bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selected growth parameters of farm-raised mallard (Anas platyrhynchos L.) ducklings
Authors: Murawska Daria , Hanzal Vladimir , Janiszewski Pawel , Lambert Barry D. , Gesek Michal , Zawacka Magdalena , Michalik Danuta , Borkowski Rafal 
Published: June 2016

The aim of this study was to determine changes in selected growth parameters of farm-raised mallard ducklings from hatch to 42 d of age. The largest increases in body and carcass weights of ducklings and weights of the analyzed tissue components were noted during the first 28 d of the rearing period, except for breast and wing muscles. In comparison with other muscle groups, the growth rate of breast and wing muscles was lower from hatch to 14 d of age, greatest between 14 and 28 d, and remained high up to 42 d of age. The average body weight of mallard ducklings increased more than 16-fold (from 39.7 to 644.8 g, P ≤ 0.01), and the average carcass weight increased more than 26-fold (from 14.4 to 384.5 g, P ≤ 0.01). The growth rates of carcass and tissue components varied considerably. Wing weight increased 84.5-fold (from 0.80 to 67.6 g, P ≤ 0.01), followed by breast weight, which increased 48-fold (from 1.7 to 82.9 g, P ≤ 0.01). Slower growth rates were noted in the remaining carcass parts: back, 23-fold; neck, 19.2-fold; and legs, 17.1-fold (from 5.4 to 92.2 g, P ≤ 0.01).
Hydrothermal dolomitization: simulation by reaction transport modelling
Authors: Consonni Alberto , Frixa Alfredo , Maragliulo Chiara 
Published: June 2016

Abstract
Reaction transport modelling (RTM) has been successfully used to simulate dolomitization and to predict the lateral extension of dolomitized bodies as potential hydrocarbon reservoirs in the subsurface as well as to give insights into the dolomitization process itself. Geological configurations that have been tested include reflux dolomitization, thermal convection and dolomitization in compactional burial settings. In this study the hydrothermal dolomitization model has been tested with a RTM approach where a limestone reservoir in an intermediate burial setting is fluxed in the presence of deep feeding faults. Hydrothermal fluids migrate upwards from the deep basin areas through extensional fault conduits reaching more permeable levels in the reservoir. The fluids enter the primary interparticle porosity and dolomitize the limestone creating moldic and vuggy porosity. The simulations demonstrate the importance of faulting in this dolomitization process. An effective control on dolomitization is thus exerted by the permeability distribution. Moreover, the type and reactivity of the fluids entering the limestone reservoir exert important controls on the extent of the dolomite bodies.
Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome
Authors: You Sungyong , Knudsen Beatrice S. , Erho Nicholas , Alshalalfa Mohammed , Takhar Mandeep , Al-deen Ashab Hussam , Davicioni Elai , Karnes R. Jeffrey , Klein Eric A. , Den Robert B. , Ross Ashley E. , Schaeffer Edward M. , Garraway Isla P. , Kim Jayoung , Freeman Michael R. 
Published: June 2016

Abstract
Prostate cancer is a biologically heterogeneous disease with variable molecular alterations underlying cancer initiation and progression. Despite recent advances in understanding prostate cancer heterogeneity, better methods for classification of prostate cancer are still needed to improve prognostic accuracy and therapeutic outcomes. In this study, we computationally assembled a large virtual cohort (n = 1,321) of human prostate cancer transcriptome profiles from 38 distinct cohorts and, using pathway activation signatures of known relevance to prostate cancer, developed a novel classification system consisting of three distinct subtypes (named PCS1–3). We validated this subtyping scheme in 10 independent patient cohorts and 19 laboratory models of prostate cancer, including cell lines and genetically engineered mouse models. Analysis of subtype-specific gene expression patterns in independent datasets derived from luminal and basal cell models provides evidence that PCS1 and PCS2 tumors reflect luminal subtypes, while PCS3 represents a basal subtype. We show that PCS1 tumors progress more rapidly to metastatic disease in comparison with PCS2 or PCS3, including PSC1 tumors of low Gleason grade. To apply this finding clinically, we developed a 37-gene panel that accurately assigns individual tumors to one of the three PCS subtypes. This panel was also applied to circulating tumor cells (CTC) and provided evidence that PCS1 CTCs may reflect enzalutamide resistance. In summary, PCS subtyping may improve accuracy in predicting the likelihood of clinical progression and permit treatment stratification at early and late disease stages. Cancer Res; 76(17); 4948–58. ©2016 AACR.
Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade
Authors: Chen Pei-Ling , Roh Whijae , Reuben Alexandre , Cooper Zachary A. , Spencer Christine N. , Prieto Peter A. , Miller John P. , Bassett Roland L. , Gopalakrishnan Vancheswaran , Wani Khalida , De Macedo Mariana Petaccia , Austin-Breneman Jacob L. , Jiang Hong , Chang Qing , Reddy Sangeetha M. , Chen Wei-Shen , Tetzlaff Michael T. , Broaddus Russell J. , Davies Michael A. , Gershenwald Jeffrey E. , Haydu Lauren , Lazar Alexander J. , Patel Sapna P. , Hwu Patrick , Hwu Wen-Jen , Diab Adi , Glitza Isabella C. , Woodman Scott E. , Vence Luis M. , Wistuba Ignacio I. , Amaria Rodabe N. , Kwong Lawrence N. , Prieto Victor , Davis R. Eric , Ma Wencai , Overwijk Willem W. , Sharpe Arlene H. , Hu Jianhua , Futreal P. Andrew , Blando Jorge , Sharma Padmanee , Allison James P. , Chin Lynda , Wargo Jennifer A. 
Published: June 2016

AbstractImmune checkpoint blockade represents a major breakthrough in cancer therapy; however, responses are not universal. Genomic and immune features in pretreatment tumor biopsies have been reported to correlate with response in patients with melanoma and other cancers, but robust biomarkers have not been identified. We studied a cohort of patients with metastatic melanoma initially treated with cytotoxic T-lymphocyte–associated antigen-4 (CTLA4) blockade (n = 53) followed by programmed death-1 (PD-1) blockade at progression (n = 46), and analyzed immune signatures in longitudinal tissue samples collected at multiple time points during therapy. In this study, we demonstrate that adaptive immune signatures in tumor biopsy samples obtained early during the course of treatment are highly predictive of response to immune checkpoint blockade and also demonstrate differential effects on the tumor microenvironment induced by CTLA4 and PD-1 blockade. Importantly, potential mechanisms of therapeutic resistance to immune checkpoint blockade were also identified.Significance: These studies demonstrate that adaptive immune signatures in early on-treatment tumor biopsies are predictive of response to checkpoint blockade and yield insight into mechanisms of therapeutic resistance. These concepts have far-reaching implications in this age of precision medicine and should be explored in immune checkpoint blockade treatment across cancer types. Cancer Discov; 6(8); 827–37. ©2016 AACR.See related commentary by Teng et al., p. 818.This article is highlighted in the In This Issue feature, p. 803
Temporal Trends in the Clinical and Pathological Characteristics of Victims of Sudden Cardiac Death in the Absence of Previously Identified Heart Disease
Authors: Junttila M. Juhani , Hookana Eeva , Kaikkonen Kari S. , Kortelainen Marja-Leena , Myerburg Robert J. , Huikuri Heikki V. 
Published: June 2016

Background—
Coronary artery disease is identified in ≈80% of victims of sudden cardiac death (SCD). Because the prevention strategies and public awareness have changed during the past decades, we studied the temporal trends in the pathogenesis of SCD.

Methods and Results—

FinGesture (n=4031) is a prospective study designed to classify the phenotype and genotype profiles of SCD in a consecutive series of victims of SCD in Northern Finland. On the basis of Finnish law, all subjects who die suddenly undergo autopsy. We analyzed the characteristics of SCD victims and autopsy findings in 1998 to 2002, 2003 to 2007, and 2008 to 2012. Among victims of SCD as a first cardiac event (n=2697), the proportion with coronary artery disease decreased during the 2008 to 2012 time period, compared with the 2 preceding 5-year periods: 74.0% in 1998 to 2002, 73.1% in 2003 to 2007, and 66.4% in 2008 to 2012 (
P
<0.001). Proportion of SCDs associated with hypertensive heart disease with left ventricular hypertrophy in the absence of coronary artery disease increased from 1.7% in 1998 to 2002 to 5.8% in 2003 to 2007 and 8.9% in 2008 to 2012 (
P
<0.001). Similarly, myocardial fibrosis in the absence of myocarditis or left ventricular hypertrophy, or other known pathogeneses, was 6.7% in the past 5-year period compared with 2 previous 5-year periods (3.7% and 4.0%;
P
<0.001 between 1998–2002 and 2008–2012 and between 2003–2007 and 2008–2012).

Conclusions—
The proportion of SCDs attributable to coronary artery disease, in the absence of a history of heart disease, has decreased, whereas the proportion associated with hypertensive heart disease and idiopathic fibrosis has increased during the past 15 years.
Eligibility and Predictors for Acute Revascularization Procedures in a Stroke Center
Authors: Vanacker Peter , Lambrou Dimitris , Eskandari Ashraf , Mosimann Pascal J. , Maghraoui Ali , Michel Patrik 
Published: June 2016

Background and Purpose—
Endovascular treatment (EVT) is a new standard of care for selected, large vessel occlusive strokes. We aimed to determine frequency of potentially eligible patients for intravenous thrombolysis (IVT) and EVT in comprehensive stroke centers. In addition, predictors of EVT eligibility were derived.

Methods—
Patients from a stroke center–based registry (2003–2014), admitted within 24 hours of last proof of usual health, were selected if they had all data to determine IVT and EVT eligibility according to American Heart Association/American Stroke Association (AHA/ASA) guidelines (class I–IIa recommendations). Moreover, less restrictive criteria adapted from randomized controlled trials and clinical practice were tested. Maximum onset-to-door time windows for IVT eligibility were 3.5 hours (allowing door-to-needle delay of ≤60 minutes) and 4.5 hours for EVT eligibility (door-to-groin delay ≤90 minutes). Demographic and clinical information were used in logistic regression analysis to derive variables associated with EVT eligibility.

Results—
A total of 2704 patients with acute ischemic stroke were included, of which 26.8% were transfers. Of all patients with stroke arriving at our comprehensive stroke center, a total proportion of 12.4% patients was eligible for IVT. Frequency of EVT eligibility differed between AHA/ASA guidelines and less restrictive approach: 2.9% versus 4.9%, respectively, of all patients with acute ischemic stroke and 10.5% versus 17.7%, respectively, of all patients arriving within <6 hours. Predictors for AHA–EVT eligibility were younger, shorter onset-to-admission delays, higher National Institutes of Health Stroke Scale (NIHSS), decreased vigilance, hemineglect, absent cerebellar signs, atrial fibrillation, smoking, and decreasing glucose levels (area under the curve=0.86).

Conclusions—
Of patients arriving within 6 hours at a comprehensive stroke center, 10.5% are EVT eligible according to AHA/ASA criteria, 17.7% according to criteria resembling randomized controlled trials, and twice as many patients are IVT eligible (36.2%).
Prothrombotic State in Patients With a Left Atrial Appendage Thrombus of Unknown Origin and Cerebrovascular Events
Authors: Meus Rafal , Son Maksim , Sobczyk Dorota , Undas Anetta 
Published: June 2016

Background and Purpose—
We hypothesized that formation of left atrial appendage (LAA) thrombi of unknown origin is associated with altered fibrin clot properties and blood hypercoagulability.

Methods—
In a case–control study, we investigated 32 patients with a history of LAA thrombus after successful anticoagulant treatment versus 32 control subjects matched for age, sex, and diabetes mellitus. All subjects had previous ischemic stroke, transient ischemic attack, or migraine associated with patent foramen ovale. Patients with documented atrial fibrillation were excluded. We determined plasma fibrin clot permeability, fibrinolytic efficiency, thrombin generation, platelet and endothelial markers. Stroke or transient ischemic attack were assessed during a median follow-up of 74 (range 19–98) months.

Results—

Compared with controls, patients with LAA thrombus more frequently were smokers (43.8% versus 18.8%) and had 20% prolonged clot lysis time, lower plasminogen (−14%), and higher plasminogen activator inhibitor-1 (+17%), thrombin–antithrombin complexes (+17%), CD40 ligand (+30%), P-selectin (+29%), and von Willebrand factor (+30%, all
P
<0.05). Occurrence of LAA thrombus was predicted by von Willebrand factor (β=0.038,
P
=0.004), plasminogen (β=−0.048,
P
=0.01), plasminogen activator inhibitor-1 (β=−0.161,
P
=0.03), and clot permeability (β=−1.076,
P
=0.03). During follow-up, cerebrovascular events occurred in 10 (33.33%) of the 30 available patients in the LAA thrombus group, including 7 (23.3%) with recurrent LAA thrombus and 4 (13.33%) with documented atrial fibrillation. Recurrent LAA thrombus was associated with lower baseline
K
s
and higher thrombin generation, fibrinogen, plasminogen activator inhibitor-1, and soluble CD40 ligand (all
P
<0.05).

Conclusions—
Prothrombotic blood alterations could be involved in the LAA thrombus formation in patients without documented atrial fibrillation and are associated with increased risk of stroke or transient ischemic attack during follow-up.
Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage
Authors: Ottosen Tobias Pilgaard , Grijota Miriam , Hansen Morten Lock , Brandes Axel , Damgaard Dorte , Husted Steen Elkjær , Johnsen Søren Paaske 
Published: June 2016

Background and Purpose—
The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage and examined the impact of subsequent AT use on the long-term clinical outcome.

Methods—
We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were identified and followed up. We estimated the hazard ratio of all-cause death, thromboembolic events, or major bleeding according to use of AT.

Results—
We identified 6369 patients between 2005 and 2013. Among these patients, 2978 (47%) had indication for AT, and during the follow-up, (median: 2.3 year) 1281 (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence interval, 0.43–0.82) and thromboembolic events (adjusted hazard ratio 0.58; 95% confidence interval, 0.35–0.97) and no increased risk of major bleeding (adjusted hazard ratio 0.65; 95% confidence interval, 0.41–1.02). In contrast, use of platelet inhibitors among patients with indication for platelet inhibitors was not related to statistically significantly improved clinical outcome.

Conclusions—
Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality and thromboembolic events and no increased risk of major bleeding.
Magnetic Resonance Imaging of Plaque Morphology, Burden, and Distribution in Patients With Symptomatic Middle Cerebral Artery Stenosis
Authors: Dieleman Nikki , Yang Wenjie , Abrigo Jill M. , Chu Winnie Chiu Wing , van der Kolk Anja G. , Siero Jeroen C.W. , Wong Ka Sing , Hendrikse Jeroen , Chen Xiang Yan 
Published: June 2016

Background and Purpose—
Intracranial atherosclerosis is a major cause of ischemic stroke worldwide. Intracranial vessel wall imaging is an upcoming field of interest to assess intracranial atherosclerosis. In this study, we investigated total intracranial plaque burden in patients with symptomatic middle cerebral artery stenosis, assessed plaque morphological features, and compared features of symptomatic and asymptomatic lesions using a 3T vessel wall sequence.

Methods—

Nineteen consecutive Chinese patients with ischemic stroke and transient ischemic attack (mean age: 67 years; 7 females) with a middle cerebral artery stenosis were scanned at 3T magnetic resonance imaging; the protocol included a time-of-flight magnetic resonance angiography and the T1-weighted volumetric isotropically reconstructed turbo spin echo acquisition sequence before and after (83%) contrast administration. Chi-square tests were used to assess associations between different plaque features. Statistical significance was set at
P
<0.05.

Results—

Vessel wall lesions were identified in 18 patients (95%), totaling 57 lesions in 494 segments (12% of segments). Lesions were located primarily in the anterior circulation (82%). Eccentric lesions were associated with a focal thickening pattern and concentric lesions with a diffuse thickening pattern (
P
<0.001). When differentiating between asymptomatic and symptomatic lesions, an association (
P
<0.05) was found between eccentricity and asymptomatic lesions, but not for enhancement or a specific thickening pattern. Symptomatic lesions did not have any specific morphological features.

Conclusions—
Our results lead to a 2-fold conclusion: (1) The classification system of both thickening pattern and distribution of the lesion can be simplified by using distribution pattern only and (2) differentiation between symptomatic and asymptomatic atherosclerotic lesions was possible using intracranial vessel wall imaging.
Orosomucoid, Carotid Plaque, and Incidence of Stroke
Authors: Berntsson John , Östling Gerd , Persson Margaretha , Smith J. Gustav , Hedblad Bo , Engström Gunnar 
Published: June 2016

Background and Purpose—
Orosomucoid (α-1-acid glycoprotein) is an acute-phase protein that has been implicated in anti-inflammatory, immunomodulating, and angiogenic pathways. Orosomucoid has also been associated with coronary disease and stroke. The relationship between orosomucoid, carotid plaque, and stroke incidence were explored in this study.

Methods—
Plasma levels of orosomucoid were assessed in 4285 subjects (39.8% men; mean age 57.5±5.9 years) without cardiovascular disease, who participated in the Malmö Diet and Cancer Study, between 1991 and 1994. The right carotid artery was examined for plaque using B-mode ultrasound examination. Incidence of stroke was followed up during a median follow-up time of 17.7 years.

Results—

Carotid plaque was present in 43.5% at baseline. Orosomucoid was significantly higher in subjects with carotid plaque (mean±SD: 0.72±0.22 versus 0.69±0.20 g/L;
P
<0.001). A total of 234 subjects were diagnosed with ischemic stroke during follow-up. Orosomucoid was associated with ischemic stroke after adjustment for risk factors, with hazard ratio 1.48 (95% confidence interval, 1.02–2.16) comparing the third versus first tertile. In subjects with plaque and belonging to the top tertile of orosomucoid, the hazard ratio was 2.07 (95% confidence interval, 1.38–3.11) compared with those without plaque and with orosomucoid in the first and second tertiles, after adjustment for C-reactive protein and other risk factors.

Conclusions—
Elevated levels of orosomucoid are associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke. The combination of high orosomucoid and carotid plaque substantially increase the risk of stroke.
Previous Statin Use and High-Resolution Magnetic Resonance Imaging Characteristics of Intracranial Atherosclerotic Plaque
Authors: Chung Jong-Won , Hwang Jaechun , Lee Mi Ji , Cha Jihoon , Bang Oh Young 
Published: June 2016

Background and Purpose—
Although statin use has been linked to the stabilization of systemic atherosclerosis, its effect on symptomatic intracranial atherosclerotic plaques has yet to be explored. We hypothesized that premorbid statin use is associated with plaque instability in intracranial arteries and may lead to differential patterns (size and distribution) of ischemic lesions in patients with acute intracranial atherosclerotic stroke.

Methods—
One hundred and thirty-six patients with acute infarcts caused by intracranial atherosclerotic stroke underwent high-resolution magnetic resonance imaging. Patients were categorized into 3 groups based on their premorbid statin use: nonuser, low-dose user, and high-dose user, according to the 2013 American College of Cardiology/American Heart Association guidelines on blood cholesterol. Symptomatic lesions in intracranial arteries were analyzed using high-resolution magnetic resonance imaging for vascular morphology (degree of stenosis, remodeling index, and wall index) and plaque activation (pattern and volume of enhancement). The cortical distribution and volume of ischemic brain lesions were measured using diffusion-weighted imaging.

Results—

Among the enrolled patients, 38 (27.94%) were taking statins before the index stroke (22 low-dose statins and 16 high-dose statins). The degree of stenosis, remodeling index, and wall index did not differ between the 3 groups. However, the volume of plaque enhancement was significantly lower in statin users (nonuser, 33.26±40.72; low-dose user, 13.15±17.53; high-dose user, 3.13±5.26;
P
=0.002). Premorbid statin use was associated with a higher prevalence of nonembolic stroke and a decrease in large cortical infarcts (
P
=0.012).

Conclusions—
Premorbid statin usage is independently associated with reduced plaque enhancement and a decrease in large cortical lesions in patients with intracranial atherosclerotic stroke.
Intravenous Thrombolysis With Recombinant Tissue-Type Plasminogen Activator in a Stroke Patient Receiving Dabigatran Anticoagulant After Antagonization With Idarucizumab
Authors: Berrouschot Jörg , Stoll Anett , Hogh Theresa , Eschenfelder Christoph Cyrill 
Published: June 2016

Background and Purpose—
Therapeutic options for acute ischemic stroke patients presenting on effective anticoagulation are limited. Idarucizumab, a humanized, monoclonal antibody fragment for immediate reversal of dabigatran, may allow this subgroup of orally anticoagulated patients to regain eligibility for thrombolysis.

Methods—
We report the first successful acute antagonization of dabigatran by idarucizumab before intravenous thrombolysis with recombinant tissue-type plasminogen activator.

Results—
Idarucizumab was given to a 76-year-old male patient on dabigatran ≈3.5 hours after his last dose. Neurological status on admission was NIHSS (National Institutes of Health Stroke Scale) 11. Recombinant tissue-type plasminogen activator was initiated immediately after dabigatran reversal. The patient was discharged with a favorable outcome of NHISS 1 on day 7. No complications were observed.

Conclusions—
This case represents a new therapeutic paradigm. It is further supported by in vitro data showing no nonspecific interactions of idarucizumab with recombinant tissue-type plasminogen activator–induced thrombolysis. Thus, patients effectively anticoagulated with dabigatran who were previously contraindicated for thrombolytic therapy in this situation may now receive treatment because of the ability to rapidly reverse the anticoagulant activity of dabigatran with idarucizumab.