bluuebunny/crossref_metadata_2025_split huggingface dataset:
Al-doped graphene as an effective adsorber for some toxic derivatives of aromatic hydrocarbons
Authors: Ji Min , Cheng Xinlu , Wu Weidong 
Published: January 2017

The density functional theory (DFT) was used to investigate some toxic derivatives of aromatic hydrocarbons adsorption on perfect graphene (pG) and graphene-doped with B/Al/Ga (BG/AlG/GaG). And the parallel and vertical adsorptions were considered for the position relation between the adsorbent and adsorbate. The adsorption energy, adsorption distance, charge transfer and density of states (DOS) were discussed in optimized structures. The greater adsorption energy, shorter adsorption distance and more charge transfer were found in AlG by studying the four kinds of molecules (phenol/m-cresol/PCP/p-NP) adsorption on pG/BG/AlG/GaG. Then, 10 derivatives adsorption on AlG were reported, and the adsorption energy increased in the order of pentachlorophenol [Formula: see text] 2,4,6-trichlorophenol [Formula: see text] 2,4-dichlorophenol [Formula: see text] p-cresol [Formula: see text] m-cresol [Formula: see text] phenol [Formula: see text] o-chlorophenol [Formula: see text] o-cresol [Formula: see text] 2,4,6-trintrotoluene [Formula: see text] para-nitrophenol. The interaction between these derivatives and the substrate was chemisorption for AlG and physisorption for pG. The oxygen atom in nitro group was more closer to the substrate than in hydroxyl group about optimized structures.
LKB1 Expression Correlates with Increased Survival in Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy and Bevacizumab
Authors: Bonanno Laura , De Paoli Angela , Zulato Elisabetta , Esposito Giovanni , Calabrese Fiorella , Favaretto Adolfo , Santo Antonio , Conte Alessandro Del , Chilosi Marco , Oniga Francesco , Sozzi Gabriella , Moro Massimo , Ciccarese Francesco , Nardo Giorgia , Bertorelle Roberta , Candiotto Cinzia , De Salvo Gian Luca , Amadori Alberto , Conte PierFranco , Indraccolo Stefano 
Published: January 2017

Abstract
Purpose: LKB1 is a key sensor of metabolic stress, including hypoxia and glucose deprivation, two features of the tumor microenvironment exacerbated by antiangiogenic therapy. We investigated the role of LKB1 as a potential predictive marker of sensitivity to bevacizumab in advanced non–small cell lung cancer (aNSCLC).
Experimental design: We retrospectively analyzed LKB1 expression by IHC in 98 samples from 125 patients with aNSCLC, including 59 patients treated with chemotherapy and 39 treated with chemotherapy plus bevacizumab. IHC intensity was recoded in two classes (negative/weak vs. moderate/intense) and correlated with outcome according to treatment arm. Patient-derived tumor xenografts (PDXs) were used to investigate mechanisms involved in preclinical models.
Results: In the whole study population (125), median OS and PFS were 11.7 [95% confidence interval (CI), 9.1–15.3] and 6.7 (95% CI, 5.7–7.2) months, respectively. Differential impact of the marker on outcome of the 98 patients was highlighted according to the treatment. Patients with negative/weak LKB1 status did not have a statistically significant benefit from bevacizumab added to chemotherapy (HR for patients treated with bevacizumab: 0.89; 95% CI, 0.51–1.56; P = 0.6803), whereas patients expressing moderate/intense LKB1 and receiving bevacizumab had significant lower risk of death compared with those not receiving bevacizumab (HR, 0.26; 95% CI, 0.10–0.64; P = 0.0035). Loss of LKB1 was associated with reduced AMPK activation in PDXs and increased tumor necrosis following bevacizumab administration, highlighting impaired control of the metabolic stress caused by this antiangiogenic drug.
Conclusions: Our data hint at a possible predictive impact of LKB1 expression in patients with aNSCLC treated with chemotherapy plus bevacizumab. Clin Cancer Res; 23(13); 3316–24. ©2017 AACR.
Genome-wide DNA Methylation Profiling Reveals Methylation Markers Associated with 3q Gain for Detection of Cervical Precancer and Cancer
Authors: Verlaat Wina , Snijders Peter J.F. , Novianti Putri W. , Wilting Saskia M. , De Strooper Lise M.A. , Trooskens Geert , Vandersmissen Johan , Van Criekinge Wim , Wisman G. Bea A. , Meijer Chris J.L.M. , Heideman Daniëlle A.M. , Steenbergen Renske D.M. 
Published: January 2017

Abstract
Purpose: Epigenetic host cell changes involved in cervical cancer development following a persistent high-risk human papillomavirus (hrHPV) infection, provide promising markers for the management of hrHPV-positive women. In particular, markers based on DNA methylation of tumor suppressor gene promoters are valuable. These markers ideally identify hrHPV-positive women with precancer (CIN2/3) in need of treatment. Here, we set out to identify biologically relevant methylation markers by genome-wide methylation analysis of both hrHPV-transformed cell lines and cervical tissue specimens.
Experimental Design and Results: Genome-wide discovery by next-generation sequencing (NGS) of methyl-binding domain–enriched DNA (MBD-Seq) yielded 20 candidate methylation target genes. Further verification and validation by multiplex-targeted bisulfite NGS and (quantitative) methylation-specific PCR (MSP) resulted in 3 genes (GHSR, SST, and ZIC1) that showed a significant increase in methylation with severity of disease in both tissue specimens and cervical scrapes (P &lt; 0.005). The area under the ROC curve for CIN3 or worse varied between 0.86 and 0.89. Within the group of CIN2/3, methylation levels of all 3 genes increased with duration of lesion existence (P &lt; 0.0005), characterized by duration of preceding hrHPV infection, and were significantly higher in the presence of a 3q gain (P &lt; 0.05) in the corresponding tissue biopsy.
Conclusions: By unbiased genome-wide DNA methylation profiling and comprehensive stepwise verification and validation studies using in vitro and patient-derived samples, we identified 3 promising methylation markers (GHSR, SST, and ZIC1) associated with a 3q gain for the detection of cervical (pre)cancer. Clin Cancer Res; 23(14); 3813–22. ©2017 AACR.
Usefulness of KIR3DL2 to Diagnose, Follow-Up, and Manage the Treatment of Patients with Sézary Syndrome
Authors: Hurabielle Charlotte , Thonnart Nicolas , Ram-Wolff Caroline , Sicard Hélène , Bensussan Armand , Bagot Martine , Marie-Cardine Anne 
Published: January 2017

Abstract
Purpose: KIR3DL2 is a recently discovered marker of the malignant clonal cell population in Sézary syndrome. We intended to evaluate the expression of KIR3DL2 on blood T cells as a diagnostic, prognostic, and follow-up marker of Sézary syndrome.
Experimental Design: Sixty-four patients diagnosed with Sézary syndrome were included in this monocentric study. We collected the percentage of KIR3DL2+ cells among CD3+ T cells, obtained by flow cytometry, and other classical diagnostic criteria for Sézary syndrome at diagnosis and during the follow-up.
Results: Compared with the classical diagnostic factors, KIR3DL2 was the most sensitive diagnostic factor for Sézary syndrome. Univariate and multivariate analyses established that an eosinophil cell count &gt;700/mm3 and a percentage of KIR3DL2+ cells within the CD3+ T cells &gt;85% at diagnosis were associated with a significantly reduced disease-specific survival. Moreover, KIR3DL2 immunostaining allowed the assessment of treatment efficiency and specificity toward tumor cells, the detection of the residual disease following treatment, and the occurrence of relapse, even though patients clinically experienced complete remission and/or undetectable circulating Sézary cells by cytomorphologic analysis.
Conclusions: We show that KIR3DL2 expression is the most sensitive diagnostic criterion of Sézary syndrome when compared with all other available biological criteria. It also represents the best independent prognostic factor for Sézary syndrome–specific death and the most relevant feature for the follow-up of Sézary syndrome, showing the invasion of the functional lymphocytes pool by Sézary cells. KIR3DL2 therefore represents a valuable tool for routine use as a clinical parameter at diagnosis, for prognosis and during patient follow-up. Clin Cancer Res; 23(14); 3619–27. ©2017 AACR.
In Vitro and In Vivo Synergistic Antitumor Activity of the Combination of BKM120 and Erlotinib in Head and Neck Cancer: Mechanism of Apoptosis and Resistance
Authors: Anisuzzaman Abu Syed Md , Haque Abedul , Wang Dongsheng , Rahman Mohammad Aminur , Zhang Chao , Chen Zhengjia , Chen Zhuo Georgia , Shin Dong M. , Amin A.R.M. Ruhul 
Published: January 2017

Abstract
We previously reported that the EGFR-targeted inhibitor erlotinib induces G1 arrest of squamous cell carcinoma of the head and neck (SCCHN) cell lines without inducing significant apoptosis. Large-scale genomic studies suggest that &gt;50% of SCCHN cases have activation of PI3K pathways. This study investigated whether cotargeting of EGFR and PI3K has synergistic antitumor effects and apoptosis induction. We examined growth suppression, apoptosis, and signaling pathway modulation resulting from single and combined targeting of EGFR and PI3K with erlotinib and BKM120, respectively, in a panel of SCCHN cell lines and a xenograft model of SCCHN. In a panel of 12 cell lines, single targeting of EGFR with erlotinib or PI3K with BKM120 suppressed cellular growth without inducing significant apoptosis. Cotargeting of EGFR and PI3K synergistically inhibited SCCHN cell line and xenograft tumor growth, but induced variable apoptosis; some lines were highly sensitive, others were resistant. Mechanistic studies revealed that the combination inhibited both axes of the mTORC1 (S6 and 4EBP1) pathway in apoptosis-sensitive cell lines along with translational inhibition of Bcl-2, Bcl-xL, and Mcl-1, but failed to inhibit p-4EBP1, Bcl-2, Bcl-xL, and Mcl-1 in an apoptosis-resistant cell line. siRNA-mediated knockdown of eIF4E inhibited Bcl-2 and Mcl-1 and sensitized this cell line to apoptosis. Our results strongly suggest that cotargeting of EGFR and PI3K is synergistic and induces apoptosis of SCCHN cell lines by inhibiting both axes of the AKT–mTOR pathway and translational regulation of antiapoptotic Bcl-2 proteins. These findings may guide the development of clinical trials using this combination of agents.
Exploiting AR-Regulated Drug Transport to Induce Sensitivity to the Survivin Inhibitor YM155
Authors: Nyquist Michael D. , Corella Alexandra , Burns John , Coleman Ilsa , Gao Shuai , Tharakan Robin , Riggan Luke , Cai Changmeng , Corey Eva , Nelson Peter S. , Mostaghel Elahe A. 
Published: January 2017

Abstract
Androgen receptor (AR) signaling is fundamental to prostate cancer and is the dominant therapeutic target in metastatic disease. However, stringent androgen deprivation therapy regimens decrease quality of life and have been largely unsuccessful in curtailing mortality. Recent clinical and preclinical studies have taken advantage of the dichotomous ability of AR signaling to elicit growth-suppressive and differentiating effects by administering hyperphysiologic levels of testosterone. In this study, high-throughput drug screening identified a potent synergy between high-androgen therapy and YM155, a transcriptional inhibitor of survivin (BIRC5). This interaction was mediated by the direct transcriptional upregulation of the YM155 transporter SLC35F2 by the AR. Androgen-mediated YM155-induced cell death was completely blocked by the overexpression of multidrug resistance transporter ABCB1. SLC35F2 expression was significantly correlated with intratumor androgen levels in four distinct patient-derived xenograft models, and with AR activity score in a large gene expression dataset of castration-resistant metastases. A subset of tumors had significantly elevated SLC35F2 expression and, therefore, may identify patients who are highly responsive to YM155 treatment.
Implications: The combination of androgen therapy with YM155 represents a novel drug synergy, and SLC35F2 may serve as a clinical biomarker of response to YM155. Mol Cancer Res; 15(5); 521–31. ©2017 AACR.
Three Arterial Grafts Improve Late Survival
Authors: Gaudino Mario , Puskas John D. , Di Franco Antonino , Ohmes Lucas B. , Iannaccone Mario , Barbero Umberto , Glineur David , Grau Juan B. , Benedetto Umberto , D’Ascenzo Fabrizio , Gaita Fiorenzo , Girardi Leonard N. , Taggart David P. 
Published: January 2017

Background:
Little evidence shows whether a third arterial graft provides superior outcomes compared with the use of 2 arterial grafts in patients undergoing coronary artery bypass grafting. A meta-analysis of all the propensity score-matched observational studies comparing the long-term outcomes of coronary artery bypass grafting with the use of 2-arterial versus 3-arterial grafts was performed.

Methods:
A literature search was conducted using MEDLINE, EMBASE, and Web of Science to identify relevant articles. Long-term mortality in the propensity score-matched populations was the primary end point. Secondary end points were in-hospital/30-day mortality for the propensity score-matched populations and long-term mortality for the unmatched populations. In the matched population, time-to-event outcome for long-term mortality was extracted as hazard ratios, along with their variance. Statistical pooling of survival (time-to-event) was performed according to a random effect model, computing risk estimates with 95% confidence intervals.

Results:

Eight propensity score-matched studies reporting on 10 287 matched patients (2-arterial graft: 5346; 3-arterial graft: 4941) were selected for final comparison. The mean follow-up time ranged from 37.2 to 196.8 months. The use of 3 arterial grafts was not statistically associated with early mortality (hazard ratio, 0.93; 95% confidence interval, 0.71–1.22;
P
=0.62). The use of 3 arterial grafts was associated with statistically significantly lower hazard for late death (hazard ratio, 0.8; 95% confidence interval, 0.75–0.87;
P
<0.001), irrespective of sex and diabetic mellitus status. This result was qualitatively similar in the unmatched population (hazard ratio, 0.57; 95% confidence interval, 0.33–0.98;
P
=0.04).

Conclusions:
The use of a third arterial conduit in patients with coronary artery bypass grafting is not associated with higher operative risk and is associated with superior long-term survival, irrespective of sex and diabetic mellitus status.
YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy)
Authors: Aoki Junya , Kimura Kazumi , Morita Naomi , Harada Masafumi , Metoki Norifumi , Tateishi Yohei , Todo Kenichi , Yamagami Hiroshi , Hayashi Kouji , Terasawa Yuka , Fujita Koji , Yamamoto Nobuaki , Deguchi Ichiro , Tanahashi Norio , Inoue Takeshi , Iwanaga Takeshi , Kaneko Nobuyuki , Mitsumura Hidetaka , Iguchi Yasuyuki , Ueno Yasushi , Kuramoto Yoji , Ogata Toshiyasu , Fujimoto Shigeru , Yokoyama Mutsumi , Nagahiro Shinji 
Published: January 2017

Background and Purpose—
We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion.

Methods—
The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization).

Results—

One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69–85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (
P
=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%;
P
=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (
P
=0.443). The favorable outcome (modified Rankin Scale score of 0–2) at 3 months was also similar between the groups (53% versus 57%;
P
=0.738).

Conclusions—
The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy.

Clinical Trial Registration—

URL:
http://www.umin.ac.jp/ctr/index-j.htm
. Unique identifier: UMIN000006330.
Cervical Carotid Pseudo-Occlusions and False Dissections
Authors: Grossberg Jonathan A. , Haussen Diogo C. , Cardoso Fabricio B. , Rebello Leticia C. , Bouslama Mehdi , Anderson Aaron M. , Frankel Michael R. , Nogueira Raul G. 
Published: January 2017

Background and Purpose—
Pseudo-occlusion (PO) of the cervical internal carotid artery (ICA) refers to an isolated occlusion of the intracranial ICA that appears as an extracranial ICA occlusion on computed tomography angiography (CTA) or digital subtraction angiography because of blockage of distal contrast penetration by a stagnant column of unopacified blood. We aim to better characterize this poorly recognized entity.

Methods—
Retrospective review of an endovascular database (2010–2015; n=898). Only patients with isolated intracranial ICA occlusions as confirmed by angiographic exploration were included. CTA and digital subtraction angiography images were categorized according to their apparent site of occlusion as (1) extracranial ICA PO or (2) discernible intracranial ICA occlusion.

Results—

Cervical ICA PO occurred in 21/46 (46%) patients on CTA (17 proximal cervical; 4 midcervical). Fifteen (71%) of these patients also had PO on digital subtraction angiography. A flame-shaped PO mimicking a carotid dissection was seen in 7 (33%) patients on CTA and in 6 (29%) patients on digital subtraction angiography. Patients with and without CTA PO had similar age (64.8±17.1 versus 60.2±15.7 years;
P
=0.35), sex (male, 47% versus 52%;
P
=1.00), and intravenous tissue-type plasminogen activator use (38% versus 40%;
P
=1.00). The rates of modified Treatment In Cerebral Ischemia 2b-3 reperfusion were 71.4% in the PO versus 100% in the non-PO cohorts (
P
<0.01). The rates of parenchymal hematoma, 90-day modified Rankin Scale score 0–2, and 90-day mortality were 4.8% versus 8% (
P
=0.66), 40% versus 66.7% (
P
=0.12), and 25% versus 21% (
P
=0.77) in PO versus non-PO patients, respectively. Multivariate analysis indicated that PO patients had lower chances of modified Treatment In Cerebral Ischemia 3 reperfusion (odds ratio 0.14; 95% confidence interval 0.02–0.70;
P
=0.01).

Conclusions—
Cervical ICA PO is a relatively common entity and may be associated with decreased reperfusion rates.
Automated Software System to Promote Anticoagulation and Reduce Stroke Risk
Authors: Holt Tim A. , Dalton Andrew , Marshall Tom , Fay Matthew , Qureshi Nadeem , Kirkpatrick Susan , Hislop Jenny , Lasserson Daniel , Kearley Karen , Mollison Jill , Yu Ly-Mee , Hobbs F.D. Richard , Fitzmaurice David 
Published: January 2017

Background and Purpose—
Oral anticoagulants (OAC) substantially reduce risk of stroke in atrial fibrillation, but uptake is suboptimal. Electronic health records enable automated identification of people at risk but not receiving treatment. We investigated the effectiveness of a software tool (AURAS-AF [Automated Risk Assessment for Stroke in Atrial Fibrillation]) designed to identify such individuals during routine care through a cluster-randomized trial.

Methods—
Screen reminders appeared each time the electronic health records of an eligible patient was accessed until a decision had been taken over OAC treatment. Where OAC was not started, clinicians were prompted to indicate a reason. Control practices continued usual care. The primary outcome was the proportion of eligible individuals receiving OAC at 6 months. Secondary outcomes included rates of cardiovascular events and reports of adverse effects of the software on clinical decision-making.

Results—

Forty-seven practices were randomized. The mean proportion–prescribed OAC at 6 months was 66.3% (SD=9.3) in the intervention arm and 63.9% (9.5) in the control arm (adjusted difference 1.21% [95% confidence interval −0.72 to 3.13]). Incidence of recorded transient ischemic attack was higher in the intervention practices (median 10.0 versus 2.3 per 1000 patients with atrial fibrillation;
P
=0.027), but at 12 months, we found a lower incidence of both all cause stroke (
P
=0.06) and hemorrhage (
P
=0.054). No adverse effects of the software were reported.

Conclusions—
No significant change in OAC prescribing occurred. A greater rate of diagnosis of transient ischemic attack (possibly because of improved detection or overdiagnosis) was associated with a reduction (of borderline significance) in stroke and hemorrhage over 12 months.

Clinical Trial Registration—

URL:
http://www.isrctn.com
. Unique Identifier: ISRCTN55722437.
What is an Ersatz Part?
Authors: Miller Kristie , Hariman Johann 
Published: January 2017

This paper develops four proposals for explicating the notion of an ersatz part. It then evaluates each proposal with respect to a number of jobs for which ersatz parts are posited. We argue that each of the four notions of ersatz parthood do better with respect to some jobs, and worse with respect to others. Thus, we think, it’s horses for courses: which notion of ersatz part one chooses will be sensitive to which metaphysical project one is pursuing.
Recent Wind-Driven Variability in Atlantic Water Mass Distribution and Meridional Overturning Circulation
Authors: Evans Dafydd Gwyn , Toole John , Forget Gael , Zika Jan D. , Naveira Garabato Alberto C. , Nurser A. J. George , Yu Lisan 
Published: January 2017

AbstractInterannual variability in the volumetric water mass distribution within the North Atlantic Subtropical Gyre is described in relation to variability in the Atlantic meridional overturning circulation. The relative roles of diabatic and adiabatic processes in the volume and heat budgets of the subtropical gyre are investigated by projecting data into temperature coordinates as volumes of water using an Argo-based climatology and an ocean state estimate (ECCO version 4). This highlights that variations in the subtropical gyre volume budget are predominantly set by transport divergence in the gyre. A strong correlation between the volume anomaly due to transport divergence and the variability of both thermocline depth and Ekman pumping over the gyre suggests that wind-driven heave drives transport anomalies at the gyre boundaries. This wind-driven heaving contributes significantly to variations in the heat content of the gyre, as do anomalies in the air–sea fluxes. The analysis presented suggests that wind forcing plays an important role in driving interannual variability in the Atlantic meridional overturning circulation and that this variability can be unraveled from spatially distributed hydrographic observations using the framework presented here.