bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twice weekly pulse and daily continuous‐dose erlotinib as initial treatment for patients with epidermal growth factor receptor–mutant lung cancers and brain metastases
Authors: Arbour Kathryn C. , Kris Mark G. , Riely Gregory J. , Ni Ai , Beal Kathryn , Daras Mariza , Hayes Sara A. , Young Robert J. , Rodriguez Christopher R. , Ahn Linda , Pao William , Yu Helena A. 
Published: September 2017

BACKGROUNDIn a phase 1 study of pulse/continuous‐dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)–mutant lung cancers with untreated brain metastases.METHODSPatients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly. The primary endpoints were the overall and CNS response rates (according to version 1.1 of the Response Evaluation Criteria in Solid Tumors).RESULTSBetween May 2015 and August 2016, 19 patients were enrolled. Forty‐two percent of the patients had target brain lesions, and the median size of the target brain lesions was 13 mm. Overall, 14 patients (74%; 95% confidence interval [CI], 51%‐89%) had partial responses. The response rate in brain metastases was 75%. The overall median progression‐free survival was 10 months (95% CI, 7 months to not reached). Only 3 patients (16%) had CNS progression. To date, 4 patients required CNS radiation at some time during their course. The adverse events (any grade) seen in 10% or more of the patients were rash, diarrhea, nausea, an increase in alanine aminotransferase, and fatigue.CONCLUSIONSPulse/continuous‐dose erlotinib produced a 74% overall response rate and a 75% response rate in brain metastases in patients with EGFR‐mutant lung cancers and untreated brain metastases. CNS control persisted even after progression elsewhere. Although this regimen did not improve progression‐free survival or delay the emergence of EGFR T790M, it prevented progression in the brain and could be useful in situations in which CNS control is critical. Cancer 2018;124:105‐9. © 2017 American Cancer Society.
Pharmacokinetics, Safety, and Tolerability of Vortioxetine Following Single‐ and Multiple‐Dose Administration in Healthy Japanese Adults
Authors: Matsuno Kumi , Nakamura Koki , Aritomi Yutaka , Nishimura Akira 
Published: September 2017

AbstractThree phase 1 randomized single‐center studies assessed the pharmacokinetics, safety, and tolerability of vortioxetine after single‐ and multiple‐dose administration in healthy Japanese adults. Study 1 assessed the pharmacokinetics of vortioxetine after administration of single rising doses to men and multiple doses to men and women; study 2 evaluated vortioxetine pharmacokinetics in elderly adults; and study 3 assessed food effects on vortioxetine pharmacokinetics in healthy men. The primary end points included pharmacokinetic parameters of vortioxetine and incidence of adverse events (AEs). Across all studies, 130 participants were randomized and 128 participants completed the studies. Vortioxetine was absorbed and eliminated from plasma slowly, and exposure to vortioxetine increased in an almost dose‐proportional manner. No clinically significant differences in the pharmacokinetics of vortioxetine or its metabolites were observed between the sexes in young and elderly adults. Study 3 demonstrated that vortioxetine and its metabolites had similar pharmacokinetics when administered in the fasted and fed states. Importantly, vortioxetine was safe and tolerated, with incidence of AEs comparable to that of placebo. No deaths or serious AEs leading to trial discontinuation were observed. Overall, vortioxetine pharmacokinetics, safety, and tolerability in Japanese adults were comparable to reports in non‐Japanese populations.
LY2963016 Insulin Glargine and Insulin Glargine (Lantus) Produce Comparable Pharmacokinetics and Pharmacodynamics at Two Dose Levels
Authors: Zhang Xin , Lam Eric Chen Quin , Seger Mary E. , Coutant David , Chua Laiyi , Tan Lai Hock , Soon Danny , Linnebjerg Helle 
Published: September 2017

AbstractLY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products with identical amino acid sequences. This was a phase 1 single‐site, randomized, subject‐ and investigator‐blinded, 4‐treatment, 4‐period crossover study to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of LY IGlar and IGlar at 2 different doses. Fasted healthy subjects were randomly assigned to receive 2 single doses of LY IGlar and IGlar (0.3 and 0.6 U/kg for each product). Blood samples were collected up to 24 hours postdose to assess PK, and a euglycemic clamp lasting up to 24 hours postdose was conducted to assess PD. Twenty‐four healthy subjects aged 23 to 52 years participated in the study. The primary PK parameters (area under the concentration versus time curve from 0 to 24 hours [AUC0–24] and maximum observed drug concentration [Cmax]) and PD parameters (total amount of glucose infused during the clamp [Gtot] and maximum glucose infusion rate [Rmax]) were not statistically different between LY IGlar and IGlar at either dose. No safety concerns were noted with either drug. The study demonstrated that the PK and PD parameters for LY IGlar and IGlar were comparable following single doses at both 0.3 and 0.6 U/kg.
Reactive Electrophilic OI− Species Evidenced in High‐Performance Iridium Oxohydroxide Water Oxidation Electrocatalysts
Authors: Massué Cyriac , Pfeifer Verena , van Gastel Maurice , Noack Johannes , Algara‐Siller Gerardo , Cap Sébastien , Schlögl Robert 
Published: September 2017

AbstractAlthough quasi‐amorphous iridium oxohydroxides have been identified repeatedly as superior electrocatalysts for the oxygen evolution reaction (OER), an exact description of the performance‐relevant species has remained a challenge. In this context, we report the characterization of hydrothermally prepared iridium(III/IV) oxohydroxides that exhibit exceptional OER performances. Holes in the O 2p states of the iridium(III/IV) oxohydroxides result in reactive OI− species, which are identified by characteristic near‐edge X‐ray absorption fine structure (NEXAFS) features. A prototypical titration reaction with CO as a probe molecule shows that these OI− species are highly susceptible to nucleophilic attack at room temperature. Similarly to the preactivated oxygen involved in the biological OER in photosystem II, the electrophilic OI− species evidenced in the iridium(III/IV) oxohydroxides are suggested to be precursors to species involved in the O−O bond formation during the electrocatalytic OER. The CO titration also highlights a link between the OER performance and the surface/subsurface mobility of the OI− species. Thus, the superior electrocatalytic properties of the iridium (III/IV) oxohydroxides are explained by their ability to accommodate preactivated electrophilic OI− species that can migrate within the lattice.
Increased grassland arthropod production with mammalian herbivory and eutrophication: a test of mediation pathways
Authors: Lind Eric M. , La Pierre Kimberly J. , Seabloom Eric W. , Alberti Juan , Iribarne Oscar , Firn Jennifer , Gruner Daniel S. , Kay Adam D. , Pascal Jesus , Wright Justin P. , Yang Louie , Borer Elizabeth T. 
Published: September 2017

AbstractIncreases in nutrient availability and alterations to mammalian herbivore communities are a hallmark of the Anthropocene, with consequences for the primary producer communities in many ecosystems. While progress has advanced understanding of plant community responses to these perturbations, the consequences for energy flow to higher trophic levels in the form of secondary production are less well understood. We quantified arthropod biomass after manipulating soil nutrient availability and wild mammalian herbivory, using identical methods across 13 temperate grasslands. Of experimental increases in nitrogen, phosphorus, and potassium, only treatments including nitrogen resulted in significantly increased arthropod biomass. Wild mammalian herbivore removal had a marginal, negative effect on arthropod biomass, with no interaction with nutrient availability. Path analysis including all sites implicated nutrient content of the primary producers as a driver of increased arthropod mean size, which we confirmed using 10 sites for which we had foliar nutrient data. Plant biomass and physical structure mediated the increase in arthropod abundance, while the nitrogen treatments accounted for additional variation not explained by our measured plant variables. The mean size of arthropod individuals was 2.5 times more influential on the plot‐level total arthropod biomass than was the number of individuals. The eutrophication of grasslands through human activity, especially nitrogen deposition, thus may contribute to higher production of arthropod consumers through increases in nutrient availability across trophic levels.
New Energy and Weather Services in the Context of the Energy Transition
Authors: Ciriminna Rosaria , Albanese Lorenzo , Meneguzzo Francesco , Pagliaro Mario 
Published: September 2017

AbstractThe potential of weather forecasting is increasingly being exploited by power generators and transmission‐system operators as renewable electricity generation has become a significant and increasing part of the energy mix in many countries. Showing how the forecasts are interpreted and actually used, we suggest avenues for policy makers on how best utilizing meteorology in the unfolding energy transition through new, integrated meteorology and energy services.
Drug therapy adherence and health outcomes in the presence of physician and patient unobserved heterogeneity
Authors: Atella Vincenzo , Belotti Federico , Depalo Domenico 
Published: September 2017

AbstractUnderstanding the role that drug adherence has on health outcomes in everyday clinical practice is central for the policy maker. This is particularly true when patients suffer from asymptomatic chronic conditions (e.g., hypertension, hypercholesterolaemia, and diabetes). By exploiting a unique longitudinal dataset at patient and physician level in Italy, we show that patients and physicians unobserved characteristics play an important role in determining health status, at least as important as drug adherence. Most importantly, we find that both adherence and prescribed treatment regimen effects are highly heterogeneous across physicians, highlighting their crucial role in shaping patients' health status.
The life‐saving effect of hospital proximity
Authors: Bertoli Paola , Grembi Veronica 
Published: September 2017

SummaryWe provide a new assessment of the effect of hospital proximity in an emergency situation—road‐traffic accidents—exploiting the exogenous variation in the proximity to cities that are legally allowed to have a hospital on the basis of their population size. Our instrumental variable results show that a one‐standard‐deviation increase in the distance to the nearest hospital (5 km) raises the fatality rate by 13.84% at the sample average. This figure is equal to 0.92 additional deaths per 100 accidents. We show that both ordinary least squares and difference‐in‐differences estimates, common approaches in the literature, provide a downward‐biased measure of the true effect of hospital proximity because they do not fully solve spatial sorting problems. Proximity is more important when the level of road safety is low, when emergency services are less responsive, and when the nearest hospital has relatively low quality standards.
Improvements on the density of maximal 1‐planar graphs
Authors: Barát János , Tóth Géza 
Published: September 2017

AbstractA graph is 1‐planar if it can be drawn in the plane such that each edge is crossed at most once. A graph, together with a 1‐planar drawing is called 1‐plane. A graph is maximal 1‐planar (1‐plane), if we cannot add any missing edge so that the resulting graph is still 1‐planar (1‐plane). Brandenburg et al. showed that there are maximal 1‐planar graphs with only edges and maximal 1‐plane graphs with only edges. On the other hand, they showed that a maximal 1‐planar graph has at least edges, and a maximal 1‐plane graph has at least edges. We improve both lower bounds to .
Effective factors on not using the N95 respirators among health care workers: Application of Fuzzy Delphi and Fuzzy Analytic Hierarchy Process (FAHP)
Authors: Honarbakhsh Marzieh , Jahangiri Mehdi , Farhadi Payam 
Published: September 2017

AbstractUsing respiratory protective equipment (RPE) including N95 respirators is one of the most important ways to protect health care workers (HCWs) against respiratory hazards. The aim of this study was to identify and prioritize the problems and obstacles in using N95 respirators among HCWs in Iran. In this cross‐sectional study, problems and obstacles in using N95 respirators were identified and ranked by experts, using Fuzzy Delphi and Fuzzy Analytic Hierarchy Process (FAHP). Additionally, HCWs were asked to give their opinions about obstacles in using N95 respirators in order to form an opinion. Of 15 important obstacles in using N95 respirators identified by Fuzzy Delphi method, 6 factors were entered into the FAHP model: heat around the face, inaccessibility to respirator, difficulty breathing, pressure on the nose, trouble communicating with patients and colleagues, and no one does it. Identified problems and obstacles in using N95 respirators could be controlled during the selection of respirators, as well as by training and administrative measures.
Distributed ledger technology: Applications and implications
Authors: Maull Roger , Godsiff Phil , Mulligan Catherine , Brown Alan , Kewell Beth 
Published: September 2017

AbstractDistributed ledger technologies (DLTs) are rewriting conventional notions of business transacting, creating fresh opportunities for value creation and capture. Using qualitative interview data as a primary resource, the proposed five‐point model synthesizes these possibilities, demonstrating how they may lead to “disruptive innovation.” A further conceptual model is subsequently provided with a view to assisting future problem solving in the area.
Building the blockchain world: Technological commonwealth or just more of the same?
Authors: Manski Sarah 
Published: September 2017

AbstractBlockchain technologies are reconfiguring the global economy, though often in contradictory ways. Blockchain technologies are disrupting key economic and financial sectors. Some blockchain applications allow for democratization of finance, services, agriculture, and governance, yet they may also deepen inequality and weaken democracy. We need new understandings of the countervailing tendencies of blockchain technologies and the contingencies that shape their deployment.
Novel chelant‐based washing method for soil contaminated with Pb and other metals: A pilot‐scale study
Authors: Lestan Domen 
Published: September 2017

AbstractRemediation with chelants can restore metal‐contaminated soils for use as a natural resource. Calcareous soil from Meza Valley, Slovenia, and acidic soils from Arnoldstein, Austria, and Pribram, Czech Republic (with 1,028, 862, and 926 mg ∙Pb∙kg−1, respectively), were washed with 60–100 mmol EDTA per kilogram of air‐dried soil in series of 30 batches (50 kg soil batch−1). The approach involves a novel reaction that incorporates alkaline substitution, precipitation and adsorption of toxic metals on polysaccharides, and chelant acidic precipitation via 83% EDTA (on average) and complete process water recycling (no wastewater was generated). The pH gradient was imposed by Ca(OH)2 and H2SO4, and excess reagent was removed with the remediated soil as CaSO4, thereby preventing the salification of the recycled waters. Remediation removed 60%, 78%, and 71% of the Pb from the Meza, Arnoldstein, and Pribram soils, respectively, and reduced the Pb bioaccessibility levels in the simulated human gastrointestinal phase by 5.0, 7.7, and 8.1 times. Residual emissions (EDTA, toxic metals) were reduced with soil aging and remediated soil deposition on a reactive permeable barrier. The solid waste generated from the process totaled 10.8 kg tons−1 of the air‐dried soil, and the material/energy costs of remediation reached 20.6 € tons−1. These results demonstrate the robustness, efficiency, and safety of this novel approach.
Third‐generation bisphosphonates for cochlear otosclerosis stabilizes sensorineural hearing loss in long‐term follow‐up
Authors: Jan Taha A. , Remenschneider Aaron K. , Halpin Christopher , Seton Margaret , McKenna Michael J. , Quesnel Alicia M. 
Published: September 2017

ObjectiveTo assess long‐term hearing outcomes in patients treated with third‐generation bisphosphonates for otosclerosis‐related progressive sensorineural hearing loss (SNHL).Study DesignRetrospective case series reviewMethodsWe performed a retrospective case series review of patients with otosclerosis and progressive SNHL. Patients were treated with either risedronate or zoledronate after a diagnosis of otosclerosis with a significant SNHL component. Bone conduction pure tone threshold averages (BC‐PTAs) and word recognition scores (WRS) before and after bisphosphonate administration in long‐term follow‐up was analyzed. Significant change in BC‐PTA was defined as greater than 10dB or between 4% and 18% in WRS based on binomial variance.ResultsSeven patients were identified and 14 ears met inclusion criteria. Three patients were female and the mean age was 48.3 ± 10.3 years. The mean duration between treatment with bisphosphonate administration and long‐term post‐treatment follow‐up audiometry was 87.6 ± 18.3 months, with a range of 61.6 to 109.1 months and median of 89.2 months. Analysis using BC‐PTA and WRS demonstrated that 11 ears remained stable while 2 improved and 1 worsened. No patient experienced any major complication as the result of bisphosphonate therapy.ConclusionTreatment with third‐generation bisphosphonates is associated with stability in otosclerosis‐related sensorineural hearing over 5‐ to 9‐year period. These results suggest that such medications may prevent the progression of SNHL in patients with otosclerosis.Level of Evidence4 (Case series).
Tear drop‐free anterolateral thigh flap, a versatile design for lower limb reconstruction after trauma
Authors: Razzano Sergio , Ramadan Sami , Figus Andrea , Haywood Richard M. 
Published: September 2017

AbstractBackgroundIn lower limb reconstruction the cosmetic outcome is influenced by the contouring of the flap at the recipient site as well as by the donor site closure. It is also important to minimise compression of the flap pedicle. We discuss the outcomes of a versatile ALT flap design that allows freedom in skin paddle tailoring without elongating the scar, reduction of the tension over the pedicle and improved cosmetic results of both donor and recipient sites.MethodsBetween January 2009 and October 2015, 27 patients underwent reconstruction using tear drop ALTs. The age ranged between 20 and 89 years. Seventeen were elective procedures and 10 were urgent. The locations of the defects were: knee (1 case), achilles tendon (2 cases), os calcis (1 case), lateral malleolus (1 case), fibula (3 cases), tibia (6 cases), tibia/fibula (5 cases), and ankle (8 cases). The sizes of the defects ranged from 4 × 3 cm to 9 × 7 cm.ResultsThe size of the flap ranged from 6 × 4 cm to 11 × 7 cm. One venous congestion and a wound dehiscence occurred, no flap loss. Two defatting procedures were performed. The mean follow‐up was 16.44 months. Final outcomes showed good functional and cosmetic results in both the donor and recipient sites.ConclusionsThe tear drop ALT is a useful tool in lower limb reconstruction allowing to improve skin paddle tailoring without elongating the donor site scar. It allows minimal tension over the pedicle while optimizing the contour of both the donor and recipient sites.
Molecular sieves supported recyclable catalyst for atom transfer radical polymerization using hydration approach
Authors: Aggarwal Ravi , Baskaran Durairaj 
Published: September 2017

ABSTRACTMolecular Sieves (MS) were used as a recyclable support for atom transfer radical polymerization. The catalyst complex, CuBr2/ligand was supported on hydrated MS and used for the polymerization of benzyl methacrylate at room temperature in anisole. The polymerization using CuBr2/PMDETA (pentamethyl diethyltetraamine) catalyst that is physically held by the hydration of MS exhibited moderate control and produced catalyst free polymers (<0.1 ppm) with narrow molecular weight distribution (Mw/Mn ≤ 1.33). The polymerization occurred at the interface between the hydrated support and the solution containing initiator and monomer. The hydrated MS supported catalyst was recycled efficiently without a significant loss in activity. The polymerization proceeded in a “living”/controlled manner as was evident from first‐order time conversion plots. The split kinetics experiment affirmed that there was no propagation in the solution in the absence of the supported catalyst. The reaction order plot showed zero‐order dependence on the bulk initiator concentration in solution. The results of MS supported catalyst were compared to Na‐clay supported catalyst system and the improved results were attributed to high self‐diffusion coefficient and low diffusion activation energy of water on its surface. Published 2017.§ J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3875–3883
PAMAM Dendrimers Attached to Collagen via a Malondialdehyde Linker
Authors: Zaręba Magdalena , Uram Łukasz , Białońska Agata , Stompor Monika , Wołowiec Stanisław 
Published: September 2017

AbstractFunctionalization of polyamidoamine dendrimers (PAMAM) for use as macromolecular drug carriers with aldehydes was performed using aminoacetaldehyde dimethylacetal (AADA) and malondialdehyde (MDA). AADA was used to obtain low molecular weight product upon reaction with dimethyl succinate and PAMAM G‐0.5. The structure of succinate bis‐(dimethylacetal)acetamide was elucidated by X‐ray crystallography. This product, as well as the product of condensation of PAMAM G‐0.5 with AADA, were resistant to hydrolysis. MDA reacted withiso‐butylamine and polyamidoamine PAMAM G0 dendrimers to give 3‐[N‐(2‐methylpropyl)amino]prop‐2‐enal and PAMAM G0 with four arms ending with prop‐2‐enal groups. The compounds were characterized by NMR, MS and/or elemental analysis. PAMAM G3 was also converted to aldehyde‐terminated dendrimer with excess MDA, however, the product was water insoluble. The low molecular weight water soluble analogue prop‐2‐enal terminated PAMAM G0 dendrimer was tested for toxicity on normal human fibroblasts and glioblastoma cell cultures. The toxicity of prop‐2‐enal terminated PAMAM G0 was comparable with that of amine ending PAMAM G0. Finally, fluorescein‐labeled PAMAM G3 was covalently attached to a collagen scaffold via a MDA linker as demonstrated by confocal microcopy. This rapid method of covalent attachment of PAMAM‐drug conjugates to MDA‐activated collagen opens new pathways for delivery of drugs into tissue.