bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin B12status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: results from two National Diet and Nutrition Surveys
Authors: Sukumar Nithya , Adaikalakoteswari Antonysunil , Venkataraman Hema , Maheswaran Hendramoorthy , Saravanan Ponnusamy 
Published: August 2016

ObjectiveTo assess serum B12, folate and the associated homocysteine (Hcy) levels among women of childbearing age in the UK and examine their association with dietary intake in relation to the UK Recommended Nutrient Intakes (RNIs) for B12and folate.DesignCross-sectional study.SettingData from two publicly available National Diet and Nutrition Surveys (NDNS 2000/2001 and 2008/2012) were used. These were population-based surveys of randomly selected samples of adults which were carried out in their households.ParticipantsWomen of childbearing age (aged 19–39 years), representative of the UK population. Those who were pregnant or breastfeeding were excluded.Outcome measuresThe associations between micronutrient intakes and blood levels of B12, folate and Hcy were assessed by correlation and stepwise linear regression. B12intake was divided into quintiles and plotted against blood B12and Hcy concentrations to determine the threshold of any associations.Results299 women from the first NDNS cohort had complete intake and biomarker data. The prevalence of serum vitamin B12(≤150 pmol/L) and serum folate (≤10 nmol/L) deficiency and hyperhomocysteinemia (≥12 µmol/L) was 12.4%, 6.4% and 21.2%, respectively, despite seemingly adequate B12intakes (median 3.8 μg/day, 96% consumed more than the UK RNI of 1.5 μg/day). B12concentrations increased across all quintiles of intake with serum levels in quintiles 4 and 5 (median intake 4.9 and 7.1 μg/day, respectively) significantly higher than quintile 1. However, Hcy concentrations levelled off between quintiles 4 and 5. Comparison of micronutrient intake between the two surveys found that folate intake has reduced in the more recent cohort.ConclusionsThe UK RNI for B12intake should be increased for women of childbearing age with intakes of around 5–7 μg/day likely to be associated with stable biomarker levels. B12levels should also be measured in women preconceptionally or in early pregnancy given the high rates of deficiency.
HALON—hysterectomy by transabdominal laparoscopy or natural orifice transluminal endoscopic surgery: a randomised controlled trial (study protocol)
Authors: Baekelandt Jan , De Mulder Peter A , Le Roy Ilse , Mathieu Chantal , Laenen Annouschka , Enzlin Paul , Weyers Steven , Mol Ben WJ , Bosteels Jan JA 
Published: August 2016

IntroductionNatural orifice transluminal endoscopic surgery (NOTES) uses natural body orifices to access the cavities of the human body to perform surgery. NOTES limits the magnitude of surgical trauma and has the potential to reduce postoperative pain. This is the first randomised study in women bound to undergo hysterectomy for benign gynaecological disease comparing NOTES with classical laparoscopy.Methods and analysisAll women aged 18–70 years, regardless of parity, consulting at our practice with an indication for hysterectomy due to benign gynaecological disease will be eligible. After stratification according to uterine size on clinical examination, participants will be randomised to be treated by laparoscopy or by transvaginal NOTES. Participants will be evaluated on day 0, days 1–7 and at 3 and 6 months. The following data will be collected: the proportion of women successfully treated by removing the uterus by the intended approach as randomised; the proportion of women admitted to the inpatient hospital; postoperative pain scores measured twice daily by the women from day 1 to 7; the total amount of analgesics used from day 1 to 7; readmission during the first 6 weeks; presence and intensity of dyspareunia and sexual well-being at baseline, 3 and 6 months (Short Sexual Functioning Scale (SSFS) scale); duration of surgery; postoperative infection or other surgical complications; direct and indirect costs incurred up to 6 weeks following surgery. The primary outcome will be the proportion of women successfully treated by the intended technique; all other outcomes are secondary.Ethics and disseminationThe study was approved on 1 December 2015 by the Ethics Committee of the Imelda Hospital, Bonheiden, Belgium. The first patient was randomised on 17 December 2015. The last participant randomised should be treated before 30 November 2017. The results will be presented in peer-reviewed journals and at scientific meetings within 4 years after starting recruitment.Trial registration numberNCT02631837; Pre-results.
False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review
Authors: Imberger Georgina , Thorlund Kristian , Gluud Christian , Wetterslev Jørn 
Published: August 2016

ObjectiveMany published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered meta-analyses.MethodsWe screened The Cochrane Database of Systematic Reviews and selected 100 meta-analyses with a binary outcome, a negative result and sufficient power. We defined a negative result as one where the 95% CI for the effect included 1.00, a positive result as one where the 95% CI did not include 1.00, and sufficient power as the required information size for 80% power, 5% type 1 error, relative risk reduction of 10% or number needed to treat of 100, and control event proportion and heterogeneity taken from the included studies. We re-conducted the meta-analyses, using conventional cumulative techniques, to measure how many false positives would have occurred if these meta-analyses had been updated after each new trial. For each false positive, we performed TSA, using three different approaches.ResultsWe screened 4736 systematic reviews to find 100 meta-analyses that fulfilled our inclusion criteria. Using conventional cumulative meta-analysis, false positives were present in seven of the meta-analyses (7%, 95% CI 3% to 14%), occurring more than once in three. The total number of false positives was 14 and TSA prevented 13 of these (93%, 95% CI 68% to 98%). In a post hoc analysis, we found that Cochrane meta-analyses that are negative are 1.67 times more likely to be updated (95% CI 0.92 to 2.68) than those that are positive.ConclusionsWe found false positives in 7% (95% CI 3% to 14%) of the included meta-analyses. Owing to limitations of external validity and to the decreased likelihood of updating positive meta-analyses, the true proportion of false positives in meta-analysis is probably higher. TSA prevented 93% of the false positives (95% CI 68% to 98%).
General practitioners’ experiences with out-of-hours cardiorespiratory consultations: a qualitative study
Authors: Schols Angel M R , van Boekholt Tessa A , Oversier Lex M R , Dinant Geert-Jan , Cals Jochen W L 
Published: August 2016

ObjectivesTo explore general practitioners’ (GPs’) experiences with and views on the diagnosis and management of patients with cardiorespiratory symptoms during GP out-of-hours care. We also aimed to identify ways of (diagnostic) support during these consultations.DesignQualitative study; face-to-face semistructured interviews.SettingGP out-of-hours care in the Netherlands.Participants15 GPs in the province of Limburg, the Netherlands.ResultsOverall, GPs find cardiorespiratory consultations challenging and difficult. Tension and uncertainty as well as defensive behaviour were the key themes that characterised GPs’ experiences. We identified several subthemes underlying the key themes: setting, potentially severe consequences, absence of a pre-existing relationship and little knowledge of the patient's background, difficulties differentiating between possible causes of symptoms, changed public opinion and patient population, and previous experiences. GPs approach cardiorespiratory consultations differently and their threshold for referring patients and performing diagnostic tests is lower. We identified differing views on the use of additional diagnostic tests at GP out-of-hours services.ConclusionsThis study sheds further light on how GPs experience cardiorespiratory consultations during out-of-hours care and how this leads to a high number of cardiorespiratory referrals. GPs relate cardiorespiratory consultation during out-of-hours care with tension and uncertainty leading to defensive behaviour, which can be translated into a different approach towards cardiorespiratory consultations and a lower threshold for referring patients and performing diagnostic tests. Opinions on the possible added value of additional diagnostics in reducing the number of referrals should be further investigated, as we identified differing views on the use of additional diagnostic tests at GP out-of-hours services.
Surface CO
2
emission and rising bubble plumes from degassing of crater lakes in São Miguel Island, Azores
Authors: Melián Gladys , Somoza Luís , Padrón Eleazar , Pérez Nemesio M. , Hernández Pedro A. , Sumino Hirochika , Forjaz Victor H. , França Zilda 
Published: August 2016

Abstract

We report the first detailed study on the types and distributions of active subaqueous fumaroles and surface diffuse CO
2
degassing in the three main volcanic lakes of São Miguel Island (Sete Cidades, Fogo and Furnas), Azores archipelago, Portugal. The results of the surveys, carried out in May 2011 using a floating accumulation chamber and a dual beam 50 and 200 kHz echo sounder, revealed a very low surface CO
2
degassing at the three lakes, in the range of 32–608 kg d
−1
. However, dense subaqueous degassing plumes were found in the north of the Furnas crater lake (7.5–9 plumes per 100 m
2
), and moderate-density degassing in the Fogo (1.5–2 plumes per 100 m
2
) and Sete Cidades crater lakes (1–1.5 plumes per 100 m
2
). The echo sounder detected hydroacoustic signatures interpreted as acoustic flares, ‘puffing’ bubble plumes or walls of bubbles associated with numerous subaqueous fumaroles. The recorded echograms show that the bubbles rise at average speeds of between 19 and 30 cm s
−1
at the bottom, with frequencies of release from 1–2 to 31 s. Most subaqueous fumaroles disappear due to the dissolution of CO
2
before reaching the lake surface. These dissolution processes are enhanced by the pH range observed in the three volcanic lakes (
c.
7–9). Observed dissolved CO
2
values indicate that the pressure of this gas in the three lakes remained much lower than the hydrostatic pressure and the risk of a limnic eruption is therefore negligible. We suggest that the rising levels of CO
2
from the subaqueous bubbles could constitute a critical fuel for subsurface phytoplankton layers, interpreted as horizontal acoustic layers with high backscattering values. The highest density of subaqueous bubbling correlates with recent submerged secondary craters formed around the caldera rims of the three Late Quaternary stratovolcano complexes of São Miguel Island. Our results emphasize the need to perform regular surface degassing studies as an important volcanic surveillance tool in the Azores archipelago.
The petroleum geology of the West Africa margin: an introduction
Authors: Sabato Ceraldi Teresa , Hodgkinson Richard , Backé Guillaume 
Published: August 2016

Abstract
The continental margin of West Africa formed as result of the south-to-north rifting of Gondwana and the progressive separation of the South American and African continents. This margin has enjoyed a rich and varied exploration history and, in the 70 years or so since the first significant exploration began in the onshore area, the margin has emerged as a significant hydrocarbon-producing region. The amalgamation of hydrocarbon exploration approaches and imaginative ideas, leveraged with modern technologies, is yielding significant scientific and economic successes.

The main objective of this Special Publication is to provide an overview of the advances in our understanding of the crustal structure, tectonic evolution and Mesozoic to Cenozoic stratigraphy of the West Africa margin both onshore and offshore, with a particular focus on the petroleum geology. The papers contained in this Special Publication represent a selection from the 37 abstracts presented at the original conference in March 2014, which covered the entirety of the margin from South Africa to Morocco as well as stratigraphy from the crystalline basement to the most recent strata. The original abstracts from the conference are available through the Geological Society of London website at:
http://www.geolsoc.org.uk/pgresources
RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells
Authors: Di Cecilia Serena , Zhang Fan , Sancho Ana , Li SiDe , Aguiló Francesca , Sun Yifei , Rengasamy Madhumitha , Zhang Weijia , Del Vecchio Luigi , Salvatore Francesco , Walsh Martin J. 
Published: August 2016

Abstract
Cancer-initiating cells (CIC) undergo asymmetric growth patterns that increase phenotypic diversity and drive selection for chemotherapeutic resistance and tumor relapse. WNT signaling is a hallmark of colon CIC, often caused by APC mutations, which enable activation of β-catenin and MYC. Accumulating evidence indicates that long noncoding RNAs (lncRNA) contribute to the stem-like character of colon cancer cells. In this study, we report enrichment of the lncRNA RBM5-AS1/LUST during sphere formation of colon CIC. Its silencing impaired WNT signaling, whereas its overexpression enforced WNT signaling, cell growth, and survival in serum-free media. RBM5-AS1 has been little characterized previously, and we determined it to be a nuclear-retained transcript that selectively interacted with β-catenin. Mechanistic investigations showed that silencing or overexpression of RBM5-AS1 caused a respective loss or retention of β-catenin from TCF4 complexes bound to the WNT target genes SGK1, YAP1, and MYC. Our work suggests that RBM5-AS1 activity is critical for the functional enablement of colon cancer stem-like cells. Furthermore, it defines the mechanism of action of RBM5-AS1 in the WNT pathway via physical interactions with β-catenin, helping organize transcriptional complexes that sustain colon CIC function. Cancer Res; 76(19); 5615–27. ©2016 AACR.
Extracellular Matrix Invasion in Metastases and Angiogenesis: Commentary on the Matrigel “Chemoinvasion Assay”
Authors: Albini Adriana 
Published: August 2016

Abstract
Invasive and metastatic cells must cross the basement membrane's extracellular matrix to disseminate to distant sites. Although in the eighties the concept was well established, no easy in vitro functional assay was available. Working in Hynda Kleinman's and George Martin's laboratory at NIH (Bethesda, MD), where the reconstituted basement membrane Matrigel was discovered, I had the intuition that Matrigel coating of migration filters could represent a valid tool to mimic in vitro biological matrix barriers. The “chemoinvasion assay” using Matrigel in Boyden blind-well chambers was developed in 1985–1986 and published in Cancer Research in 1987. It was a rapid and easy tool for studying invasion, a crucial step in cancer metastasis. Since its conception, the assay has been employed for studies on the metastatic process, angiogenesis, and for the screening of drugs that are potentially able to decrease cell invasion. It was adapted to be easily employed as a routine assay and commercialized. In that historical article, we also described the use of thick layers of Matrigel for the study of morphogenesis of invasive cells, a simple and visual assay, adaptable to reproduce collective cell migration in vitro. To date, in its diverse optimized variants, the chemoinvasion assay is still widely used, contributing to novel data production. In the era of precision medicine and next-generation sequencing, the cheap, fast, and reproducible chemoinvasion assay may have further developments, including possible applications in the investigations on cancer stem cells, immunity and immune modulators, applications with siRNA silencing, selection of aggressive cell populations, and phenotypes and genetic evaluations. Cancer Res; 76(16); 4595–7. ©2016 AACR.
See related article by Albini A et al., Cancer Res 1987;47:3239–45.
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Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma
Authors: Reinartz Roman , Wang Shanshan , Kebir Sied , Silver Daniel J. , Wieland Anja , Zheng Tong , Küpper Marius , Rauschenbach Laurèl , Fimmers Rolf , Shepherd Timothy M. , Trageser Daniel , Till Andreas , Schäfer Niklas , Glas Martin , Hillmer Axel M. , Cichon Sven , Smith Amy A. , Pietsch Torsten , Liu Ying , Reynolds Brent A. , Yachnis Anthony , Pincus David W. , Simon Matthias , Brüstle Oliver , Steindler Dennis A. , Scheffler Björn 
Published: August 2016

AbstractPurpose: Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors.Experimental Design: Here, we used 33 single cell–derived subclones generated from five clinical glioblastoma specimens for exploring intra- and interindividual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacologic sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors.Results: Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential antiglioblastoma compounds. A more comprehensive intratumoral analysis revealed that stable genetic and phenotypic characteristics of coexisting subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacologic profiles could be shown for establishing rational strategies for individualized secondary lines of treatment.Conclusions: Our data provide a previously unrecognized strategy for revealing functional consequences of intratumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. Clin Cancer Res; 23(2); 562–74. ©2016 AACR.
Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival
Authors: Bandera Elisa V. , Lee Valerie S. , Rodriguez-Rodriguez Lorna , Powell C. Bethan , Kushi Lawrence H. 
Published: August 2016

Abstract
Purpose: Among patients with ovarian cancer, African American (AA) women experience poorer survival compared with other race/ethnicity groups. This has been attributed to differences in access to health care.
Experimental Design: We evaluated racial/ethnic differences in chemotherapy dosing and survival in a cohort study among members of Kaiser Permanente Northern California, and thus with equivalent access to health care. Analyses included epithelial-invasive ovarian cancer cases (n = 793) receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent, with median follow-up of 50 months. Relative dose intensity (RDI) was computed for carboplatin and paclitaxel separately as dose administered per week divided by expected dose per week, and average RDI (ARDI) was then calculated for the regimen. Proportional hazards regression was used to calculate HRs and 95% confidence intervals (CIs) after adjusting for relevant covariates.
Results: Compared with whites, AAs were more likely to have dose reduction (ARDI &lt; 85%), treatment delay, and early discontinuation. Hispanics were also more likely to have dose reduction, but less likely to have early discontinuation or treatment delay. After controlling for prognostic factors including ARDI, AA women had the worst survival. Compared with whites, adjusted HRs (95% CI) for overall mortality were 1.56 (1.01–2.39) for AAs; 0.89 (0.61–1.31) for Asians; and 1.41 (0.98–2.04) for Hispanics. Findings for ovarian cancer–specific mortality were similar.
Conclusions: Disparities in ovarian cancer treatment and survival in AA persisted among women with equal access to care. These findings warrant further evaluation of biological, personal, and social factors that may be responsible for these differences. Clin Cancer Res; 22(23); 5909–14. ©2016 AACR.
Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle–Invasive Bladder Cancer Patients
Authors: Derré Laurent , Cesson Valérie , Lucca Ilaria , Cerantola Yannick , Valerio Massimo , Fritschi Urs , Vlamopoulos Yannis , Burruni Rodolfo , Legris Anne-Sophie , Dartiguenave Florence , Gharbi Dalila , Martin Virginie , Vaucher Laurent , Speiser Daniel E. , Romero Pedro , Jichlinski Patrice , Nardelli-Haefliger Denise 
Published: August 2016

AbstractPurpose: Treatments with cancer vaccines may be delivered as combination therapies for better efficacy. Addition of intravesical immunostimulation with bacteria promotes vaccine-specific T cells in the bladder and tumor-regression in murine bladder cancer models. Here, we determined whether an adjuvanted cancer vaccine can be safely administered with concomitant standard intravesical Bacillus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle–invasive bladder cancer (NMIBC).Experimental Design: In a nonrandomized phase I open-label exploratory study, 24 NMIBC patients, apportioned in three groups, received 5 injections of a subunit cancer vaccine (recMAGE-A3 protein+AS15) alone or in two combinations of intravesical BCG-instillations. Safety profiles were compared between the three treatment groups, considering single vaccine injections or BCG instillations and concomitant interventions. Immune responses in blood and urine were compared between treatment groups and upon BCG instillations.Results: The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AEs were not increased by the double interventions, suggesting that BCG did not exacerbate the AE caused by the MAGE-A3 vaccine and vice-versa. All patients seroconverted after MAGE-A3 vaccination. In half of the patients, vaccine-specific T cells were induced in blood, irrespective of BCG treatment. Interestingly, such T cells were only detected in urine upon BCG-induced T-cell infiltration.Conclusions: Cancer vaccines, including strong adjuvants, can be safely combined with intravesical BCG therapy. The increase of vaccine-specific T cells in the bladder upon BCG provides proof-of-principle evidence that cancer vaccines with local immunostimulation may be beneficial. Clin Cancer Res; 23(3); 717–25. ©2016 AACR.
Immunotherapy Gone Viral: Bortezomib and oHSV Enhance Antitumor NK-Cell Activity
Authors: Suryadevara Carter M. , Riccione Katherine A. , Sampson John H. 
Published: August 2016

Abstract
Oncolytic viruses, proteasome inhibitors, and natural killer (NK)-cell immunotherapy have all been studied extensively as monotherapies but have never been evaluated in combination. Synergetic treatment of oncolytic virus–infected glioblastomas with a proteasome inhibitor induces necroptotic cell death to enhance NK-cell immunotherapy, prolonging survival against human glioblastoma. Clin Cancer Res; 22(21); 5164–6. ©2016 AACR.
See related article by Yoo et al., p. 5265