bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term extrapulmonary comorbidities after lung transplantation in cystic fibrosis: Update of specificities
Authors: Jardel Sabine , Reynaud Quitterie , Durieu Isabelle 
Published: April 2018

AbstractLung transplantation (LT) is the standard therapeutic option for cystic fibrosis (CF) patients with end‐stage lung disease. Both conditions lead to extrarespiratory complications, such as diabetes, renal insufficiency, bone disease, and cancer. The purpose of this study was to provide an update of the nonrespiratory comorbidities following LT in adult patients with CF and their specificities regarding their multisystemic underlying condition despite their younger age compared to other patients undergoing LT. Diabetes, renal insufficiency, metabolic bone disease, hypertension, liver disease, and cancer are the comorbidities considered in this review. The increase in CF adults living with a lung transplant justifies an update of knowledge for this specific situation (the prevalence of these complications, underlying risk factors), to provide better medical care and establish early diagnosis strategies.
Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure‐FLT3 Relationship
Authors: Liu Tao , Ivaturi Vijay , Sabato Philip , Gobburu Jogarao V. S. , Greer Jacqueline M. , Wright John J. , Smith B. Douglas , Pratz Keith W. , Rudek Michelle A. ,   on behalf of the ETCTN‐6745 study team
Published: April 2018

AbstractSorafenib administered at the approved dose continuously is not tolerated long‐term in patients with acute myeloid leukemia (AML). The purpose of this study was to optimize the dosing regimen by characterizing the sorafenib exposure‐response relationship in patients with AML. A one‐compartment model with a transit absorption compartment and enterohepatic recirculation described the exposure. The relationship between sorafenib exposure and target modulation of kinase targets (FMS‐like tyrosine kinase 3 (FLT3)‐ITD and extracellular signal‐regulated kinase (ERK)) were described by an inhibitory maximum effect (Emax) model. Sorafenib could inhibit FLT3‐ITD activity by 100% with an IC50 of 69.3 ng/mL and ERK activity by 84% with an IC50 of 85.7 ng/mL (both adjusted for metabolite potency). Different dosing regimens utilizing 200 or 400 mg at varying frequencies were simulated based on the exposure‐response relationship. Simulations demonstrate that a 200 mg twice daily (b.i.d.) dosing regimen showed similar FLT3‐ITD and ERK inhibitory activity compared with 400 mg b.i.d. and is recommended in further clinical trials in patients with AML.
Mountaintop removal mining alters stream salamander population dynamics
Authors: Price Steven J. , Freytag Sara Beth , Bonner Simon J. , Drayer Andrea N. , Muncy Brenee' L. , Hutton Jacob M. , Barton Christopher D. 
Published: April 2018

AbstractAimPopulation dynamics are often tightly linked to the condition of the landscape. Focusing on a landscape impacted by mountaintop removal coal mining (MTR), we ask the following questions: (1) How does MTR influence vital rates including occupancy, colonization and persistence probabilities, and conditional abundance of stream salamander species and life stages? (2) Do species and life stages respond similar to MTR mining or is there significant variation among species and life stages?LocationFreshwater and terrestrial habitats in Central Appalachia (South‐eastern Kentucky, USA).MethodsWe conducted salamander counts for three consecutive years in 23 headwater stream reaches in forested or previously mined landscapes. We used a hierarchical, N‐mixture model with dynamic occupancy to calculate species‐ and life stage‐specific occupancy, colonization and persistence rates, and abundance given occupancy. We examined the coefficients of the hierarchical priors to determine population variation among species and life stages.ResultsOver 3 years, reference sites had greater salamander abundances and were occupied at a much higher rate than streams impacted by MTR. At sites impacted by MTR mining, most salamander species and life stages exhibited reduced initial occupancy, colonization rates, persistence rates and conditional abundance relative to reference stream reaches. Furthermore, the rates in MTR sites showed low variance, reinforcing that species and life stages were responding similar to MTR.Main conclusionsSalamander populations in landscapes modified by MTR mining exhibited significantly reduced vital rates compared to reference sites. Yet, similarity in responses across species suggests that management or restoration may benefit the entire salamander assemblage. For example, reforestation could reduce landscape resistance, repair altered hydrologic regimes and allow for higher rates of colonization and persistence in streams impacted by MTR.
Defining the Potential of Nanoscale Re‐Os Isotope Systematics Using Atom Probe Microscopy
Authors: Daly Luke , Bland Phil A. , Tessalina Svetlana , Saxey David W. , Reddy Steven M. , Fougerouse Denis , Rickard William D.A. , Forman Lucy V. , La Fontaine Alexandre , Cairney Julie M. , Ringer Simon P. , Schaefer Bruce F. , Schwander Daniel 
Published: April 2018

Atom probe microscopy (APM) is a relatively new in situ tool for measuring isotope fractions from nanoscale volumes (< 0.01 μm3). We calculate the theoretical detectable difference of an isotope ratio measurement result from APM using counting statistics of a hypothetical data set to be ± 4δ or 0.4% (2s). However, challenges associated with APM measurements (e.g., peak ranging, hydride formation and isobaric interferences), result in larger uncertainties if not properly accounted for. We evaluate these factors for Re‐Os isotope ratio measurements by comparing APM and negative thermal ionisation mass spectrometry (N‐TIMS) measurement results of pure Os, pure Re, and two synthetic Re‐Os‐bearing alloys from Schwander et al. (2015, Meteoritics and Planetary Science, 50, 893) [the original metal alloy (HSE) and alloys produced by heating HSE within silicate liquid (SYN)]. From this, we propose a current best practice for APM Re‐Os isotope ratio measurements. Using this refined approach, mean APM and N‐TIMS 187Os/189Os measurement results agree within 0.05% and 2s (pure Os), 0.6–2% and 2s (SYN) and 5–10% (HSE). The good agreement of N‐TIMS and APM 187Os/189Os measurements confirms that APM can extract robust isotope ratios. Therefore, this approach permits nanoscale isotope measurements of Os‐bearing alloys using the Re‐Os geochronometer that could not be measured by conventional measurement principles.
The opposing roles of CD4+ T cells in anti‐tumour immunity
Authors: Ahrends Tomasz , Borst Jannie 
Published: April 2018

SummaryCancer immunotherapy focuses mainly on anti‐tumour activity of CD8+ cytotoxic T lymphocytes (CTLs). CTLs can directly kill all tumour cell types, provided they carry recognizable antigens. However, CD4+ T cells also play important roles in anti‐tumour immunity. CD4+ T cells can either suppress or promote the anti‐tumour CTL response, either in secondary lymphoid organs or in the tumour. In this review, we highlight opposing mechanisms of conventional and regulatory T cells at both sites. We outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients.
Early programming and late‐acting checkpoints governing the development of CD4 T‐cell memory
Authors: Dhume Kunal , McKinstry Karl Kai 
Published: April 2018

SummaryCD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T‐cell generation into vaccine strategies therefore offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long‐term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains. A major barrier in the design of such vaccines is that the mechanisms controlling the efficiency with which memory cells form remain incompletely understood. Here, we discuss recent insights into fate decisions controlling memory generation. We focus on the importance of three general cues: interleukin‐2, antigen and co‐stimulatory interactions. It is increasingly clear that these signals have a powerful influence on the capacity of CD4 T cells to form memory during two distinct phases of the immune response. First, through ‘programming’ that occurs during initial priming, and second, through ‘checkpoints’ that operate later during the effector stage. These findings indicate that novel vaccine strategies must seek to optimize cognate interactions, during which interleukin‐2‐, antigen‐ and co‐stimulation‐dependent signals are tightly linked, well beyond initial antigen encounter to induce robust memory CD4 T cells.
Detection of selection signatures for agonistic behaviour in cattle
Authors: Eusebi P.G. , Cortés O. , Carleos C. , Dunner S. , Cañon J. 
Published: April 2018

SummaryThe identification of genomic regions including signatures of selection produced by domestication and its subsequent artificial selection processes allows the understanding of the evolution of bovine breeds. Although several studies describe the genomic variability among meat or milk production cattle breeds, there are limited studies orientated towards bovine behavioural features. This study is focused on mapping genomic signatures of selection which may provide insights of differentiation between neutral and selected polymorphisms. Their effects are studied in the Lidia cattle traditionally selected for agonistic behaviour compared with Spanish breeds showing tamed behaviour. Two different approaches, BayeScan and SelEstim, were applied using genotypic 50K SNP BeadChip data. Both procedures detected two genomic regions bearing genes previously related to behavioural traits. The frequencies of the selected allele in these two regions in Lidia breed were opposite to those found in the tamed breeds. In these genomic regions, several putative genes associated with enriched metabolic pathways related to the behavioural development were identified, as neurochondrin gene (NCDN) or glutamate ionotropic receptor kainate type subunit 3 (GRIK3) both located at BTA3 or leucine‐rich repeat and Ig domain containing 2 (LINGO2) and phospholipase A2‐activating protein (PLAA) at BTA8.
Rates of woody encroachment in African savannas reflect water constraints and fire disturbance
Authors: Axelsson Christoffer R. , Hanan Niall P. 
Published: April 2018

AbstractAimThe aims of this study were to (1) estimate current rates of woody encroachment across African savannas; (2) identify relationships between change in woody cover and potential drivers, including water constraints, fire frequency and livestock density. The found relationships led us to pursue a third goal: (3) use temporal dynamics in woody cover to estimate potential woody cover.LocationSub‐Saharan African savannas.MethodsThe study used very high spatial resolution satellite imagery at sites with overlapping older (2002–2006) and newer (2011–2016) imagery to estimate change in woody cover. We sampled 596 sites in 38 separate areas across African savannas. Areas with high anthropogenic impact were avoided in order to more clearly identify the influence of environmental factors. Relationships between woody cover change and potential drivers were identified using linear regression and simultaneous autoregression, where the latter accounts for spatial autocorrelation.ResultsThe mean annual change in woody cover across our study areas was 0.25% per year. Although we cannot explain the general trend of encroachment based on our data, we found that change rates were positively correlated with the difference between potential woody cover and actual woody cover (a proxy for water availability; p < .001), and negatively correlated with fire frequency (p < .01). Using the relationship between rates of encroachment and initial cover, we estimated potential woody cover at different rainfall levels.Main conclusionsThe results indicate that woody encroachment is ongoing and widespread across African savannas. The fact that the difference between potential and actual cover was the most significant predictor highlights the central role of water availability and tree–tree competition in controlling change in woody populations, both in water‐limited and mesic savannas. Our approach to derive potential woody cover from the woody cover change trajectories demonstrates that temporal dynamics in woody populations can be used to infer resource limitations.
Leaf age affects the efficacy of insecticides to control Asian citrus psyllid, Diaphorina citri (Hemiptera: Liviidae)
Authors: De Carli L. F. , Miranda M. P. , Volpe H. X. L. , Zanardi O. Z. , Vizoni M. C. , Martini F. M. , Lopes J. P. A. 
Published: April 2018

AbstractHuanglongbing (HLB), the most destructive citrus disease worldwide, is associated with the bacteria transmitted by the psyllid Diaphorina citri Kuwayama (Hemiptera: Liviidae). One of the main tactics used to manage this disease is the chemical control of D. citri. In this study, the efficacy of four insecticides commonly used by the citrus growers against the D. citri adults was assessed in two vegetative growth stages of flush: young shoots (~ 10 cm in length) and mature leaves. The bioassays were carried out under the greenhouse and field conditions. The insecticides bifenthrin, dimethoate, imidacloprid and thiamethoxam were tested at the recommended rates of 15, 450, 40 and 25 mg/L of water, respectively. The insecticides were sprayed onto the leaves of each stage until runoff. Psyllid mortality was assessed at different periods after insecticide application (0, 1 and 2 weeks). In both greenhouse and field trees, the period of control was shorter in the young shoots than in the mature leaves. In addition, the efficacy of insecticides rapidly decreased in the young shoots over time, mainly for imidacloprid and bifenthrin (less than 1 week). Thus, these results suggest that the number of spray applications to control D. citri should be more frequent during the flushing period.
Adaptation of evidence‐based guideline recommendations to address urinary incontinence in nursing home residents according to the ADAPTE‐process
Authors: Hoedl Manuela , Schoberer Daniela , Halfens Ruud J. G. , Lohrmann Christa 
Published: April 2018

Aims and objectivesTo adapt international guideline recommendations for the conservative management of urinary incontinence (UI), defined as any involuntary loss of urine, in Austrian nursing home residents following the ADAPTE‐process.BackgroundMany international guidelines for managing UI are available. Nevertheless, the international recommendations have not yet been adapted to address the Austrian nursing home context. This crucial adaptation process will enhance the acceptance and applicability of the recommendations as well as encourage adherence among Austrian nurses and nursing home residents.DesignThis study is a methodological study based on the ADAPTE‐process, including a systematic search, quality appraisal of the guidelines using the Appraisal of Clinical Guidelines for REsearch & Evaluation II (AGREE II) instrument as well as an external review by means of a Delphi technique. The guidelines had to be topic‐relevant, published within the last 3 years and achieve a rigor of development score of 80% using the AGREE II instrument.MethodsWe searched international guideline databases to identify adequate guidelines. Two raters assessed the quality of each guideline, ascertaining that it fulfilled the inclusion criteria using the AGREE II instrument. We translated the identified recommendations into German and externally reviewed for their applicability in the Austrian context.ResultsWe identified 1,612 hits in 10 databases. After applying inclusion and exclusion criteria, we assessed five international clinical guidelines for quality using the AGREE II instrument. One clinical guideline fulfilled the inclusion criteria. This clinical guideline contains 116 recommendations, of which 29 were applicable in the Austrian nursing home setting.ConclusionWe identified only one suitable guideline, possibly due to the stringent nature of the inclusion criteria. However, following low‐quality guidelines may result in the use of recommendations that are not based on evidence and, therefore, may lead to suboptimal nursing care and outcomes.
Phytomelatonin receptor PMTR1‐mediated signaling regulates stomatal closure in Arabidopsis thaliana
Authors: Wei Jian , Li Dong‐Xu , Zhang Jia‐Rong , Shan Chi , Rengel Zed , Song Zhong‐Bang , Chen Qi 
Published: April 2018

AbstractMelatonin has been detected in plants in 1995; however, the function and signaling pathway of this putative phytohormone are largely undetermined due to a lack of knowledge about its receptor. Here, we discovered the first phytomelatonin receptor (CAND2/PMTR1) in Arabidopsis thaliana and found that melatonin governs the receptor‐dependent stomatal closure. The application of melatonin induced stomatal closure through the heterotrimeric G protein α subunit‐regulated H2O2 and Ca2+ signals. The Arabidopsis mutant lines lacking AtCand2 that encodes a candidate G protein‐coupled receptor were insensitive to melatonin‐induced stomatal closure. Accordingly, the melatonin‐induced H2O2 production and Ca2+ influx were completely abolished in cand2. CAND2 is a membrane protein that interacts with GPA1 and the expression of AtCand2 was tightly regulated by melatonin in various organs and guard cells. CAND2 showed saturable and specific 125I‐melatonin binding, with apparent Kd (dissociation constant) of 0.73 ± 0.10 nmol/L (r2 = .99), demonstrating this protein is a phytomelatonin receptor (PMTR1). Our results suggest that the phytomelatonin regulation of stomatal closure is dependent on its receptor CAND2/PMTR1‐mediated H2O2 and Ca2+signaling transduction cascade.
Melatonin and its derivatives counteract the ultraviolet B radiation‐induced damage in human and porcine skin ex vivo
Authors: Skobowiat Cezary , Brożyna Anna A. , Janjetovic Zorica , Jeayeng Saowanee , Oak Allen S. W. , Kim Tae‐Kang , Panich Uraiwan , Reiter Russel J. , Slominski Andrzej T. 
Published: April 2018

AbstractMelatonin and its derivatives (N1‐acetyl‐N2‐formyl‐5‐methoxykynurenine [AFMK] and N‐acetyl serotonin [NAS]) have broad‐spectrum protective effects against photocarcinogenesis, including both direct and indirect antioxidative actions, regulation of apoptosis and DNA damage repair; these data were primarily derived from in vitro models. This study evaluates possible beneficial effects of melatonin and its active derivatives against ultraviolet B (UVB)‐induced harm to human and porcine skin ex vivo and to cultured HaCaT cells. The topical application of melatonin, AFMK, or NAS protected epidermal cells against UVB‐induced 8‐OHdG formation and apoptosis with a further increase in p53ser15 expression, especially after application of melatonin or AFMK but not after NAS use. The photoprotective action was observed in pre‐ and post‐UVB treatment in both human and porcine models. Melatonin along with its derivatives upregulated also the expression of antioxidative enzymes after UVB radiation of HaCaT cells. The exogenous application of melatonin or its derivatives represents a potent and promising tool for preventing UVB‐induced oxidative stress and DNA damage. This protection results in improved genomic, cellular, and tissue integrity against UVB‐induced carcinogenesis, especially when applied prior to UV exposure. In addition, our ex vivo experiments provide fundamental justification for further testing the clinical utility of melatonin and metabolites as protectors again UVB in human subjects. Our ex vivo data constitute the bridge between vitro to vivo translation and thus justifies the pursue for further clinical utility of melatonin in maintaining skin homeostasis.
Why Did God Make Me This Way? Religious Coping and Framing in the Virtuous Pedophile Community
Authors: Cranney Stephen 
Published: April 2018

Abstract“Virtuous Pedophiles” (or VPs) have a sexual attraction to children but view child/adult sexual relations as wrong. Research on VPs is nascent but has theoretical importance for our understanding of sexuality, labeling, and extreme stigma. Their relevance is particularly acute in regard to religious coping and framing. As their primary stressor is a predisposition towards a highly stigmatized (or “sinful”) activity, religious VPs find themselves in a unique situation, and it is unknown to what extent they employ conventional religious coping mechanisms. I investigate how VPs use their religious frameworks to make sense of and react to their pedophilia with a survey of respondents recruited from an online VP forum, a content analysis of forum discussions, and several in‐depth, semistructured interviews. Religious VPs tend to employ the same basic religious coping mechanisms (both positive and negative) but customize their approaches to accommodate their unique situation. Positive and negative religious coping show the same relationships with mental health as found in other populations. Religiosity is associated with both lower mental distress as well as less cognitive distortions associated with sexual offending.
Airway persistence by the emerging multi‐azole‐resistant Rasamsonia argillacea complex in cystic fibrosis
Authors: Abdolrasouli Alireza , Bercusson Amelia C. , Rhodes Johanna L. , Hagen Ferry , Buil Jochem B. , Tang Alison Y. Y. , de Boer Leonard L. , Shah Anand , Milburn Andrew J. , Elborn J. Stuart , Jones Andrew L. , Meis Jacques F. , Fisher Matthew C. , Schelenz Silke , Simmonds Nicholas J. , Armstrong‐James Darius 
Published: April 2018

SummaryInfections caused by Rasamsonia argillacea complex have been reported in various clinical settings. Cystic fibrosis (CF) is one of the main underlying conditions. An observational cohort study of CF patients with Rasamsonia in respiratory samples was conducted. Eight isolates from 6 patients were identified as R. argillacea complex and tested for antifungal susceptibility. All isolates had high MICs to voriconazole and posaconazole and low MECs to echinocandins. Four patients experienced lung function decline in the year preceding first Rasamsonia isolation. This continued in the year following first isolation in 3 out of 4 cases. Antifungal therapy was initiated in 2 patients, to which only one exhibited a clinical response. Three out of 6 patients died within 3 years of isolating Rasamsonia. Genotyping suggests that similar genotypes of Rasamsonia can persist in CF airways. Consistent with other fungi in CF, the clinical impact of airway colonisation by Rasamsonia is variable. In certain patients, Rasamsonia may be able to drive clinical decline. In others, though a clear impact on lung function may be difficult to determine, the appearance of Rasamsonia acts as a marker of disease severity. In others it does not appear to have an obvious clinical impact on disease progression.