bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of RDR1/RDR2/RDR6-independent small RNAs in Arabidopsis thaliana improves MIRNA annotations and reveals novel siRNA loci
Authors: Polydore Seth , Axtell Michael J. 
Published: December 2017

SummaryPlant small RNAs regulate key physiological mechanisms through post-transcriptional and transcriptional silencing of gene expression. sRNAs fall into two major categories: those that are reliant on RNA Dependent RNA Polymerases (RDRs) for biogenesis and those that aren’t. Known RDR-dependent sRNAs include phased and repeat-associated short interfering RNAs, while known RDR-independent sRNAs are primarily microRNAs and other hairpin-derived sRNAs. In this study, we produced and analyzed small RNA-seq libraries from rdr1/rdr2/rdr6 triple mutant plants. Only a small fraction of all sRNA loci were RDR1/RDR2/RDR6-independent; most of these were microRNA loci or associated with predicted hairpin precursors. We found 58 previously annotated microRNA loci that were reliant on RDR1, −2, or −6 function, casting doubt on their classification. We also found 38 RDR1/2/6-independent small RNA loci that are not MIRNAs or otherwise hairpin-derived, and did not fit into other known paradigms for small RNA biogenesis. These 38 small RNA-producing loci have novel biogenesis mechanisms, and are frequently located in the vicinity of protein-coding genes. Altogether, our analysis suggest that these 38 loci represent one or more new types of small RNAs in Arabidopsis thaliana.Significance StatementSmall RNAs regulate gene expression in plants and are produced through a variety of previously-described mechanisms. Here, we examine a set of previously undiscovered small RNA-producing loci that are produced by novel mechanisms.
CYRI1-mediated inhibition of RAC1 signalling restrictsSalmonellaTyphimurium infection
Authors: Yuki Kyoko E , Marei Hadir , Fiskin Evgenij , Eva Megan M , Gopal Angelica A , Schwartzentruber Jeremy A , Majewski Jacek , Cellier Mathieu , Mandl Judith N , Vidal Silvia M , Malo Danielle , Dikic Ivan 
Published: December 2017

AbstractSalmonellapresents a global public health concern. Central toSalmonellapathogenicity is an ability to subvert host defence mechanisms through bacterial effectors that target key host proteins implicated in restricting infection. Thus, to gain insight into host-pathogen interactions governingSalmonellainfection, a thorough understanding of host defence mechanisms is needed. To tackle this, we performed anin vivogenome-wide ENU mutagenesis screen to uncover novel host defence proteins. Through this screen we identified an uncharacterised protein, which we name CYRI1 (CYFIP-relatedRAC1 Interacting protein1) that serves as aSalmonellaresistance factor. We show that CYRI1 binds to the small GTPase RAC1 through a conserved domain present in CYFIP proteins, which are known RAC1 effectors that stimulate actin polymerisation. However, unlike CYFIP proteins, CYRI1 negatively regulates RAC1-driven actin cytoskeleton remodelling, thereby attenuating processes such as phagocytosis and cell migration. This, in turn, enables CYRI1 to counteractSalmonellaat various stages of infection, including bacterial entry into epithelial cells, internalisation into myeloid-derived phagocytes as well as phagocyte-mediated bacterial dissemination. Together, this outlines a novel host defence mechanism that is crucial for determining bacterial fate.
Emergence of reward expectation signals in identified dopamine neurons
Authors: Coddington Luke T. , Dudman Joshua T. 
Published: December 2017

AbstractCoherent control of purposive actions emerges from the coordination of multiple brain circuits during learning. Dissociable brain circuits and cell-types are thought to preferentially participate in distinct learning mechanisms. For example, the activity of midbrain dopamine (mDA) neurons is proposed to primarily, or even exclusively, reflect reward prediction error signals in well-trained animals. To study the specific contribution of individual circuits requires observing changes before tight functional coordination is achieved. However, little is known about the detailed timing of the emergence of reward-related representations in dopaminergic neurons. Here we recorded activity of identified dopaminergic neurons as naïve mice learned a novel stimulus-reward association. We found that at early stages of learning mDA neuron activity reflected both external (sensory) and internal (action initiation) causes of reward expectation. The increasingly precise correlation of action initiation with sensory stimuli rather than an evaluation of outcomes governed mDA neuron activity. Thus, our data demonstrate that mDA neuron activity early in learning does not reflect errors, but is more akin to a Hebbian learning signal - providing new insight into a critical computation in a highly conserved, essential learning circuit.
Experimental Evolution Across Different Thermal Regimes Yields Genetic Divergence in Recombination Fraction But No Divergence in Temperature-Associated Plastic Recombination
Authors: Kohl Kathryn P. , Singh Nadia D. 
Published: December 2017

AbstractPhenotypic plasticity is pervasive in nature. One mechanism underlying the evolution and maintenance of such plasticity is environmental heterogeneity. Indeed, theory indicates that both spatial and temporal variation in the environment should favor the evolution of phenotypic plasticity under a variety of conditions. Cyclical environmental conditions have also been shown to yield evolved increases in recombination frequency. Here were use a panel of replicated experimental evolution populations ofD. melanogasterto test whether variable environments favor enhanced plasticity in recombination rate and/or increased recombination rate in response to temperature. In contrast to expectation, we find no evidence for either enhanced plasticity in recombination or increased rates of recombination in the variable environment lines. Our data confirm a role of temperature in mediating recombination fraction inD. melanogaster, and indicate that recombination is genetically and plastically depressed under lower temperatures. Our data further suggest that the genetic architectures underlying plastic recombination and population-level variation in recombination rate are likely to be distinct.
Routine habitat switching alters the likelihood and persistence of infection with a pathogenic parasite
Authors: Daversa David R. , Manica Andrea , Bosch Jaime , Jolles Jolle W. , Garner Trenton W. J. 
Published: December 2017

AbstractAnimals switch habitats on a regular basis, and when habitats vary in suitability for parasitism, routine habitat switching alters the frequency of parasite exposure and may affect post‐infection parasite proliferation. However, the effects of routine habitat switching on infection dynamics are not well understood.We performed infection experiments, behavioural observations and field surveillance to evaluate how routine habitat switching by adult alpine newts (Ichthyosaura alpestris) influences infection dynamics of the pathogenic parasite,Batrachochytrium dendrobatidis(Bd).We show that when newts are exposed to equal total doses ofBdin aquatic habitats,differences in exposure frequency and post‐exposure habitat alter infection trajectories: newts developed more infections that persisted longer when doses were broken into multiple, reduced‐intensity exposures. Intensity and persistence of infections were reduced among newts that were switched to terrestrial habitats following exposure.When presented with a choice of habitats, newts did not avoid exposure toBd, but heavily infected newts were more prone to reduce time spent in water.Accounting for routine switching between aquatic and terrestrial habitat in the experiments generated distributions of infection loads that were consistent with those in two populations of wild newts.Together, these findings emphasize that differential habitat use and behaviours associated with daily movement can be important ecological determinants of infection risk and severity.Aplain language summaryis available for this article.
Exploring the perceived usefulness of practical food groups in day treatment for individuals with eating disorders
Authors: Biddiscombe Rachel J. , Scanlan Justin Newton , Ross Jessica , Horsfield Sarah , Aradas Jessica , Hart Susan 
Published: December 2017

Background/aimRecovery from eating disorders is a challenging process. Emerging literature suggests that occupational therapists may provide a useful contribution in delivering purposeful eating‐related interventions as a potential treatment to support sustained cognitive and behavioural changes for individuals with eating disorders. This study aimed to evaluate participants’ perceptions of the contribution of occupational therapy practical food groups (food based outings and cooking groups) in supporting their functional recovery.MethodsIndividuals attended practical food groups as part of standard treatment at an outpatient eating disorders day program. Ninety‐nine participants completed questionnaires at discharge and up to three follow‐up points (6, 12 and 24 months). Questions related to practical food groups were analysed, exploring participants’ experiences and perceived usefulness of groups using rating‐scale and open‐ended questions. Open‐ended responses were analysed using thematic analysis. Descriptive statistics were calculated for responses to rating‐scale questions.ResultsAt discharge, participants rated the importance and usefulness of practical food groups as high (4.73 and 4.43 on 5‐point scales, respectively), but tended to rate their enjoyment of the groups lower (3.50 on a 5‐point scale). Some skill transfer was typically reported by participants at discharge (3.92 on a 5‐point scale). One core theme, ‘success through participation’, emerged from qualitative comments. Six subthemes were also identified: helpful components of practical food groups; perceived benefit of exposure; impact of applying cognitive and behavioural skills; challenges affecting participation; facilitating adaptation; and influence of eating disorders on challenging feared foods.ConclusionThis study highlights that participation in practical food groups was perceived as useful in assisting individuals to improve eating behaviours and, in some circumstances, transfer these skills into their lives outside of day program. Results suggest that occupational therapists may have an important contribution in delivering these interventions to support recovery and facilitate application of adaptive coping strategies.
Using the cognitive interviewing process to improve survey design by allied health: A qualitative study
Authors: Howlett Owen , McKinstry Carol , Lannin Natasha A. 
Published: December 2017

Background/aimAllied health professionals frequently use surveys to collect data for clinical practice and service improvement projects. Careful development and piloting of purpose‐designed surveys is important to ensure intended measuring (that respondents correctly interpret survey items when responding). Cognitive interviewing is a specific technique that can improve the design of self‐administered surveys. The aim of this study was to describe the use of the cognitive interviewing process to improve survey design, which involved a purpose‐designed, online survey evaluating staff use of functional electrical stimulation.MethodsA qualitative study involving one round of cognitive interviewing with three occupational therapists and three physiotherapists.ResultsThe cognitive interviewing process identified 11 issues with the draft survey, which could potentially influence the validity and quality of responses. The raised issues included difficulties with: processing the question to be able to respond, determining a response to the question, retrieving relevant information from memory and comprehending the written question. Twelve survey amendments were made following the cognitive interviewing process, comprising four additions, seven revisions and one correction.ConclusionsThe cognitive interviewing process applied during the development of a purpose‐designed survey enabled the identification of potential problems and informed revisions to the survey prior to its use.
Immediate post‐insertion tip migration of peripherally inserted central catheters dependent on arm position and depth of inspiration
Authors: De Carvalho Bruno R , Eagar Gerard M 
Published: December 2017

AbstractIntroductionThe purpose of this study is to assess the degree of PICC tip migration with breathing and arm movement to determine whether accurate positioning is feasible or futile.MethodsA prospective cohort of 218 consecutive patients undergoing PICC insertion at our institution between January and August 2015 was selected, of which 129 met inclusion criteria. The position of insertion was used as control with the arm at 90° during inspiration, followed by three study images: expiration with arm unchanged, inspiration with arm fully adducted and inspiration with arm fully abducted. Mean and standard deviations (SD) of change in PICC position were determined. ANOVA, Pearson correlation coefficients and Chi‐square tests were used to assess the effects of vessel choice, PICC calibre and angle of arm abduction. Complications were recorded.ResultsMovement was predominantly caudal with a mean of 10.4 mm (SD 16.5) with similar degrees of movement in the expiration (12.3 mm) and adduction (12.9 mm) views (P = 0.709). Arm abduction resulted in a mean caudal movement of 6.5 mm. (SD 18.6); however, the degree of abduction had no predictable effect on PICC movement. Thirty‐two per cent of cases demonstrated movement into the right atrium. Neither vessel choice nor type of PICC was shown to have a significant effect on PICC movement.ConclusionThere is large amplitude of PICC tip position change with depth of inspiration and arm position resulting in frequent right atrial position. Despite this there were no associated complications in our cohort which compliments emerging international opinion regarding intra‐atrial PICC tip position.
Under‐utilisation of high‐dose‐rate brachytherapy boost in men with intermediate‐high risk prostate cancer treated with external beam radiotherapy
Authors: Ong Wee Loon , Evans Sue M , Millar Jeremy L 
Published: December 2017

AbstractIntroductionThe aim of this study was to evaluate the use of high‐dose‐rate brachytherapy (HDR‐BT) boost with definitive external beam radiotherapy (EBRT) in prostate cancer (CaP) management.MethodsThe study population comprised men with intermediate‐high risk CaP captured in the population‐based Prostate Cancer Outcome Registry Victoria (PCOR‐Vic), treated with EBRT from January 2010 to December 2015. The primary outcome is the proportion of men who received HDR‐BT boost. Multivariate logistic regressions were used to evaluate the effect of patient‐, tumour‐ and treatment‐factors on the likelihood of HDR‐BT use. Medicare Benefit Schedule (MBS) data was accessed to evaluate the Australia‐wide pattern of HDR‐BT use.ResultsOne thousand eight hundred and six patients were included in this study – 886 (49%) intermediate‐risk, and 920 (51%) high‐risk CaP patients. Overall, only 124 (7%) patients had EBRT + HDR‐BT – 47 (5%) intermediate‐risk and 77 (8%) high‐risk CaP patients (P = 0.01). There is higher proportion of patients who had HDR‐BT in public institutions (7% public vs. 3% private, P = 0.005) and in metropolitan centres (9% metropolitan vs. 2% regional, P < 0.001). In multivariate analyses, older patients were less likely to have HDR‐BT (OR = 0.92; 95% CI = 0.89–0.94, P < 0.001), while patients with high‐risk CaP (OR = 1.8; 95% CI = 1.3–2.7; P = 0.002) treated in metropolitan centres (OR = 5.0; 95% CI = 2.6–9.8; P < 0.001) and public institutions (OR = 3.8; 95% CI = 1.5–9.4; P = 0.005) were more likely to have EBRT + HDR‐BT. There was significant decline in numbers of HDR‐BT performed throughout Australia, from 313 cases in 2010 to 125 cases in 2015.ConclusionHigh‐dose‐rate brachytherapy is under‐utilised with EBRT in this contemporary population‐based cohort of Victorian men with CaP. The decline in HDR‐BT use was also observed nationally.
Are early‐life antecedents of suicide mortality associated with psychiatric disorders and suicidal ideation in midlife?
Authors: Geoffroy M.‐C. , Gunnell D. , Clark C. , Power C. 
Published: December 2017

ObjectiveTo establish whether previously identified early‐life antecedents of suicide mortality (i.e. low birthweight, younger maternal age, higher birth order, externalizing problems and adversities) are associated with proximal psychiatric disorders and suicidal ideation, which are themselves associated with an increased risk of suicide.MethodsParticipants were from the 1958 British birth‐cohort (N = 8905) with information on prenatal/childhood experiences and the Clinical Interview Schedule‐Revised at age 45 years. Outcomes were as follows: any internalizing disorder (anxiety disorder/depressive episode), depressive episode, alcohol use disorder and suicidal ideation.ResultsAfter adjustment, higher birth order (Ptrend = 0.043), younger maternal age (Ptrend = 0.017) and increased number of childhood adversities (Ptrend = 0.026) were associated with an increased risk of internalizing disorders. For example, the OR (95% CI) in fourth‐ or later‐born children was 1.48 (1.06–2.07) and for young maternal age (<19 years) was 1.31 (0.89–1.91). Effect sizes were similar in magnitude for depressive episode and suicidal ideation, although associations did not reach conventional significance levels. No associations were found for low birthweight and externalizing problems (in males) and investigated outcomes.ConclusionAssociations for younger maternal age, higher birth order and adversities with adult internalizing disorders suggest that psychiatric disorders may be on the pathway linking some early‐life factors and suicide.
Get SET: aligning anatomy demonstrator programmes with Surgical Education and Training selection criteria
Authors: Rhodes Danielle , Fogg Quentin A. , Lazarus Michelle D. 
Published: December 2017

BackgroundPrevocational doctors aspiring to surgical careers are commonly recruited as anatomy demonstrators for undergraduate and graduate medical programmes. Entry into Surgical Education and Training (SET) is highly competitive and a unique opportunity exists to align anatomy demonstrator programmes with the selection criteria and core competencies of SET programmes. This study used a qualitative approach to (i) determine what criteria applicants for SET are assessed on and (ii) identify criteria that could be aligned with and enhanced by an anatomy demonstrator programme.MethodsThe selection guidelines of all nine surgical specialties for the 2017 intake of SET trainees were analysed using qualitative content analysis methodology.ResultsThe Royal Australasian College of Surgeons adopted a holistic approach to trainee selection that assessed both discipline‐specific and discipline‐independent skills. Qualitative content analysis identified eight categories of key selection criteria: medical expertise, scholarly activity, professional identity, interpersonal skills, integrity, self‐management, insight and self‐awareness and community involvement. The structured curriculum vitae was heavily weighted towards discipline‐specific skills, such as medical expertise and scholarly activity. Insufficient information was available to determine the weighting of selection criteria assessed by the structured referee reports or interviews.ConclusionAnatomy demonstrator programmes provide prevocational doctors with unique opportunities to develop surgical skills and competencies in a non‐clinical setting. Constructively aligned anatomy demonstrator programmes may be particularly beneficial for prevocational doctors seeking to improve their anatomical knowledge, teaching skills or scholarly activity.
Letter: dose‐response analysis revealed closer relationship between obesity and perioperative outcomes in patients after liver transplantation
Authors: Liu Z. , Mardinoglu A. , Que S. 
Published: December 2017

Linked ContentThis article is linked to Barone et al papers. To view these articles visit https://doi.org/10.1111/apt.14139 and https://doi.org/10.1111/apt.14446.
Viral kinetics analysis and virological characterization of treatment failures in patients with chronic hepatitis C treated with sofosbuvir and an NS5A inhibitor
Authors: Fourati S. , Guedj J. , Chevaliez S. , Nguyen T. H. T. , Roudot‐Thoraval F. , Ruiz I. , Soulier A. , Scoazec G. , Varaut A. , Poiteau L. , Francois M. , Mallat A. , Hézode C. , Pawlotsky J.‐M. 
Published: December 2017

SummaryBackgroundThe combination of sofosbuvir (SOF) plus an NS5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and NS5A inhibitor are rapidly decreasing, the combination of these DAAs will be the standard treatment in most low‐ to middle‐income countries in the future.AimTo identify key predictors of response that can be used to tailor treatment decisions.MethodsA cohort of 216 consecutive patients infected with HCV genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (SOF) + daclatasvir (n = 176) or SOF + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear HCV.ResultsThe overall SVR rate was high (94.4%; n = 204), regardless of the time to viral suppression or low‐level viraemia at the end of treatment. The model‐based predicted HCV RNA levels at the end of treatment could not differentiate patients who did from those who did not achieve SVR. The presence of NS5A resistance‐associated substitutions [position 28 (OR = 70.3, P<.001) and/or 31 (OR = 61.6, P = .002)] at baseline was predictive of virological failure in cirrhotic patients but was not associated with on‐treatment viral kinetics.ConclusionThis real‐world study confirms the excellent results of clinical trials with therapies based on a combination of SOF plus an NS5A inhibitor. It suggests that a personalized approach including baseline NS5A inhibitor resistance testing may inform treatment decisions in cirrhotic patients.
General Single-Index Survival Regression Models for Incident and Prevalent Covariate Data and Prevalent Data Without Follow-Up
Authors: Chen Shih-Wei , Chiang Chin-Tsang 
Published: December 2017

Summary
This article mainly focuses on analyzing covariate data from incident and prevalent cohort studies and a prevalent sample with only baseline covariates of interest and truncation times. Our major task in both research streams is to identify the effects of covariates on a failure time through very general single-index survival regression models without observing survival outcomes. With a strict increase of the survival function in the linear predictor, the ratio of incident and prevalent covariate densities is shown to be a non-degenerate and monotonic function of the linear predictor under covariate-independent truncation. Without such a structural assumption, the conditional density of a truncation time in a prevalent cohort is ensured to be a non-degenerate function of the linear predictor. In light of these features, some innovative approaches, which are based on the maximum rank correlation estimation or the pseudo least integrated squares estimation, are developed to estimate the coefficients of covariates up to a scale factor. Existing theoretical results are further used to establish the -consistency and asymptotic normality of the proposed estimators. Moreover, extensive simulations are conducted to assess and compare the finite-sample performance of various estimators. To illustrate the methodological ideas, we also analyze data from the Worcester Heart Attack Study and the National Comorbidity Survey Replication.