bluuebunny/crossref_metadata_2025_split huggingface dataset:
External Validation of Medicare Claims Codes for Digital Mammography and Computer-Aided Detection
Authors: Fenton Joshua J. , Zhu Weiwei , Balch Steven , Smith-Bindman Rebecca , Lindfors Karen K. , Hubbard Rebecca A. 
Published: August 2012

Abstract
Background: While Medicare claims are a potential resource for clinical mammography research or quality monitoring, the validity of key data elements remains uncertain. Claims codes for digital mammography and computer-aided detection (CAD), for example, have not been validated against a credible external reference standard.
Methods: We matched Medicare mammography claims for women who received bilateral mammograms from 2003 to 2006 to corresponding mammography data from the Breast Cancer Surveillance Consortium (BCSC) registries in four U.S. states (N = 253,727 mammograms received by 120,709 women). We assessed the accuracy of the claims-based classifications of bilateral mammograms as either digital versus film and CAD versus non-CAD relative to a reference standard derived from BCSC data.
Results: Claims data correctly classified the large majority of film and digital mammograms (97.2% and 97.3%, respectively), yielding excellent agreement beyond chance (κ = 0.90). Claims data correctly classified the large majority of CAD mammograms (96.6%) but a lower percentage of non-CAD mammograms (86.7%). Agreement beyond chance remained high for CAD classification (κ = 0.83). From 2003 to 2006, the predictive values of claims-based digital and CAD classifications increased as the sample prevalences of each technology increased.
Conclusion: Medicare claims data can accurately distinguish film and digital bilateral mammograms and mammograms conducted with and without CAD.
Impact: The validity of Medicare claims data regarding film versus digital mammography and CAD suggests that these data elements can be useful in research and quality improvement. Cancer Epidemiol Biomarkers Prev; 21(8); 1344–7. ©2012 AACR.
The Role of Obesity in Cancer Survival and Recurrence
Authors: Demark-Wahnefried Wendy , Platz Elizabeth A. , Ligibel Jennifer A. , Blair Cindy K. , Courneya Kerry S. , Meyerhardt Jeffrey A. , Ganz Patricia A. , Rock Cheryl L. , Schmitz Kathryn H. , Wadden Thomas , Philip Errol J. , Wolfe Bruce , Gapstur Susan M. , Ballard-Barbash Rachel , McTiernan Anne , Minasian Lori , Nebeling Linda , Goodwin Pamela J. 
Published: August 2012

Abstract
Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions. Cancer Epidemiol Biomarkers Prev; 21(8); 1244–59. ©2012 AACR.
Confirmation of the HOXB13 G84E Germline Mutation in Familial Prostate Cancer
Authors: Breyer Joan P. , Avritt T. Grant , McReynolds Kate M. , Dupont William D. , Smith Jeffrey R. 
Published: August 2012

Abstract
Background: A recent study of familial and early onset prostate cancer reported a recurrent rare germline mutation of HOXB13 among men of European descent. The gene resides within the 17q21 hereditary prostate cancer linkage interval.
Methods: We evaluated the G84E germline mutation (rs138213197) of HOXB13 in a case–control study of familial prostate cancer at Vanderbilt University (Nashville, TN) to independently evaluate the association of the mutation with familial prostate cancer. We genotyped 928 familial prostate cancer probands and 930 control probands without a personal or family history of prostate cancer.
Results: Our study confirmed the association between the G84E mutation of HOXB13 and risk of prostate cancer among subjects of European descent. We observed the mutation in 16 familial cases and in two controls, each as heterozygotes. The odds ratio (OR) for prostate cancer was 7.9 [95% confidence interval, (CI) 1.8–34.5, P = 0.0062] among carriers of the mutation. The carrier rate was 1.9% among all familial case probands and 2.7% among probands of pedigrees with ≥3 affected. In a separate case series of 268 probands of European descent with no additional family history of prostate cancer, the carrier rate was 1.5%.
Conclusions: The germline mutation G84E of HOXB13 is a rare but recurrent mutation associated with elevated risk of prostate cancer in men of European descent, with an effect size that is greater than observed for previously validated risk variants of genome wide association studies.
Impact: This study independently confirms the association of a germline HOXB13 mutation with familial prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(8); 1348–53. ©2012 AACR.
Common Genetic Variants in the MicroRNA Biogenesis Pathway Are Not Associated with Breast Cancer Risk in Asian Women
Authors: Sung Hyuna , Zhang Ben , Choi Ji-Yeob , Long Jirong , Park Sue K. , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Zheng Wei , Kang Daehee 
Published: August 2012

Abstract
Background: Although the role of miRNA in cancer development and progression has been well established, the association between genetic variants in miRNA biogenesis pathway genes and breast cancer risk has been yet unclear.
Methods: We analyzed data from two genome-wide association studies conducted in East Asian women including 5,066 cases and 4,337 controls. Among the single-nucleotide polymorphisms (SNP), which were directly genotyped or imputed, we selected 237 SNPs in 32 genes involved in miRNA biogenesis pathway and its regulation.
Results: Although eight SNPs were nominally associated with breast cancer risk in combined samples (P &lt; 0.05), none of them were significant after adjustment for multiple comparisons.
Conclusions: The common genetic variants in miRNA biogenesis pathway genes may not be associated with breast cancer risk.
Impact: This study suggests no association between the polymorphisms in miRNA biogenesis pathway genes and breast cancer risk. Studies with large sample size and more genetic variants should be warranted to adequately evaluate the potential association. Cancer Epidemiol Biomarkers Prev; 21(8); 1385–7. ©2012 AACR.
Individual Patient-Specific Immunity against High-Grade Glioma after Vaccination with Autologous Tumor Derived Peptides Bound to the 96 KD Chaperone Protein
Authors: Crane Courtney A. , Han Seunggu J. , Ahn Brian , Oehlke Jessica , Kivett Valerie , Fedoroff Anne , Butowski Nicholas , Chang Susan M. , Clarke Jennifer , Berger Mitchel S. , McDermott Michael W. , Prados Michael D. , Parsa Andrew T. 
Published: August 2012

AbstractPurpose: Cancer immunotherapy offers hope of a highly specific nontoxic adjuvant treatment. Heat shock protein peptide complexes (HSPPCs) found in cancer cells carry tumor-specific antigenic proteins and can facilitate adaptive and innate immune responses. Here we show that peptides bound to a 96 kD chaperone protein (HSP-96) from brain tissue containing glioblastoma multiforme (GBM) can be used to safely immunize patients with recurrent GBM.Experimental Design: Multimodality immunomonitoring was completed on 12 patients with recurrent GBM before and after immunization with an autologous HSPPC vaccine derived from surgically resected tumor. Clinical endpoints included safety assessments and overall survival.Results: No adverse events attributable to the vaccine were found. Testing of peripheral blood leukocytes before and after vaccination revealed a significant peripheral immune response specific for the peptides bound to HSP-96, in 11 of the 12 patients treated. Brain biopsies of immune responders after vaccination revealed focal CD4, CD8, and CD56 IFNγ positive cell infiltrates, consistent with tumor site specific immune responses. Immune responders had a median survival of 47 weeks after surgery and vaccination, compared with 16 weeks for the single nonresponder.Conclusions: These data provide the first evidence in humans of individual patient-specific immune responses against autologous tumor derived peptides bound to HSP-96. Clin Cancer Res; 19(1); 205–14. ©2012 AACR.
Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy
Authors: Hu Lingmin , Wu Chen , Zhao Xueying , Heist Rebecca , Su Li , Zhao Yang , Han Baohui , Cao Songyu , Chu Minjie , Dai Juncheng , Dong Jing , Shu Yongqian , Xu Lin , Chen Yijiang , Wang Yi , Lu Feng , Jiang Yue , Yu Dianke , Chen Hongyan , Tan Wen , Ma Hongxia , Chen Jiaping , Jin Guangfu , Wu Tangchun , Lu Daru , Christiani David C. , Lin Dongxin , Hu Zhibin , Shen Hongbing 
Published: August 2012

Abstract
Purpose: Genetic variation may influence chemotherapy response and overall survival in cancer patients.
Experimental design: We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA).
Results: Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population.
Conclusion: In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients. Clin Cancer Res; 18(19); 5507–14. ©2012 AACR.
Mutation distribution in the von Willebrand factor gene related to the different von Willebrand disease (VWD) types in a cohort of VWD patients
Authors: Yadegari Hamideh , Driesen Julia , Pavlova Anna , Biswas Arijit , Hertfelder Hans-Jörg , Oldenburg Johannes 
Published: August 2012

SummaryVon Willebrand disease (VWD) is the most common inherited bleeding disorder caused by quantitative or qualitative defects of the von Willebrand factor (VWF). VWD is classified into three types – type 1 (partial quantitative deficiencies), type 2 (qualitative defects) and type 3 (complete deficiency of VWF). In this study we explored genotype and phenotype characteristics of patients with VWD with the aim of dissecting the distribution of mutations in different types of VWD. One hundred fourteen patients belonging to 78 families diagnosed to have VWD were studied. Mutation analysis was performed by direct sequencing of the VWF. Large deletions were investigated by multiplex ligation-dependent probe amplification (MLPA) analysis. The impact of novel candidate missense mutations and potential splice site mutations was predicted by in silico assessments. We identified mutations in 66 index patients (IPs) (84.6%). Mutation detection rate was 68%, 94% and 94% for VWD type 1, 2 and 3, respectively. In total, 68 different putative mutations were detected comprising 37 missense mutations (54.4%), 10 small deletions (14.7%), two small insertions (2.9%), seven nonsense mutations (10.3%), five splice-site mutations (7.4%), six large deletions (8.8%) and one silent mutation (1.5%). Twenty-six of these mutations were novel. Furthermore, in type 1 and type 2 VWD, the majority of identified mutations (74% vs. 88.1%) were missense substitutions while mutations in type 3 VWD mostly caused null alleles (82%). Genotyping in VWD is a helpful tool to further elucidate the pathogenesis of VWD and to establish the relationship between genotype and phenotype.
Effect of the VKORC1 D36Y variant on warfarin dose requirement and pharmacogenetic dose prediction
Authors: Qasim Husam , Sominsky Sophie , Lubetsky Aharon , Markovits Noa , Li Chun , Stein C. , Halkin Hillel , Gak Eva , Loebstein Ronen , Kurnik Daniel 
Published: August 2012

SummaryPharmacogenetic dosing algorithms help predict warfarin maintenance doses, but their predictive performance differs in different populations, possibly due to unsuspected population-specific genetic variants. The objectives of this study were to quantify the effect of the VKORC1 D36Y variant (a marker of warfarin resistance previously described in 4% of Ashkenazi Jews) on warfarin maintenance doses and to examine how this variant affects the performance of the International Warfarin Pharmacogenetic Consortium (IWPC) dose prediction model. In 210 Israeli patients on chronic warfarin therapy recruited at a tertiary care centre, we applied the IWPC model and then added D36Y genotype as covariate to the model (IWPC+D36Y) and compared predicted with actual doses. Median weekly warfarin dose was 35 mg (interquartile range [IQR], 24.5 to 52.5 mg). Among 16 heterozygous D36Y carriers (minor allele frequency = 3.8%), warfarin weekly dose was increased by a median of 43.7 mg (IQR, 40.5 to 47.2 mg) compared to non-carriers after adjustment for all IWPC parameters, a greater than two-fold dose increase. The IWPC model performed suboptimally (coefficient of determination R2=27.0%; mean absolute error (MAE), 14.4 ± 16.2 mg/ week). Accounting for D36Y genotype using the IWPC+D36Y model resulted in a significantly better model performance (R2=47.2%, MAE=12.6±12.4 mg/week). In conclusion, even at low frequencies, variants with a strong impact on warfarin dose may greatly decrease the performance of a commonly used dose prediction model. Unexpected discrepancies of the performance of universal prediction models in subpopulations should prompt searching for unsuspected confounders, including rare genetic variants.
Translating the effects of statins: From redox regulation to suppression of vascular wall inflammation
Authors: Antonopoulos Alexios , Margaritis Marios , Shirodaria Cheerag , Antoniades Charalambos 
Published: August 2012

SummaryVascular oxidative stress is a key feature of atherogenesis, and targeting vascular redox signalling is a rational therapeutic goal in vascular disease pathogenesis. 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins are potent lipid-lowering drugs that improve cardiovascular outcomes. It is now widely accepted that cardiovascular disease prevention by statins is dependent not only on their lipid lowering effects, but also on their beneficial effects on vascular redox signalling. Cell culture and animal models have provided important findings on the effects of statins on vascular redox and nitric oxide bioavailability. Recent evidence from studies on human vessels has further enhanced our understanding of the “pleiotropic” effects of statins on vascular wall. Reversal of endothelial dysfunction in human vessels by statins is dependent on the mevalonate pathway and Rac1 inhibition. These critical steps are responsible for reducing NADPH-oxidase activity and improving tetrahydrobiopterin bioavailability and nitric oxide synthase (NOS) coupling in human vessels. However, mevalonate pathway inhibition has been also held responsible for some of the side effects observed after statin treatment. In this review we summarise the existing knowledge on the effects of statins on vascular biology by discussing key findings from basic science as well as recent evidence from translational studies in humans. Finally, we discuss emerging aspects of statin pleiotropy, such as their effects on adipose tissue biology and adipokine synthesis that may light additional mechanistic links between statin treatment and improvement of clinical outcome in primary and secondary prevention.
Do we know enough about the immune pathogenesis of acute coronary syndromes to improve clinical practice?
Authors: Matusik Pawel , Guzik Bartlomiej , Weber Christian , Guzik Tomasz J. 
Published: August 2012

SummaryMorbidities related to atherosclerosis, such as acute coronary syndromes (ACS) including unstable angina and myocardial infarction, remain leading causes of mortality. Unstable plaques are inflamed and infiltrated with macrophages and T lymphocytes. Activated dendritic cells interact with T cells, yielding predominantly Th1 responses involving interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), while the role of interleukin 17 (IL-17) is questionable. The expansion of CD28nullCD4 or CD8 T cells as well as pattern recognition receptors activation (especially Toll-like receptors; TLR2 and TLR4) is characteristic for unstable plaque. Inflammation modifies platelet and fibrin clot characteristics, which are critical for ACS. Understanding of the inflammatory mechanisms of atherothrombosis, bridging inflammation, oxidative stress and immune regulation, will allow for the detection of subjects at risk, through the use of novel biomarkers and imaging techniques including intravascular ultrasound, molecular targeting, magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Moreover, understanding the specific inflammatory pathways of plaque rupture and atherothrombosis may allow for immunomodulation of ACS. Statins and anti-platelet drugs are anti-inflammatory, but importance of immune events in ACS warrants the introduction of novel, specific treatments directed either on cytokines, TLRs or inflammasomes. While the prime time for the introduction of immunologically inspired diagnostic tests and treatments for atherosclerosis have not come yet, we are closer than ever before to finally being able to benefit from this vast body of experimental and clinical evidence. This paper provides a comprehensive review of the role of the immune system and inflammation in ACS.Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.
Prosthesis Oversizing in Balloon-Expandable Transcatheter Aortic Valve Implantation Is Associated With Contained Rupture of the Aortic Root
Authors: Blanke Philipp , Reinöhl Jochen , Schlensak Christian , Siepe Matthias , Pache Gregor , Euringer Wulf , Geibel-Zehender Annette , Bode Christopher , Langer Mathias , Beyersdorf Friedhelm , Zehender Manfred 
Published: August 2012

Background—
To retrospectively investigate the potential cause of contained rupture of the aortic root in balloon-expandable transcatheter aortic valve implantation (TAVI) by means of pre- and postinterventional multislice computed tomography.

Methods and Results—

Seventy-two patients (mean age 82±7 years, mean aortic valve area 0.69±0.19 cm
2
) underwent balloon-expandable TAVI using the EdwardsSAPIEN Transcatheter Heart Valve (23 mm, n=19; 26 mm, n=50; 29 mm, n=3). Aortic annulus dimensions were quantified by multislice computed tomography–based cross-sectional area assessment and average diameter calculation (CAAD) before and after TAVI. Post-TAVI multislice computed tomography data sets were available in 65 patients; contained aortic root rupture was diagnosed in 3 patients. Pre-TAVI CAAD was 23.1±1.8 mm; post-TAVI CAAD was 22.9±1.3 mm. Median relative change in CAAD pre- and post-TAVI was −0.5% (interquartile range, 3.6%). Relative increase of 5% to 10% was observed in 4 patients (1 with contained rupture), relative increase >10% in 2 patients, both with contained rupture. Mean relative oversizing, calculated as the relative difference in diameter between pre-TAVI CAAD and nominal diameter of the selected prosthesis, was 9.8%±7.8%. Relative oversizing was significantly higher in patients with contained rupture compared with patients without contained rupture (24.6%±5.4% versus 9.1%±6.6%;
P
<0.001). Relative oversizing ≥20% occurred in 6 patients (3 with contained rupture).

Conclusions—
Contained rupture of the aortic root in balloon-expandable TAVI is associated with severe prosthesis oversizing. Multislice computed tomography–based assessment of aortic annulus dimension in conjunction with adapted sizing guidelines may reduce the incidence of severe oversizing.
Transport Time and Care Processes for Patients Transferred With ST-Segment–Elevation Myocardial Infarction
Authors: Muñoz Daniel , Roettig Mayme L. , Monk Lisa , Al-Khalidi Hussein , Jollis James G. , Granger Christopher B 
Published: August 2012

Background—
For patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention, guidelines have called for device activation within 90 minutes of initial presentation. Fewer than 20% of transferred patients are treated in such a timely fashion. We examine the association between transfer drive times and door-to-device (D2D) times in a network of North Carolina hospitals. We compare the feasibility of timely percutaneous coronary intervention using ground versus air transfer.

Methods and Results—
We perform a retrospective analysis of the relationship between transfer drive times and D2D times in a 119-hospital ST-segment–elevation myocardial infarction statewide network. Between July 2008 and December 2009, 1537 ST-segment–elevation myocardial infarction patients underwent interhospital transfer for reperfusion via primary percutaneous coronary intervention. For ground transfers, median D2D time was 93 minutes for drive times ≤30 minutes, 117 minutes for drive times of 31 to 45 minutes, and 121 minutes for drive times >45 minutes. For air transfers, median D2D time was 125 minutes for drive times of 31 to 45 minutes and 138 minutes for drive times >45 minutes. Helicopter transport was associated with longer door-in door-out times and, ultimately, was associated with median D2D times that exceeded guideline recommendations, no matter the transfer drive time category.

Conclusions—
In a well-developed ST-segment–elevation myocardial infarction system, D2D times within 90 to 120 minutes appear most feasible for hospitals within 30-minute transfer drive time. Helicopter transport did not offer D2D time advantages for transferred STEMI patients. This finding appears to be attributable to comparably longer door-in door-out times for air transfers.