bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Behavior Pain Assessment Tool for critically ill adults: a validation study in 28 countries
Authors: Gélinas Céline , Puntillo Kathleen A. , Levin Pavel , Azoulay Elie 
Published: March 2017

Abstract
Many critically ill adults are unable to communicate their pain through self-report. The study purpose was to validate the use of the 8-item Behavior Pain Assessment Tool (BPAT) in patients hospitalized in 192 intensive care units from 28 countries. A total of 4812 procedures in 3851 patients were included in data analysis. Patients were assessed with the BPAT before and during procedures by 2 different raters (mostly nurses and physicians). Those who were able to self-report were asked to rate their pain intensity and pain distress on 0 to 10 numeric rating scales. Interrater reliability of behavioral observations was supported by moderate (0.43-0.60) to excellent (>0.60) kappa coefficients. Mixed effects multilevel logistic regression models showed that most behaviors were more likely to be present during the procedure than before and in less sedated patients, demonstrating discriminant validation of the tool use. Regarding criterion validation, moderate positive correlations were found during procedures between the mean BPAT scores and the mean pain intensity (r = 0.54) and pain distress (r = 0.49) scores (P < 0.001). Regression models showed that all behaviors were significant predictors of pain intensity and pain distress, accounting for 35% and 29% of their total variance, respectively. A BPAT cut-point score >3.5 could classify patients with or without severe levels (≥8) of pain intensity and distress with sensitivity and specificity findings ranging from 61.8% to 75.1%. The BPAT was found to be reliable and valid. Its feasibility for use in practice and the effect of its clinical implementation on patient pain and intensive care unit outcomes need further research.
A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9
Authors: Dagdas Yavuz S. , Chen Janice S. , Sternberg Samuel H. , Doudna Jennifer A. , Yildiz Ahmet 
Published: March 2017

AbstractThe Cas9 endonuclease is widely utilized for genome engineering applications by programming its single-guide RNA and ongoing work is aimed at improving the accuracy and efficiency of DNA targeting. DNA cleavage of Cas9 is controlled by the conformational state of the HNH nuclease domain, but the mechanism that governs HNH activation at on-target DNA while reducing cleavage activity at off-target sites remains poorly understood. Using single-molecule FRET, we identified an intermediate state of S. pyogenes Cas9, representing a conformational checkpoint between DNA binding and cleavage. Upon DNA binding, the HNH domain transitions between multiple conformations before docking into its active state. HNH docking requires divalent cations, but not strand scission, and this docked conformation persists following DNA cleavage. Sequence mismatches between the DNA target and guide RNA prevent transitions from the checkpoint intermediate to the active conformation, providing selective avoidance of DNA cleavage at stably bound off-target sites.
Should a few null findings falsify prefrontal theories of conscious perception?
Authors: Odegaard Brian , Knight Robert T. , Lau Hakwan 
Published: March 2017

AbstractIs activity in prefrontal cortex (PFC) critical for conscious perception? Major theories of consciousness make distinct predictions about the role of PFC, providing an opportunity to arbitrate between these views empirically. Here we address three common misconceptions: i) PFC lesions do not affect subjective perception; ii) PFC activity does not reflect specific perceptual content; iii) PFC involvement in studies of perceptual awareness is solely driven by the need to make reports required by the experimental tasks, rather than subjective experienceperse. These claims are incompatible with empirical findings, unless one focuses only on studies using methods with limited sensitivity. The literature highlights PFC’s essential role in enabling the subjective experience in perception,contrathe objective capacity to perform visual tasks; conflating the two can also be a source of confusion.
Post-inference Methods of Prior Knowledge Incorporation in Gene Regulatory Network Inference
Authors: Nair Ajay , Chetty Madhu 
Published: March 2017

AbstractThe regulatory interactions in a cell control cellular response to environmental and genetic perturbations. Gene regulatory network (GRN) inference from high-throughput gene expression data helps to identify unknown regulatory interactions in a cell. One of the main challenges in the GRN inference is to identify complex biological interactions from the limited information contained in the gene expression data. Using prior biological knowledge, in addition to the gene expression data, is a common method to overcome this challenge. However, only a few GRN inference methods can inherently incorporate the prior knowledge and these methods are also not among the best-ranked in benchmarking studies.We propose to incorporate the prior knowledge after the GRN inference so that any inference method can be used. Two algorithms have been developed and tested on the well studiedEscherichia coli, yeast, and realistic in silico networks. Their accuracy is higher than the best-ranking method in the latest community-wide benchmarking study. Further, one of the algorithms identifies and removes wrong interactions predicted by the inference methods. With half of the available prior knowledge of interactions, around 970 additional correct edges were obtained and 1300 wrong interactions were removed. Moreover, the limitation that only a few GRN inference methods can incorporate the prior knowledge is overcome. Therefore, a post-inference method of incorporating the prior knowledge improves accuracy, removes wrong edges, and overcomes the limitation of GRN inference methods.
Semblance of heterogeneity in collective cell migration
Authors: Schumacher Linus J. , Maini Philip K. , Baker Ruth E. 
Published: March 2017

AbstractCell population heterogeneity is increasingly a focus of inquiry in biological research. For example, cell migration studies have investigated the heterogeneity of invasiveness and taxis in development, wound healing, and cancer. However, relatively little effort has been devoted to explore when heterogeneity is mechanistically relevant and how to reliably measure it. Statistical methods from the animal movement literature offer the potential to analyse heterogeneity in collections of cell tracking data. A popular measure of heterogeneity, which we use here as an example, is the distribution of delays in directional cross-correlation. Employing a suitably generic, yet minimal, model of collective cell movement in three dimensions, we show how using such measures to quantify heterogeneity in tracking data can result in the inference of heterogeneity where there is none. Our study highlights a potential pitfall in the statistical analysis of cell population heterogeneity, and we argue this can be mitigated by the appropriate choice of null models.Highlightsgroups of identical cells appear heterogeneous due to limited sampling and experimental repeatabilityheterogeneity bias increases with attraction/repulsion between cellsmovement in confined environments decreases apparent heterogeneityhypothetical applications in neural crest andin vitrocancer systemsIn BriefWe use a mathematical model to show how cell populations can appear heterogeneous in their migratory characteristics, even though they are made up of identically-behaving individual cells. This has important consequences for the study of collective cell migration in areas such as embryo development or cancer invasion.
Migration of human mesenchymal stem cells stimulated with pulsed electric field and the dynamics of the cell surface glycosylation
Authors: Jezierska-Wozniak Katarzyna , Lipiński Seweryn , Grabarczyk Łukasz , Barczewska Monika , Habich Aleksandra , Wojtkiewicz Joanna , Maksymowicz Wojciech 
Published: March 2017

AbstractThe objective of our study was to develop novel techniques for investigations of cell motility, and to assess whether the electric field of the therapeutic spinal cord stimulation system usedin vivocontributes to the migration of human mesenchymal stem cells (hMSCs)in vitro.We have investigated electrotaxis of bone marrow-derived MSCs using pulsed electric field (PEF) in range 16-80 mV/mm and frequency 130 Hz and 240 Hz. The PEF-related dynamics of the cell surface glycosylation was evaluated using six plant lectins.PEF at physiological levels (10mV/mm; 130 Hz) did not influence cellular motilityin vitro, what may correspond to the maintenance of the transplanted cells at the lesion sitein vivo. Increase of the PEF intensity and frequency above physiological levels resulted in the increase in the cellular migration ratein vitro. PEF elevated above physiological intensity and frequency (40-80 mV/mm; 240 Hz), but not at physiological levels, resulted in changes of the cell surface glycosylation.We find the described approach as convenient for investigations and for thein vitromodeling of the cellular systems intended for the regenerative cell transplantationsin vivo. Probing cell surface glycomes may provide valuable biomarkers to assess competence of transplanted cells.
Methicillin resistantStaphylococcus aureusemerged long before the introduction of methicillin in to clinical practice
Authors: Harkins Catriona P. , Pichon Bruno , Doumith Michel , Parkhill Julian , Westh Henrik T. , Tomasz Alexander , de Lencastre Herminia , Bentley Stephen D. , Kearns Angela M. , Holden Matthew T.G. 
Published: March 2017

AbstractThe spread of drug-resistant bacterial pathogens pose a major threat to global health. It is widely recognised that the widespread use of antibiotics has generated selective pressures that have driven the emergence of resistant strains. Methicillin-resistantStaphylococcus aureus(MRSA) was first observed in 1960, less than one year after the introduction of this second generation β-lactam antibiotic into clinical practice. Epidemiological evidence has always suggested that resistance arose around this period, when themecAgene encoding methicillin resistance carried on an SCCmecelement, was horizontally transferred to an intrinsically sensitive strain ofS. aureus. Whole genome sequencing a collection of the very first MRSA isolates allowed us to reconstruct the evolutionary history of the archetypal MRSA. Bayesian phylogenetic reconstruction was applied to infer the time point at which this early MRSA lineage arose and when SCCmecwas acquired. MRSA emerged in the mid 1940s, following the acquisition of an ancestral type I SCCmecelement, some fourteen years prior to the first therapeutic use of methicillin. Methicillin use was not the original driving factor in the evolution of MRSA as previously thought. Rather it was the widespread use of first generation β-lactams such as penicillin in the years prior to the introduction of methicillin, which selected forS. aureusstrains carrying themecAdeterminant. Crucially this highlights how new drugs, introduced to circumvent known resistance mechanisms, can be rendered ineffective by unrecognised adaptations in the bacterial population due to the historic selective landscape created by the widespread use of other antibiotics.
Aligning single-cell developmental and reprogramming trajectories identifies molecular determinants of reprogramming outcome
Authors: Cacchiarelli Davide , Qiu Xiaojie , Srivatsan Sanjay , Ziller Michael , Overbey Eliah , Grimsby Jonna , Pokharel Prapti , Livak Ken , Li Shuqiang , Meissner Alex , Mikkelsen Tarjei , Rinn John , Trapnell Cole 
Published: March 2017

AbstractCellular reprogramming through manipulation of defined factors holds great promise for large-scale production of cell types needed for use in therapy, as well as for expanding our understanding of the general principles of gene regulation. MYOD-mediated myogenic reprogramming, which converts many cell types into contractile myotubes, remains one of the best characterized model system for direct conversion by defined factors. However, why MYOD can efficiently convert some cell types into myotubes but not others remains poorly understood. Here, we analyze MYOD-mediated reprogramming of human fibroblasts at pseudotemporal resolution using single-cell RNA-Seq. Successfully reprogrammed cells navigate a trajectory with two branches that correspond to two barriers to reprogramming, with cells that select incorrect branches terminating at aberrant or incomplete reprogramming outcomes. Differential analysis of the major branch points alongside alignment of the successful reprogramming path to a primary myoblast trajectory revealed Insulin and BMP signaling as crucial molecular determinants of an individual cell’s reprogramming outcome, that when appropriately modulated, increased efficiency more than five-fold. Our single-cell analysis reveals that MYOD is sufficient to reprogram cells only when the extracellular milieu is favorable, supporting MYOD with upstream signaling pathways that drive normal myogenesis in development.
Community participation and mental health prior to treatment
Authors: McGaffin Breanna , Deane Frank P. , Kelly Peter J. 
Published: March 2017

Purpose
The purpose of this paper is to investigate Keyes’ (2007) model of mental health, the presence (flourishing) or absence (languishing) of social, emotional and psychological wellbeing, in the context of drug and alcohol misuse and the frequency and pattern of community participation (engaging in society).

Design/methodology/approach
Participants were 1,815 individuals (70 per cent male) who entered residential substance misuse treatment provided by The Salvation Army. Questionnaires were completed at intake assessments with The Salvation Army staff. The data were compared with population norms of community participation utilising t-tests, while multiple linear regression was used to examine continuous mental health.

Findings
Although participants have lower levels of community participation compared to Australian population norms, those participants who were experiencing flourishing mental health had higher rates of community participation than Australian norms. Keeping in touch with friends and family was the most common form of participation. Informal social connectedness and civic engagement were the strongest predictors of mental health over and above more traditional substance use outcomes such as cravings.

Originality/value
This is one of the first studies to describe the relationships between community participation, substance use and mental health in participants seeking treatment for substance misuse. Despite having a drug or alcohol addiction requiring treatment, those participants with flourishing mental health have higher levels of community participation than community norms. Furthermore, community participation predicts mental health. This offers promise for interventions that increase community participation but further research using longitudinal designs is needed to replicate and clarify the direction of these relationships.
LMX differentiation, diversity, and group performance
Authors: Lee Kihyun , Chae Yeon Joo 
Published: March 2017

PurposeThe impact of leader-member exchange (LMX) differentiation on group performance has been considered ambiguous. The purpose of this paper is to resolve this ambiguity by theorizing and examining a curvilinear relationship between LMX differentiation and group performance, and the moderating effects of group diversity on this relationship.Design/methodology/approachData were drawn from 63 work groups (consisting of 322 members and 63 group leaders) selected from 27 technology service companies in South Korea. Group members rated their perceived LMX quality, while the human resource (HR) directors of each company assessed group performance.FindingsThe results showed that LMX differentiation had an inverted U-shaped relationship with group performance and that gender diversity and age diversity negatively moderated that relationship. However, the interaction between LMX differentiation and education-level diversity was not significant.Originality/valueThis study extends extant research by addressing the inconsistency among theoretical perspectives on the effects of LMX differentiation. This study transcends earlier research by considering the complex process of LMX differentiation, such as the curvilinear relationship between LMX differentiation and group performance, and the moderating effects of group diversity on that relationship.
Saudi women’s work challenges and barriers to career advancement
Authors: Al-Asfour Ahmed , Tlaiss Hayfaa A. , Khan Sami A. , Rajasekar James 
Published: March 2017

Purpose
Few studies have explored the work challenges and career barriers faced by women in the Kingdom of Saudi Arabia (KSA). Drawing on Institutional Theory, the purpose of this paper is to explore the experiences of employed Saudi women through in-depth interviews.

Design/methodology/approach
The paper employs a phenomenological qualitative approach drawing on 12 in-depth semi-structured interviews with Saudi women.

Findings
The findings reveal a significant number of prominent societal and organizational structural and attitudinal barriers to the advancement of Saudi women in paid employment. Among others, these barriers include a lack of mobility; the salience of gender stereotypes; gender discrimination in the workplace; limited opportunities for growth, development, and career advancement; excessive workload caused by a lack of family-work balance; and gender-based challenges related to dealing with pregnancy.

Research limitations/implications
Despite the contributions of this study, it also has limitations, particularly the convenience sampling approach and the focus on the KSA. The small sample size means that the findings cannot be generalized to all women employed in Saudi Arabia and should be generalized within Saudi Arabia and other Arab societies only with caution.

Originality/value
The paper contributes to the understanding of work challenges and barriers of Saudi women in the workforce. It provides fresh insights to the issues surrounding women in Saudi Arabia and the need to address them in order to provide support for their career advancement.
The role of mentoring in early career physics teachers’ professional identity construction
Authors: Cameron David , Grant Anna 
Published: March 2017

PurposeThe purpose of this paper is to explore the ways in which external subject-specific mentoring can influence the professional identity construction of early career physics teachers (ECPT).Design/methodology/approachThe methodology evolved from the evaluation of a mentoring project, involving semi-structured interviews with a number of early career teachers. Responses from 18 teachers, which related to the impact of the mentoring relationship on their professional identity development, were subject to a process of iterative thematic coding in the context of interpretative repertoires via a collaborative “developmental dialogue” between the managers of the mentoring project and its external evaluators.FindingsThe analysis of participants’ responses suggested that the nature of the relationship between early career teacher and mentor played a role in the emergence, or suppression, of their professional identities as physics teachers at the start of their teaching careers. In some cases, mentoring provision was little short of a “lifeline” for the teachers.Practical implicationsMentors need the opportunity to develop their professional practice and identity through contact with the community of teacher educators. The practice of training, mentoring and coaching teachers should be valued at least as much as teaching itself and should be recognised as its own professional practice.Originality/valueThis study builds on a number of well-established pieces of research and concepts relating to the challenges facing early career teachers and their professional identity construction. It provides insight into the challenges facing ECPTs specifically, which includes the risk of isolation and unrealistic expectations from colleagues. It not only confirms the merits of external mentoring, but also demonstrates the significant responsibility, which comes with the mentor’s role and the negative impact on teachers’ professional identity construction caused by deficiencies in mentoring.
Formal and informal long term care work: policy conflict in a liberal welfare state
Authors: Murphy Caroline , Turner Thomas 
Published: March 2017

PurposeThe undervaluing of care work, whether conducted informally or formally, has long been subject to debate. While much discussion, and indeed reform has centred on childcare, there is a growing need, particularly in countries with ageing populations, to examine how long-term care (LTC) work is valued. The purpose of this paper is to provide an overview of the way in which employment policies (female labour market participation, retirement age, and precarious work) and social policies (care entitlements and benefits/leave for carers) affect both informal carers and formal care workers in a liberal welfare state with a rapidly ageing population.Design/methodology/approachDrawing the adult worker model the authors use the existing literature on ageing care and employment to examine the approach of a liberal welfare state to care work focusing on both supports for informal carers and job quality in the formal care sector.FindingsThe research suggests that employment policies advocating increased labour participation, delaying retirement and treating informal care as a form of welfare are at odds with LTC strategies which encourage informal care. Furthermore, the latter policy acts to devalue formal care roles in an economic sense and potentially discourages workers from entering the formal care sector.Originality/valueTo date research investigating the interplay between employment and LTC policies has focused on either informal or formal care workers. In combining both aspects, we view informal and formal care workers as complementary, interdependent agents in the care process. This underlines the need to develop social policy regarding care and employment which encompasses the needs of each group concurrently.