bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic significance of incomplete revascularization and untreated coronary anatomy following percutaneous coronary intervention: An analysis of 6,755 patients with multivessel disease
Authors: Iqbal M. Bilal , Smith Robert D. , Lane Rebecca , Patel Niket , Mattar Wala , Kabir Tito , Panoulas Vasileios , Mason Mark , Dalby Miles C. , Grocott‐Mason Richard , Ilsley Charles D. ,   on behalf of the Harefield Cardiac Outcomes Group Investigators
Published: September 2017

AbstractBackgroundMore than half of the patients undergoing percutaneous coronary intervention (PCI) have multivessel disease. Whether complete revascularization impacts long‐term mortality or whether selected patients or those with specific coronary anatomy benefit from complete revascularization is unclear.MethodsA total of 14,452 patients underwent PCI between 2004 and 2015 at Harefield Hospital, UK. Of these, 7,076 patients had multivessel disease. We excluded 321 patients with left main‐stem stenosis ≥50%, with 6,755 patients included in the analysis (936 patients had complete revascularization).ResultsThe unadjusted 3‐year mortality rates were lower with complete revascularization (10.8% vs 13.1%, P = 0.047). However, multivariable‐adjusted analyses indicated that complete revascularization was not independently associated with mortality (HR = 1.01, 95% CI: 0.78–1.31, P = 0.939). These findings were unchanged when addressing measured confounding using propensity‐matched analyses (HR = 1.16, 95% CI: 0.81–1.65, P = 0.417) and inverse probability treatment weighted analyses (HR = 1.01, 95% CI: 0.77–1.33, P = 0.950); and unmeasured confounding using instrumental variable analyses (Δ = 0.9%, 95% CI: −2.5%, 4.3%, P = 0.958). There was no association with mortality and untreated LAD disease (HR = 0.92, 95% CI: 0.72–1.17, P = 0.482) and LCx disease (HR = 0.90, 95% CI: 0.74–1.10, P = 0.999). However, untreated proximal LAD disease (HR = 1.23, 95% CI: 1.06–1.51, P = 0.045) and RCA disease (HR = 1.36, 95% CI: 1.08–1.65, P = 0.007) was associated with increased mortality, particularly in patients with ST‐elevation acute coronary syndrome (STEACS).ConclusionsIn this study of unselected patients undergoing PCI, complete revascularization did not confer a mortality benefit. However, the presence of untreated proximal LAD and RCA disease was prognostic in patients with STEACS. Thus, complete revascularization may be considered in select patient groups with anatomical subsets of coronary disease.
Catalytic N−H Bond Activation and Breaking by a Well‐Defined CoII1O4 Site of a Heterogeneous Catalyst
Authors: Khivantsev Konstantin , Biancardi Alessandro , Fathizadeh Mahdi , Almalki Fahad , Grant Job L. , Tien Huynh Ngoc , Shakouri Abolfazl , Blom Douglas A. , Makris Thomas M. , Regalbuto John R. , Caricato Marco , Yu Miao 
Published: October 2017

AbstractCatalytic N−H bond activation and breaking by well‐defined molecular complexes or their heterogeneous analogues is considered to be a challenge in chemical science. Metal(0) nanoparticles catalytically decompose NH3; they are, however, ill defined and contain a range of contiguous metal sites with varying coordination numbers and catalytic properties. So far, no well‐defined/molecular Mn+‐containing materials have been demonstrated to break strong N−H bonds catalytically, especially in NH3, the molecule with the strongest N−H bonds. Recently, noncatalytic activation of NH3 with the liberation of molecular H2 on an organometallic molybdenum complex was demonstrated. Herein, we show the catalytic activation and breaking of N−H bonds on a singly dispersed, well‐defined, and highly thermally resistant (even under reducing environments) CoII1O4 site of a heterogeneous catalyst for organic (ethylamine) and inorganic (NH3, with the formation of N2 and H2) molecules. The single‐site material serves as a viable precursor to ultrasmall (2.7 nm and less) silica‐supported cobalt nanoparticles; thus, we directly compare the activity of isolated cationic cobalt sites with small cobalt nanoparticles. Density functional theory (DFT) calculations suggest a unique mechanism involving breaking of the N−H bonds in NH3 and N−N coupling steps taking place on a Co1O4 site with the formation of N2H4, which then decomposes to H2 and N2H2; N2H2 subsequently decomposes to H2 and N2. In contrast, Co1N4 sites are not catalytically active, which implies that the ligand environment around a single atom of a heterogeneous catalyst largely controls reactivity. This may open a new chapter for the design of well‐defined heterogeneous materials for N−H bond‐activation reactions.
Rhodococcus erythropolis Oleate Hydratase: a New Member in the Oleate Hydratase Family Tree—Biochemical and Structural Studies
Authors: Lorenzen Jan , Driller Ronja , Waldow Ayk , Qoura Farah , Loll Bernhard , Brück Thomas 
Published: October 2017

AbstractRecently, the enzyme family of oleate hydratases (OHs: EC 4.2.1.53) has gained increasing scientific and economic interest, as these FAD‐binding bacterial enzymes do not require cofactor recycling and possess high thermal and pH stability. Their products, hydroxy fatty acids, are used in specialty chemical applications including surfactant and lubricant formulations. The “oleate hydratase engineering database”, established by Schmid et al. (2017), divides all OHs into 11 families (HFam1 to 11). To date, only two crystal structures of homodimeric OHs from the families HFam2 and HFam11 have been reported. In this study, we biophysically characterized an OH belonging to the HFam3 family, originating from the marine bacterium Rhodococcus erythropolis, for the first time. The crystal structure revealed that this new OH (OhyRe) surprisingly is a monomer in its active form. This particular feature provides new avenues for enzyme engineering and recycling through immobilization.
Development of a Dynamic Process Model for the Mechanical Fluid Separation in Decanter Centrifuges
Authors: Gleiss Marco , Hammerich Simon , Kespe Michael , Nirschl Hermann 
Published: October 2017

AbstractA dynamic process model for the simulation of the separation process in countercurrent decanter centrifuges is presented. The numerical approach uses an interconnection of compartments to characterize the residence time distribution of the particles within the centrifuge. First, the theoretical basis of the numerical approach is described. Compared to the state‐of‐the‐art modeling of decanter centrifuges, the proposed approach allows the simulation of the temporal filling process. The short computing time results in further advantages of the dynamic process model. The so‐called real‐time simulation is an opportunity for a model‐based control of the separation process. An exemplary simulation with the product limestone demonstrates the main features of the numerical approach.
Sensing site‐specific structural characteristics and chirality using vibrational circular dichroism of isotope labeled peptides
Authors: Keiderling Timothy A. 
Published: October 2017

AbstractIsotope labeling has a long history in chemistry as a tool for probing structure, offering enhanced sensitivity, or enabling site selection with a wide range of spectroscopic tools. Chirality sensitive methods such as electronic circular dichroism are global structural tools and have intrinsically low resolution. Consequently, they are generally insensitive to modifications to enhance site selectivity. The use of isotope labeling to modify vibrational spectra with unique resolvable frequency shifts can provide useful site‐specific sensitivity, and these methods have been recently more widely expanded in biopolymer studies. While the spectral shifts resulting from changes in isotopic mass can provide resolution of modes from specific parts of the molecule and can allow detection of local change in structure with perturbation, these shifts alone do not directly indicate structure or chirality. With vibrational circular dichroism (VCD), the shifted bands and their resultant sign patterns can be used to indicate local conformations in labeled biopolymers, particularly if multiple labels are used and if their coupling is theoretically modeled. This mini‐review discusses selected examples of the use of labeling specific amides in peptides to develop local structural insight with VCD spectra.
Fast liquid chromatography for racemic atenolol acetate separation—The analytical protocol
Authors: Agustian Joni , Kamaruddin Azlina Harun , Aboul‐Enein Hassan Y. 
Published: September 2017

AbstractKinetic resolution of (R,S)‐atenolol is a faster strategy to produce (S)‐atenolol. Since this racemate is a less soluble compound, resolution of its ester offers high concentrations in the process. A good analytical method is required to observe the enantiomer concentrations. This paper described application of ultra‐fast liquid chromatography on the atenolol ester separation using different resolution media and analytical procedures. Chiralcel OD column resolved the ester. The chromatograms indicated different characteristics of the process. The enantiomers could be recognized by the column in less than 1 (one) hour. Symmetrical peaks were obtained, but several procedures produced peaks with wide bases and slanted baselines. Efficient enantioresolution was obtained at high mobile phase flow rate, decreased concentration of amine‐type modifier, but increased alcohol content in the mobile phase. High UV detection wavelength was required. At 1.0 mL/min, the (90/10/0.5) composition resulted α = 1.46 and RS = 0.9998 that were good separation.
Early detection versus primary prevention in the PLCO flexible sigmoidoscopy screening trial: Which has the greatest impact on mortality?
Authors: Doroudi Maryam , Schoen Robert E. , Pinsky Paul F. 
Published: October 2017

BACKGROUNDScreening for colorectal cancer (CRC) with flexible sigmoidoscopy (FS) has been shown to reduce CRC mortality. The current study examined whether the observed mortality reduction was due primarily to the prevention of incident CRC via removal of adenomatous polyps or to the early detection of cancer and improved survival.METHODSThe Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomized 154,900 men and women aged 55 to 74 years. Individuals underwent FS screening at baseline and at 3 or 5 years versus usual care. CRC‐specific survival was analyzed using Kaplan‐Meier curves and proportional hazards modeling. The authors estimated the percentage of CRC deaths averted by early detection versus primary prevention using a model that applied intervention arm survival rates to CRC cases in the usual‐care arm and vice versa.RESULTSA total of 1008 cases of CRC in the intervention arm and 1291 cases of CRC in the usual‐care arm were observed. Through 13 years of follow‐up, there was no significant difference noted between the trial arms with regard to CRC‐specific survival for all CRC (68% in the intervention arm vs 65% in the usual‐care arm; P =.16) or proximal CRC (68% vs 62%, respectively; P = .11) cases; however, survival in distal CRC cases was found to be higher in the intervention arm compared with the usual‐care arm (77% vs 66%; P<.0001). Within each arm, symptom‐detected cases had significantly worse survival compared with screen‐detected cases. Overall, approximately 29% to 35% of averted CRC deaths were estimated to be due to early detection and 65% to 71% were estimated to be due to primary prevention.CONCLUSIONSCRC‐specific survival was similar across arms in the PLCO trial, suggesting a limited role for early detection in preventing CRC deaths. Modeling suggested that approximately two‐thirds of avoided deaths were due to primary prevention. Future CRC screening guidelines should emphasize primary prevention via the identification and removal of precursor lesions. Cancer 2017;123:4815‐22. © 2017 American Cancer Society.
First‐in‐human trial of the PI3Kβ‐selective inhibitor SAR260301 in patients with advanced solid tumors
Authors: Bédard Philippe L. , Davies Michael A. , Kopetz Scott , Juric Dejan , Shapiro Geoffrey I. , Luke Jason J. , Spreafico Anna , Wu Bin , Castell Christelle , Gomez Corinne , Cartot‐Cotton Sylvaine , Mazuir Florent , Dubar Michel , Micallef Sandrine , Demers Brigitte , Flaherty Keith T. 
Published: October 2017

BACKGROUNDPhosphoinositide 3‐kinase (PI3K) β is the dominant isoform for PI3K activity in many phosphatase and tensin homolog (PTEN)‐deficient tumor models. This was a first‐in‐human study to determine the maximum tolerated dose, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of SAR260301, a potent PI3Kβ‐selective inhibitor (clinicaltrials.gov identifier NCT01673737).METHODSSuccessive cohorts of patients with advanced solid tumors received increasing doses of oral SAR260301 according to a Bayesian escalation with an overdose‐control process based on the occurrence of dose‐limiting toxicity in the first 28‐day cycle. Adverse events, tumor response, PK, and the effect of food on PK were evaluated. Target engagement was assessed in platelets. Physiologically‐based PK modeling was used for exposure predictions.RESULTSTwenty‐one patients received treatment at doses ranging from 100 mg once daily to 440 mg/m2 twice daily. Dose‐limiting toxicities included 1 episode of grade 3 pneumonitis (400 mg twice daily) and 1 grade 3 γ‐glutamyltransferase increase (600 mg twice daily). The maximum tolerated dose was not reached. The most frequently occurring treatment‐related adverse events were nausea, vomiting, and diarrhea (14% each). Pharmacologically active concentrations were reached, but SAR260301 was rapidly cleared, and exposures associated with antitumor activity in preclinical models were not maintained at the highest dose tested. Food further decreased SAR260301 exposure.CONCLUSIONSSAR260301 had an acceptable safety profile, but exposure sufficient to inhibit the PI3K pathway was unachievable because of rapid clearance, and clinical development was terminated. These results demonstrate the importance of PK and pharmacodynamic assessments in early drug development. Cancer 2018;124:315‐24. © 2017 American Cancer Society.
Adherence to tyrosine kinase inhibitors among Medicare Part D beneficiaries with chronic myeloid leukemia
Authors: Shen Chan , Zhao Bo , Liu Lei , Shih Ya‐Chen Tina 
Published: October 2017

BACKGROUNDTyrosine kinase inhibitors (TKIs) improve the survival of patients with chronic myeloid leukemia (CML) dramatically; however, nonadherence to TKI therapy may lead to resistance to the therapy. TKIs are very expensive and are covered under Part D insurance for Medicare patients. To the authors' knowledge, the impact of low‐income subsidy status and cost sharing on adherence among this group has not been well studied in the literature.METHODSSurveillance, Epidemiology, and End Results (SEER) registry data linked with Medicare Part D data from the years 2007 through 2012 were used in the current study. The authors identified 836 patients with CML with Medicare Part D insurance coverage who were new TKI users. Treatment nonadherence was defined as a binary variable indicating the percentage of days covered was <80% during the 180‐day period after the initiation of TKI therapy. Logistic regression was used to examine the relationship between out‐of‐pocket costs per 30‐day drug supply, Medicare Part D plan characteristics, and treatment adherence while controlling for other patient characteristics.RESULTSOverall, 244 of the 836 patients with CML (29%) were nonadherent to targeted oral therapy during the 180 days after the initiation of treatment with TKIs. The multivariable logistic regression demonstrated that patients with heavily subsidized (odds ratio, 6.7; 95% confidence interval, 2.8‐15.9) and moderately subsidized (odds ratio, 3.0; 95% confidence interval, 1.4‐6.5) Medicare Part D plans were much more likely to demonstrate nonadherence compared with patients without a subsidy.CONCLUSIONSThe current population‐based study found a significantly higher rate of nonadherence among heavily subsidized patients with substantially lower out‐of‐pocket costs, which suggests that future research is needed to help lower the nonadherence rate among these individuals. Cancer 2018;124:364‐73. © 2017 American Cancer Society.
Treatment seeking for eating disorders: Results from a nationally representative study
Authors: Bohrer Brittany K. , Carroll Ian A. , Forbush Kelsie T. , Chen Po‐Yi 
Published: September 2017

AbstractObjectiveEating disorders (EDs) are associated with substantial morbidity and mortality, yet up to 45% of individuals with EDs never receive treatment for their eating‐related problems. This study sought to identify whether comorbidity, suicidality, discrimination, family cohesion, employment status, income, sex, age, marital status, religious belongingness, and ED‐specific variables (body mass index and past‐year ED diagnoses) were associated with treatment seeking in a nationally representative sample of individuals with EDs (N = 595; 77.8% women; 72.4% ethnic minority).MethodStructural equation modeling was used to identify significant predictors of treatment seeking.ResultsIn the full sample, age was associated with a greater probability of treatment seeking, and men had a lower probability of seeking treatment. No variables were significant predictors of treatment seeking among individuals in Hispanic or Caucasian subgroups.DiscussionTo our knowledge, this was the largest study to characterize predictors of treatment seeking in adults with EDs. Results from this study were consistent with existing literature documenting age and sex differences in treatment seeking among adolescents with an ED. Findings suggest a need for improved ED education and outreach—including greater mental health/ED literacy and decreased stigmatization for patients, providers, and the general public—and additional persuasive public‐health messages to change community knowledge about treatment options for younger persons and men with EDs.
Environmental correlates of internal coloration in frogs vary throughout space and lineages
Authors: Franco‐Belussi Lilian , Provete Diogo Borges , De Oliveira Classius 
Published: October 2017

AbstractInternal organs of ectotherms have melanin‐containing cells that confer different degrees of coloration to them. Previous experimental studies analyzed their developmental origin, role in immunity, and hormonal regulation. For example, melanin increases with ultraviolet radiation (UV) and temperature in frogs and fish. However, little is known about how environmental variables influence the amount of coloration on organs among amphibian species over a large spatial extent. Here, we tested how climatic variables (temperature, UV, and photoperiod) influence the coloration of internal organs of anurans. We recorded the level of melanin pigmentation using four categories on 12 internal organs and structures of 388 specimens from 43 species belonging to six anuran families. Then, we tested which climatic variables had the highest covariation with the pigmentation on each organ after controlling for spatial autocorrelation in climatic variables and phylogenetic signal in organ coloration using the extended version of the RLQ ordination. Coloration in all organs was correlated with the phylogeny. However, the coloration of different organs was affected by different variables. Specifically, the coloration of the heart, kidneys, and rectum of hylids, Rhinella schneideri, some Leptodactylus, and Proceratophrys strongly covaried with temperature and photoperiod, whereas that of the testicle, lumbar parietal peritoneum, lungs, and mesenterium of Leiuperinae, Hylodidae, Adenomera, and most Leptodactylus had highest covariation with UV‐B and temperature. Our results support the notion that melanin pigmentation on the surface of organs of amphibians has an adaptive function conferred by the protective functions of the pigment. But most importantly, internal melanin seems to respond differently to climatic variables depending on the lineage and locality in which species occur.
Syntopic frogs reveal different patterns of interaction with the landscape: A comparative landscape genetic study of Pelophylax nigromaculatus and Fejervarya limnocharis from central China
Authors: Garcia Vhon Oliver S. , Ivy Catherine , Fu Jinzhong 
Published: October 2017

AbstractAmphibians are often considered excellent environmental indicator species. Natural and man‐made landscape features are known to form effective genetic barriers to amphibian populations; however, amphibians with different characteristics may have different species–landscape interaction patterns. We conducted a comparative landscape genetic analysis of two closely related syntopic frog species from central China, Pelophylax nigromaculatus (PN) and Fejervarya limnocharis (FL). These two species differ in several key life history traits; PN has a larger body size and larger clutch size, and reaches sexual maturity later than FL. Microsatellite DNA data were collected and analyzed using conventional (FST, isolation by distance (IBD), AMOVA) and recently developed (Bayesian assignment test, isolation by resistance) landscape genetic methods. As predicted, a higher level of population structure in FL (FST′ = 0.401) than in PN (FST′ = 0.354) was detected, in addition to FL displaying strong IBD patterns (r = .861) unlike PN (r = .073). A general north–south break in FL populations was detected, consistent with the IBD pattern, while PN exhibited clustering of northern‐ and southern‐most populations, suggestive of altered dispersal patterns. Species‐specific resistant landscape features were also identified, with roads and land cover the main cause of resistance to FL, and elevation the main influence on PN. These different species–landscape interactions can be explained mostly by their life history traits, revealing that closely related and ecologically similar species have different responses to the same landscape features. Comparative landscape genetic studies are important in detecting such differences and refining generalizations about amphibians in monitoring environmental changes.
T cell receptor alpha variable 12‐2 bias in the immunodominant response to Yellow fever virus
Authors: Bovay Amandine , Zoete Vincent , Dolton Garry , Bulek Anna M. , Cole David K. , Rizkallah Pierre J. , Fuller Anna , Beck Konrad , Michielin Olivier , Speiser Daniel E. , Sewell Andrew K. , Fuertes Marraco Silvia A. 
Published: October 2017

AbstractThe repertoire of human αβ T‐cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen‐specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA‐A*0201‐restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8+ T cell response to the highly effective YF‐17D vaccine. We discover that these A2/LLW‐specific CD8+ T cells are highly biased for the TCR α chain TRAV12‐2. This bias is already present in A2/LLW‐specific naïve T cells before vaccination with YF‐17D. Using CD8+ T cell clones, we show that TRAV12‐2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline‐encoded complementarity determining region (CDR) 1α loop of TRAV12‐2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T‐cell responses specific for the A2/LLW epitope.