bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer
Authors: Alba Emilio , Lluch Ana , Ribelles Nuria , Anton-Torres Antonio , Sanchez-Rovira Pedro , Albanell Joan , Calvo Lourdes , García-Asenjo Jose Antonio Lopez , Palacios Jose , Chacon Jose Ignacio , Ruiz Amparo , De la Haba-Rodriguez Juan , Segui-Palmer Miguel A. , Cirauqui Beatriz , Margeli Mireia , Plazaola Arrate , Barnadas Agusti , Casas Maribel , Caballero Rosalia , Carrasco Eva , Rojo Federico 
Published: January 2016

AbstractBackground.In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.Patients and Methods.We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).Results.A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 &gt;50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 &gt;50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.Conclusion.Basal Ki67 proliferation index &gt;50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.
Phase II Study of Olaparib (AZD-2281) After Standard Systemic Therapies for Disseminated Colorectal Cancer
Authors: Leichman Lawrence , Groshen Susan , O’Neil Bert H. , Messersmith Wells , Berlin Jordan , Chan Emily , Leichman Cynthia G. , Cohen Steven J. , Cohen Deirdre , Lenz Heinz-Josef , Gold Philip , Boman Bruce , Fielding Anitra , Locker Gershon , Cason Ronald C. , Hamilton Stan R. , Hochster Howard S. 
Published: January 2016

Abstract

Background.
Effective new agents for patients with colorectal cancer (CRC) with disease progression during standard therapy regimens are needed. We hypothesized that poly ADP ribose polymerase (PARP) inhibitor therapy in patients with CRC and inefficient tumor DNA repair mechanisms, such as those with high-level microsatellite instability (MSI-H), would result in synthetic lethality.

Methods.
This was an open-label phase II trial testing olaparib 400 mg p.o. b.i.d. for patients with disseminated, measurable CRC failing standard therapies with centrally confirmed tumor MSI status. The primary endpoint was the tumor response, assessed by RECIST, version 1.0. The secondary endpoints were safety/toxicity, progression-free survival (PFS), and overall survival (OS).

Results.
Thirty-three patients (20 microsatellite stable [MSS], 13 MSI-H) were enrolled. The median age for all patients was 57 years and for MSS and MSI-H patients was 51 and 61 years, respectively. All patients received at least one 28-day cycle of olaparib. No patient had a complete or partial response. Nausea (48%), fatigue (36%), and vomiting (33%) were the most commonly reported treatment-related adverse events. The median PFS for all patients was 1.84 months. No statistically significant differences were found in the median PFS or OS for the MSS group compared with the MSI-H group.

Conclusion.
Single-agent olaparib delivered after failure of standard systemic therapy did not demonstrate activity for CRC patients, regardless of microsatellite status. Future trials, testing PARP inhibitors in patients with CRC should focus on the use of DNA-damaging chemotherapy and/or radiation therapy, combined with PARP inhibitors, remembering the toxicity reported in the present study.
Comparison of Three-Dimensional Planning-Assisted and Conventional Acetabular Cup Positioning in Total Hip Arthroplasty
Authors: Sariali Elhadi , Boukhelifa Nadia , Catonne Yves , Pascal Moussellard Hugues 
Published: January 2016

Background:
Malpositioning of the acetabular cup during total hip arthroplasty increases the risk of dislocation, edge-loading, squeaking, early wear, and loosening. We hypothesized that the use of three-dimensional (3-D) visualization tools to identify the planned cup position relative to the acetabular edge intraoperatively would increase the accuracy of cup orientation. The purpose of this study was to compare 3-D planning-assisted implantation and freehand insertion of the acetabular cup.

Methods:
This was a prospective randomized controlled study of two groups of twenty-eight patients each. In the first group, cup positioning was guided by 3-D views of the cup within the acetabulum obtained during 3-D preoperative planning. In the control group, the cup was placed freehand. All of the patients were operated on by the same surgeon, through a minimally invasive direct anterior approach with the patient in the supine position. Cup anteversion and abduction angles were measured on 3-D computed tomography (CT) reconstructions. The main evaluation criterion was the percentage of outliers according to the Lewinnek safe zone.

Results:
Operative time did not differ between the two groups. The cup anteversion was more accurate in the 3-D planning group (mean difference from the planned angle [and standard deviation], −2.7° ± 5.4°) compared with the freehand-placement group (6.6° ± 9.5°). According to the Lewinnek safe zone, overall, the percentage of outliers was lower in the 3-D planning group (21%; six patients) than in the control group (46%; thirteen patients). According to the Callanan safe zone, the percentage of outliers was also lower in the 3-D planning group (25% versus 64%). Although cup abduction was also restored with greater accuracy in the 3-D planning group, on the basis of the Lewinnek safe zone, the percentage of abduction outliers was comparable between groups, with fewer high-abduction values, but more low-abduction values, in the 3-D planning group.

Conclusions:
Preoperative 3-D planning increased the accuracy of anteversion restoration and reduced the percentage of outliers without increasing the operative time. In this study, the same advantage could not be demonstrated for abduction.

Level of Evidence:
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Naïve Type 2 Diabetes
Authors: Rosenstock Julio , Chuck Leonard , González-Ortiz Manuel , Merton Kate , Craig Jagriti , Capuano George , Qiu Rong 
Published: January 2016

OBJECTIVE
This study assessed the efficacy/safety of canagliflozin (CANA), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, plus metformin extended-release (MET) initial therapy in drug-naïve type 2 diabetes.

RESEARCH DESIGN AND METHODS
This 26-week, double-blind, phase 3 study randomized 1,186 patients to CANA 100 mg (CANA100)/MET, CANA 300 mg (CANA300)/MET, CANA100, CANA300, or MET. Primary end point was change in HbA1c at week 26 for combinations versus monotherapies. Secondary end points included noninferiority in HbA1c lowering with CANA monotherapy versus MET; changes in fasting plasma glucose, body weight, and blood pressure; and proportion of patients achieving HbA1c &lt;7.0% (&lt;53 mmol/mol).

RESULTS
From mean baseline HbA1c of 8.8% (73 mmol/mol), CANA100/MET and CANA300/MET significantly lowered HbA1c versus MET (median dose, 2,000 mg/day) by –1.77%, –1.78%, and –1.30% (–19.3, –19.5, and –14.2 mmol/mol; differences of −0.46% and –0.48% [–5.0 and –5.2 mmol/mol]; P = 0.001) and versus CANA100 and CANA300 by –1.37% and –1.42% (–15.0 and –15.5 mmol/mol; differences of –0.40% and –0.36% [–4.4 and –3.9 mmol/mol]; P = 0.001). CANA100 and CANA300 monotherapy met noninferiority for HbA1c lowering and had significantly more weight loss versus MET (–2.8, –3.7, and –1.9 kg [–3.0%, –3.9%, and –2.1%]; P = 0.016 and P = 0.002). Greater attainment of HbA1c &lt;7.0% (50%, 57%, and 43%) and significantly more weight loss (–3.2, –3.9, and –1.9 kg [–3.5%, –4.2%, and –2.1%]; P = 0.001) occurred with CANA100/MET and CANA300/MET versus MET. The incidence of adverse events (AEs) related to SGLT2 inhibition (genital mycotic infections, osmotic diuresis– and volume depletion–related AEs) was higher in the CANA arms (0.4–4.4%) versus MET (0–0.8%). AE-related discontinuation rates were 1.3–3.0% across groups. The incidence of hypoglycemia was 3.0–5.5% in the CANA arms and 4.6% with MET.

CONCLUSIONS
Initial therapy with CANA plus MET was more effective and generally well tolerated versus each monotherapy in drug-naïve type 2 diabetes. CANA monotherapy demonstrated noninferior HbA1c lowering versus MET.
Diabetes and the Association of Postoperative Hyperglycemia With Clinical and Economic Outcomes in Cardiac Surgery
Authors: Greco Giampaolo , Ferket Bart S. , D’Alessandro David A. , Shi Wei , Horvath Keith A. , Rosen Alexander , Welsh Stacey , Bagiella Emilia , Neill Alexis E. , Williams Deborah L. , Greenberg Ann , Browndyke Jeffrey N. , Gillinov A. Marc , Mayer Mary Lou , Keim-Malpass Jessica , Gupta Lopa S. , Hohmann Samuel F. , Gelijns Annetine C. , O'Gara Patrick T. , Moskowitz Alan J. 
Published: January 2016

OBJECTIVE
The management of postoperative hyperglycemia is controversial and generally does not take into account pre-existing diabetes. We analyzed clinical and economic outcomes associated with postoperative hyperglycemia in cardiac surgery patients, stratifying by diabetes status.

RESEARCH DESIGN AND METHODS
Multicenter cohort study in 4,316 cardiac surgery patients operated on in 2010. Glucose was measured at 6-h intervals for 48 h postoperatively. Outcomes included cost, hospital length of stay (LOS), cardiac and respiratory complications, major infections, and death. Associations between maximum glucose levels and outcomes were assessed with multivariable regression and recycled prediction analyses.

RESULTS
In patients without diabetes, increasing glucose levels were associated with a gradual worsening of outcomes. In these patients, hyperglycemia (≥180 mg/dL) was associated with an additional cost of $3,192 (95% CI 1,972 to 4,456), an additional hospital LOS of 0.8 days (0.4 to 1.3), an increase in infections of 1.6% (0.5 to 2.8), and an increase in respiratory complications of 2.6% (0.0 to 5.3). However, among patients with insulin-treated diabetes, optimal outcomes were associated with glucose levels considered to be hyperglycemic (180 to 240 mg/dL). This level of hyperglycemia was associated with cost reductions of $6,225 (−12,886 to −222), hospital LOS reductions of 1.6 days (−3.7 to 0.4), infection reductions of 4.1% (−9.1 to 0.0), and reductions in respiratory complication of 12.5% (−22.4 to −3.0). In patients with non–insulin-treated diabetes, outcomes did not differ significantly when hyperglycemia was present.

CONCLUSIONS
Glucose levels &lt;180 mg/dL are associated with better outcomes in most patients, but worse outcomes in patients with diabetes with a history of prior insulin use. These findings support further investigation of a stratified approach to the management of patients with stress-induced postoperative hyperglycemia based on prior diabetes status.
A MULTIPLE SCATTERING POLARIZED RADIATIVE TRANSFER MODEL: APPLICATION TO HD 189733b
Authors: Kopparla Pushkar , Natraj Vijay , Zhang Xi , Swain Mark R. , Wiktorowicz Sloane J. , Yung Yuk L. 
Published: January 2016

ABSTRACT
We present a multiple scattering vector radiative transfer model that produces disk integrated, full phase polarized light curves for reflected light from an exoplanetary atmosphere. We validate our model against results from published analytical and computational models and discuss a small number of cases relevant to the existing and possible near-future observations of the exoplanet HD 189733b. HD 189733b is arguably the most well observed exoplanet to date and the only exoplanet to be observed in polarized light, yet it is debated if the planet’s atmosphere is cloudy or clear. We model reflected light from clear atmospheres with Rayleigh scattering, and cloudy or hazy atmospheres with Mie and fractal aggregate particles. We show that clear and cloudy atmospheres have large differences in polarized light as compared to simple flux measurements, though existing observations are insufficient to make this distinction. Futhermore, we show that atmospheres that are spatially inhomogeneous, such as being partially covered by clouds or hazes, exhibit larger contrasts in polarized light when compared to clear atmospheres. This effect can potentially be used to identify patchy clouds in exoplanets. Given a set of full phase polarimetric measurements, this model can constrain the geometric albedo, properties of scattering particles in the atmosphere, and the longitude of the ascending node of the orbit. The model is used to interpret new polarimetric observations of HD 189733b in a companion paper.
SECOND EPOCH HUBBLE SPACE TELESCOPE OBSERVATIONS OF KEPLER’S SUPERNOVA REMNANT: THE PROPER MOTIONS OF BALMER FILAMENTS*
Authors: Sankrit Ravi , Raymond John C. , Blair William P. , Long Knox S. , Williams Brian J. , Borkowski Kazimierz J. , Patnaude Daniel J. , Reynolds Stephen P. 
Published: January 2016

ABSTRACT
We report on the proper motions of Balmer-dominated filaments in Kepler’s supernova remnant using high resolution images obtained with the Hubble Space Telescope at two epochs separated by about 10 years. We use the improved proper motion measurements and revised values of shock velocities to derive a distance to Kepler of

kpc. The main shock around the northern rim of the remnant has a typical speed of 1690 km s−1 and is encountering material with densities of about 8 cm−3. We find evidence for the variation of shock properties over small spatial scales, including differences in the driving pressures as the shock wraps around a curved cloud surface. We find that the Balmer filaments ahead of the ejecta knot on the northwest boundary of the remnant are becoming fainter and more diffuse. We also find that the Balmer filaments associated with circumstellar material in the interior regions of the remnant are due to shocks with significantly lower velocities and that the brightness variations among these filaments trace the density distribution of the material, which may have a disk-like geometry.
3D SIMULATIONS OF REALISTIC POWER HALOS IN MAGNETOHYDROSTATIC SUNSPOT ATMOSPHERES: LINKING THEORY AND OBSERVATION
Authors: Rijs Carlos , Rajaguru S. P. , Przybylski Damien , Moradi Hamed , Cally Paul S. , Shelyag Sergiy 
Published: January 2016

ABSTRACT
The well-observed acoustic halo is an enhancement in time-averaged Doppler velocity and intensity power with respect to quiet-Sun values that is prominent for the weak and highly inclined field around the penumbra of sunspots and active regions. We perform 3D linear wave modeling with realistic distributed acoustic sources in a magnetohydrostatic sunspot atmosphere and compare the resultant simulation enhancements with multiheight SDO observations of the phenomenon. We find that simulated halos are in good qualitative agreement with observations. We also provide further proof that the underlying process responsible for the halo is the refraction and return of fast magnetic waves that have undergone mode conversion at the critical a = c atmospheric layer. In addition, we also find strong evidence that fast Alfvén mode conversion plays a significant role in the structure of the halo, taking energy away from photospheric and chromospheric heights in the form of field-aligned Alfvén waves. This conversion process may explain the observed “dual-ring” halo structure at higher (>8 mHz) frequencies.
DEEP NEAR-IR OBSERVATIONS OF THE GLOBULAR CLUSTER M4: HUNTING FOR BROWN DWARFS
Authors: Dieball A. , Bedin L. R. , Knigge C. , Rich R. M. , Allard F. , Dotter A. , Richer H. , Zurek D. 
Published: January 2016

ABSTRACT
We present an analysis of deep Hubble Space Telescope (HST)/Wide Field Camera 3 near-IR (NIR) imaging data of the globular cluster (GC) M4. The best-photometry NIR color–magnitude diagram (CMD) clearly shows the main sequence extending toward the expected end of the hydrogen-burning limit and going beyond this point toward fainter sources. The white dwarf (WD) sequence can be identified. As such, this is the deepest NIR CMD of a GC to date. Archival HST optical data were used for proper-motion cleaning of the CMD and for distinguishing the WDs from brown dwarf (BD) candidates. Detection limits in the NIR are around F110W ≈ 26.5 mag and F160W ≈ 27 mag, and in the optical around F775W ≈ 28 mag. Comparing our observed CMDs with theoretical models, we conclude that we have reached beyond the H-burning limit in our NIR CMD and are probably just above or around this limit in our optical–NIR CMDs. Thus, any faint NIR sources that have no optical counterpart are potential BD candidates, since the optical data are not deep enough to detect them. We visually inspected the positions of NIR sources that are fainter than the H-burning limit in F110W and for which the optical photometry did not return a counterpart. We found in total five sources for which we did not get an optical measurement. For four of these five sources, a faint optical counterpart could be visually identified, and an upper optical magnitude was estimated. Based on these upper optical magnitude limits, we conclude that one source is likely a WD, one source could be either a WD or BD candidate, and the remaining two sources agree with being BD candidates. No optical counterpart could be detected for just one source, which makes this source a good BD candidate. We conclude that we found in total four good BD candidates.
THE CHEMICAL HOMOGENEITY OF OPEN CLUSTERS
Authors: Bovy Jo 
Published: January 2016

ABSTRACT
Determining the level of chemical homogeneity in open clusters is of fundamental importance in the study of the evolution of star-forming clouds and that of the Galactic disk. Yet limiting the initial abundance spread in clusters has been hampered by difficulties in obtaining consistent spectroscopic abundances for different stellar types. Without reference to any specific model of stellar photospheres, a model for a homogeneous cluster is that it forms a one-dimensional sequence, with any differences between members due to variations in stellar mass and observational uncertainties. I present a novel method for investigating the abundance spread in open clusters that tests this one-dimensional hypothesis at the level of observed stellar spectra, rather than constraining homogeneity using derived abundances as is traditionally done. Using high-resolution APOGEE spectra for 49 giants in M67, NGC 6819, and NGC 2420 I demonstrate that these spectra form one-dimensional sequences for each cluster. With detailed forward modeling of the spectra and Approximate Bayesian Computation, I derive strong limits on the initial abundance spread of 15 elements: <0.01 (0.02)

for C and Fe, ≲0.015 (0.03)

for N, O, Mg, Si, and Ni, ≲0.02 (0.03)

for Al, Ca, and Mn, and ≲0.03 (0.05)

for Na, S, K, Ti, and V (at 68% and 95% confidence, respectively). The strong limits on C and O imply that no pollution by massive core-collapse supernovae occurred during star formation in open clusters, which, thus, need to form within ≲6

. Further development of this and related techniques will bring the power of differential abundances to stars other than solar twins in large spectroscopic surveys and will help unravel the history of star formation and chemical enrichment in the Milky Way through chemical tagging.
VARIATIONS ON DEBRIS DISKS. III. COLLISIONAL CASCADES AND GIANT IMPACTS IN THE TERRESTRIAL ZONES OF SOLAR-TYPE STARS
Authors: Kenyon Scott J. , Bromley Benjamin C. 
Published: January 2016

ABSTRACT
We analyze two new sets of coagulation calculations for solid particles orbiting within the terrestrial zone of a solar-type star. In models of collisional cascades, numerical simulations demonstrate that the total mass, the mass in 1 mm and smaller particles, and the dust luminosity decline with time more rapidly than predicted by analytic models,

with n ≈ 1.1–1.2 instead of 1. Size distributions derived from the numerical calculations follow analytic predictions at r ≲ 0.1 km but are shallower than predicted at larger sizes. In simulations of planet formation, the dust luminosity declines more slowly than in pure collisional cascades, with n ≈ 0.5–0.8 instead of 1.1–1.2. Throughout this decline, giant impacts produce large, observable spikes in dust luminosity that last ∼0.01–0.1 Myr and recur every 1–10 Myr. If most solar-type stars have Earth mass planets with a ≲1–2 AU, observations of debris around 1–100 Myr stars allow interesting tests of theory. Current data preclude theories where terrestrial planets form out of 1000 km or larger planetesimals. Although the observed frequency of debris disks among ≳30 Myr old stars agrees with our calculations, the observed frequency of warm debris among 5–20 Myr old stars is smaller than predicted.
“REFSDAL” MEETS POPPER: COMPARING PREDICTIONS OF THE RE-APPEARANCE OF THE MULTIPLY IMAGED SUPERNOVA BEHIND MACSJ1149.5+2223
Authors: Treu T. , Brammer G. , Diego J. M. , Grillo C. , Kelly P. L. , Oguri M. , Rodney S. A. , Rosati P. , Sharon K. , Zitrin A. , Balestra I. , Bradač M. , Broadhurst T. , Caminha G. B. , Halkola A. , Hoag A. , Ishigaki M. , Johnson T. L. , Karman W. , Kawamata R. , Mercurio A. , Schmidt K. B. , Strolger L.-G. , Suyu S. H. , Filippenko A. V. , Foley R. J. , Jha S. W. , Patel B. 
Published: January 2016

ABSTRACT
Supernova “Refsdal,” multiply imaged by cluster MACS1149.5+2223, represents a rare opportunity to make a true blind test of model predictions in extragalactic astronomy, on a timescale that is short compared to a human lifetime. In order to take advantage of this event, we produced seven gravitational lens models with five independent methods, based on Hubble Space Telescope (HST) Hubble Frontier Field images, along with extensive spectroscopic follow-up observations by HST, the Very Large and the Keck Telescopes. We compare the model predictions and show that they agree reasonably well with the measured time delays and magnification ratios between the known images, even though these quantities were not used as input. This agreement is encouraging, considering that the models only provide statistical uncertainties, and do not include additional sources of uncertainties such as structure along the line of sight, cosmology, and the mass sheet degeneracy. We then present the model predictions for the other appearances of supernova “Refsdal.” A future image will reach its peak in the first half of 2016, while another image appeared between 1994 and 2004. The past image would have been too faint to be detected in existing archival images. The future image should be approximately one-third as bright as the brightest known image (i.e.,

mag at peak and

mag six months before peak), and thus detectable in single-orbit HST images. We will find out soon whether our predictions are correct.