bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERCP cannulation success benchmarking: implications for certification and validation
Authors: Sheppard D P , Craddock S J , Warner B D , Wilkinson M L 
Published: September 2014

ObjectiveInvestigate success rates of cannulating a ‘virgin’ papilla during endoscopic retrograde cholangiopancreatography (ERCP) at a tertiary referral centre; determine reasons for failure and propose learnings for consideration in future revision of success benchmarking.DesignReview of all ERCPs recorded on Endosoft database from 2006 to 2012 (n=1862). Specifically, ‘virgin’ papillae, defined as those with no evidence of prior surgical intervention, stentsin situor sphincterotomy (n=947). Virgin papillae present the most challenging target for endoscopists.SettingGastroenterology department, St Thomas’ Hospital, London.PatientsAll patients who underwent an ERCP recorded on Endosoft from 2006 to 2012 (n=1134). A proportion of these patients underwent repeat procedures, all considered virgin provided the aforementioned criteria were met.InterventionsNone, retrospective audit and benchmarking exercise.Main outcome measuresDetermine criteria for successful cannulation of a virgin papilla.ResultsOverall success of cannulation of a virgin papilla at ERCP was 79.5%, 753 out of a total of 947 virgin papillae cases. Per patient with a virgin papilla, the success rate was 79.7%, 693 out of 869. Eliminating cases with features complicating cannulation increased success rates to 86% and 87%, respectively. Chronic pancreatitis was the single Indication associated with a failed cannulation (OR=3.9, CI 2.1 to 7.1), while biliary stones were significantly associated with a successful cannulation (OR=0.3, CI 0.2 to 0.4). Reasons for failure included patient agitation (OR=27.1, CI 7.9 to 92.7), duodenal stricturing (OR=12.5, CI 5.5 to 28.5), previous anatomy-changing surgery (OR=12.2, CI 3.3 to 45.4), tumour impingement (OR=9.5, CI 4.1 to 22.3) and equipment failure (OR=7.9, CI 1.4=43.5).ConclusionsThe Joint Advisory Group’s 80% success rate for completion of therapeutic intent must be viewed in light of published difficulty rating scales, if fair comparisons and standards are to be met. This highlights the need for standardised success criterion for ERCP training and accreditation.
A decision tree model for the implementation of a safety strategy in the horse-racing industry
Authors: Hitchens Peta L , Curry Beverley , Blizzard C Leigh , Palmer Andrew J 
Published: September 2014

ObjectivesThe profession of a horse-racing jockey is a dangerous one. We developed a decision tree model quantifying the effects of implementing different safety strategies on jockey fall and injury rates and their associated costs.MethodsData on race-day falls were obtained from stewards’ reports from August 2002 to July 2009. Insurance claim data were provided by Principal Racing Authorities and workers’ compensation authorities in each jurisdiction. Fall and claim incidence data were used as baseline rates. The model considered (1) the status quo, in which policy was unchanged; and (2) compared it with four hypothetical changes in policy that restricted apprentice jockeys from riding less-accomplished horses, with the aim of improving safety by reducing incidence of injurious jockey falls. Second-order Monte Carlo simulations were conducted to account for uncertainties.ResultsThe point estimate for mean costs of falls under the status quo was $30.73/ride, with falls by apprentice jockeys with <250 career race rides riding horses with less than five race starts contributing the highest costs ($98.49/ride). The hypothetical safety strategies resulted in a 1.04%–5.07% decrease in fall rates versus status quo. For three of the four strategies, significant reductions of 8.74%–13.13% in workers’ compensation costs over one single race season were predicted. Costs were highly sensitive to large claims.ConclusionsThis model is a useful instrument for comparing potential changes in cost and risks associated with implementing new safety strategies in the horseracing industry.
Non-fatal work-related traumatic brain injuries treated in US hospital emergency departments, 1998–2007
Authors: Konda Srinivas , Reichard Audrey , Tiesman Hope M , Hendricks Scott 
Published: September 2014

PurposeLittle is known about work-related traumatic brain injuries (WRTBI). This study describes non-fatal WRTBIs treated in US emergency departments (ED) from 1998 through 2007.MethodsNon-fatal WRTBIs were identified from the National Electronic Injury Surveillance System occupational supplement (NEISS-Work) using the diagnoses of concussion, internal organ injury to the head and skull fracture. WRTBI rates and rate ratios were calculated, and the trend in rates was assessed.ResultsAn estimated 586 600 (95% CI=±150 000) WRTBIs were reported during the 10-year period at a rate of 4.3 (CI=±1.1) per 10 000 full-time equivalent (FTE) workers (1 FTE=2000 h per year). From 1998 through 2007, the rate of WRTBIs increased at an average of 0.21 per 10 000 FTE per year (p<0.0001) and the rate of fall-related WRTBIs increased at an average of 0.10 per 10 000 FTE (p<0.0001). During the same period, the annual rate of WRTBIs resulting in hospitalisation increased 0.04 per 10 000 FTE (p<0.0001). Ten percent of WRTBIs were hospitalised, compared with hospitalisation of 2% all NEISS-Work injuries. Also, workers with highest fall-related TBI rates per 10 000 FTE were the youngest (2.4; CI=±1.4) and oldest (55 and older) workers (1.9; CI=±0.8).ConclusionsNon-fatal WRTBIs are one of the most serious workplace injuries among ED-treated work-related injuries. Non-fatal WRTBIs are much more likely to result in hospitalisation compared with other types of injuries. The upward trend of WRTBI rates from 1998 through 2007 underscore the need for more directed effective prevention methods to reduce WRTBI injuries.
Assessment of suitability of the one step nucleic acid amplification (OSNA) assay as an intraoperative procedure for detection of metastasis in sentinel lymph nodes of breast cancer
Authors: Jara-Lazaro Ana Richelia , Hussain Ilyana Huda Mohamed , Thike Aye Aye , Wong Chow Yin , Ho Gay Hui , Yong Wei Sean , Ong Kong Wee , Madhukumar Preetha , Tan Benita Kiat Tee , Oey Chung Lie , Hwang Jacqueline Siok Gek , Tan Puay Hoon 
Published: September 2014

AimWe aimed to assess the one step nucleic acid amplification (OSNA) assay as an intraoperative method in comparison with frozen sections (FS) for detection of metastasis in sentinel lymph nodes (SLNs) of breast cancer.Method100 SLNs from patients with breast carcinoma were enrolled within a 3-month period. Alternate 2 mm node slices were subjected to routine FS, and later to permanent histology, and the rest for automated molecular detection of CK19 mRNA using OSNA. FS and OSNA findings were compared with permanent histology results. Difference in turnaround time was also noted.ResultsWith permanent histology as gold standard, OSNA was discrepant in 8 of 98 (3 false negative, 5 false positive) included SLNs whereas FS had 2 false negative cases. FS had higher sensitivity (89%, p=<0.001), specificity (100%, p=0.001) and concordance rate (98%) than OSNA (83%, 94% and 92%, respectively). FS showed almost perfect agreement (κ=0.929) whereas OSNA showed substantial agreement (κ=0.740) when compared with permanent histology. OSNA turnaround time was twice longer (mean of 47.7 min) than FS.ConclusionsAutomation of SLN assessment using OSNA is a potentially useful intraoperative diagnostic tool with acceptable accuracy. Discordant findings in this study may be due to sampling allocation. Since OSNA is more time-consuming, its practical advantage over routine FS requires further study in view of current technical workflow considerations.
Comparison of genomic abnormality in malignant mesothelioma by the site of origin
Authors: Takeda Maiko , Kasai Takahiko , Enomoto Yasunori , Takano Masato , Morita Kohei , Nakai Tokiko , Iizuka Norishige , Maruyama Hiroshi , Ohbayashi Chiho 
Published: September 2014

AimsMalignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes are losses in 9p21, 1p36, 22q12 and 14q32, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. We have examined various genomic losses and gains in MM and benign mesothelial proliferation by fluorescence in situ hybridisation (FISH) analysis. 9p21 deletion was reported to be less frequent in peritoneal than in pleural MMs. This study analysed various genomic losses and gains in MM by the site of origin using FISH analysis.Materials and methodsWe performed FISH analysis using paraffin-embedded tissues from 54 cases (40 pleural and 14 peritoneal) of MMs and compared the frequency of genomic abnormality by the site of origin.Results9p21 deletion was shown in 34 of 40 cases (85%) of pleural MMs, and was less frequent in five of 14 cases (36%) of peritoneal MMs (p<0.001) by FISH analysis. By contrast, 5p15 and 7p12 amplification was more significantly frequent in peritoneal than in pleural MMs. No difference between the two sites of MM in other genes was found.Conclusions9p21 homozygous deletion assessed by FISH has been reported to be useful for differentiating MM from reactive mesothelial proliferation, but it should be noted that 9p21 deletion was less frequent in peritoneal MM. Our study suggests that the pathway of the genetic abnormality might vary between pleural and peritoneal MM.
Explaining the excess mortality in Scotland compared with England: pooling of 18 cohort studies
Authors: McCartney Gerry , Russ Tom C , Walsh David , Lewsey Jim , Smith Michael , Davey Smith George , Stamatakis Emmanuel , Batty G David 
Published: September 2014

BackgroundMortality in Scotland is higher than in the rest of west and central Europe and is improving more slowly. Relative to England and Wales, the excess is only partially explained by area deprivation. We tested the extent to which sociodemographic, behavioural, anthropometric and biological factors explain the higher mortality in Scotland compared with England.MethodsPooled data from 18 nationally representative cohort studies comprising the Health Surveys for England (HSE) and the Scottish Health Survey (SHS). Cox regression analysis was used to quantify the excess mortality risk in Scotland relative to England with adjustment for baseline characteristics.ResultsA total of 193 873 participants with a mean of 9.6 years follow-up gave rise to 21 345 deaths. The age-adjusted and sex-adjusted all-cause mortality HR for Scottish respondents compared with English respondents was 1.40 (95% CI 1.34 to 1.47), which attenuated to 1.29 (95% CI 1.23 to 1.36) with the addition of the baseline socioeconomic and behavioural characteristics. Cause-specific mortality HRs attenuated only marginally to 1.43 (95% 1.28 to 1.60) for ischaemic heart disease, 1.37 (95% CI 1.15 to 1.63) for stroke, 1.41 (95% CI 1.30 to 1.53) for all cancers, 3.43 (95% CI 1.85 to 6.36) for illicit drug-related poisoning and 4.64 (95% CI 3.55 to 6.05) for alcohol-related mortality. The excess was greatest among young adults (16–44 years) and was observed across all occupational social classes with the greatest excess in the unskilled group.ConclusionsOnly a quarter of the excess mortality among Scottish respondents could be explained by the available baseline risk factors. Greater understanding is required on the lived experience of poverty, the role of social support, and the historical, environmental, cultural and political influences on health in Scotland.
Predicting the risk of physical disability in old age using modifiable mid-life risk factors
Authors: Wong Evelyn , Stevenson Christopher , Backholer Kathryn , Woodward Mark , Shaw Jonathan E , Peeters Anna 
Published: September 2014

BackgroundWe aimed to investigate the relationship between potentially modifiable risk factors in middle age and disability after 13 years using the Framingham Offspring Study (FOS). We further aimed to develop a disability risk algorithm to estimate the risk of future disability for those aged 45–65 years.MethodsFOS is a longitudinal study. We used examination 5 (1991–1995; ‘baseline’) and examination 8 (2005–2008; ‘follow-up’). We included participants aged between 45–65 years at ‘baseline’ with complete predictor and outcome measures (n=2031; mean age 53.9 years). Predictors considered were body mass index, smoking, hypertension, diabetes and dyslipidaemia. We used multinomial logistic regression to identify predictors of disability or death.We assessed external validity using Australian data.ResultsBy examination 8, 156 participants had disability and 198 had died. Disability was associated with smoking (OR (95% CI) 1.81 (1.18 to 2.78)); obesity (2.95 (1.83 to 4.77)); diabetes 1.96 (1.11 to 3.45) and being female (OR 1.67 (1.13 to 2.45). The model performed moderately well in predicting disability and death in an Australian population. Based on our algorithm, a 45-year-old man/woman with the combined risk factors of obesity, diabetes and smoking has similar likelihood of surviving free of disability to a 65-year-old man/woman without any of the same risk factors.Conclusions and relevanceThe derived risk algorithm allows, for the first time, quantification of the substantial combined impact on future disability of key modifiable risk factors in mid-life. Here we demonstrated the combined impact of obesity, diabetes and smoking to be similar to 20 years of aging.
MicroRNA100 Inhibits Self-Renewal of Breast Cancer Stem–like Cells and Breast Tumor Development
Authors: Deng Lu , Shang Li , Bai Shoumin , Chen Ji , He Xueyan , Martin-Trevino Rachel , Chen Shanshan , Li Xiao-yan , Meng Xiaojie , Yu Bin , Wang Xiaolin , Liu Yajing , McDermott Sean P. , Ariazi Alexa E. , Ginestier Christophe , Ibarra Ingrid , Ke Jia , Luther Tahra , Clouthier Shawn G. , Xu Liang , Shan Ge , Song Erwei , Yao Herui , Hannon Gregory J. , Weiss Stephen J. , Wicha Max S. , Liu Suling 
Published: September 2014

AbstractmiRNAs are essential for self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here, we report evidence implicating the miR100 in self-renewal of cancer stem–like cells (CSC). We found that miR100 expression levels relate to the cellular differentiation state, with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline-inducible lentivirus to elevate expression of miR100 in human cells, we found that increasing miR100 levels decreased the production of breast CSCs. This effect was correlated with an inhibition of cancer cell proliferation in vitro and in mouse tumor xenografts due to attenuated expression of the CSC regulatory genes SMARCA5, SMARCD1, and BMPR2. Furthermore, miR100 induction in breast CSCs immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR100 expression in breast cancer specimens and patient survival. Our results suggest that miR100 is required to direct CSC self-renewal and differentiation. Cancer Res; 74(22); 6648–60. ©2014 AACR.
Distinct Subpopulations of Head and Neck Cancer Cells with Different Levels of Intracellular Reactive Oxygen Species Exhibit Diverse Stemness, Proliferation, and Chemosensitivity
Authors: Chang Ching-Wen , Chen Yu-Syuan , Chou Shiu-Huey , Han Chia-Li , Chen Yu-Ju , Yang Cheng-Chieh , Huang Chih-Yang , Lo Jeng-Fan 
Published: September 2014

AbstractHead and neck squamous cell carcinoma (HNSCC) is driven by cancer-initiating cells (CIC), but their maintenance mechanisms are obscure. For hematopoietic stem cells, low levels of intracellular reactive oxygen species (ROSLow) is known to help sustain stemness properties. In this report, we evaluated the hypothesis that ROSLow character conferred CIC properties in HNSCC. Sphere cultures define CIC in HNSCC cell populations (HN-CIC). We found that ROSLow cells in HN-CIC defined in this manner were more numerous than in parental HNSCC cells. Further, ROSLow cells frequently coexpressed CIC surface markers such as memGrp78 and Glut3. Exploiting flow cytometry to sort cells on the basis of their ROS level, we found that isolated ROSLow cells displayed relatively more CIC properties, including quiescence, chemoresistance, in vitro malignant properties, and tumorigenicity. Pharmacological depletion of ROS modulators in cisplatin-treated HN-CIC reduced CIC properties, enhancing cell differentiation and enhancing cisplatin-induced cell death. Overall, our work defined cell subpopulations in HNSCC on the basis of differential intracellular ROS levels, which associated with stemness and chemoresistance properties. On the basis of our findings, we suggest that strategies to promote intracellular ROS levels may heighten the efficacy of conventional chemotherapy used for HNSCC treatment. Cancer Res; 74(21); 6291–305. ©2014 AACR.
Microenvironment-Derived HGF Overcomes Genetically Determined Sensitivity to Anti-MET Drugs
Authors: Pennacchietti Selma , Cazzanti Manuela , Bertotti Andrea , Rideout William M. , Han May , Gyuris Jeno , Perera Timothy , Comoglio Paolo M. , Trusolino Livio , Michieli Paolo 
Published: September 2014

Abstract
Cell-based drug screenings indicate that tumors displaying c-MET gene amplification are “addicted” to MET signaling and therefore are very sensitive to MET-targeted agents. However, these screenings were conducted in the absence of the MET ligand, hepatocyte growth factor (HGF), which is abundant in the tumor microenvironment. Sensitivity of six MET-addicted human tumor cells to three MET kinase inhibitors (JNJ-38877605, PHA-665752, crizotinib) and one antagonistic anti-MET antibody (DN30 Fab) was analyzed in the absence or presence of HGF, in a stroma–tumor coculture system, and by combining anti-MET drugs with an HGF neutralizing antibody (ficlatuzumab) in human HGF knock-in mice bearing c-MET–amplified tumors. In all models examined, HGF promoted resistance to MET-targeted agents, affecting both their potency and efficacy. HGF-induced resistance was due to restoration of physiologic GAB1–mediated PI3K activation that compensated for loss of aberrant HER3-dependent PI3K signaling. Ficlatuzumab restored sensitivity to MET-targeted agents in coculture systems and overcame resistance to JNJ-38877605, crizotinib, and DN30 Fab in human HGF knock-in mice. These data suggest that c-MET–amplified tumor cells—which normally exhibit ligand-independent, constitutive MET activation—become dependent on HGF for survival upon pharmacologic MET inhibition. Because HGF is frequently overexpressed in human cancer, this mechanism may represent a major cause of resistance to anti-MET therapies. The ability of ficlatuzumab to overcome HGF-mediated resistance generates proof of principle that vertical inhibition of both a tyrosine kinase receptor and its ligand can be therapeutically beneficial and opens new perspectives for the treatment of MET-dependent tumors. Cancer Res; 74(22); 6598–609. ©2014 AACR.
The Notch Pathway Inhibits TGFβ Signaling in Breast Cancer through HEYL-Mediated Crosstalk
Authors: Han Liangfeng , Diehl Adam , Nguyen Nguyen K. , Korangath Preethi , Teo Weiwen , Cho Soonweng , Kominsky Scott , Huso David L. , Feigenbaum Lionel , Rein Alan , Argani Pedram , Landberg Goran , Gessler Manfred , Sukumar Saraswati 
Published: September 2014

Abstract
Acquired resistance to TGFβ is a key step in the early stages of tumorigenesis. Mutations in TGFβ signaling components are rare, and little is known about the development of resistance in breast cancer. On the other hand, an activated Notch pathway is known to play a substantial role in promoting breast cancer development. Here, we present evidence of crosstalk between these two pathways through HEYL. HEYL, a basic helix–loop–helix transcription factor and a direct target of Notch signaling, is specifically overexpressed in breast cancer. HEYL represses TGFβ activity by binding to TGFβ-activated Smads. HeyL−/− mice have defective mammary gland development with fewer terminal end buds. On the other hand, HeyL transgenic mice show accelerated mammary gland epithelial proliferation and 24% of multiparous mice develop mammary gland cancer. Therefore, repression of TGFβ signaling by Notch acting through HEYL may promote initiation of breast cancer. Cancer Res; 74(22); 6509–18. ©2014 AACR.
Modeling Lung Cancer Evolution and Preclinical Response by Orthotopic Mouse Allografts
Authors: Ambrogio Chiara , Carmona Francisco J. , Vidal August , Falcone Mattia , Nieto Patricia , Romero Octavio A. , Puertas Sara , Vizoso Miguel , Nadal Ernest , Poggio Teresa , Sánchez-Céspedes Montserrat , Esteller Manel , Mulero Francisca , Voena Claudia , Chiarle Roberto , Barbacid Mariano , Santamaría David , Villanueva Alberto 
Published: September 2014

Abstract
Cancer evolution is a process that is still poorly understood because of the lack of versatile in vivo longitudinal studies. By generating murine non–small cell lung cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations, and the appearance of naturally occurring intratumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the preclinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for patients with NSCLC. Cancer Res; 74(21); 5978–88. ©2014 AACR.
Targeted Noninvasive Imaging of EGFR-Expressing Orthotopic Pancreatic Cancer Using Multispectral Optoacoustic Tomography
Authors: Hudson Shanice V. , Huang Justin S. , Yin Wenyuan , Albeituni Sabrin , Rush Jamie , Khanal Anil , Yan Jun , Ceresa Brian P. , Frieboes Hermann B. , McNally Lacey R. 
Published: September 2014

Abstract
Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe before MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a nonspecific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at 6 hours postinjection, demonstrating specific intratumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of the EGF receptor. Cancer Res; 74(21); 6271–9. ©2014 AACR.