bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma
Authors: Arnes Luis , Liu Zhaoqi , Wang Jiguang , Maurer Carlo , Sagalovskiy Irina , Sanchez-Martin Marta , Bommakanti Nikhil , Garofalo Diana C , Balderes Dina A , Sussel Lori , Olive Kenneth P , Rabadan Raul 
Published: February 2018

ObjectivePancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease with limited therapeutic options. Genome and transcriptome analyses have identified signalling pathways and cancer driver genes with implications in patient stratification and targeted therapy. However, these analyses were performed in bulk samples and focused on coding genes, which represent a small fraction of the genome.DesignWe developed a computational framework to reconstruct the non-coding transcriptome from cross-sectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome. We validated the results in an independent cohort of paired epithelial and stromal RNA-Seq derived from laser capture microdissected human pancreatic tumours, allowing us to annotate the compartment specificity of their expression. We employed systems and experimental biology approaches to interrogate the function of epithelial long non-coding RNAs (lncRNAs) associated with genetic traits and clinical outcome in PDA.ResultsWe generated a catalogue of PDA-associated lncRNAs. We showed that lncRNAs define molecular subtypes with biological and clinical significance. We identified lncRNAs in genomic regions with SCNA and single nucleotide polymorphisms associated with lifetime risk of PDA and associated with clinical outcome using genomic and clinical data in PDA. Systems biology and experimental functional analysis of two epithelial lncRNAs (LINC00673andFAM83H-AS1) suggest they regulate the transcriptional profile of pancreatic tumour samples and PDA cell lines.ConclusionsOur findings indicate that lncRNAs are associated with genetic marks of pancreatic cancer risk, contribute to the transcriptional regulation of neoplastic cells and provide an important resource to design functional studies of lncRNAs in PDA.
Mechanical thrombectomy of acute ischemic stroke with a new intermediate aspiration catheter: preliminary results
Authors: Sallustio Fabrizio , Pampana Enrico , Davoli Alessandro , Merolla Stefano , Koch Giacomo , Alemseged Fana , Panella Marta , D’Agostino Vittoria Carla , Mori Francesco , Morosetti Daniele , Konda Daniel , Fabiano Sebastiano , Diomedi Marina , Gandini Roberto 
Published: February 2018

Background and purposeTo report clinical and procedural outcomes of acute ischemic stroke patients after endovascular treatment with the new thromboaspiration catheter AXS Catalyst 6.MethodsPatients with anterior and posterior circulation stroke were selected. Successful reperfusion defined as a Thrombolysis in Cerebral Infarction (TICI) score ≥2 b and 3-month functional independence defined as a modified Rankin Scale (mRS) ≤2 were the main efficacy outcomes. Symptomatic intracranial hemorrhage and mortality were the main safety outcomes.Results107 patients were suitable for analysis. Mean age was 73.18±12.62 year and median baseline NIHSS was 17 (range: 3–32). The most frequent site of occlusion was the middle cerebral artery (MCA) (60.7%). 76.6% of patients were treated with AXS Catalyst 6 alone without the need for rescue devices or thromboaspiration catheters. Successful reperfusion was achieved in 84.1%, functional independence in 47.6%, symptomatic intracranial hemorrhage occurred in 3.7%, and mortality in 21.4%.ConclusionsEndovascular treatment with AXS Catalyst 6 proved to be safe, technically feasible, and effective. Comparison analyses with other devices for mechanical thrombectomy are needed.
Cardiovascular effects among workers exposed to multiwalled carbon nanotubes
Authors: Kuijpers Eelco , Pronk Anjoeka , Kleemann Robert , Vlaanderen Jelle , Lan Qing , Rothman Nathaniel , Silverman Debra , Hoet Peter , Godderis Lode , Vermeulen Roel 
Published: February 2018

ObjectivesThe increase in production of multiwalled carbon nanotubes (MWCNTs) has led to growing concerns about health risks. In this study, we assessed the association between occupational exposure to MWCNTs and cardiovascular biomarkers.MethodsA cross-sectional study was performed among 22 workers of a company commercially producing MWCNTs (subdivided into lab personnel with low or high exposure and operators), and a gender and age-matched unexposed population (n=42). Exposure to MWCNTs and 12 cardiovascular markers were measured in participants’ blood (phase I). In a subpopulation of 13 exposed workers and six unexposed workers, these measures were repeated after 5 months (phase II). We analysed associations between MWCNT exposure and biomarkers of cardiovascular risk, adjusted for age, body mass index, sex and smoking.ResultsWe observed an upward trend in the concentration of endothelial damage marker intercellular adhesion molecule-1 (ICAM-1), with increasing exposure to MWCNTs in both phases. The operator category showed significantly elevated ICAM-1 geometric mean ratios (GMRs) compared with the controls (phase I: GMR=1.40, P=1.30E-3; phase II: GMR=1.37, P=0.03). The trends were significant both across worker categories (phase I: P=1.50E-3; phase II: P=0.01) and across measured GM MWCNT concentrations (phase I: P=3.00E-3; phase II: P=0.01). No consistent significant associations were found for the other cardiovascular markers.ConclusionThe associations between MWCNT exposure and ICAM-1 indicate endothelial activation and an increased inflammatory state in workers with MWCNT exposure.
Effects of a matrix-coated organic acids and medium-chain fatty acids blend on performance, and in vitro fecal noxious gas emissions in growing pigs fed in-feed antibiotic-free diets
Authors: Hossain M.M. , Jayaraman B. , Kim S.C. , Lee K.Y. , Kim I.H. , Nyachoti C.M. 
Published: February 2018

This study evaluated the efficacy of a matrix-coated organic acids and medium-chain fatty acids blend (MCOFA) in growing pigs. Ninety six pigs [(Yorkshire × Landrace) × Duroc] with an average body weight (BW) of 47.71 ± 3.73 kg were used in a 6 wk experiment. Pigs were allotted to diets containing 0 or 2 g kg−1 of MCOFA, and 0 or 2.5 g kg−1 of antibiotic growth promoters (AGP) according to a 2 × 2 factorial arrangement of treatments. Pigs fed diets supplemented with MCOFA had improved growth efficiency compared with those fed a diet without MCOFA (P < 0.05). Pigs receiving the diets supplemented with both AGP and MCOFA had higher apparent total tract digestibility of crude protein, dry matter, fat, and gross energy (P < 0.05). Pigs fed AGP × MCOFA diet had increased serum urea nitrogen (P < 0.05). Pigs fed diets supplemented with AGP had reduced fecal ammonia (NH3) gas emissions compared with those fed without AGP (P < 0.05). Moreover, pigs fed diets supplemented with MCOFA had reduced fecal NH3 and acetic acid gas emissions compared with those fed without MCOFA (P < 0.05). In conclusion, dietary supplementation with MCOFA improved performance in growing pigs.
Carcass characteristics of grass-fed crossbred bulls and steers slaughtered at two different ages
Authors: Pogorzelska-Przybyłek Paulina , Nogalski Zenon , Sobczuk-Szul Monika , Purwin Cezary , Momot Martyna 
Published: February 2018

The aim of this study was to evaluate beef production potential and meat quality in young crossbred bulls and steers raised indoors and fed grass-based diets. One half of 96 bull calves were castrated at 2–3 wk of age. The calves were fed standard diets, and starting at 7 mo of age, they received grass silage supplemented with concentrates. At the end of the fattening period (18 and 21 mo of age), the animals were slaughtered, carcass quality was evaluated, and samples of musculus longissimus thoracis were collected to determine the proximate composition and meat quality. The semi-intensive feeding system contributed to higher daily gains (0.835 kg) in Holstein-Friesian (HF) × Hereford (HH) crosses. In comparison with steers, bulls were characterized by a higher dressing percentage (+1.33%), higher weight of five most valuable primal cuts (+6.7 kg), and higher lean meat content of three-rib cuts (+7.54%). Meat from steer carcasses, which had higher fat content was more tender and had desirable aroma, juiciness, and flavor. In semi-intensive production systems, steers performed better than bulls, and HF × HH crosses were more suitable than HF × Limousin (LM) and HF × Charolais (CH) crosses. Dairy-beef crosses should be slaughtered at 21 mo of age to improve carcass quality.
Oncogenic Kinase–Induced PKM2 Tyrosine 105 Phosphorylation Converts Nononcogenic PKM2 to a Tumor Promoter and Induces Cancer Stem–like Cells
Authors: Zhou Zhifen , Li Min , Zhang Lin , Zhao Hong , Şahin Özgür , Chen Jing , Zhao Jean J. , Songyang Zhou , Yu Dihua 
Published: February 2018

Abstract
The role of pyruvate kinase M2 isoform (PKM2) in tumor progression has been controversial. Previous studies showed that PKM2 promoted tumor growth in xenograft models; however, depletion of PKM2 in the Brca1-loss–driven mammary tumor mouse model accelerates tumor formation. Because oncogenic kinases are frequently activated in tumors and PKM2 phosphorylation promotes tumor growth, we hypothesized that phosphorylation of PKM2 by activated kinases in tumor cells confers PKM2 oncogenic function, whereas nonphosphorylated PKM2 is nononcogenic. Indeed, PKM2 was phosphorylated at tyrosine 105 (Y105) and formed oncogenic dimers in MDA-MB-231 breast cancer cells, whereas PKM2 was largely unphosphorylated and formed nontumorigenic tetramers in nontransformed MCF10A cells. PKM2 knockdown did not affect MCF10A cell growth but significantly decreased proliferation of MDA-MB-231 breast cancer cells with tyrosine kinase activation. Multiple kinases that are frequently activated in different cancer types were identified to phosphorylate PKM2-Y105 in our tyrosine kinase screening. Introduction of the PKM2-Y105D phosphomimetic mutant into MCF10A cells induced colony formation and the CD44hi/CD24neg cancer stem–like cell population by increasing Yes-associated protein (YAP) nuclear localization. ErbB2, a strong inducer of PKM2-Y105 phosphorylation, boosted nuclear localization of YAP and enhanced the cancer stem–like cell population. Treatment with the ErbB2 kinase inhibitor lapatinib decreased PKM2-Y105 phosphorylation and cancer stem–like cells, impeding PKM2 tumor-promoting function. Taken together, phosphorylation of PKM2-Y105 by activated kinases exerts oncogenic functions in part via activation of YAP downstream signaling to increase cancer stem–like cell properties.
Significance: These findings reveal PKM2 promotes tumorigenesis by inducing cancer stem-like cell properties and clarify the paradox of PKM2′s dichotomous functions in tumor progression. Cancer Res; 78(9); 2248–61. ©2018 AACR.
Molecular Characterization of Renal Cell Carcinoma: A Potential Three-MicroRNA Prognostic Signature
Authors: Lokeshwar Soum D. , Talukder Asif , Yates Travis J. , Hennig Martin J.P. , Garcia-Roig Michael , Lahorewala Sarrah S. , Mullani Naureen N. , Klaassen Zachary , Kava Bruce R. , Manoharan Murugesan , Soloway Mark S. , Lokeshwar Vinata B. 
Published: February 2018

Abstract
Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach.
Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241).
Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2–4-fold) and miR-192 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors (&lt;4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21+194; miR-21+142-5p+194) significantly predicted metastasis and/or disease-specific mortality; miR-21+142-5p+194 (for metastasis): P = 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75–0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21+142-5p+194: P &lt; 0.0001; OR, 0.37; 95% CI, 0.58–0.23).
Conclusions: The interconnected discovery–validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients.
Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464–72. ©2018 AACR.
Endo-/Epicardial Catheter Ablation of Atrial Fibrillation
Authors: Piorkowski Christopher , Kronborg Mads , Hourdain Jerome , Piorkowski Judith , Kirstein Bettina , Neudeck Sebastian , Wechselberger Simon , Päßler Ellen , Löwen Anastasia , El-Armouche Ali , Mayer Julia , Ulbrich Stefan , Pu Liying , Richter Utz , Gaspar Thomas , Huo Yan 
Published: February 2018

Background:
Until today, catheter interventional mapping and ablation of atrial fibrillation (AF) has been limited to the right and left atrial endocardium. We report feasibility, electrophysiological findings, and clinical outcome using a combined endo-/epicardial catheter approach for mapping and ablation of AF.

Methods and Results:
Fifty-nine patients with permanence of pulmonary vein isolation and further symptomatic recurrences of paroxysmal AF, persistent AF, or atrial tachycardia underwent reablation using biatrial endo-/epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. Using continuous monitoring and a 3-month blanking period, freedom from AF/atrial tachycardia ≥2 minutes was defined as primary end point. In all patients, endo-/epicardial mapping and ablation was feasible using standard technologies of catheter access, 3-dimensional mapping, and radiofrequency ablation. Epicardial mapping and ablation did not add procedural risks. Exclusively epicardial low voltage substrates were found in 14% of the patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human AF patients (19% of the cohort). Epicardial ablation was needed in 80% of the patients. Over 23±10 months of follow-up freedom from arrhythmia recurrences measured 73%.

Conclusions:
Catheter-based endo-/epicardial mapping and ablation of AF was feasible and safe. Epicardial mapping provided new insights into AF mechanisms. Epicardial ablation increased transmurality of ablation lesions. Clinical outcome in this cohort of complex AF patients was favorable, indicating potential further development of current AF treatment.
“Malignant” Left Ventricular Hypertrophy Identifies Subjects at High Risk for Progression to Asymptomatic Left Ventricular Dysfunction, Heart Failure, and Death: MESA (Multi‐Ethnic Study of Atherosclerosis)
Authors: Peters Matthew N. , Seliger Stephen L. , Christenson Robert H. , Hong‐Zohlman Susie N. , Daniels Lori B. , Lima Joao A.C. , de Lemos James A. , Neeland Ian J. , deFilippi Christopher R. 
Published: February 2018

Background

As heart failure (
HF
)‐associated morbidity and mortality continue to escalate, enhanced focus on prevention is increasingly important. “Malignant” left ventricular (LV) hypertrophy (
LVH
):
LVH
combined with an elevated cardiac biomarker reflecting either injury (high‐sensitivity cardiac troponin T), or strain (amino‐terminal pro‐B‐type natriuretic peptide) has predicted accelerated progression to
HF
. We sought to determine whether malignant
LVH
identified community‐dwelling adults initially free of cardiovascular disease at high risk of asymptomatic decline in
LV
ejection fraction or a clinical cardiovascular event.

Methods and Results

A total of 4985 of 6814 individuals without prevalent
cardiovascular disease
underwent baseline cardiac magnetic resonance for
LVH
in combination with measurement of plasma high‐sensitivity cardiac troponin T and amino‐terminal pro‐B‐type natriuretic peptide as part of MESA (Multi‐Ethnic Study of Atherosclerosis) and were subsequently divided into 4 groups: (1) No
LVH
, no elevated biomarkers (n=2206; 44.3%); (2) No
LVH
, ≥1 elevated biomarkers (n=2275; 45.7%); (3)
LVH
, no elevated biomarkers (n=153; 3.0%); and (4)
LVH
, ≥1 elevated biomarkers (malignant
LVH
; n=351; 7.0%).
Cardiac magnetic resonance
was repeated 10 years later (n=2831) for assessment of
LV ejection fraction
<50%. Median follow‐up was 12.2 years. Malignant
LVH
was associated with 7.0‐, 3.5‐, and 2.6‐fold adjusted increases in incidence of
HF
,
cardiovascular
death, and asymptomatic
LV
dysfunction, respectively, versus group 1. New‐onset
HF
was predominately
HF
with reduced ejection fraction (9.5‐fold increase).

Conclusions

Malignant
LVH
is predictive of progression to asymptomatic
LV
dysfunction,
HF
(particularly
HF
with reduced ejection fraction), and
cardiovascular
death. Consequently, malignant
LVH
represents a high‐risk phenotype among individuals without known
cardiovascular disease
, which should be targeted for increased surveillance and more‐aggressive therapies.
Bilateral Transcutaneous Electrical Nerve Stimulation Improves Lower‐Limb Motor Function in Subjects With Chronic Stroke: A Randomized Controlled Trial
Authors: Kwong Patrick W. H. , Ng Gabriel Y. F. , Chung Raymond C. K. , Ng Shamay S. M. 
Published: February 2018

Background

Transcutaneous electrical nerve stimulation (
TENS
) has been used to augment the efficacy of task‐oriented training (
TOT
) after stroke. Bilateral intervention approaches have also been shown to be effective in augmenting motor function after stroke. The purpose of this study was to compare the efficacy of bilateral
TENS
combined with
TOT
versus unilateral
TENS
combined with
TOT
in improving lower‐limb motor function in subjects with chronic stroke.

Methods and Results

Eighty subjects were randomly assigned to bilateral
TENS
+
TOT
or to unilateral
TENS
+
TOT
and underwent 20 sessions of training over a 10‐week period. The outcome measures included the maximal strength of the lower‐limb muscles and the results of the Lower Extremity Motor Coordination Test, Berg Balance Scale, Step Test, and Timed Up and Go test. Each participant was assessed at baseline, after 10 and 20 sessions of training and 3 months after the cessation of training. The subjects in the bilateral
TENS
+
TOT
group showed greater improvement in paretic ankle dorsiflexion strength (β=1.32;
P
=0.032) and in the completion time for the Timed Up and Go test (β=−1.54;
P
=0.004) than those in the unilateral
TENS
+
TOT
group. However, there were no significant between‐group differences for other outcome measures.

Conclusions

The application of bilateral
TENS
over the common peroneal nerve combined with
TOT
was superior to the application of unilateral
TENS
combined with
TOT
in improving paretic ankle dorsiflexion strength after 10 sessions of training and in improving the completion time for the Timed Up and Go test after 20 sessions of training.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02152813.
Age at Menarche and Cardiometabolic Health: A Sibling Analysis in the Scottish Family Health Study
Authors: Magnus Maria C. , Lawlor Debbie A. , Iliodromiti Stamatina , Padmanabhan Sandosh , Nelson Scott M. , Fraser Abigail 
Published: February 2018

Background
Previous studies of age at menarche and cardiometabolic health report conflicting findings, and only a few could account for childhood characteristics. We aimed to estimate the associations of age at menarche with cardiovascular risk factors in unrelated women and within sister groups, under the assumption that within‐sibship estimates will be better adjusted for shared genetics and early life environment.

Methods and Results

Our study included 7770 women, from 5984 sibships, participating in the GS:SFHS (Generation Scotland: Scottish Family Health Study). We used fixed‐ and between‐effects linear regression to estimate the associations within sister groups and between unrelated individuals, respectively. Within sibships, the mean difference between sisters with early menarche (≤11 years) and sisters with menarche at 12 to 13 years was 1.73 mm Hg (95% confidence interval [CI], −0.41 to 3.86) for systolic blood pressure, 1.26 mm Hg (95% CI, −0.02 to 2.55) for diastolic blood pressure, −0.06 nmol/L (95% CI, −0.11 to −0.02) for high‐density lipoprotein, 0.20 nmol/L (95% CI, 0.08–0.32) for non–high‐density lipoprotein, −0.34% (95% CI, −1.98 to 1.30) for glucose, 1.60 kg/m
2
(95% CI, 0.92–2.28) for body mass index, and 2.75 cm (95% CI, 1.06–4.44) for waist circumference. There was weak evidence of associations between later menarche (14–15 or ≥16 years) and lower body mass index, waist circumference, and blood pressure. We found no strong evidence that estimates from within‐ and between‐sibship analyses differed (all
P
values >0.1). The associations with other cardiovascular risk factors were attenuated after adjustment for adult body mass index.

Conclusions
Our results suggest that confounding by shared familial characteristics is unlikely to be a major driver of the association between early menarche and adverse cardiometabolic health but do not exclude confounding by individual‐level characteristics.