstanding issue for ethnoracial minorities, especially for Blacks. Not well understood, however, is the role that ethnoracial segregation within a city plays in this distrust. While segregation is typically associated with neighborhood ills, there is evidence that it can also moderate distrust. This study draws on the 2008 wave of the Public Health Management Corporation's Southeastern Pennsylvania Household Health Survey and the 2005–2009 American Community Survey to explore the possibility that segregation affects healthcare system distrust. Using hierarchical linear modeling, we find that residence in predominantly Black neighborhoods was associated with less distrust in the healthcare system for Black respondents, while residence in mixed neighborhoods was associated with more distrust for Black respondents. These findings call for a reevaluation of how healthcare system distrust is understood. Distrust has been connected to poorer health outcomes, playing into wider gaps in ethnoracial minority health outcomes.
Immediate placement of tapered implants with a moderately rough anodized surface and smooth collar in fresh extraction sockets: A retrospective analysis with 10‐year follow‐up
Authors: Mura Priamo
Published: February 2019

Background

There is limited long‐term data on hard‐ and soft‐tissue outcomes of implants immediately placed in postextraction sockets with immediate or early loading.

Purpose

To evaluate the clinical outcomes of immediately placed anodized tapered implants in consecutive patients with at least 10 years of follow up.

Materials and Methods

This retrospective analysis evaluated outcomes of 61 consecutive patients who received 89 tapered implants with an anodized implant body and machined collar. Implants were placed in fresh extraction sites and functionalized using an immediate‐ or early‐loading protocol. Outcome measures included survival, marginal bone level change (ΔMBL), and papilla index.

Results

The 10‐year cumulative survival rate was 100%. ΔMBL at the 10‐year follow up was −0.86 ± 2.10 mm. At 10 years, patients had mesial and distal papilla index scores of 2 or 3 for 95.9% and 87.8% of implants, respectively.

Conclusions

When used for immediate placement and immediate‐ or early‐loading protocols, this implant produced excellent long‐term hard‐ and soft‐tissue outcomes.
Colorectal trainees in the UK struggle to meet JAG certification standards in colonoscopy by the end of their training
Authors: Malik K. I. , Siau K. , Dunckley P. , Ward S. T.
Published: February 2019

Aim

Colonoscopy certification in the UK is taken in two parts – provisional and full – mandating lifetime procedure counts of 200 or 300, respectively. The aim of this study was to determine the number of procedures performed by colorectal trainees by the end of training compared with their gastroenterology peers and to determine the factors associated with achieving the 300‐procedure target for full certification.

Method

Dates of entry onto the specialist register were obtained from the General Medical Council. This list was cross‐referenced with procedure counts from the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) Endoscopy Training System database to determine the number of colonoscopies and polypectomies performed during training. Factors associated with achieving 300 procedures were analysed by logistic regression.

Results

Procedures numbers were obtained for 234 gastroenterology and 148 colorectal surgery trainees. Over the last 5 years, the number of colonoscopies performed during training has declined for colorectal surgery trainees but increased for gastroenterology trainees. Gastroenterology trainees are more likely to achieve provisional and full certification. For trainees completing training in 2017, 19% of colorectal surgery trainees compared with 88% of gastroenterology trainees were able to reach the threshold of 300 procedures for full certification.

Conclusion

Colorectal surgery trainees lag behind their gastroenterology counterparts in accruing endoscopy experience. This affects the ability of colorectal surgery trainees to achieve certification prior to completion of training. An urgent debate is required to decide what endoscopy training is required of a colorectal surgeon and how a robust training system can be put in place to ensure this is achieved.
Epstein‐Barr virus latent gene EBNA‐1 genetic diversity among transplant patients compared with patients with infectious mononucleosis
Authors: Sullivan Katie , Isabel Sandra , Khodai‐Booran Nasser , Paton Tara A. , Abdulnoor Mariana , Dipchand Anne I. , Hébert Diane , Ng Vicky L. , Allen Upton D.
Published: February 2019

Introduction

As a step toward evaluating the association between Epstein‐Barr virus genetic diversity and post‐transplant lymphoproliferative disorder (PTLD), we conducted a preliminary study to compare the genetic diversity of the EBNA‐1 gene among transplant patients and patients with infectious mononucleosis (IM).

Methods

We sequenced the EBNA‐1 gene in blood samples from study subjects using Sanger methodology. The sequences were aligned with a reference strain and compared with publicly available sequences.

Results

We analyzed 33 study samples and 25 publicly available sequences along with the reference strain B95‐8. The evaluable samples were from sixteen patients with IM (median age 14.0 years, range 2‐24) and 17 transplant patients. There were six children without PTLD (median age 1.93 years, range 0.79‐7.46) and 11 who developed PTLD (median age 5.67 years, range 0.96‐17.45). A predominant EBNA‐1 variant (P‐thr) was identified across the study groups. Differences were observed between the samples from the IM patients compared with the transplant samples.

Conclusion

The predominant EBNA‐1 strain is in contrast to reports of the predominant strain in North America. The results suggest differences between the EBNA‐1 strains among the study groups. Further studies will examine the relationship between EBNA‐1 strains and PTLD occurrence and outcomes.
Use of Titration as a Therapeutic Individualization Strategy: An Analysis of Food and Drug Administration–Approved Drugs
Authors: Schuck Robert N. , Pacanowski Michael , Kim Sarah , Madabushi Rajanikanth , Zineh Issam
Published: February 2019

Selecting a dose regimen that is both safe and effective for patients is one of the most critical elements of a successful drug development program. Titrating the dose regimen of a drug based on patient response may help to identify safe and effective dosages at the individual patient level. Therefore, we quantified and characterized the use of response‐guided titration for drugs recently approved by the US Food and Drug Administration (FDA) to assess how frequently this dosing strategy is used and how titration regimens are evaluated during drug development. Most of the 181 drugs approved from 2013–2017 (78%) had only one approved dosing regimen. Only 30 of 76 (39%) drugs that were considered amenable to response‐guided dosing strategies had information in labeling about such strategies. These findings indicate that although response‐guided titration can be found in labeling, this strategy is used in a minority of drugs for which it may be useful. Careful consideration should be made early in drug development as to whether a new drug is amenable to response‐guided titration as an approach to reducing interpatient variability.
Clonal expansion of hepatic progenitor cells and differentiation into hepatocyte‐like cells
Authors: Liu Wenbin , Wang Yujia , Sun Yufen , Wu Yingchuan , Ma Qiwang , Shi Yun , He Ruoxu , Zhang Ting , Ma Yu , Zuo Wei , Wu Zhongjun
Published: February 2019

Hepatic progenitor cells (HPCs) in adult liver are promising for treatment of liver diseases. A biliary‐derived HPC population in adult mice has been characterized by co‐expression of stem cell marker Sry (sex determining region Y)‐box 9 (SOX9) and biliary marker cytokeratin 7 (CK7). However, isolation of these HPCs in adult healthy liver without any selection procedures remains a big challenge in this field. Here, by establishing a simple and efficient method to isolate and expand the CK7+SOX9+ HPCs in vitro as clones, we acquired a stable and largely scalable cell source. The CK7+SOX9+ progenitor cells were then further induced to differentiate into hepatocyte‐like cells with expression of mature hepatocyte markers albumin (Alb) and hepatocyte nuclear factor 4 alpha (HNF4α), both in vitro and in vivo in the presence of hepatocyte growth factor (HGF) and fibroblast growth factor 9 (FGF9). Furthermore, we found that the HPCs are highly responsive to transforming growth factor‐beta (TGF‐β) signals. Collectively, we identified and harvested a CK7+SOX9+ progenitor cell population from adult mouse liver by a simple and efficient approach. The exploration of this HPC population offers an alternative strategy of generating hepatocyte‐like cells for cell‐based therapies of acute and chronic liver disorders.