bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoporosis therapy and outcomes for postmenopausal patients with hormone receptor–positive breast cancer: NCIC CTG MA.27
Authors: Lipton Allan , Chapman Judith‐Anne W. , Leitzel Kim , Garg Ashwani , Pritchard Kathleen I. , Ingle James N. , Budd G. Thomas , Ellis Matthew J. , Sledge George W. , Rabaglio Manuela , Han Lei , Elliott Catherine R. , Shepherd Lois E. , Goss Paul E. , Ali Suhail M. 
Published: May 2017

BACKGROUNDBreast cancer patients in the MA.27 trial had similar outcomes with steroidal aromatase inhibitor (AI) exemestane and nonsteroidal anastrozole. AIs increase the risk of osteoporosis. This study examined the effects of self‐reported osteoporosis and osteoporosis therapy (OPT) on outcomes.METHODSThe MA.27 phase 3 adjuvant trial enrolled 7576 postmenopausal women. The primary outcome was event‐free survival (EFS), and the secondary outcome was distant disease–free survival (DDFS). Patients were permitted bisphosphonates to prevent or treat osteopenia/osteoporosis. In a multivariate, stratified Cox regression, factors were significant with a 2‐sided Wald test P value ≤ .05.RESULTSOsteoporosis was reported at the baseline by 654 of the 7576 women (8.6%) and in total by 1294 patients. Oral OPT was received at the baseline by 815 of the 7576 women (10.8%) and in total by 2711 patients (36%). With a median follow‐up of 4.1 years, 693 EFS events (9.15%) and 321 DDFS events (4.2%) occurred. Osteoporosis was not associated with EFS or DDFS. Few EFS events occurred before the initiation of OPT, with no substantive evidence of a time‐differing effect on outcomes (nonproportional hazards). OPT (yes vs no) was significantly associated with improved EFS (hazard ratio [HR] for yes vs no, 0.67; 95% confidence interval [CI], 0.57‐0.80; P < .001) and DDFS (HR, 0.57; 95% CI, 0.44‐0.73; P <. 001). Time‐differing (time‐dependent) OPT was not (EFS; P = .45). OPT did not alter the incidence of visceral‐only metastasis (P = .31).CONCLUSIONSOral OPT, administered to postmenopausal breast cancer patients receiving adjuvant AI therapy, was associated with improved EFS and DDFS; the time of OPT initiation (a time‐dependent effect) did not affect the outcome. OPT did not alter the risk of visceral metastasis. Cancer 2017;123:2444–51. © 2017 American Cancer Society.
Prognostic modeling in diffuse large B‐cell lymphoma in the era of immunochemotherapy: Where do we go from here?
Authors: Koff Jean L. , Flowers Christopher R. 
Published: May 2017

The model and approach described by Howlader et al could form a foundation for future risk‐prediction models that incorporate data on known differences in demographic, socioeconomic, clinical, and biological factors. Data from large diffuse large B‐cell lymphoma patient cohorts that capture host and tumor genomics and known clinical prognostic factors will be necessary to provide the resources for constructing meaningful prognostic models and to establish prediction models that will allow us to limit therapy and therapy‐related toxicity for favorable subsets of patients while optimizing directed approaches for poor‐risk subsets.See also pages 3326‐34.
Pharmacokinetics, Safety, and Tolerability Following Single and Multiple Doses of Pibrentasvir in a First‐in‐Human Study
Authors: Lin Chih‐Wei , Dutta Sandeep , Asatryan Armen , Wang Haoyu , Clifton Jack , Campbell Andrew , Liu Wei 
Published: May 2017

AbstractThis first‐in‐human dose‐ascending study investigated pharmacokinetics, safety, and tolerability of pibrentasvir following single and multiple doses in healthy volunteers. Additionally, the effects of food and ritonavir on pibrentasvir were assessed in a crossover study design. The starting dose of pibrentasvir was selected based on the no‐observed‐adverse‐effect‐level exposure from preclinical studies. Dose escalations of subsequent cohorts were dependent on reviews of the safety, tolerability, and pharmacokinetic data from previous dose cohorts. Pibrentasvir exposures increased in a greater than dose‐proportional manner across the 1.5‐ to 120‐mg dose range and became linear across the 120‐ to 600‐mg dose range. Following multiple dosing, pibrentasvir steady state was attained by day 5 with an accumulation ratio of 25% to 35%. Pibrentasvir harmonic mean terminal half‐life ranged from 20 to 22 hours. Food had minimal effect (<14%) on pibrentasvir bioavailability, but ritonavir increased pibrentasvir peak concentration and area under the concentration‐time curve by 60% and 89%, respectively. All adverse events were assessed by the investigator as mild, and no clinically significant vital signs, electrocardiogram, or clinical laboratory values were observed. The pharmacokinetic results from this study support once‐daily dosing and administration of pibrentasvir without regard to food. A maximum tolerated dose was not attained in the single‐ and multiple‐ascending‐dose assessments for pibrentasvir.
Beyond Simple Homology Searches: Multiple Sequence Alignments and Phylogenetic Trees
Authors: Zufall Rebecca A. 
Published: May 2017

AbstractPhylogenetic trees represent hypotheses about evolutionary relationships between organisms or nucleotide or amino acid sequences. Because the best BLAST hit often does not represent the most closely related sequence, phylogenetic analyses are an essential extension of inquiry into any new protein or gene. In this unit, the reader will first learn how to create a multiple sequence alignment and then will learn how to use that alignment to build a neighbor‐joining phylogeny using the software program MEGA. Finally, the user will learn how to interpret a phylogeny in light of the research questions. © 2017 by John Wiley & Sons, Inc.
Evaluating Solvent Effects at the Aqueous/Pt(111) Interface
Authors: Iyemperumal Satish Kumar , Deskins N. Aaron 
Published: May 2017

AbstractLiquid–metal interfaces occur in a number of surface processes, and it is fundamentally important to accurately model them. Herein, it is systematically determined how the presence of water affects several processes by using density functional theory with implicit solvation models. Adsorption of 41 common adsorbates and four catalytic reactions in both vacuum and water over the Pt(111) surface were modeled. The results show that adsorption energies for some species can change significantly in the presence of water (by up to 0.44 eV). It is further shown that solvation effects can be explained and predicted by analyzing simple chemical descriptors such as dipole moment and adsorbate charge. Models from artificial neural networks involving several potential descriptors, including gas‐phase solvation energy, adsorbate charge, dipole moment, and surface area, are also reported. When water is present, reaction energies change by up to 0.23 eV, although it appears that water solvent negligibly affects several elementary reaction steps. The results show that hydrogen bonding can be important for a number of reactions, but is largely absent in the implicit solvation models. Furthermore, other solvents besides water were also modeled, and if a solvent has a small dielectric constant, then small solvation effects occur. This work provides guidelines on when solvation effects may be important for surface chemistry, and also provides valuable insights into modeling such effects.
The Role of the DNA Backbone in Minor‐Groove Ligand Binding
Authors: Díaz‐Gómez Dalia G. , Galindo‐Murillo Rodrigo , Cortés‐Guzmán Fernando 
Published: May 2017

AbstractMolecular recognition between ligands and nucleic acids plays a key role in therapeutic activity. Some molecules interact with DNA in a nonbonded manner through intercalation or through the DNA grooves. The recognition of minor‐groove binders is attributed to a set of hydrogen‐bonding interactions between the binders and the hydrogen‐bond‐acceptor groups on the groove floor and walls. It is commonly considered that interactions with the sugar groups of the DNA backbone are insignificant and do not contribute to the binding affinity or the specificity. However, our group has found that the deoxyribose rings have a central function in the recognition and the intercalation of metal complexes into DNA. Herein, we determined the specific interactions between the binder CGP 40215A and the minor‐groove atoms, based on the local properties of electron density. We found that specific interactions between the deoxyribose moiety within the backbone of DNA and the binder are essential for molecular recognition, and they are responsible for one third of the interaction energy.
Annual climate variation modifies nitrogen induced carbon accumulation ofPinus sylvestrisforests
Authors: Lim Hyungwoo , Oren Ram , Linder Sune , From Fredrik , Nordin Annika , Fahlvik Nils , Lundmark Tomas , Näsholm Torgny 
Published: May 2017

AbstractWe report results from long‐term simulated external nitrogen (N) input experiments in three northernPinus sylvestrisforests, two of moderately high and one of moderately low productivity, assessing effects on annual net primary production (NPP) of woody mass and its interannual variation in response to variability in weather conditions. A sigmoidal response of woodNPPto external N inputs was observed in the both higher and lower productivity stands, reaching a maximum of ~65% enhancement regardless of the native site productivity, saturating at an external N input of 4–5 g N·m−2·yr−1. The rate of increase in woodNPPand the N response efficiency (REN, increase in woodNPPper external N input) were maximized at an external N input of ~3 g N·m−2·yr−1, regardless of site productivity. The maximumRENwas greater in the higher productivity than the lower productivity stand (~20 vs. ~14 g C/g N). The N‐induced enhancement of woodNPPand itsRENwere, however, markedly contingent on climatic variables. In both of the higher and lower productivity stands, woodNPPincreased with growing season precipitation (P), but only up to ~400 mm. The sensitivity of the response toPincreased with increasing external N inputs. Increasing growing season temperature (T) somewhat increased the N‐induced drought effect, whereas decreasingTreduced the drought effect. These responses of woodNPPinfused a large temporal variation toREN, making the use of a fixed value unadvisable. Based on these results, we suggest that regional climate conditions and future climate scenarios should be considered when modeling carbon sequestration in response to N deposition in borealP. sylvestris, and possibly other forests.
Novel approach to heritability detection suggests robustness to paternal genotype in a complex morphological trait
Authors: Winston Max E. , Thompson Andrea , Trujillo Gabriel , Burchill Andrew T. , Moreau Corrie S. 
Published: May 2017

AbstractHeritable variation is essential for evolution by natural selection. In Neotropical army ants, the ecological role of a given species is linked intimately to the morphological variation within the sterile worker caste. Furthermore, the army ant Eciton burchellii is highly polyandrous, presenting a unique opportunity to explore heritability of morphological traits among related workers sharing the same colonial environment. In order to exploit the features of this organismal system, we generated a large genetic and morphological dataset and applied our new method that employs geometric morphometrics (GM) to detect the heritability of complex morphological traits. After validating our approach with an existing dataset of known heritability, we simulated our ability to detect heritable variation given our sampled genotypes, demonstrating the method can robustly recover heritable variation of small effect size. Using this method, we tested for genetic caste determination and heritable morphological variation using genetic and morphological data on 216 individuals of E. burchellii. Results reveal this ant lineage (1) has the highest mating frequency known in ants, (2) demonstrates no paternal genetic caste determination, and (3) suggests a lack of heritable morphological variation in this complex trait associated with paternal genotype. We recommend this method for leveraging the increased resolution of GM data to explore and understand heritable morphological variation in nonmodel organisms.
Behavioral evidence of hunting and foraging techniques by a top predator suggests the importance of scavenging for preadults
Authors: Margalida Antoni , Colomer MªÀngels , Sánchez Roberto , Sánchez Francisco Javier , Oria Javier , González Luis Mariano 
Published: May 2017

AbstractScavenging may be a regular feeding behavior for some facultative raptor species occupying low quality habitats and/or with little experience in hunting techniques. However, its importance has been largely underestimated due to methodological limitations in identifying the real proportion in the diet. Here, through direct observations, we assessed the hunting and foraging success of the threatened Spanish imperial eagleAquila adalbertidetermining the influence of age, sex, breeding status, habitat quality, prey type, and landscape characteristics. From 465 observations, Spanish imperial eagles used hunting inflight(42%),scavenging(30%), hunting from aperch(16%) andkleptoparasitism(12%). Our model suggests thatPrey sizeandPrey typebest explain hunting success, followed byLandscapeandSex. Our findings suggest that Spanish imperial eagles increase hunting success with age, with scavenging and kleptoparasitism regularly used as juveniles. The absence of relationships with any of the variables considered suggests that kleptoparasitism is an opportunistic behavior used sporadically. Scavenging is also independent of habitat quality and landscape characteristics. Accordingly, low prey density is not a driver of carrion use for preadult individuals, suggesting that a lack of hunting ability obliges this age‐class to use this alternative feeding technique regularly. As a result, the threatened Spanish imperial eagle population is also prone to mortality related to the illegal use of poison baits and, potentially, veterinary drugs (i.e., diclofenac).
Predator‐mediated negative effects of overabundant snow geese on arctic‐nesting shorebirds
Authors: Lamarre Jean‐François , Legagneux Pierre , Gauthier Gilles , Reed Eric T. , Bêty Joël 
Published: May 2017

AbstractOverabundant species can strongly impact ecosystem functioning through trophic cascades. The strong increase in several arctic geese populations, primarily due to changes in agricultural practices in temperate regions, can have severe direct impacts on tundra ecosystems through vegetation degradation. However, predator‐mediated negative effects of goose overabundance on other tundra species can also be significant but are poorly understood. We tested the hypothesis that goose abundance negatively affects arctic‐nesting shorebirds by increasing nest predation pressure. We used six years of data collected within and near a greater snow goose colony (Chen caerulescens atlantica) to evaluate the effect of geese on the spatial variation in (1) the occurrence of shorebird nest predators, (2) the nest predation risk (with artificial shorebird nests), and (3) the occurrence of nesting shorebirds. We found that the goose colony had a strong influence on the spatial distribution of nest predators and nesting shorebirds. Occurrence of predators decreased, while occurrence of nesting shorebirds increased with distance from the centroid of the colony. The strength of these effects was modulated by lemming density, the preferred prey for predators. Shorebird nest predation risk also decreased with distance from the colony. Overall, these results indicate that goose abundance negatively affects arctic‐nesting shorebirds through shared predators. Therefore, we show that the current decline of some arctic shorebird populations may be in part mediated by a negative effect of an overabundant species.
Factors influencing fire severity under moderate burning conditions in the Klamath Mountains, northern California,USA
Authors: Estes Becky L. , Knapp Eric E. , Skinner Carl N. , Miller Jay D. , Preisler Haiganoush K. 
Published: May 2017

AbstractTopography, weather, and fuels are known factors driving fire behavior, but the degree to which each contributes to the spatial pattern of fire severity under different conditions remains poorly understood. The variability in severity within the boundaries of the 2006 wildfires that burned in the Klamath Mountains, northern California, along with data on burn conditions and new analytical tools, presented an opportunity to evaluate factors influencing fire severity under burning conditions representative of those where management of wildfire for resource benefit is most likely. Fire severity was estimated as the percent change in canopy cover (0–100%) classified from the Relativized differenced Normalized Burn Ratio (RdNBR), and spatial data layers were compiled to determine strength of associations with topography, weather, and variables directly or indirectly linked to fuels, such as vegetation type, number of previous fires, and time since last fire. Detailed fire progressions were used to estimate weather (e.g., temperature, relative humidity, temperature inversions, and solar radiation) at the time of burning. A generalized additive regression model with random effects and an additional spatial term to account for autocorrelation between adjacent locations was fitted to fire severity. In this fire year characterized by the relative absence of extreme fire weather, topographical complexity most strongly influenced severity. Upper‐ and mid‐slopes tended to burn at higher fire severity than lower‐slopes. East‐ and southeast‐facing aspects tended to burn at higher severity than other aspects. Vegetation type and fire history were also important predictors of fire severity. Shrub vegetation was more likely to burn at higher severity than mixed hardwood/conifer or hardwood vegetation. As expected, fire severity was positively associated with time since previous fire, but the relationship was non‐linear. Of the weather variables analyzed, temperature inversions, common in the complex topography of the Klamath Mountains, showed the strongest association with fire severity. Inversions trapped smoke and had a dampening effect on severity within the landscape underneath the inversion. Understanding the spatial controls on mixed‐severity fires allows managers to better plan for future wildfires and aide in the decision making when managing lightning ignitions for resource benefit might be appropriate.
The interacting roles of climate, soils, and plant production on soil microbial communities at a continental scale
Authors: Waldrop M. P. , Holloway J. M. , Smith D. B. , Goldhaber M. B. , Drenovsky R. E. , Scow K. M. , Dick R. , Howard D. , Wylie B. , Grace J. B. 
Published: May 2017

AbstractSoil microbial communities control critical ecosystem processes such as decomposition, nutrient cycling, and soil organic matter formation. Continental scale patterns in the composition and functioning of microbial communities are related to climatic, biotic, and edaphic factors such as temperature and precipitation, plant community composition, and soil carbon, nitrogen, and pH. Although these relationships have been well explored individually, the examination of the factors that may act directly on microbial communities vs. those that may act indirectly through other ecosystem properties has not been well developed. To further such understanding, we utilized structural equation modeling (SEM) to evaluate a set of hypotheses about the direct and indirect effects of climatic, biotic, and edaphic variables on microbial communities across the continental United States. The primary goals of this work were to test our current understanding of the interactions among climate, soils, and plants in affecting microbial community composition, and to examine whether variation in the composition of the microbial community affects potential rates of soil enzymatic activities. A model of interacting factors created through SEM shows several expected patterns. Distal factors such as climate had indirect effects on microbial communities by influencing plant productivity, soil mineralogy, and soil pH, but factors related to soil organic matter chemistry had the most direct influence on community composition. We observed that both plant productivity and soil mineral composition were important indirect influences on community composition at the continental scale, both interacting to affect organic matter content and microbial biomass and ultimately community composition. Although soil hydrolytic enzymes were related to the moisture regime and soil carbon, oxidative enzymes were also affected by community composition, reflected in the abundance of soil fungi. These results highlight that soil microbial communities can be modeled within the context of multiple interacting ecosystem properties acting both directly and indirectly on their composition and function, and this provides a rich and informative context with which to examine communities. This work also highlights that variation in climate, microbial biomass, and microbial community composition can affect maximum rates of soil enzyme activities, potentially influencing rates of decomposition and nutrient mineralization in soils.
Protocol update and preliminary results of EACVI/HFA Cardiac Oncology Toxicity (COT) Registry of the European Society of Cardiology
Authors: Lancellotti Patrizio , Galderisi Maurizio , Donal Erwan , Edvardsen Thor , Popescu Bogdan A. , Farmakis Dimitrios , Filippatos Gerasimos , Habib Gilbert , Lestuzzi Chiara , Santoro Ciro , Moonen Marie , Jerusalem Guy , Andarala Maryna , Anker Stefan D. ,   on behalf of the ESC Cardiac Oncology Toxicity Long‐Term Registry Investigators
Published: May 2017

AbstractAimsEuropean Association of Cardiovascular Imaging/Heart Failure Association Cardiac Oncology Toxicity Registry was launched in October 2014 as a European Society of Cardiology multicentre registry of breast cancer patients referred to imaging laboratories for routine surveillance, suspected, or confirmed anticancer drug‐related cardiotoxicity (ADRC). After a pilot phase (1 year recruitment and 1 year follow‐up), some changes have been made to the protocol (version 1.0) and electronic case report form.Methods and resultsMain changes of the version 2.0 concerned exclusion criteria, registry duration, and clarification of the population characteristics. Breast cancer radiotherapy has been removed as an exclusion criterion, which involves now only history of a pre‐chemotherapy left ventricular dysfunction. The period for long‐term registry recruitment has been reduced (December 2017), but the target study population was extended to 3000 patients. The characteristics of the population are now better defined: patients seen in an imaging lab, which will include patients undergoing chemotherapy with associated targeted therapy or no targeted therapy, at increased risk of ADRC. In total, 1294 breast cancer patients have been enrolled, and 783 case report forms locked from October 2014 to November 2016. Of these, 481 (61.4%) were seen at first evaluation and 302 (38.6%) while on oncologic treatment with anticancer drugs. Fifty‐two patients (17.2%) were not in targeted therapies, 191 (63.3%) were ongoing targeted therapy, and 59 (19.5%) had completed it. Twenty‐three (2.9%) patients had a suspected diagnosis and 35 (4.5%) a confirmed diagnosis of ADRC. Arterial hypertension was the most prevalent cardiovascular risk factor (29.2%) followed by diabetes (6.1%). Previous history of heart failure accounted for 0.5%, whereas previous cardiac disease was identified in 6.3% of population.ConclusionThe changes of the original protocol of the COT Registry and first update allow a first glance to the panorama of cardiovascular characteristics of breast cancer patients enrolled.