bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled Analysis of Mitochondrial DNA Copy Number and Lung Cancer Risk in Three Prospective Studies
Authors: Kim Christopher , Bassig Bryan A. , Seow Wei Jie , Hu Wei , Purdue Mark P. , Shu Xiao-Ou , Huang Wen-Yi , Liu Chin-San , Cheng Wen-Ling , Lin Ta-Tsung , Xiang Yong-Bing , Ji Bu-Tian , Gao Yu-Tang , Chow Wong-Ho , Männistö Satu , Weinstein Stephanie J. , Albanes Demetrius , Zheng Wei , Hosgood H. Dean , Lim Unhee , Rothman Nathaniel , Lan Qing 
Published: October 2014

Abstract
Background: We previously reported that higher levels of mitochondrial DNA copy number (mtDNA CN) were associated with lung cancer risk among male heavy smokers (i.e., ≥20 cigarettes per day) in the Alpha-Tocopherol Beta-Carotene (ATBC) study. Here, we present two additional prospective investigations nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and the Shanghai Women's Health Study (SWHS), and pooled with previously published data from ATBC.
Materials: All DNA were extracted from peripheral whole blood samples using the phenol–chloroform method, and mtDNA CN was assayed by fluorescence-based qPCR. Multivariate unconditional logistic regression models were used to estimate ORs and 95% confidence intervals for the association of mtDNA CN and lung cancer risk.
Results: Overall, mtDNA CN was not associated with lung cancer risk in the PLCO, SWHS, or pooled populations (all P trends &gt; 0.42, P heterogeneity = 0.0001), and mtDNA CN was inversely associated with lung cancer risk among male smokers in PLCO, the opposite direction observed in ATBC. In addition, the mtDNA CN association observed among male heavy smokers in ATBC was the opposite direction in PLCO.
Conclusions: mtDNA CN was not consistently associated with lung cancer risk across three prospective study populations from Europe, Asia, and the United States.
Impact: This pooled study suggests no consistent association between prediagnostic mtDNA CN levels and lung cancer risk across several populations. Cancer Epidemiol Biomarkers Prev; 23(12); 2977–80. ©2014 AACR.
Efficacy of Anti-RON Antibody Zt/g4–Drug Maytansinoid Conjugation (Anti-RON ADC) as a Novel Therapeutics for Targeted Colorectal Cancer Therapy
Authors: Feng Liang , Yao Hang-Ping , Wang Wei , Zhou Yong-Qing , Zhou Jianwei , Zhang Ruiwen , Wang Ming-Hai 
Published: October 2014

Abstract
Purpose: The receptor tyrosine kinase RON is critical in epithelial tumorigenesis and a drug target for cancer therapy. Here, we report the development and therapeutic efficacy of a novel anti-RON antibody Zt/g4–maytansinoid (DM1) conjugates for targeted colorectal cancer (CRC) therapy.
Experimental Design: Zt/g4 (IgG1a/κ) was conjugated to DM1 via thioether linkage to form Zt/g4–DM1 with a drug-antibody ratio of 4:1. CRC cell lines expressing different levels of RON were tested in vitro to determine Zt/g4–DM1-induced RON endocytosis, cell-cycle arrest, and cytotoxicity. Efficacy of Zt/g4–DM1 in vivo was evaluated in mouse xenograft CRC tumor model.
Results: Zt/g4–DM1 rapidly induced RON endocytosis, arrested cell cycle at G2–M phase, reduced cell viability, and caused massive cell death within 72 hours. In mouse xenograft CRC models, Zt/g4–DM1 at a single dose of 20 mg/kg body weight effectively delayed CRC cell-mediated tumor growth up to 20 days. In a multiple dose-ranging study with a five injection regimen, Zt/g4–DM1 inhibited more than 90% tumor growth at doses of 7, 10, and 15 mg/kg body weight. The minimal dose achieving 50% of tumor inhibition was approximately 5.0 mg/kg. The prepared Zt/g4–DM1 is stable at 37°C for up to 30 days. At 60 mg/kg, Zt/g4–DM1 had a moderate toxicity in vivo with an average of 12% reduction in mouse body weight.
Conclusion: Zt/g4–DM1 is highly effective in targeted inhibition of CRC cell-derived tumor growth in mouse xenograft models. This work provides the basis for development of humanized Zt/g4–DM1 for RON-targeted CRC therapy in the future. Clin Cancer Res; 20(23); 6045–58. ©2014 AACR.
miR-204-5p Inhibits Proliferation and Invasion and Enhances Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating RAB22A
Authors: Yin Yuan , Zhang Binbin , Wang Weili , Fei Bojian , Quan Chao , Zhang Jiwei , Song Mingxu , Bian Zehua , Wang Qifeng , Ni Shujuan , Hu Yaling , Mao Yong , Zhou Leyuan , Wang Yugang , Yu Jian , Du Xiang , Hua Dong , Huang Zhaohui 
Published: October 2014

Abstract
Purpose: miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer development and progression.
Experimental Design: We measured the expression of miR-204-5p and determined its correlation with patient prognoses. Ectopic expression in colorectal cancer cells, xenografts, and pulmonary metastasis models was used to evaluate the effects of miR-204-5p on proliferation, migration, and chemotherapy sensitivity. Luciferase assay and Western blotting were performed to validate the potential targets of miR-204-5p after the preliminary screening by a microarray analysis and computer-aided algorithms.
Results: miR-204-5p is frequently downregulated in colorectal cancer tissues, and survival analysis showed that the downregulation of miR-204-5p in colorectal cancer was associated with poor prognoses. Ectopic miR-204-5p expression repressed colorectal cancer cell growth both in vitro and in vivo. Moreover, restoring miR-204-5p expression inhibited colorectal cancer migration and invasion and promoted tumor sensitivity to chemotherapy. Mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in colorectal cancer. Furthermore, RAB22A protein levels in colorectal cancer tissues were frequently increased and negatively associated with miR-204-5p levels and survival time.
Conclusions: Our results demonstrate for the first time that miR-204-5p acts as a tumor suppressor in colorectal cancer through inhibiting RAB22A and reveal RAB22A to be a new oncogene and prognostic factor for colorectal cancer. Clin Cancer Res; 20(23); 6187–99. ©2014 AACR.
New Strategies in Chronic Lymphocytic Leukemia: Shifting Treatment Paradigms
Authors: Awan Farrukh T. , Byrd John C. 
Published: October 2014

Abstract
Over the past two decades, slow but deliberate progress has been made in understanding the genetics of chronic lymphocytic leukemia (CLL) and how the surrounding microenvironment influences leukemia cell survival. The complexity of CLL with respect to different chromosomal aberrations, lack of a common aberrant signaling pathway activation, and associated immune suppression of the disease has been seen a major stumbling block for developing a single targeted therapy similar to imatinib used in chronic myeloid leukemia. The upcoming therapeutic era we are entering with the B-cell receptor (BCR) tyrosine kinase inhibitors ibrutinib and idelalisib appears to be overcoming this obstacle. Indeed, for the large majority of patients, it appears that application of BCR kinase inhibitors can promote durable remissions without the need for chemotherapy. Where other very active targeted agents such as ABT-199, therapeutic antibodies, and chimeric antigen receptor–modified T-cells will be used in CLL also represents a major question that future clinical trials will answer. Clin Cancer Res; 20(23); 5869–74. ©2014 AACR.
Clinical Outcomes After Continuous-Flow Left Ventricular Assist Device
Authors: McIlvennan Colleen K. , Magid Kate H. , Ambardekar Amrut V. , Thompson Jocelyn S. , Matlock Daniel D. , Allen Larry A. 
Published: October 2014

Background—
Conveying the complex trade-offs of continuous-flow left ventricular assist devices is challenging and made more difficult by absence of an evidence summary for the full range of possible outcomes. We aimed to summarize the current evidence on outcomes of continuous-flow left ventricular assist devices.

Methods and Results—
PubMed and Cochrane Library were searched from January 2007 to December 2013, supplemented with manual review. Three reviewers independently assessed each study for saliency on patient-centered outcomes. Data were summarized in tabular form. Overall study characteristics encouraged inclusion of all indications (destination therapy and bridge to transplant) and prevented meta-analysis. The electronic search identified 465 abstracts, of which 50 met inclusion criteria; manual review added 2 articles in press. The articles included 10 industry-funded trials and registries, 10 multicenter reports, and the remainder single-center observational experiences. Estimated actuarial survival after continuous-flow left ventricular assist devices ranged from 56% to 87% at 1 year, 43% to 84% at 2 years, and 47% at 4 years. Improvements in functional class and quality of life were reported, but missing data complicated interpretation. Adverse events were experienced by the majority of patients, but estimates for bleeding, stroke, infection, right heart failure, arrhythmias, and rehospitalizations varied greatly.

Conclusions—
The totality of data for continuous-flow left ventricular assist devices show consistent improvements in survival and quality of life counterbalanced by a range of common complications. Although this summary should provide a practical resource for healthcare provider-led discussions with patients, it highlights the critical need for high-quality patient-centered data collected with standard definitions.
Spontaneous Coronary Artery Dissection
Authors: Saw Jacqueline , Aymong Eve , Sedlak Tara , Buller Christopher E. , Starovoytov Andrew , Ricci Donald , Robinson Simon , Vuurmans Tycho , Gao Min , Humphries Karin , Mancini G.B. John 
Published: October 2014

Background—
Nonatherosclerotic spontaneous coronary artery dissection (NA-SCAD) is underdiagnosed and an important cause of myocardial infarction in young women. The frequency of predisposing and precipitating conditions and cardiovascular outcomes remains poorly described.

Methods and Results—
Patients with NA-SCAD prospectively evaluated (retrospectively or prospectively identified) at Vancouver General Hospital were included. Angiographic SCAD diagnosis was confirmed by 2 experienced interventional cardiologists and categorized as type 1 (multiple lumen), 2 (diffuse stenosis), or 3 (mimic atherosclerosis). Fibromuscular dysplasia screening of renal, iliac, and cerebrovascular arteries were performed with angiography or computed tomographic angiography/MR angiography. Baseline, predisposing and precipitating conditions, angiographic, revascularization, in-hospital, and long-term events were recorded. We prospectively evaluated 168 patients with NA-SCAD. Average age was 52.1±9.2 years, 92.3% were women (62.3% postmenopausal). All presented with myocardial infarction. ECG showed ST-segment elevation in 26.1%, and 3.6% had ventricular tachycardia/ventricular fibrillation arrest. Fibromuscular dysplasia was diagnosed in 72.0%. Precipitating emotional or physical stress was reported in 56.5%. Majority had type 2 angiographic SCAD (67.0%), only 29.1% had type 1, and 3.9% had type 3. The majority (134/168) were initially treated conservatively. Overall, 6 of 168 patients had coronary artery bypass surgery and 33 of 168 had percutaneous coronary intervention in-hospital. Of those treated conservatively (n=134), 3 required revascularization for SCAD extension, and all 79 who had repeat angiogram ≥26 days later had spontaneous healing. Two-year major adverse cardiac events were 16.9% (retrospectively identified group) and 10.4% (prospectively identified group). Recurrent SCAD occurred in 13.1%.

Conclusions—
Majority of patients with NA-SCAD had fibromuscular dysplasia and type 2 angiographic SCAD. Conservative therapy was associated with spontaneous healing. NA-SCAD survivors are at risk for recurrent cardiovascular events, including recurrent SCAD.
Derivation and External Validation of a Case Mix Model for the Standardized Reporting of 30-Day Stroke Mortality Rates
Authors: Bray Benjamin D. , Campbell James , Cloud Geoffrey C. , Hoffman Alex , James Martin , Tyrrell Pippa J. , Wolfe Charles D.A. , Rudd Anthony G. 
Published: October 2014

Background and Purpose—
Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data.

Methods—
Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots.

Results—
Two final models were derived. Model A included age (<60, 60–69, 70–79, 80–89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84–0.89) and 0.86 (95% confidence interval, 0.83–0.89) for models A and B, respectively.

Conclusions—
We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction.
On the Warm Core of a Tropical Cyclone Formed near the Tropopause
Authors: Ohno Tomoki , Satoh Masaki 
Published: October 2014

Abstract
On the basis of numerical results of a three-dimensional model diagnosed using balance dynamics, a mechanism by which the upper-level warm core of tropical cyclones (TCs) forms is proposed. The numerical results reveal that an upper-level warm core develops when TCs intensify just prior to reaching the mature stage. Potential temperature budget analysis reveals that for the tendency of potential temperature, the azimuthal-mean component of advection is dominant at the upper level of the eye at the mature stage. Sawyer–Eliassen diagnosis shows that tendencies due to forced flow by diabatic heating and diffusion of tangential wind are dominant in the eye and are negatively correlated to each other. The distributions of the diabatic heating in the simulated TC are not peculiar. Therefore, it is unlikely that the heating distribution itself is the primary cause of the flow from the lower stratosphere. The analyses of forced circulations of idealized vortices show that the upper-level subsidence is enhanced in the eye when the vortex is sufficiently tall to penetrate the statically stable stratosphere. This result is deduced because the stronger inertial stability extends the response to the heating of the lower stratosphere and causes upper-level adiabatic warming. Therefore, the upper-level warm core emerges if angular momentum is transported into the lower stratosphere due to processes such as convective bursts. The present analysis suggests that TCs can be even stronger than that expected by theories in which the TC vortex is confined in the troposphere.
The Life Cycle of the North Atlantic Storm Track*
Authors: Novak Lenka , Ambaum Maarten H. P. , Tailleux Rémi 
Published: October 2014

Abstract
The North Atlantic eddy-driven jet exhibits latitudinal variability with evidence of three preferred latitudinal locations: south, middle, and north. Here the authors examine the drivers of this variability and the variability of the associated storm track. The authors investigate the changes in the storm-track characteristics for the three jet locations and propose a mechanism by which enhanced storm-track activity, as measured by upstream heat flux, is responsible for cyclical downstream latitudinal shifts in the jet. This mechanism is based on a nonlinear oscillator relationship between the enhanced meridional temperature gradient (and thus baroclinicity) and the meridional high-frequency (periods of shorter than 10 days) eddy heat flux. Such oscillations in baroclinicity and heat flux induce variability in eddy anisotropy, which is associated with the changes in the dominant type of wave breaking and a different latitudinal deflection of the jet. The authors’ results suggest that high heat flux is conducive to a northward deflection of the jet, whereas low heat flux is conducive to a more zonal jet. This jet-deflecting effect was found to operate most prominently downstream of the storm-track maximum, while the storm track and the jet remain anchored at a fixed latitudinal location at the beginning of the storm track. These cyclical changes in storm-track characteristics can be viewed as different stages of the storm track’s spatiotemporal life cycle.
Computed tomography features of benign and malignant solid thyroid nodules
Authors: Kim Dong Wook , Jung Soo Jin , Baek Hye Jin 
Published: October 2014

Background No previous study has investigated computed tomography (CT) features of benign and malignant solid thyroid nodules using detailed CT features and histopathological results. Purpose To assess CT features of benign and malignant solid thyroid nodules in patients who underwent thyroid surgery. Material and Methods From January to April 2014, 151 consecutive patients underwent neck CT before thyroid surgery. In each case, neck CT was retrospectively examined by a single radiologist. We evaluated the diagnostic accuracy of specific CT features for differentiating malignant from benign thyroid nodules using histopathological results as a reference standard. Results Of 173 thyroid nodules in 142 patients, 162 (mean diameter, 12.8 ± 10.3 mm; range, 5.0–93.7 mm) were visualized on neck CT. Of 162 nodules in 133 patients, 116 were malignant and 46 were benign as confirmed by histopathology. A multivariate logistic regression analysis showed a significant difference between malignant and benign thyroid nodules in the degree and pattern of nodular enhancement, but there were no significant differences in other CT features. In particular, thyroid nodules with exophytic configuration, irregular margin, taller-than-wide shape, punctate calcifications, or homogeneously decreased enhancement showed a high malignancy rate. Conclusion The study demonstrated that the degree and pattern of nodular enhancement are helpful CT features for differentiating malignant from benign solid thyroid nodules.
Curing myeloma at last: defining criteria and providing the evidence
Authors: Barlogie Bart , Mitchell Alan , van Rhee Frits , Epstein Joshua , Morgan Gareth J. , Crowley John 
Published: October 2014

Abstract
Does the dogma that multiple myeloma is incurable still hold?. The genomic chaos and resulting resistance to apoptosis of myeloma, long considered an obstacle to cure, formed the basis of Total Therapy (TT) program. The TT approach uses all myeloma-active drugs upfront to target drug-resistant subclones during initial treatment to prevent later relapse. Long-term follow-up of 1202 patients (TT1: n = 231, median follow-up: 21 years; TT2: 668, median follow-up: 12 years; TT3a: n = 303, median follow-up: 9 years) permitted investigation of whether progression-free survival (PFS) and complete response (CR) duration were consistent with curability, ie observation of plateaus in Kaplan-Meier plots for PFS and CR duration. In the subset of 627 patients with plasma cell gene expression profiling data, cure plateaus were apparent at 5 years in the 14% with high-risk myeloma compared with 10 years in the remainder with low-risk disease. A parametric model based on PFS and CR duration supported an increase in curability: 10-year PFS and CR estimates increased from 8.8%/17.9% in TT1 to 15.5%/28.2% in TT2’s control arm to 25.1%/35.6% in TT2’s thalidomide arm and to 32.9%/48.8% in TT3a. Toward developing novel therapies, we recommend a concerted focus on patients with high-risk myeloma whose outcome has not been advanced.
Sequential intranodal immunotherapy induces antitumor immunity and correlated regression of disseminated follicular lymphoma
Authors: Kolstad Arne , Kumari Shraddha , Walczak Mateusz , Madsbu Ulf , Hagtvedt Trond , Bogsrud Trond Velde , Kvalheim Gunnar , Holte Harald , Aurlien Ellen , Delabie Jan , Tierens Anne , Olweus Johanna 
Published: October 2014

Key Points
Local immunotherapy induced systemic responses in patients with disseminated FL. Clinical responses correlated with systemic antitumor T-cell immunity.
Facile synthesis of folate-conjugated magnetic/fluorescent bifunctional microspheres
Authors: Shen Mao , Jia Wenping , Lin Caiping , Fan Guodong , Jin Yangmin , Chen Xiaoying , Chen Guang 
Published: October 2014

Abstract
In this paper, we investigated the functional imaging properties of magnetic microspheres composed of magnetic core and CdTe quantum dots in the silica shell functionalized with folic acid (FA). The preparation procedure included the preparation of chitosan-coated Fe3O4 nanoparticles (CS-coated Fe3O4 NPs) prepared by a one-pot solvothermal method, the reaction between carboxylic and amino groups under activation of NHS and EDC in order to obtain the CdTe-CS-coated Fe3O4 NPs, and finally the growth of SiO2 shell vent the photoluminescence (PL) quenching via a Stöber method (Fe3O4-CdTe@SiO2). Moreover, in order to have a specific targeting capacity, the magnetic and fluorescent bifunctional microspheres were synthesized by bonding of SiO2 shell with FA molecules via amide reaction (Fe3O4-CdTe@SiO2-FA). The morphology, size, chemical components, and magnetic property of as-prepared composite nanoparticles were characterized by ultraviolet-visible spectroscopy, fluorescent spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning transmission electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM), respectively. The results show that the magnetic and fluorescent bifunctional microspheres have strong luminescent which will be employed for immuno-labeling and fluorescent imaging of HeLa cells.