bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperthermia Synergizes with Chemotherapy by Inhibiting PARP1-Dependent DNA Replication Arrest
Authors: Schaaf Lea , Schwab Matthias , Ulmer Christoph , Heine Simon , Mürdter Thomas E. , Schmid Jens O. , Sauer Georg , Aulitzky Walter E. , van der Kuip Heiko 
Published: March 2016

Abstract
Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here, we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and whether this mechanism is involved in its sensitizing effect in BRCA-competent models of ovarian and colon cancer. Notably, we found that hyperthermia delayed the repair of DNA damage caused by cisplatin or doxorubicin, acting upstream of different repair pathways to block histone polyADP-ribosylation (PARylation), a known effect of chemotherapy. Furthermore, hyperthermia blocked this histone modification as efficiently as pharmacologic inhibitors of PARP (PARPi), producing comparable delay in DNA repair, induction of double-strand breaks (DSB), and cell cytotoxicity after chemotherapy. Mechanistic investigations indicated that inhibiting PARylation by either hyperthermia or PARPi induced lethal DSB upon chemotherapy treatment not only by reducing DNA repair but also by preventing replication fork slowing. Overall, our work reveals how PARP blockade, either by hyperthermia or small-molecule inhibition, can increase chemotherapy-induced damage in BRCA-competent cells. Cancer Res; 76(10); 2868–75. ©2016 AACR.
Extracellular Vesicles from High-Grade Glioma Exchange Diverse Pro-oncogenic Signals That Maintain Intratumoral Heterogeneity
Authors: Ricklefs Franz , Mineo Marco , Rooj Arun K. , Nakano Ichiro , Charest Al , Weissleder Ralph , Breakefield Xandra O. , Chiocca E. Antonio , Godlewski Jakub , Bronisz Agnieszka 
Published: March 2016

Abstract
A lack of experimental models of tumor heterogeneity limits our knowledge of the complex subpopulation dynamics within the tumor ecosystem. In high-grade gliomas (HGG), distinct hierarchical cell populations arise from different glioma stem-like cell (GSC) subpopulations. Extracellular vesicles (EV) shed by cells may serve as conduits of genetic and signaling communications; however, little is known about how HGG heterogeneity may impact EV content and activity. In this study, we performed a proteomic analysis of EVs isolated from patient-derived GSC of either proneural or mesenchymal subtypes. EV signatures were heterogeneous, but reflected the molecular make-up of the GSC and consistently clustered into the two subtypes. EV-borne protein cargos transferred between proneural and mesenchymal GSC increased protumorigenic behaviors in vitro and in vivo. Clinically, analyses of HGG patient data from the The Cancer Genome Atlas database revealed that proneural tumors with mesenchymal EV signatures or mesenchymal tumors with proneural EV signatures were both associated with worse outcomes, suggesting influences by the proportion of tumor cells of varying subtypes in tumors. Collectively, our findings illuminate the heterogeneity among tumor EVs and the complexity of HGG heterogeneity, which these EVs help to maintain. Cancer Res; 76(10); 2876–81. ©2016 AACR.
Urinary Metabolite Risk Biomarkers of Lung Cancer: A Prospective Cohort Study
Authors: Haznadar Majda , Cai Qiuyin , Krausz Kristopher W. , Bowman Elise D. , Margono Ezra , Noro Rintaro , Thompson Matthew D. , Mathé Ewy A. , Munro Heather M. , Steinwandel Mark D. , Gonzalez Frank J. , Blot William J. , Harris Curtis C. 
Published: March 2016

Abstract
Background: Lung cancer is a major health burden causing 160,000 and 1.6 million deaths annually in the United States and worldwide, respectively.
Methods: While seeking to identify stable and reproducible biomarkers in noninvasively collected biofluids, we assessed whether previously identified metabolite urinary lung cancer biomarkers, creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate, and indeterminate metabolite 561+, were elevated in the urines of subjects prior to lung cancer diagnosis in a well-characterized prospective Southern Community Cohort Study (SCCS). Urine was examined from 178 patients and 351 nondiseased controls, confirming that one of four metabolites was associated with lung cancer risk in the overall case–control set, whereas two metabolites were associated with lung cancer risk in European-Americans.
Results: OR of lung cancer associated with elevated CR levels, and adjusted for smoking and other potential confounders, was 2.0 [95% confidence interval (CI), 1.2–3.4; P= 0.01]. In European-Americans, both CR and NANA were significantly associated with lung cancer risk (OR = 5.3; 95% CI, 1.6–17.6; P= 0.006 and OR=3.5; 95% CI, 1.5–8.4; P= 0.004, respectively). However, race itself did not significantly modify the associations. ROC analysis showed that adding CR and NANA to a model containing previously established lung cancer risk factors led to a significantly improved classifier (P= 0.01). Increasing urinary levels of CR and NANA displayed a positive association with increasing tumor size, strengthening a previously established link to altered tumor metabolism.
Conclusion and Impact: These replicated results provide evidence that identified urinary metabolite biomarkers have a potential utility as noninvasive, clinical screening tools for early diagnosis of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 978–86. ©2016 AACR.
Leukemic Stem Cell Quantification in Newly Diagnosed Patients With Chronic Myeloid Leukemia Predicts Response to Nilotinib Therapy
Authors: Thielen Noortje , Richter Johan , Baldauf Matthias , Barbany Gisela , Fioretos Thoas , Giles Francis , Gjertsen Bjørn-Tore , Hochhaus Andreas , Schuurhuis Gerrit Jan , Sopper Sieghart , Stenke Leif , Thunberg Sarah , Wolf Dominik , Ossenkoppele Gert , Porkka Kimmo , Janssen Jeroen , Mustjoki Satu 
Published: March 2016

Abstract
Purpose: Leukemic stem cells (LSCs) may harbor important resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia (CML). We identified Philadelphia chromosome (Ph)–positive CD34+CD38− bone marrow cells (here denoted LSCs) and addressed their response-predictive value in patients with CML (n = 48) subjected to nilotinib in the ENEST1st trial (NCT01061177).
Experimental design: Two flow cytometry–based cell sorting methods were used with multiparameter-directed CD45- (MPFC) and BCR-ABL1 probe-linked (FISH) identification of Ph-positive cells, respectively.
Results: We observed a positive correlation between the proportion of LSCs at diagnosis and established prognostic markers (blast count, spleen size, Sokal score, and hemoglobin). Conversely, a high LSC burden predicted for an inferior molecular response at 3 (MPFC and FISH), 6 (MPFC), 9 (FISH), and 15 months (FISH). During nilotinib therapy, the proportion of LSCs decreased rapidly. At 3 months, a median of only 0.3% LSCs remained among CD34+CD38− cells, and in 33% of the patients the LSC clone was not detectable anymore (FISH). The response kinetics was similar in LSC fractions as it was in the progenitor and unseparated bone marrow cell fractions.
Conclusions: The proportion of LSCs at diagnosis, as analyzed by two independent methodologies, reflects the biology of the disease and appeared as a prognostic and response-predictive marker in patients with CML subjected to first-line nilotinib therapy. Clin Cancer Res; 22(16); 4030–8. ©2016 AACR.
Development of Quran Reciter Identification System Using MFCC and Neural Network
Authors: Hasan Asda Tayseer Mohammed , Surya Gunawan Teddy 
Published: March 2016

Currently, the Quran is recited by so many reciters with different ways and voices. Some people like to listen to this reciter and others like to listen to other reciters. Sometimes we hear a very nice recitation of al-Quran and want to know who the reciter is. Therefore, this paper is about the development of Quran reciter recognition and identification system based on Mel Frequency Cepstral Coefficient (MFCC) feature extraction and artificial neural network (ANN). From every speech, characteristics from the utterances will be extracted through neural network model. In this paper a database of five Quran reciters is created and used in training and testing. The feature vector will be fed into Neural Network back propagation learning algorithm for training and identification processes of different speakers. Consequently, 91.2% of the successful match between targets and input occurred with certain number of hidden layers which shows how efficient are Mel Frequency Cepstral Coefficient (MFCC) feature extraction and artificial neural network (ANN) in identifying the reciter voice perfectly.
A Review on Machine Translation Approaches
Authors: Kituku Benson , Muchemi Lawrence , Nganga Wanjiku 
Published: March 2016

There is need to fill the gap between two entities which use different languages to communicate which can be done either via human translation or machine translation means. The world has over 7000 living natural languages, thus making it costly if human translation route is taken hence need for machine translation. There is need to know the available machine translation approaches and their requirement in order to decide which one suits for particular languages or not, hence the motivation for this survey. The survey provide overview and architectures of the three major techniques available namely: rule based translation, corpus based translation and hybrid based translation plus their subcategories available in each approach.
Online Prediction of Transient Instability by Wide Area Measurement System
Authors: Namdari Farhad , Nourizadeh Maryam , Shakarami Mahmoodreza 
Published: March 2016

<p>In this paper an online accurate prediction method is proposed to enhance the speed of Transactionient stability assessment. This method is the measurement basis technique resulted from wide area measurement systems (WAMS). In the proposed method, the generators with same dynamic behavior, referred as to coherent generators, are clustered as a same group and they can be considered as an equivalent bus. So the system will be reduced into a small scale system. The admittance matrix parameters of the reduced system can be identified with the least square algorithm. Then the trajectory prediction is performed by real-time simulations. Obtained results from simulations on New England test system show the high noticeable efficiency for performance of the proposed method, capable in predicting of the disturbed trajectory under existence of unknown parameters in grid structure.. </p>
Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII
Authors: O’Sullivan Jamie M. , Jenkins P. Vince , Rawley Orla , Gegenbauer Kristina , Chion Alain , Lavin Michelle , Byrne Barry , O’Kennedy Richard , Preston Roger J.S. , Brophy Teresa M. , O’Donnell James S. 
Published: March 2016

Objective—
Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor–dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVIII.

Approach and Results—
Immunosorbant assays and surface plasmon resonance analysis confirmed that Gal-1 and Gal-3 bound purified FVIII with high affinity. Exoglycosidase removal of FVIII N-linked glycans significantly reduced binding to both Gal-1 and Gal-3. Moreover, combined removal of both the N- and O-glycans of FVIII further attenuated Gal-3 binding. Notably, specific digestion of FVIII high-mannose glycans at N239 and N2118 significantly impaired FVIII affinity for Gal-1. Importantly Gal-1, but not Gal-3, bound to free FVIII in the plasma milieu, and significantly inhibited FVIII functional activity. Interestingly, commercial recombinant FVIII (rFVIII) concentrates are manufactured in different cell lines and differ in their glycosylation profiles. Although the biological mechanism has not been defined, recent studies in previously untreated patients with severe hemophilia A reported significant differences in inhibitor development associated with different rFVIII products. Interestingly, Gal-1 and Gal-3 both displayed enhanced affinity for BHK–rFVIII compared with CHO–rFVIII. Furthermore, binding of Gal-1 and Gal-3 to BDD–FVIII was markedly reduced compared with full-length rFVIII.

Conclusions—
We have identified Gal-1 and Gal-3 as novel-binding partners for human FVIII and demonstrated that Gal-1 binding can influence the procoagulant activity of FVIII.
Local Production of Fatty Acid–Binding Protein 4 in Epicardial/Perivascular Fat and Macrophages Is Linked to Coronary Atherosclerosis
Authors: Furuhashi Masato , Fuseya Takahiro , Murata Masaki , Hoshina Kyoko , Ishimura Shutaro , Mita Tomohiro , Watanabe Yuki , Omori Akina , Matsumoto Megumi , Sugaya Takeshi , Oikawa Tsuyoshi , Nishida Junichi , Kokubu Nobuaki , Tanaka Marenao , Moniwa Norihito , Yoshida Hideaki , Sawada Norimasa , Shimamoto Kazuaki , Miura Tetsuji 
Published: March 2016

Objective—
Fatty acid–binding protein 4 (FABP4) is expressed in adipocytes and macrophages, and elevated circulating FABP4 level is associated with obesity-mediated metabolic phenotype. We systematically investigated roles of FABP4 in the development of coronary artery atherosclerosis.

Approach and Results—

First, by immunohistochemical analyses, we found that FABP4 was expressed in macrophages within coronary atherosclerotic plaques and epicardial/perivascular fat in autopsy cases and macrophages within thrombi covering ruptured coronary plaques in thrombectomy samples from patients with acute myocardial infarction. Second, we confirmed that FABP4 was secreted from macrophages and adipocytes cultured in vitro. Third, we investigated the effect of exogenous FABP4 on macrophages and human coronary artery–derived smooth muscle cells and endothelial cells in vitro. Treatment of the cells with recombinant FABP4 significantly increased gene expression of inflammatory markers in a dose-dependent manner. Finally, we measured serum FABP4 level in the aortic root (Ao-FABP4) and coronary sinus (CS-FABP4) of 34 patients with suspected or known coronary artery disease. Coronary stenosis score assessed by the modified Gensini score was weakly correlated with CS-FABP4 but was not correlated with Ao-FABP4. A stronger correlation (
r
=0.59,
P
<0.01) was observed for the relationship between coronary stenosis score and coronary veno-arterial difference in FABP4 level, (CS-Ao)-FABP4, indicating local production of FABP4 during coronary circulation in the heart. Multivariate analysis indicated that (CS-Ao)-FABP4 was an independent predictor of the severity of coronary stenosis after adjustment of conventional risk factors.

Conclusions—
FABP4 locally produced by epicardial/perivascular fat and macrophages in vascular plaques contributes to the development of coronary atherosclerosis.
Common and Rare Genetic Variation in
CCR2
,
CCR5
, or
CX3CR1
and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits
Authors: Golbus Jessica R. , Stitziel Nathan O. , Zhao Wei , Xue Chenyi , Farrall Martin , McPherson Ruth , Erdmann Jeanette , Deloukas Panos , Watkins Hugh , Schunkert Heribert , Samani Nilesh J. , Saleheen Danish , Kathiresan Sekar , Reilly Muredach P. 
Published: March 2016

Background—
The chemokine receptors CCR2, CCR5, and CX3CR1 coordinate monocyte trafficking in homeostatic and inflammatory states. Multiple small human genetic studies have variably linked single nucleotide polymorphisms in these genes to cardiometabolic disease. We interrogated genome-wide association, exome sequencing, and exome array genotyping studies to ascertain the relationship between variation in these genes and coronary artery disease (CAD), myocardial infarction (MI), and glucometabolic traits.

Methods and Results—

We interrogated the CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) (60 801 cases and 123 504 controls), the MIGen and CARDIoGRAM Exome consortia (42 335 cases and 78 240 controls), and Exome Sequencing Project and Early-Onset Myocardial Infarction (ESP EOMI; 4703 cases and 5090 controls) data sets to ascertain the relationship between common, low frequency, and rare variation in
CCR2
,
CCR5
, or
CX3CR1
with CAD and MI. We did not identify any variant associated with CAD or MI. We then explored common and low-frequency variation in South Asians through Pakistan Risk of Myocardial Infarction Study (PROMIS; 9058 cases and 8379 controls), identifying 6 variants associated with MI including
CX3CR1
V249I. Finally, reanalysis of the European HapMap imputed Diabetes Genetics Replication and Meta-Analysis (DIAGRAM), Global Lipids Genetics Consortium (GLGC), Genetic Investigation of Anthropometric Traits (GIANT), and Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) data sets revealed no association with glucometabolic traits although 3 single nucleotide polymorphisms in PROMIS were associated with type II diabetes mellitus.

Conclusions—
No chemokine receptor variant was associated with CAD, MI, or glucometabolic traits in large European ancestry cohorts. In a South Asian cohort, we identified single nucleotide polymorphism associations with MI and type II diabetes mellitus but these did not meet significance in cohorts of European ancestry. These findings suggest the need for larger studies in South Asians but exclude clinically meaningful associations with CAD and glucometabolic traits in Europeans.
HIV Infection Itself May Not Be Associated With Subclinical Coronary Artery Disease Among African Americans Without Cardiovascular Symptoms
Authors: Lai Hong , Moore Richard , Celentano David D. , Gerstenblith Gary , Treisman Glenn , Keruly Jeanne C. , Kickler Thomas , Li Ji , Chen Shaoguang , Lai Shenghan , Fishman Elliot K. 
Published: March 2016

Background

The key objectives of this study were to examine whether
HIV
infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (
ART
s) to subclinical coronary artery disease (
CAD
) in
HIV
‐infected persons.

Methods and Results

Between June 2004 and February 2015, 1429 African American (
AA
) adults with/without
HIV
infection in Baltimore, Maryland, were enrolled in an observational study of the effects of
HIV
infection, exposure to
ART
, and cocaine use on subclinical
CAD
. The prevalence of subclinical coronary atherosclerosis was 30.0% in
HIV
‐uninfected and 33.7% in
HIV
‐infected (
P
=0.17). Stratified analyses revealed that compared to
HIV
‐uninfected,
HIV
‐infected
ART
naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas
HIV
‐infected long‐term
ART
users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and
HIV
was found. Furthermore, compared to those who were
ART
naïve, long‐term
ART
users (≥36 months) were at significantly higher risk for subclinical coronary atherosclerosis in chronic cocaine users, but not in those who never used cocaine. Cocaine use was independently associated with subclinical coronary atherosclerosis.

Conclusions

Overall,
HIV
infection, per se, was not associated with subclinical coronary atherosclerosis in this population. Cocaine use was prevalent in both
HIV
‐infected and ‐uninfected individuals and itself was associated with subclinical disease. In addition, cocaine significantly elevated the risk for
ART
‐associated subclinical coronary atherosclerosis. Treating cocaine addiction must be a high priority for managing
HIV
disease and preventing
HIV
/
ART
‐associated subclinical and clinical
CAD
in individuals with
HIV
infection.
Self-harm following release from prison: A prospective data linkage study
Authors: Borschmann Rohan , Thomas Emma , Moran Paul , Carroll Megan , Heffernan Ed , Spittal Matthew J , Sutherland Georgina , Alati Rosa , Kinner Stuart A 
Published: March 2016

Objective: Prisoners are at increased risk of both self-harm and suicide compared with the general population, and the risk of suicide after release from prison is three times greater than for those still incarcerated. However, surprisingly little is known about the incidence of self-harm following release from prison. We aimed to determine the incidence of, identify risk factors for and characterise emergency department presentations resulting from self-harm in adults after release from prison. Method: Cohort study of 1325 adults interviewed prior to release from prison, linked prospectively with State correctional and emergency department records. Data from all emergency department presentations resulting from self-harm were secondarily coded to characterise these presentations. We used negative binomial regression to identify independent predictors of such presentations. Results: During 3192 person-years of follow-up (median 2.6 years per participant), there were 3755 emergency department presentations. In all, 83 (6.4%) participants presented due to self-harm, accounting for 165 (4.4%) presentations. The crude incidence rates of self-harm for males and females were 49.2 (95% confidence interval: [41.2, 58.7]) and 60.5 (95% confidence interval: [44.9, 81.6]) per 1000 person-years, respectively. Presenting due to self-harm was associated with being Indigenous (incidence rate ratio: 2.01; 95% confidence interval: [1.11, 3.62]), having a lifetime history of a mental disorder (incidence rate ratio: 2.13; 95% confidence interval: [1.19, 3.82]), having previously been hospitalised for psychiatric treatment (incidence rate ratio: 2.68; 95% confidence interval: [1.40, 5.14]) and having previously presented due to self-harm (incidence rate ratio: 3.91; 95% confidence interval: [1.85, 8.30]). Conclusion: Following release from prison, one in 15 ex-prisoners presented to an emergency department due to self-harm, within an average of 2.6 years of release. Demographic and mental health variables help to identify at-risk groups, and such presentations could provide opportunities for suicide prevention in this population. Transition from prison to the community is challenging, particularly for those with a history of mental disorder; mental health support during and after release may reduce the risk of adverse outcomes, including self-harm.