bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer
Authors: Silwal-Pandit Laxmi , Nord Silje , von der Lippe Gythfeldt Hedda , Møller Elen K. , Fleischer Thomas , Rødland Einar , Krohn Marit , Borgen Elin , Garred Øystein , Olsen Tone , Vu Phuong , Skjerven Helle , Fangberget Anne , Holmen Marit M. , Schlitchting Ellen , Wille Elisabeth , Nordberg Stokke Mette , Moen Vollan Hans Kristian , Kristensen Vessela , Langerød Anita , Lundgren Steinar , Wist Erik , Naume Bjørn , Lingjærde Ole Christian , Børresen-Dale Anne-Lise , Engebraaten Olav 
Published: May 2017

Abstract
Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab.
Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint.
Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor–positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor–positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors.
Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy. Clin Cancer Res; 23(16); 4662–70. ©2017 AACR.
Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging
Authors: Stein-Merlob Ashley F. , Hara Tetsuya , McCarthy Jason R. , Mauskapf Adam , Hamilton James A. , Ntziachristos Vasilis , Libby Peter , Jaffer Farouc A. 
Published: May 2017

Background—
The role of local alterations in endothelial functional integrity in atherosclerosis remains incompletely understood. This study used nanoparticle-enhanced optical molecular imaging to probe in vivo mechanisms involving impaired endothelial barrier function in experimental atherothrombosis.

Methods and Results—

Atherosclerosis was induced in rabbits (n=31) using aortic balloon injury and high-cholesterol diet. Rabbits received ultrasmall superparamagnetic iron oxide nanoparticles (CLIO) derivatized with a near-infrared fluorophore (CyAm7) 24 hours before near-infrared fluorescence imaging. Rabbits were then either euthanized (n=9) or underwent a pharmacological triggering protocol to induce thrombosis (n=22). CLIO-CyAm7 nanoparticles accumulated in areas of atheroma (
P
<0.05 versus reference areas). On near-infrared fluorescence microscopy, CLIO-CyAm7 primarily deposited in the superficial intima within plaque macrophages, endothelial cells, and smooth muscle cells. Nanoparticle-positive areas further exhibited impaired endothelial barrier function as illuminated by Evans blue leakage. Deeper nanoparticle deposition occurred in areas of plaque neovascularization. In rabbits subject to pharmacological triggering, plaques that thrombosed exhibited significantly higher CLIO-CyAm7 accumulation compared with nonthrombosed plaques (
P
<0.05). In thrombosed plaques, nanoparticles accumulated preferentially at the plaque-thrombus interface. Intravascular 2-dimensional near-infrared fluorescence imaging detected nanoparticles in human coronary artery–sized atheroma in vivo (
P
<0.05 versus reference segments).

Conclusions—
Plaques that exhibit impaired in vivo endothelial permeability in cell-rich areas are susceptible to subsequent thrombosis. Molecular imaging of nanoparticle deposition may help to identify biologically high-risk atheroma.
Impact of Coronary Calcification on Clinical Management in Patients With Acute Chest Pain
Authors: Bittner Daniel O. , Mayrhofer Thomas , Bamberg Fabian , Hallett Travis R. , Janjua Sumbal , Addison Daniel , Nagurney John T. , Udelson James E. , Lu Michael T. , Truong Quynh A. , Woodard Pamela K. , Hollander Judd E. , Miller Chadwick , Chang Anna Marie , Singh Harjit , Litt Harold , Hoffmann Udo , Ferencik Maros 
Published: May 2017

Background—
Coronary artery calcification (CAC) may impair diagnostic assessment of coronary computed tomography angiography (CTA). We determined whether CAC affects efficiency of coronary CTA in patients with suspected acute coronary syndrome (ACS).

Methods and Results—

This is a pooled analysis of ACRIN-PA (American College of Radiology Imaging Network–Pennsylvania) 4005 and the ROMICAT-II trial (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) comparing an initial coronary CTA strategy to standard of care in acute chest pain patients. In the CTA arms, we investigated appropriateness of downstream testing, cost, and diagnostic yield to identify patients with obstructive coronary artery disease on subsequent invasive coronary angiography across CAC score strata (Agatston score: 0, >0–10, >10–100, >100–400, >400). Out of 1234 patients (mean age 51±8.8 years), 80 (6.5%) had obstructive coronary artery disease (≥70% stenosis) and 68 (5.5%) had ACS. Prevalence of obstructive coronary artery disease (1%–64%), ACS (1%–44%), downstream testing (4%–72%), and total (2337–8484 US$) and diagnostic cost (2310–6678 US$) increased across CAC strata (
P
<0.001). As the increase in testing and cost were lower than the increase of ACS rate in patients with CAC>400, cost to diagnose one ACS was lowest in this group (19 283 US$ versus 464 399 US$) as compared with patients without CAC. The diagnostic yield of invasive coronary angiography was highest in patients with CAC>400 (87% versus 38%).

Conclusions—
Downstream testing, total, and diagnostic cost increased with increasing CAC, but were found to be appropriate because obstructive coronary artery disease and ACS were more prevalent in patients with high CAC. In patients with acute chest pain undergoing coronary CTA, cost-efficient testing and excellent diagnostic yield can be achieved even with high CAC burden.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT01084239 and NCT00933400.
Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone
Authors: Andell Pontus , Karlsson Sofia , Mohammad Moman A. , Götberg Matthias , James Stefan , Jensen Jens , Fröbert Ole , Angerås Oskar , Nilsson Johan , Omerovic Elmir , Lagerqvist Bo , Persson Jonas , Koul Sasha , Erlinge David 
Published: May 2017

Background—
Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study.

Methods and Results—
Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50–0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47–0.82). In 340 propensity score–matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37–0.80).

Conclusions—
IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.
EphA2 Expression Regulates Inflammation and Fibroproliferative Remodeling in Atherosclerosis
Authors: Finney Alexandra C. , Funk Steven D. , Green Jonette M. , Yurdagul Arif , Rana Mohammad Atif , Pistorius Rebecca , Henry Miriam , Yurochko Andrew , Pattillo Christopher B. , Traylor James G. , Chen Jin , Woolard Matthew D. , Kevil Christopher G. , Orr A. Wayne 
Published: May 2017

Background:
Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis.

Methods:

Here, we assessed the role of EphA2 in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe
−
/−
) and by assessing EphA2 function in multiple vascular cell culture models. After 8 to 16 weeks on a Western diet, male and female mice were assessed for atherosclerotic burden in the large vessels, and plasma lipid levels were analyzed.

Results:

Despite enhanced weight gain and plasma lipid levels compared with Apoe
−/−
controls, EphA2
−/−
Apoe
−/−
knockout mice show diminished atherosclerotic plaque formation, characterized by reduced proinflammatory gene expression and plaque macrophage content. Although plaque macrophages express EphA2, EphA2 deletion does not affect macrophage phenotype, inflammatory responses, and lipid uptake, and bone marrow chimeras suggest that hematopoietic EphA2 deletion does not affect plaque formation. In contrast, endothelial EphA2 knockdown significantly reduces monocyte firm adhesion under flow. In addition, EphA2
−/−
Apoe
−/−
mice show reduced progression to advanced atherosclerotic plaques with diminished smooth muscle and collagen content. Consistent with this phenotype, EphA2 shows enhanced expression after smooth muscle transition to a synthetic phenotype, and EphA2 depletion reduces smooth muscle proliferation, mitogenic signaling, and extracellular matrix deposition both in atherosclerotic plaques and in vascular smooth muscle cells in culture.

Conclusions:
Together, these data identify a novel role for EphA2 in atherosclerosis, regulating both plaque inflammation and progression to advanced atherosclerotic lesions. Cell culture studies suggest that endothelial EphA2 contributes to atherosclerotic inflammation by promoting monocyte firm adhesion, whereas smooth muscle EphA2 expression may regulate the progression to advanced atherosclerosis by regulating smooth muscle proliferation and extracellular matrix deposition.
Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation
Authors: Sharma Rishi , Oni Olurinde A. , Gupta Kamal , Sharma Mukut , Sharma Ram , Singh Vikas , Parashara Deepak , Kamalakar Surineni , Dawn Buddhadeb , Chen Guoqing , Ambrose John A. , Barua Rajat S. 
Published: May 2017

Background

Atrial fibrillation (
AF
) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (
TT
) levels were associated with a higher incidence of
AF
. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of
AF
. To date, no study has explored the effect of testosterone normalization on new incidence of
AF
after testosterone replacement therapy (
TRT
) in patients with low testosterone.

Methods and Results

Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low
TT
levels and divided them into 3 groups. Group 1 had
TRT
resulting in normalization of
TT
levels (normalized
TRT
), group 2 had
TRT
without normalization of
TT
levels (nonnormalized
TRT
), and group 3 did not receive
TRT
(no
TRT
). Propensity score–weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post‐
TRT
levels of
TT
and the incidence of
AF
. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of
AF
than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95%
CI
0.81–0.99,
P
=0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95%
CI
0.70–0.89,
P
=0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95%
CI
0.78– 1.0009,
P
=0.0675) in incidence of
AF
.

Conclusions

These novel results suggest that normalization of
TT
levels after
TRT
is associated with a significant decrease in the incidence of
AF
.
Neurocognitive Performance After Cerebral Revascularization in Adult Moyamoya Disease
Authors: Zeifert Penelope D. , Karzmark Peter , Bell-Stephens Teresa E. , Steinberg Gary K. , Dorfman Leslie J. 
Published: May 2017

Background and Purpose—
Cerebral revascularization using EC-IC bypass is widely used to treat moyamoya disease, but the effects of surgery on cognition are unknown. We compared performance on formal neurocognitive testing in adults with moyamoya disease before and after undergoing direct EC-IC bypass.

Methods—
We performed a structured battery of 13 neurocognitive tests on 84 adults with moyamoya disease before and 6 months after EC-IC bypass. The results were analyzed using reliable change indices for each test, to minimize test–retest variability and practice effects.

Results—
Twelve patients (14%) showed significant decline postoperatively, 9 patients (11%) improved, and 63 patients (75%) were unchanged. Similar results were obtained when the analysis was confined to those who underwent unilateral (33) or bilateral (51) revascularization.

Conclusions—
The majority of patients showed neither significant decline nor improvement in neurocognitive performance after EC-IC bypass surgery. Uncomplicated EC-IC bypass seems not to be a risk factor for cognitive decline in this patient population.
White Matter Imaging Correlates of Early Cognitive Impairment Detected by the Montreal Cognitive Assessment After Transient Ischemic Attack and Minor Stroke
Authors: Zamboni Giovanna , Griffanti Ludovica , Jenkinson Mark , Mazzucco Sara , Li Linxin , Küker Wilhelm , Pendlebury Sarah T. , Rothwell Peter M. 
Published: May 2017

Background and Purpose—
Among screening tools for cognitive impairment in large cohorts, the Montreal Cognitive Assessment (MoCA) seems to be more sensitive to early cognitive impairment than the Mini-Mental State Examination (MMSE), particularly after transient ischemic attack or minor stroke. We reasoned that if MoCA-detected early cognitive impairment is pathologically significant, then it should be specifically associated with the presence of white matter hyperintensities (WMHs) and reduced fractional anisotropy (FA) on magnetic resonance imaging.

Methods—
Consecutive eligible patients with transient ischemic attack or minor stroke (Oxford Vascular Study) underwent magnetic resonance imaging and cognitive assessment. We correlated MoCA and MMSE scores with WMH and FA, then specifically studied patients with low MoCA and normal MMSE.

Results—

Among 400 patients, MoCA and MMSE scores were significantly correlated (all
P
<0.001) with WMH volumes (
r
MoCA
=−0.336;
r
MMSE
=−0.297) and FA (
r
MoCA
=0.409;
r
MMSE
=0.369) and—on voxel-wise analyses—with WMH in frontal white matter and reduced FA in almost all white matter tracts. However, only the MoCA was independently correlated with WMH volumes (
r
=−0.183;
P
<0.001), average FA values (
r
=0.218;
P
<0.001), and voxel-wise reduced FA in anterior tracts after controlling for the MMSE. In addition, patients with low MoCA but normal MMSE (n=57) had higher WMH volumes (
t
=3.1;
P
=0.002), lower average FA (
t
=−4.0;
P
<0.001), and lower voxel-wise FA in almost all white matter tracts than those with normal MoCA and MMSE (n=238).

Conclusions—
In patients with transient ischemic attack or minor stroke, early cognitive impairment detected with the MoCA but not with the MMSE was independently associated with white matter damage on magnetic resonance imaging, particularly reduced FA.
XBP1 (X-Box–Binding Protein-1)–Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G
Authors: Jiang Meng , Yu Shu , Yu Zhui , Sheng Huaxin , Li Ying , Liu Shuai , Warner David S. , Paschen Wulf , Yang Wei 
Published: May 2017

Background and Purpose—
Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box–binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation). Stroke impairs endoplasmic reticulum function, which activates unfolded protein response. The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.

Methods—

Mice with
Xbp1
loss and gain of function in neurons were generated. Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice. Thiamet-G was used to increase O-GlcNAcylation.

Results—

Deletion of
Xbp1
worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent. This activation of O-GlcNAcylation was impaired in aged mice. Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice.

Conclusions—
Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome. O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice. Boosting prosurvival pathways to counterbalance the age-related decline in the brain’s self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
Forecasting Corporate Bond Returns with a Large Set of Predictors: An Iterated Combination Approach
Authors: Lin Hai , Wu Chunchi , Zhou Guofu 
Published: May 2017

Using a comprehensive return data set and an array of 27 macroeconomic, stock, and bond predictors, we find that corporate bond returns are highly predictable based on an iterated combination model. The large set of predictors outperforms traditional predictors substantially, and predictability generated by the iterated combination is both statistically and economically significant. Stock market and macroeconomic variables play an important role in forming expected bond returns. Return forecasts are closely linked to the evolution of real economy. Corporate bond premia have strong predictive power for business cycle, and the primary source of this predictive power is from the low-grade bond premium.The Internet appendix is available at https://doi.org/10.1287/mnsc.2017.2734 .This paper was accepted by Lauren Cohen, finance.
Heat Vision: Superman or Pit-Bearing Snakes?
Authors: Baek Jason 
Published: May 2017

When one reads the words ”heat vision,” it is common to imagine Superman flying through the air, blasting red beams from his eye sockets. Although this is a fairly creative image, the type of “heat vision” found in many snakes is different. When alluding to “heat vision” in snakes, one refers to the ability of certain snake species to sense heat through pit organs. These structures connect with a snake’s sense of touch, with the trigeminal nerves and ganglia being major components of this mechanism. Transient receptor potential cation channel, member A1, or PRTA1, is a protein found in the stems of trigeminal nerves. It is often asserted that the evolution of PRTA1 is directly connected to the evolution of infrared sensory pitbearing snakes. Quand une personne lit les mots ”vision de chaleur,” il est naturel que la première chose qui vient a tête est l’image de Superman qui vole dans le ciel avec des rayons rouges quit sortes de ses yeux. Bien que ceci est une image créative, le type de “vision de chaleur” qui se trouve dans les serpents est très différent. Lorsqu’on parle de “vision de chaleur” dans les serpents souvent on réfère à l’abilité que l’èspece de serpent peut sentir la chaleur à travers de ses organes. Ces structures on des connections avec le sens du toucher d’un serpent, avec les nerves trijumeau et le ganglion qui sont des composants major de cette méchanism. Le canal cationique potentiel de récepteur transitoire, membre A1, ou PRTA1, est un protéin qui se trouve dans les tuyaux des nerves trijumeau. Il est souvent affirmé que l’évolution du PRTA1 est directement connecté à l’évolution des serpents de puits avec sensorielle infrarouge.
Introducing the Arts and Science Section
Authors: Lam Adela , Yan Cathy 
Published: May 2017

The Science and arts are commonly considered to be two vastly different disciplines contrasting each other primarily in terms of methodology. The sciences value precision and the ability to control and replicate results, while arts stem from the fluid and unique expression of one’s self using different mediums. However, despite these characteristics, the ultimate goal of both areas of study is to explore the unknown. For arts, this entails delving into human emotions through abstract thoughts and ideas, while sciences use the same abstractions and imagination to experiment with and create using objects in the natural world. This combination of internal and external explorations define the intrinsic elements of the universe, which is why arts and science belong together. Les sciences et les arts sont souvent considérés comme deux disciplines vastement différents qui se contrastent surtout en terme de méthodologie. Les sciences mettent en valeur la précision et la capacité de contrôler et répéter des résultats alors que les arts proviennent de l’expression fluide et unique de soi-même en utilisant de divers moyens. Cependant, malgré ces caractéristiques, le but ultime des deux domaines d’étude est d’explorer l’inconnu.