bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between variants in inflammation and cancer‐associated genes and risk and survival of cholangiocarcinoma
Authors: Chaiteerakij Roongruedee , Juran Brian D. , Aboelsoud Mohammed M. , Harmsen William S. , Moser Catherine D. , Giama Nasra H. , Allotey Loretta K. , Mettler Teresa A. , Baichoo Esha , Zhang Xiaodan , Therneau Terry M. , Lazaridis Konstantinos N. , Roberts Lewis R. 
Published: August 2015

AbstractGenetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single‐nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case‐control, candidate gene association study of 370 CCA patients and 740 age‐, sex‐, and residential area‐matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log‐additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log‐rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX‐2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX‐2 has been shown to contribute to cholangiocarcinogenesis, the COX‐2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival.
The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis
Authors: Uchiyama Tatsuki , Kawabata Hiroshi , Miura Yasuo , Yoshioka Satoshi , Iwasa Masaki , Yao Hisayuki , Sakamoto Soichiro , Fujimoto Masakazu , Haga Hironori , Kadowaki Norimitsu , Maekawa Taira , Takaori‐Kondo Akifumi 
Published: August 2015

AbstractGrowth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor‐β superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM‐MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co‐culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM‐MSCs in vitro, and pretreatment of BM‐MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM‐MSCs.
Prognostic signature of protocadherin 10 methylation in curatively resected pathological stage I non‐small‐cell lung cancer
Authors: Harada Hiroaki , Miyamoto Kazuaki , Yamashita Yoshinori , Taniyama Kiyomi , Mihara Kazuko , Nishimura Mitsuki , Okada Morihito 
Published: August 2015

AbstractAlthough curative resection is the current treatment of choice for localized non‐small‐cell lung cancer (NSCLC), patients show a wide spectrum of survival even after complete resection of pathological stage I NSCLC. Thus, identifying molecular biomarkers that help to accurately select patients at high risk of relapse is an important key to improving the treatment strategy. The purpose of this study was to evaluate the prognostic signature of protocadherin 10 (PCDH10) promoter methylation in curatively resected pathological stage I NSCLC. Using methylation‐specific polymerase chain reaction assays, methylation of PCDH10 promoter was assessed in cancer tissues of 109 patients who underwent curative resection of pathological stage I NSCLC. Associations between PCDH10 methylation status and disease outcome was analyzed. PCDH10 promoter methylation was detected in 46/109 patients (42.2%). Patients with methylated PCDH10 showed significantly worse recurrence‐free, overall, and disease‐specific survival compared with those without methylation (P < 0.0001, P = 0.0004, P = 0.0002, respectively). Multivariate Cox proportional hazard regression analysis revealed that adjusted hazard ratios of methylated PCDH10 were 5.159 for recurrence‐free, 1.817 for overall, and 5.478 for disease‐specific survival (P = 0.0005, P = 0.1475, P = 0.0109, respectively). The pattern of recurrence was not significantly different between patients with and without PCDH10 methylation (P = 0.5074). PCDH10 methylation is a potential biomarker that predicts a poor prognosis after curative resection of pathological stage I NSCLC. Assessment of PCDH10 methylation status might assist in patient stratification for determining an appropriate adjuvant treatment and follow‐up strategy.
Comparative study of 18F‐FDG‐PET/CT imaging and serum hTERT mRNA quantification in cancer diagnosis
Authors: Ping Bingqiong , Tsuno Satoshi , Wang Xinhui , Ishihara Yoshitaka , Yamashita Taro , Miura Keigo , Miyoshi Fuminori , Shinohara Yuki , Matsuki Tsutomu , Tanabe Yoshio , Tanaka Noriaki , Ogawa Toshihide , Shiota Goshi , Miura Norimasa 
Published: August 2015

AbstractWe have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRNA quantification in sera in patients with several cancers. Positron emission tomography–computed tomography (PET/CT) using 18F‐fluorodeoxyglucose (FDG) has recently become an excellent modality for detecting cancer. We performed a diagnostic comparative study of FDG‐PET/CT and hTERT mRNA quantification in patients with cancer. Four hundred seventy subjects, including 125 healthy individuals and 345 outpatients with cancer who had received medical treatments for cancer in their own or other hospitals, were enrolled. The subjects were diagnosed by FDG‐PET/CT, and we measured their serum hTERT mRNA levels using real‐time RT‐PCR, correlating the quantified values with the clinical course. In this prospective study, we statistically assessed the sensitivity and specificity, and their clinical significance. hTERT mRNA and FDG‐PET/CT were demonstrated to be correlated with the clinical parameters of metastasis and recurrence (P < 0.001), and of recurrence and tumor number in cancer compared with noncancer patients, respectively. A multivariate analysis showed a significant difference in the detection by FDG‐PET/CT, 18F‐FDG uptake, the detection by hTERT mRNA, and age. The use of both FDG‐PET/CT and hTERT mRNA resulted in a positivity of 94.4% (221/234) for the detection of viable tumor cells. FDG‐PET/CT is superior to hTERT mRNA quantification in the early detection of cancer and combinative use of FDG‐PET/CT and hTERT mRNA may improve the diagnostic accuracy of cancer.
A window‐of‐opportunity biomarker study of etodolac in resectable breast cancer
Authors: Schwab Richard B. , Kato Shumei , Crain Brian , Pu Minya , Messer Karen , Weidner Noel , Blair Sarah L. , Wallace Anne M. , Carson Dennis A. , Parker Barbara A. 
Published: August 2015

AbstractObservational data show that nonsteroidal anti‐inflammatory drug (NSAID) use is associated with a lower rate of breast cancer. We evaluated the effect of etodolac, an FDA‐approved NSAID reported to inhibit cyclooxygenase (COX) enzymes and the retinoid X receptor alpha (RXR), on rationally identified potential biomarkers in breast cancer. Patients with resectable breast cancer planned for initial management with surgical resection were enrolled and took 400 mg of etodolac twice daily prior to surgery. Protein and gene expression levels for genes related to COX‐2 and RXRα were evaluated in tumor samples from before and after etodolac exposure. Thirty subjects received etodolac and 17 subjects were assayed as contemporaneous or opportunistic controls. After etodolac exposure mean cyclin D1 protein levels, assayed by immunohistochemistry, decreased (P = 0.03). Notably, pre‐ versus post cyclin D1 gene expression change went from positive to negative with greater duration of etodolac exposure (r = −0.64, P = 0.01). Additionally, etodolac exposure was associated with a significant increase in COX‐2 gene expression levels (fold change: 3.25 [95% CI: 1.9, 5.55]) and a trend toward increased β‐catenin expression (fold change: 2.03 [95% CI: 0.93, 4.47]). In resectable breast cancer relatively brief exposure to the NSAID etodolac was associated with reduced cyclin D1 protein levels. Effect was also observed on cyclin D1 gene expression with decreasing levels with longer durations of drug exposure. Increased COX‐2 gene expression was seen, possibly due to compensatory feedback. These data highlight the utility of even small clinical trials with access to biospecimens for pharmacodynamic studies.
ABO non‐O type as a risk factor for thrombosis in patients with pancreatic cancer
Authors: Li Donghui , Pise Mayurika N. , Overman Michael J. , Liu Chang , Tang Hongwei , Vadhan‐Raj Saroj , Abbruzzese James L. 
Published: August 2015

AbstractABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan–Meier plot, log‐rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non‐O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m2) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (≤10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (≤3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non‐O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy.
Cardiomyogenic differentiation of human sternal bone marrow mesenchymal stem cells using a combination of basic fibroblast growth factor and hydrocortisone
Authors: Hafez Pezhman , Jose Shinsmon , Chowdhury Shiplu R. , Ng Min Hwei , Ruszymah B. H. I. , Abdul Rahman Mohd Ramzisham 
Published: August 2015

AbstractThe alarming rate of increase in myocardial infarction and marginal success in efforts to regenerate the damaged myocardium through conventional treatments creates an exceptional avenue for cell‐based therapy. Adult bone marrow mesenchymal stem cells (MSCs) can be differentiated into cardiomyocytes, by treatment with 5‐azacytidine, thus, have been anticipated as a therapeutic tool for myocardial infarction treatment. In this study, we investigated the ability of basic fibroblastic growth factor (bFGF) and hydrocortisone as a combined treatment to stimulate the differentiation of MSCs into cardiomyocytes. MSCs were isolated from sternal marrow of patients undergoing heart surgery (CABG). The isolated cells were initially monitored for the growth pattern, followed by characterization using ISCT recommendations. Cells were then differentiated using a combination of bFGF and hydrocortisone and evaluated for the expression of characteristic cardiac markers such as CTnI, CTnC, and Cnx43 at protein level using immunocytochemistry and flow cytometry, and CTnC and CTnT at mRNA level. The expression levels and pattern of the cardiac markers upon analysis with ICC and qRT‐PCR were similar to that of 5‐azacytidine induced cells and cultured primary human cardiomyocytes. However, flow cytometric evaluation revealed that induction with bFGF and hydrocortisone drives MSC differentiation to cardiomyocytes with a marginally higher efficiency. These results indicate that combination treatment of bFGF and hydrocortisone can be used as an alternative induction method for cardiomyogenic differentiation of MSCs for future clinical applications.
Involvement of Notch signaling in early chick ovarian follicle development
Authors: Li Jun , Zhao Dan , Guo Changquan , Li Jian , Mi Yuling , Zhang Caiqiao 
Published: August 2015

AbstractThe formation of primordial follicles is a crucial process in the establishment of follicle pools required for the female's reproductive life span. For laying hens, ample follicles are a prerequisite for high laying performance. Notch signaling plays critical roles in germ cell cysts breakdown and in the formation of primordial follicles. Here, we investigated the role of Notch signaling in the ovarian development of post‐hatch chicks. Results showed that around post‐hatch day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by squamous pregranulosa cells, and the primordial follicles were then formed. Subsequently, we detected the expression of Notch signaling‐related genes including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target genes (Hes1, Hey1). These genes all showed expression at H4 and some of these genes were up‐regulated during primordial follicle formation. To evaluate the Notch signaling requirement for early follicular development, we adopted an in vitro ovary culture system. Suppression of Notch signaling by γ‐secretase inhibitor induced a decrease of primordial follicles and an increase of germ cells in cysts. Attenuating Notch signaling also inhibited the phosphatidylinositol 3‐kinase/protein kinase B pathways and suppressed cadherin expression. These results suggest that Notch signaling is endowed with an indispensable role in primordial follicle formation in post‐hatch chicks.
Pop goes the PA! and the aorta! iatrogenic aortopulmonary connections
Authors: “Sam” Lucas Victor 
Published: August 2015

Key Points

Iatrogenic aortopulmonary connections may occur after pulmonary artery angioplasty, stent or trans‐catheter pulmonary valve implantation
Patients with Ross autograft or arterial switch procedure may be at particular risk for this complication
Timely diagnosis is facilitated by post‐intervention aortic angiogram
Bivalirudin: An expensive heparin?
Authors: Gupta Saurabh , Cigarroa Joaquin E. 
Published: August 2015

Key Points

Bleeding rates with unfractionated heparin (UH) without concomitant use of glycoprotein IIb/IIIa inhibitors as compared to bivalirudin are similar.
Ischemic event rates during the index hospitalization are similar in the heparin and bivalirudin subgroups.
Low does heparin (60–70 units/kg) with a target ACT of 200–250 sec may obviate the historical improved safety of bivalirudin demonstrated in certain clinical trials.
Carotid artery stenting: Optimizing patient selection and technique
Authors: Safian Robert D. 
Published: August 2015

Key Points

Complex arch anatomy (type 2, type 3) and bovine configuration were identified in 34.4% and 20.5% of carotid stent patients, respectively.
Catheter manipulation time (CMT), rather than arch complexity per se, was the only independent predictor of adverse events after carotid stenting.
Careful attention to patient selection, preprocedural planning, and stent technique are important to ensure success.
Coronary perforation: What color is your parachute?
Authors: Seto Arnold H. , Kern Morton J. 
Published: August 2015

Key Points

Coronary perforation is a rare but devastating complication of PCI, requiring rescue devices such as covered stents.
This paper documents the successful use of a pericardial covered stent in 9/9 patients for coronary perforation.
Pericardial covered stents have theoretical advantages over PTFE covered stents, but clinical studies proving this are not feasible.
Cutting down on the cutdown: Time to remove the training wheels for transfemoral access for TAVR
Authors: Turi Zoltan G. 
Published: August 2015

Key Points

Percutaneous transfemoral access is replacing cutdowns, even in the absence of a high level evidence base
The evolution of smaller profile TAVR sheaths will make cutdowns largely obsolete
Patient comfort, early ambulation, and shorter length of stay, along with improved methodologies will continue to drive the move to percutaneous access and closure for TAVR
A single degree of oversize does not fit all valve types
Authors: Belardi Jorge A. , Albertal Mariano 
Published: August 2015

Key Points

Moderate valve oversize increases the risk of aortic regurgitation with self‐expandable valves, and larger oversizing may be preferable with this valve type.
Large oversizing increases the risk of aortic annular rupture in patients treated with balloon‐expandable valves and less oversizing appears safer.
Anatomical factors may also may influence procedural success and should not be overlooked.
Diabetes is not sufficient justification for IIb/IIIa use in percutaneous coronary intervention
Authors: Hillegass William B. 
Published: August 2015

Key Points

Diabetics, particularly insulin treated, have increased risk of ischemic events and bleeding with percutaneous coronary intervention (PCI). The relative risk of atherothrombotic versus bleeding events is higher in diabetics than non‐diabetics.
Bivalirudin with provisional IIb/IIIa therapy has less bleeding and lower one‐year mortality than routine IIb/IIIa therapy in diabetics undergoing PCI.
IIb/IIIa agents should be reserved for provisional and niche applications during PCI.
Very Facile Polarity Umpolung and Noncovalent Functionalization of Inorganic Nanoparticles: A Tool Kit for Supramolecular Materials Chemistry
Authors: Zeininger Lukas , Petzi Stefanie , Schönamsgruber Jörg , Portilla Luis , Halik Marcus , Hirsch Andreas 
Published: August 2015

AbstractThe facile assembly of shell‐by‐shell (SbS)‐coated nanoparticles [TiO2PAC16]@shell 1–7 (PAC16=hexadecylphosphonic acid), which are soluble in water and can be isolated as stable solids, is reported. In these functional architectures, an umpolung of dispersibility (organic apolar versus water) was accomplished by the noncovalent binding of ligands 1–7 to titania nanoparticles [TiO2PAC16] containing a first covalent coating with PAC16. Ligands 1–7 are amphiphilic and form the outer second shell of [TiO2PAC16]@shell 1–7. The tailor‐designed dendritic building blocks 3–5 contain negative and positive charges in the same molecule, and ligands 6 and 7 contain a perylenetetracarboxylic acid dimide (PDI) core (6/7) as a photoactive reporter component. In the redox and photoactive system [TiO2PAC16]@shell 7, electronic communication between the inorganic core to the PDI ligands was observed.
Strain‐Promoted Reaction of 1,2,4‐Triazines with Bicyclononynes
Authors: Horner Katherine A. , Valette Nathalie M. , Webb Michael E. 
Published: August 2015

AbstractStrain‐promoted inverse electron‐demand Diels–Alder cycloaddition (SPIEDAC) reactions between 1,2,4,5‐tetrazines and strained dienophiles, such as bicyclononynes, are among the fastest bioorthogonal reactions. However, the synthesis of 1,2,4,5‐tetrazines is complex and can involve volatile reagents. 1,2,4‐Triazines also undergo cycloaddition reactions with acyclic and unstrained dienophiles at elevated temperatures, but their reaction with strained alkynes has not been described. We postulated that 1,2,4‐triazines would react with strained alkynes at low temperatures and therefore provide an alternative to the tetrazine cycloaddition reaction for use in in vitro or in vivo labelling experiments. We describe the synthesis of a 1,2,4‐triazin‐3‐ylalanine derivative fully compatible with the fluorenylmethyloxycarbonyl (Fmoc) strategy for peptide synthesis and demonstrate its reaction with strained bicyclononynes at 37 °C with rates comparable to the reaction of azides with the same substrates. The synthetic route to triazinylalanine is readily adaptable to late‐stage functionalization of other probe molecules, and the 1,2,4‐triazine‐SPIEDAC therefore has potential as an alternative to tetrazine cycloaddition for applications in cellular and biochemical studies.
Model‐based MPI‐IO tuning with Periscope tuning framework
Authors: Liu Weifeng , Gerndt Michael , Gong Bin 
Published: August 2015

SummaryFor many parallel applications, I/O performance is a major bottleneck. MPI‐IO, defined by the MPI forum, can help parallel applications overcome the performance and portability limitations of existing parallel I/O interfaces. Although autotuning has been used to improve the performance of computing kernels, MPI‐IO autotuning has rarely been studied. To automate MPI‐IO performance tuning, we designed and implemented an automatic tuner. The tuner relies on the Periscope tuning framework for transparently passing hints to the MPI‐IO library and for automatically collecting performance data. Unlike computational code, each MPI‐IO function takes a relatively long time to complete. Thus, exhaustively searching through the entire parameter space is impractical. So we developed a performance model that can direct us to shorten the tuning time. Copyright © 2015 John Wiley & Sons, Ltd.
A high‐level and accurate energy model of parallel and concurrent workloads
Authors: Morelli Davide , Canciani Andrea , Cisternino Antonio 
Published: August 2015

SummaryThe ability to predict the energy needed by a system to perform a task, or several concurrent parallel tasks, allows the scheduler to enforce energy‐aware policies while providing acceptable performance. The approaches in literature to model energy consumption of tasks usually focus on low‐level descriptors and require invasive instrumentation of the computational environment. We developed an energy model and a methodology to automatically extract features that characterize the computational environment relying only on a single power meter that measures the energy consumption of the whole system. Once the model has been built, the energy consumption of concurrent tasks can be calculated, with a statistically insignificant error, even without any power meter. We show that our model can predict with high accuracy, even only using the utilization time of the cores in a high‐performance computing enclosure, without using performance counters. Hence, the model could be easily applicable to heterogeneous systems, where collecting representative performance counters can be problematic. Copyright © 2015 John Wiley & Sons, Ltd.