bluuebunny/crossref_metadata_2025_split huggingface dataset:
U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer
Authors: Singh Harpreet , Walker Amanda J. , Amiri-Kordestani Laleh , Cheng Joyce , Tang Shenghui , Balcazar Pamela , Barnett-Ringgold Kimberly , Palmby Todd R. , Cao Xianhua , Zheng Nan , Liu Qi , Yu Jingyu , Pierce William F. , Daniels Selena R. , Sridhara Rajeshwari , Ibrahim Amna , Kluetz Paul G. , Blumenthal Gideon M. , Beaver Julia A. , Pazdur Richard 
Published: March 2018

Abstract
On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified HR of 0.66 [95% confidence interval (CI), 0.49–0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%–95.4%) in patients treated with neratinib versus 91.9% (95% CI, 90.2%–93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (&gt;10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Clin Cancer Res; 24(15); 3486–91. ©2018 AACR.
See related commentary by Unni et al., p. 3483
CD40L Deficiency Protects Against Aneurysm Formation
Authors: Kusters Pascal J.H. , Seijkens Tom T.P. , Beckers Linda , Lievens Dirk , Winkels Holger , de Waard Vivian , Duijvestijn Adriaan , Lindquist Liljeqvist Moritz , Roy Joy , Daugherty Alan , Newby Andrew , Gerdes Norbert , Lutgens Esther 
Published: March 2018

Objective—
The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration of the aortic wall, we studied the role of the costimulatory molecule CD40L, a major driver of inflammation, in aneurysm formation.

Approach and Results—

Transcriptomics data obtained from human abdominal aortic aneurysms and normal aortas revealed increased abundance of both CD40L and CD40 in media of thrombus-free and thrombus-covered human abdominal aortic aneurysms samples. To further unravel the role of CD40L in aneurysm formation, apolipoprotein E–deficient (
Apoe
−/−
) and
Cd40l
−/−
Apoe
−/−
mice were infused with angiotensin II for 7 and 28 days. Only a minority of
Cd40l
−/−
Apoe
−/−
mice (33% and 17%) developed (dissecting) aneurysms compared with 75% and 67% of
Apoe
−/−
littermates after 7 and 28 days of infusion, respectively. Total vessel area of the aorta at the suprarenal level was 52% smaller in angiotensin II–infused
Cd40l
−/−
Apoe
−/−
mice compared with that in angiotensin II–infused
Apoe
−/−
mice. Chimeric
Apoe
−/−
mice repopulated with
Cd40l
−/−
Apoe
−/−
bone marrow afforded a similar protection against dissecting aneurysm formation. Moreover, lack of CD40L protected mice from fatal aneurysm rupture. T helper cell and macrophage accumulation in aneurysmal tissue was reduced in
Cd40l
−/−
Apoe
−/−
mice with a concomitant decrease in expression of proinflammatory chemo- and cytokines. In addition, aneurysms of
Cd40l
−/−
Apoe
−/−
mice displayed reduced abundance of matrix metalloproteinase-13 and an increase in tissue inhibitor of metalloproteinase-3 while activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 was diminished.

Conclusions—
Deficiency of (hematopoietic) CD40L protects against dissecting aneurysm formation and reduces the incidence of fatal rupture. This is associated with a decreased accumulation and activation of inflammatory cells and a dampened protease activity in the arterial wall.
Impact of Ischemic and Valvular Heart Disease on Atrial Excitation:A High‐Resolution Epicardial Mapping Study
Authors: Mouws Elisabeth M. J. P. , Lanters Eva A. H. , Teuwen Christophe P. , van der Does Lisette J. M. E. , Kik Charles , Knops Paul , Yaksh Ameeta , Bekkers Jos A. , Bogers Ad J. J. C. , de Groot Natasja M. S. 
Published: March 2018

Background

The influence of underlying heart disease or presence of atrial fibrillation (
AF
) on atrial excitation during sinus rhythm (
SR
) is unknown. We investigated atrial activation patterns and total activation times of the entire atrial epicardial surface during
SR
in patients with ischemic and/or valvular heart disease with or without
AF
.

Methods and Results

Intraoperative epicardial mapping (N=128/192 electrodes, interelectrode distances: 2 mm) of the right atrium, Bachmann's bundle (
BB
), left atrioventricular groove, and pulmonary vein area was performed during
SR
in 253 patients (186 male [74%], age 66±11 years) with ischemic heart disease (N=132, 52%) or ischemic valvular heart disease (N=121, 48%). As expected,
SR
origin was located at the superior intercaval region of the right atrium in 232 patients (92%).
BB
activation occurred via 1 wavefront from right‐to‐left (N=163, 64%), from the central part (N=18, 7%), or via multiple wavefronts (N=72, 28%). Left atrioventricular groove activation occurred via (1)
BB
: N=108, 43%; (2) pulmonary vein area: N=9, 3%; or (3)
BB
and pulmonary vein area: N=136, 54%; depending on which route had the shortest interatrial conduction time (
P
<0.001). Ischemic valvular heart disease patients more often had central
BB
activation and left atrioventricular groove activation via pulmonary vein area compared with ischemic heart disease patients (N=16 [13%] versus N=2 [2%];
P
=0.009 and N=86 [71%] versus N=59 [45%];
P
<0.001, respectively). Total activation times were longer in patients with
AF
(
AF
: 136±20 [92–186] ms; no
AF
: 114±17 [74–156] ms;
P
<0.001), because of prolongation of right atrium (
P
=0.018) and
BB
conduction times (
P
<0.001).

Conclusions

Atrial excitation during
SR
is affected by underlying heart disease and
AF
, resulting in alternative routes for
BB
and left atrioventricular groove activation and prolongation of total activation times. Knowledge of atrial excitation patterns during
SR
and its electropathological variations, as demonstrated in this study, is essential to further unravel the pathogenesis of
AF
.
Postsystolic Shortening by Speckle Tracking Echocardiography Is an Independent Predictor of Cardiovascular Events and Mortality in the General Population
Authors: Brainin Philip , Biering‐Sørensen Sofie Reumert , Møgelvang Rasmus , Søgaard Peter , Jensen Jan Skov , Biering‐Sørensen Tor 
Published: March 2018

Background

Postsystolic shortening (
PSS
) has been proposed as a novel marker of contractile dysfunction in the myocardium. Our objective was to assess the prognostic potential of
PSS
on cardiovascular events and death in the general population.

Methods and Results

The study design consisted of a prospective cohort study of 1296 low‐risk participants from the general population, who were examined by speckle tracking echocardiography. The primary end point was the composite of heart failure, myocardial infarction, and cardiovascular death, defined as major adverse cardiovascular events (
MACEs
). The secondary end point was all‐cause death. The postsystolic index (
PSI
) was defined as follows: [(maximum strain in cardiac cycle−peak systolic strain)/(maximum strain in cardiac cycle)]×100.
PSS
was regarded as present if
PSI
>20%. During a median follow‐up of 11 years, 149 participants (12%) were diagnosed as having
MACE
s and 236 participants (18%) died. Increasing number of walls with
PSS
predicted both end points, an association that persisted after adjustment for age, sex, estimated glomerular filtration rate, global longitudinal strain, hypertension, heart rate, left ventricular ejection fraction,
LV
mass index, pro‐B‐type natriuretic peptide, previous ischemic heart disease, systolic blood pressure, average peak early diastolic longitudinal mitral annular velocity (e′), ratio between peak transmitral early and late diastolic inflow velocity (E/A), and left atrial volume index:
MACEs
(hazard ratio, 1.35; 95% confidence interval, 1.09–1.67;
P
=0.006 per 1 increase in walls displaying
PSS
) and death (hazard ratio, 1.30; 95% confidence interval, 1.08–1.57;
P
=0.006 per 1 increase in walls displaying
PSS
). The strongest predictor of end points was ≥2 walls exhibiting PSS. The
PSI
also predicted increased risk of the end points, and the associations remained significant in multivariable models:
MACEs
(per 1% increase in
PSI
: hazard ratio, 1.18; 95% confidence interval, 1.02–1.36;
P
=0.024) and death (per 1% increase in
PSI
: hazard ratio, 1.18; 95% confidence interval, 1.05–1.33;
P
=0.005).

Conclusions

Presence of
PSS
in the general population provides independent and long‐term prognostic information on the occurrence of
MACEs
and death.
Age-Specific Associations of Renal Impairment With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Transient Ischemic Attack and Stroke
Authors: Liu Bian , Lau Kui Kai , Li Linxin , Lovelock Caroline , Liu Ming , Kuker Wilhelm , Rothwell Peter M. 
Published: March 2018

Background and Purpose—
It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age.

Methods—

In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m
2
) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent).

Results—

Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69–2.75;
P
<0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69–9.32;
P
=0.002; 60–79 years: OR, 1.01; 95% CI, 0.72–1.41;
P
=0.963; ≥80 years: OR, 0.95; 95% CI, 0.59–1.54;
P
=0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56–1.02;
P
=0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21–7.98;
P
=0.018). Associations of renal impairment and SVD were consistent for each SVD marker at age <60 years but were strongest for cerebral microbleeds (OR, 5.84; 95% CI, 1.45–23.53;
P
=0.013) and moderate–severe periventricular white matter hyperintensities (OR, 6.28; 95% CI, 1.54–25.63;
P
=0.010).

Conclusions—
The association of renal impairment and cerebral SVD was attenuated with adjustment for shared risk factors at older ages, but remained at younger ages, consistent with a shared susceptibility to premature disease.
Transcranial Direct Current Stimulation Does Not Improve Language Outcome in Subacute Poststroke Aphasia
Authors: Spielmann Kerstin , van de Sandt-Koenderman W. Mieke E. , Heijenbrok-Kal Majanka H. , Ribbers Gerard M. 
Published: March 2018

Background and Purpose—
The aim of the present study is to investigate the effect of transcranial direct current stimulation on word-finding treatment outcome in subacute poststroke aphasia.

Methods—
In this multi-center, double-blind, randomized controlled trial with 6-month follow-up, we included 58 patients with subacute aphasia (<3 months poststroke), who were enrolled in a stroke rehabilitation program. Patients participated in 2 separate intervention weeks. Each intervention week included 5 daily sessions of 45-minute word-finding therapy combined with either anodal transcranial direct current stimulation (1 mA, 20 minutes; experimental group) or sham transcranial direct current stimulation (control group) over the left inferior frontal gyrus. The primary outcome measure was the Boston Naming Test. Secondary outcome measures included naming performance for trained/untrained picture items and verbal communication.

Results—
Both the experimental (n=26) and the control group (n=32) improved on the Boston Naming Test over the intervention period and 6-month follow-up; however, there were no significant differences between groups. Also for the secondary outcome measures, no significant differences were found.

Conclusions—
The results of the present study do not support an effect of transcranial direct current stimulation as an adjuvant treatment in subacute poststroke aphasia.

Clinical Trial Registration—

URL:
http://www.trialregister.nl/trialreg/admin/rctview.asp
. Unique identifier: NTR4364.
Thalamic Diaschisis in Acute Ischemic Stroke
Authors: Reidler Paul , Thierfelder Kolja M. , Fabritius Matthias P. , Sommer Wieland H. , Meinel Felix G. , Dorn Franziska , Wollenweber Frank A. , Duering Marco , Kunz Wolfgang G. 
Published: March 2018

Background and Purpose—
Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus.

Methods—
One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations.

Results—

ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD− patients (each with
P
<0.001). In the ITD+ group, larger cerebral blood flow (
P
=0.002) and cerebral blood volume (
P
<0.001) deficit volumes, as well as smaller cerebral blood flow–cerebral blood volume mismatch (
P
=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with
P
>0.05). ITD had no influence on the development of subacute stroke complications.

Conclusions—
ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion–based trials.
Detection of the European pond turtle (Emys orbicularis) by environmental DNA: is eDNA adequate for reptiles?
Authors: Raemy Matthieu , Ursenbacher Sylvain 
Published: March 2018

Abstract
Recent studies have demonstrated the potential of combining molecular technologies with environmental sampling to detect various vertebrate species in aquatic ecosystems. The European pond turtle (Emys orbicularis) is a threatened and elusive aquatic reptile with shy behaviour. We aimed to develop and evaluate a methodology to detect the presence of this secretive aquatic reptile in ponds from environmental water samples. First, we determined that reptilian DNA can be isolated and amplified from water samples in artificial and natural ponds with known turtle density. Then we compared the potential of two water sampling methods (through filtration or precipitation) and found no significant differences between these approaches. Finally, we demonstrated that the eDNA concentration detected is not correlated with the number of E. orbicularis individuals or biomass. Detection of eDNA was higher in artificial ponds with small volumes of water or in the shallow waters of natural ponds. The eDNA-based methodology aims to detect the presence of specific species, even at low density, with better accuracy than visual observation. However, our study indicates that this method of population monitoring should be applied with caution to aquatic reptiles.
A molecular phylogeny of the Rhigonematomorpha De Ley & Blaxter, 2002 as inferred from SSU and LSU rDNA sequences
Authors: Mejia-Madrid Hugo H. 
Published: March 2018

SummaryA molecular hypothesis of the Infraorder Rhigonematomorpha is presented. The phylogeny recovered using combined SSU and LSU markers suggests that the Rhigonematomorpha is nested within a larger clade that includes Ascaridomorpha, Spiruromorpha and Oxyuridomorpha and is strongly supported by maximum likelihood (ML) bootstrap support values (BS) and Bayesian posterior probabilities (BPP). SSU and LSU ML and Bayesian analyses recovered Rhigonematomorpha as a paraphyletic clade. In the ML and Bayesian analyses of a combined matrix of complete to partial sequences of SSU and LSU, respectively, Rhigonematomorpha is recovered as a monophyletic clade with moderate BPP but low BS. Highly supported BS and BPP of a combined SSU and LSU matrix support a hypothesis of a monophyletic Superfamily Ransomnematoidea that includes the families Carnoyidae, Hethidae, Ransomnematidae plus aBrumptaemilius,Cattiena,Insulanemaclade, and a monophyletic Superfamily Rhigonematoidea that probably includes the paraphyletic families Rhigonematidae and Ichthyocephalidae. It is suggested that the future inclusion of more families and genera might help resolve the monophyly of the Infraorder Rhigonematomorpha as advanced here.
Beckett’s Collaborative Translations in the 1950s
Authors: Van Hulle Dirk , Verhulst Pim 
Published: March 2018

Abstract
In the 1950s, Samuel Beckett worked together with a number of writer-translators on English, French and German versions of his novels and plays. This article studies the material traces of these collaborations to analyse the collaborations as a crucial phase in a 4-step process toward a poetics of bilingualism, consisting of (1) writing in another language, (2) collaborating on the translations, (3) eventually giving preference to self-translation, and (4) finally presenting his work as a bilingual oeuvre. Beckett also appears to have played a greater part in his German translations than hitherto assumed, which calls for a reassessment of Beckett’s “trilingual” engagement with his work in the development of a “bilingual” poetics.
Bilinguisme et autotraduction à l’ œuvre dans l’ écriture de Samuel Beckett
Authors: Montini Chiara 
Published: March 2018

Résumé
L’ autotraduction dans l’ œuvre de Beckett témoigne de la tentative de miner la fonction auteur (Foucault, 1969) et le rôle de l’ original dans la littérature occidentale moderne. Censée effacer celui ‘qui parle’, non plus en tant qu’ auteur, mais en tant que “traducteur servile,” l’ autotraduction met en scène un ‘moi’ sans cesse changeant. En multipliant les ‘egos’ de l’ auteur, les langues, les références et les textes, l’ autotraduction permet d’ interroger la croyance en l’ unité de l’ origine et donc l’ aura (Benjamin, 1937) de l’ œuvre d’ art et de l’ auteur. Écriture et traduction finissent par se rencontrer : elles sont les deux têtes de Janus Bifrons. Grâce à l’ autotraduction Beckett représente ce qu’ il y a de paradoxal dans l’ écriture et dans le rapport du sujet au langage.
How Do Environmental Conditions Influence Vertical Buoyancy Structure and Shallow-to-Deep Convection Transition across Different Climate Regimes?
Authors: Zhuang Yizhou , Fu Rong , Wang Hongqing 
Published: March 2018

Abstract
We developed an entraining parcel approach that partitions parcel buoyancy into contributions from different processes (e.g., adiabatic cooling, condensation, freezing, and entrainment). Applying this method to research-quality radiosonde profiles provided by the Atmospheric Radiation Measurement (ARM) program at six sites, we evaluated how atmospheric thermodynamic conditions and entrainment influence various physical processes that determine the vertical buoyancy structure across different climate regimes as represented by these sites. The differences of morning buoyancy profiles between the deep convection (DC)/transition cases and shallow convection (SC)/nontransition cases were used to assess preconditions important for shallow-to-deep convection transition. Our results show that for continental sites such as the U.S. Southern Great Plains (SGP) and west-central Africa, surface conditions alone are enough to account for the buoyancy difference between DC and SC cases, although entrainment further enhances the buoyancy difference at SGP. For oceanic sites in the tropical west Pacific, humidity dilution in the lower to middle free troposphere (~1–6 km) and temperature mixing in the middle to upper troposphere (&gt;4 km) have the most important influences on the buoyancy difference between DC and SC cases. For the humid central Amazon region, entrainment in both the boundary layer and the lower free troposphere (~0–4 km) have significant contributions to the buoyancy difference; the upper-tropospheric influence seems unimportant. In addition, the integral of the condensation term, which represents the parcel’s ability to transform available water vapor into heat through condensation, provides a better discrimination between DC and SC cases than the integral of buoyancy or the convective available potential energy (CAPE).