bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data sharing through an NIH central database repository: a cross-sectional survey of BioLINCC users
Authors: Ross Joseph S , Ritchie Jessica D , Finn Emily , Desai Nihar R , Lehman Richard L , Krumholz Harlan M , Gross Cary P 
Published: September 2016

ObjectiveTo characterise experiences using clinical research data shared through the National Institutes of Health (NIH)'s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) clinical research data repository, along with data recipients’ perceptions of the value, importance and challenges with using BioLINCC data.Design and settingCross-sectional web-based survey.ParticipantsAll investigators who requested and received access to clinical research data from BioLINCC between 2007 and 2014.Main outcome measuresReasons for BioLINCC data request, research project plans, interactions with original study investigators, BioLINCC experience and other project details.ResultsThere were 536 investigators who requested and received access to clinical research data from BioLINCC between 2007 and 2014. Of 441 potential respondents, 195 completed the survey (response rate=44%); 89% (n=174) requested data for an independent study, 17% (n=33) for pilot/preliminary analysis. Commonly cited reasons for requesting data through BioLINCC were feasibility of collecting data of similar size and scope (n=122) and insufficient financial resources for primary data collection (n=76). For 95% of respondents (n=186), a primary research objective was to complete new research, as opposed to replicate prior analyses. Prior to requesting data from BioLINCC, 18% (n=36) of respondents had contacted the original study investigators to obtain data, whereas 24% (n=47) had done so to request collaboration. Nearly all (n=176; 90%) respondents found the data to be suitable for their proposed project; among those who found the data unsuitable (n=19; 10%), cited reasons were data too complicated to use (n=5) and data poorly organised (n=5). Half (n=98) of respondents had completed their proposed projects, of which 67% (n=66) have been published.ConclusionsInvestigators were primarily using clinical research data from BioLINCC for independent research, making use of data that would otherwise have not been feasible to collect.
Knowledge, beliefs and attitudes of Muslim footballers towards Ramadan fasting during the London 2012 Olympics: a cross-sectional study
Authors: Farooq Abdulaziz , Herrera Christopher P , Zerguini Yacine , Almudahka Fuad , Chamari Karim 
Published: September 2016

ObjectivesMuslims observe fasting during the month of Ramadan by abstaining from eating and drinking from dawn to sunset. Available literature shows that although several studies have been conducted on athletes to determine the effects of Ramadan fasting in terms of physical fitness and performance, little data are available regarding the knowledge, beliefs and attitudes of athletes (particularly footballers) towards Ramadan fasting during high-level competitions. This study explored the knowledge, beliefs and attitudes towards Ramadan fasting among football players participating in the London 2012 Olympics football tournament.DesignCross-sectional study.SettingsTeam training facility.Participants54 Muslim footballers participating in the London Olympics, 2012Outcome measuresEach participant was asked to complete a pre-validated structured questionnaire to assess knowledge, beliefs and attitudes regarding Ramadan fasting and their intention to fast during London 2012.ResultsOf the 54 participating athletes, 21(39%) reported that they intended to fast during Ramadan, but not on a match day. This attitude differed across three teams interviewed —83%, 15% and 0%—showing cross-cultural variation. Overall, there was a lack of knowledge among footballers regarding the effects of Ramadan fasting on sleep and performance; around 30% of athletes gave incorrect responses. This knowledge was independent of their decision to fast on non-competition days (p>0.05).ConclusionsThis is the first study to describe the knowledge, beliefs and attitudes towards Ramadan fasting among athletes from Muslim-majority countries participating in a high-level competition. Appropriate knowledge can ensure optimum performance for athletes during Ramadan fasting. Coaches, family members and friends also in possession of this knowledge can provide moral support to the players.
Is tuberculosis health education reaching the public in China? A cross-sectional survey in Guizhou Province
Authors: Chen Wei , Li Yang , Yang Haiqin , Ehiri John , Chen Zaiping , Liu Ying , Wang Mei , Liu Shili , Tang He , Li Ying 
Published: September 2016

BackgroundKnowledge about tuberculosis (TB) is important for TB control, and China's national TB control guidelines emphasise TB health promotion. A 2010 national TB epidemiology survey showed that the general public had limited knowledge and awareness of TB.ObjectiveTo assess the level of TB knowledge after 5 years of TB health promotion in Guizhou Province, one of the regions with the highest TB burden in China.Design and settingA community-based, cross-sectional survey of 10 237 residents of Guizhou Province from June to August 2015. Multiple logistic regression models were used to examine factors associated with core TB knowledge and TB health education among respondents.ResultsOverall, residents of Guizhou Province had inadequate knowledge of TB. The overall awareness of TB was 41.5%. Less than 30% of respondents were familiar with China's policy of free treatment for TB or knew that the disease could be cured. Factors associated with core TB knowledge included gender, age, ethnicity, education, occupation, region, and having received TB health education. Women, older adults, people employed in non-government institutions, and those living in counties with low TB burdens had little access to TB health education, whereas people with higher education levels had greater access. Respondents' sources of TB knowledge did not necessarily match their preferred channels for delivery of TB health education.ConclusionsOur findings indicate that TB health education should be further strengthened in China and other countries with a high TB burden. TB health education programmes require further formative and implementation research in order to improve programme effectiveness.
Diluted honey inhibits biofilm formation: potential application in urinary catheter management?
Authors: Emineke Somadina , Cooper Alan J , Fouch Sarah , Birch Brian R , Lwaleed Bashir A 
Published: September 2016

AimsBiofilms are ubiquitous and when mature have a complex structure of microcolonies in an extracellular polysaccharide and extracellular DNA matrix. Indwelling medical devices harbour biofilms which have been shown to cause infections and act as reservoirs for pathogens. Urinary catheters are often in place for considerable periods of time and are susceptible to both encrustation and biofilm formation. Strategies for minimising biofilm occurrence underpin an active research area in biomedicine. Manuka honey has, inter alia,well-established antibacterial properties. This study aims to assess the influence of honey on early biofilm formation in an established in vitro model.MethodsAn established model of early biofilm formation using static bacterial cultures in vinyl 96-well plates was used to growEscherichia coli, strain ATC 25922 andProteus mirabilis, strain 7002. Planktonic cells were removed and the residual biofilm was stained with crystal violet, which were subsequently eluted and quantified spectrophotometrically. Manuka honey (Unique Manuka Factor 15+) was added either with the bacteria or up to 72 hours after.ResultsBiofilms in this model was developed over 3 days, after which growth stalled. Mixed (1:1) cultures ofE. coliandP. mirabilisgrew slower than monocultures. In mixed cultures, honey gave a dose-dependent reduction in biofilm formation (between 3.3 and 16.7%w/v). At 72 hours, all concentrations inhibited maximally (p<0.001). Application of honey to cultures after 24 and 48 hours also reduced the adherent bacterial biomass (p<0.05–p<0.01).ConclusionManuka honey at dilutions as low as 3.3% w/v in some protocols and at 10% or above in all protocols tested significantly inhibits bacterial attachment to a vinyl substrate and reduces further early biofilm development. No augmentation of growth over untreated controls was observed in any experiment.
The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer
Authors: Jaca Anelisa , Govender Padmini , Locketz Michael , Naidoo Richard 
Published: September 2016

AimsThe study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer.MethodsH&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) was performed. The miRNA-21 expression levels were determined using qRT-PCR and the data was analysed using the relative quantification method. The Fisher's exact and Pearson's χ2tests were used to correlate snail-1, E-cadherin, miRNA-21 and clinicopathological data.ResultsOur results showed a statistically significant correlation between high miRNA-21 expression levels and E-cadherin positive cases. There was also an association between high miRNA-21 expression levels and negative snail-1 expression. No significant correlation was seen between miRNA-21 expression levels and clinicopathological features. Moreover, high expression levels of miRNA-21 were significantly associated with the sporadic cases.ConclusionsOur data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease.
A rare but morbid neurosurgical target: petrous aneurysms and their endovascular management in the stent/flow diverter era
Authors: Gross Bradley A , Moon Karam , Ducruet Andrew F , Albuquerque Felipe C 
Published: September 2016

Background/objectiveThe rarity of petrous internal carotid artery (ICA) aneurysms has largely precluded analyses of their presentation and management in case series format.MethodsWe performed a retrospective analysis of our endovascular database of patients treated from January 2001 to May 2016 to identify patients with petrous ICA aneurysms. We evaluated the treatment approach and results for patients managed in the era of dedicated intracranial stents and flow diverters, noting clinical and angiographic results.ResultsOur database search identified 10 patients with petrous ICA aneurysms. Six aneurysms were managed in the era of dedicated intracranial stents and flow diverters. Two patients presented with cranial nerve palsies, two with incidental but enlarging aneurysms that had completely eroded through the petrous bone, one with transient ischemic attacks, and one with pulsatile tinnitus. Five aneurysms were large and one was small but symptomatic. In three cases the aneurysm was treated by flow diversion with adjunctive coiling; two patients with at least 4-month follow-up had complete occlusion of their aneurysm and significant improvement of mass effect symptoms. In one case the aneurysm was treated with balloon-assisted coiling with resultant near-complete occlusion. In two cases, prior to the introduction of flow diverters, the aneurysm was treated via stent-assisted coiling with resultant near-complete obliteration; one patient had resolution of pretreatment pulsatile tinnitus. There were no intraprocedural or postprocedural complications; no patients underwent retreatment.ConclusionsEndovascular treatment of large or symptomatic petrous ICA aneurysms, in the era of flow diversion, is associated with excellent angiographic and clinical outcomes.
The renin-angiotensin-aldosterone system in heart failure for the non-specialist: the past, the present and the future
Authors: Orsborne Christopher , Chaggar Parminder S , Shaw Steven M , Williams Simon G 
Published: September 2016

ABSTRACTHeart failure is one of the major public health challenges facing the Western world. Its prevalence is increasing as the population ages and modern techniques are implemented to manage cardiac disease. In response, there has been a sustained effort to develop novel strategies to address the high levels of associated morbidity and mortality. Indeed, agents that target the renin-angiotensin-aldosterone system (RAAS) have transformed the way in which we manage heart failure. Despite this, mortality in heart failure is poorer than in many malignancies and a large burden of morbidity and recurrent hospitalisation remains. Here, we review the role of RAAS modulation within the field of systolic heart failure. In particular, we provide practical guidance on using current RAAS blockade agents and focus on the recent emergence of new agents that promise additional substantial benefit to those living with left ventricular systolic dysfunction.
Fracture networks of normal faults in fine-grained sedimentary rocks: examples from Kilve Beach, SW England
Authors: Skar Tore , Berg Silje S. , Gabrielsen Roy H. , Braathen Alvar 
Published: September 2016

Abstract
Interbedded shale and limestone successions in the Kilve Beach area, Bristol Channel Basin, UK, provide insights on fracture networks around normal faults in fine-grained lithologies. Fracture sets with distinct orientations are characteristic of both shale and limestone beds. Shear fractures (mode II) predominate in the shaly units, and they have typically more gentle dips and a larger spread in orientations than extension veins and shear fractures in the limestones. Fracture intensities decrease away from the fault core, but maximum intensities, total number of fractures and widths of the damage zones appear to be independent of throw for normal faults with offsets of less than 20 m. Thus, there is no clear systematic relationship between fault throw and damage zone width in the shales studied by us. However, an asymmetry in the fracture distribution is evidenced by a wider hanging-wall damage zone and differences in fracture orientations in some cases. We interpret the asymmetry and spread in fracture orientations to be the result of propagating fault-tip process zones and the tempo-spatial impact of fault-slip events.
Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and Autophagy in Ovarian Cancer and Melanoma
Authors: Clark Curtis A. , Gupta Harshita B. , Sareddy Gangadhara , Pandeswara Srilakshmi , Lao Shunhua , Yuan Bin , Drerup Justin M. , Padron Alvaro , Conejo-Garcia José , Murthy Kruthi , Liu Yang , Turk Mary Jo , Thedieck Kathrin , Hurez Vincent , Li Rong , Vadlamudi Ratna , Curiel Tyler J. 
Published: September 2016

AbstractPD-L1 antibodies produce efficacious clinical responses in diverse human cancers, but the basis for their effects remains unclear, leaving a gap in the understanding of how to rationally leverage therapeutic activity. PD-L1 is widely expressed in tumor cells, but its contributions to tumor pathogenicity are incompletely understood. In this study, we evaluated the hypothesis that PD-L1 exerts tumor cell–intrinsic signals that are critical for pathogenesis. Using RNAi methodology, we attenuated PD-L1 in the murine ovarian cell line ID8agg and the melanoma cell line B16 (termed PD-L1lo cells), which express basal PD-L1. We observed that PD-L1lo cells proliferated more weakly than control cells in vitro. As expected, PD-L1lo cells formed tumors in immunocompetent mice relatively more slowly, but unexpectedly, they also formed tumors more slowly in immunodeficient NSG mice. RNA sequencing analysis identified a number of genes involved in autophagy and mTOR signaling that were affected by PD-L1 expression. In support of a functional role, PD-L1 attenuation augmented autophagy and blunted the ability of autophagy inhibitors to limit proliferation in vitro and in vivo in NSG mice. PD-L1 attenuation also reduced mTORC1 activity and augmented the antiproliferative effects of the mTORC1 inhibitor rapamycin. PD-L1lo cells were also relatively deficient in metastasis to the lung, and we found that anti-PD-L1 administration could block tumor cell growth and metastasis in NSG mice. This therapeutic effect was observed with B16 cells but not ID8agg cells, illustrating tumor- or compartmental-specific effects in the therapeutic setting. Overall, our findings extend understanding of PD-L1 functions, illustrate nonimmune effects of anti-PD-L1 immunotherapy, and suggest broader uses for PD-L1 as a biomarker for assessing cancer therapeutic responses. Cancer Res; 76(23); 6964–74. ©2016 AACR.
ZIC5 Drives Melanoma Aggressiveness by PDGFD-Mediated Activation of FAK and STAT3
Authors: Satow Reiko , Nakamura Tomomi , Kato Chiaki , Endo Miku , Tamura Mana , Batori Ryosuke , Tomura Shiori , Murayama Yumi , Fukami Kiyoko 
Published: September 2016

Abstract
Insights into mechanisms of drug resistance could extend the efficacy of cancer therapy. To probe mechanisms in melanoma, we performed siRNA screening of genes that mediate the development of neural crest cells, from which melanocytes are derived. Here, we report the identification of ZIC5 as a mediator of melanoma drug resistance. ZIC5 is a transcriptional suppressor of E-cadherin expressed highly in human melanoma. ZIC5 enhanced melanoma cell proliferation, survival, drug resistance, in vivo growth and metastasis. Microarray analysis revealed that ZIC5 downstream signaling included PDGFD and FAK activation, which contributes to drug resistance by enhancing STAT3 activation. Silencing of ZIC5 or PDGFD enhanced the apoptotic effects of BRAF inhibition and blocked survival of melanoma cells resistant to BRAF inhibitors. Furthermore, inhibition of FAK or STAT3 suppressed expression of ZIC5, which was positively regulated by PDGFD, FAK, and STAT3 in a positive feedback loop. Taken together, our results identify ZIC5 and PDGFD as candidate therapeutic targets to overcome drug resistance in melanoma. Cancer Res; 77(2); 366–77. ©2016 AACR.
SPINK6 Promotes Metastasis of Nasopharyngeal Carcinoma via Binding and Activation of Epithelial Growth Factor Receptor
Authors: Zheng Li-Sheng , Yang Jun-Ping , Cao Yun , Peng Li-Xia , Sun Rui , Xie Ping , Wang Meng-Yao , Meng Dong-Fang , Luo Dong-Hua , Zou Xiong , Chen Ming-Yuan , Mai Hai-Qiang , Guo Ling , Guo Xiang , Shao Jian-Yong , Huang Bi-Jun , Zhang Wei , Qian Chao-Nan 
Published: September 2016

AbstractNasopharyngeal carcinoma has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. The underlying molecular mechanisms of nasopharyngeal carcinoma metastasis are not fully understood. Here, we report the identification of serine protease inhibitor Kazal-type 6 (SPINK6) as a functional regulator of nasopharyngeal carcinoma metastasis via EGFR signaling. SPINK6 mRNA was upregulated in tumor and highly metastatic nasopharyngeal carcinoma cells. Immunohistochemical staining of 534 nasopharyngeal carcinomas revealed elevated SPINK6 expression as an independent unfavorable prognostic factor for overall, disease-free, and distant metastasis–free survival. Ectopic SPINK6 expression promoted in vitro migration and invasion as well as in vivo lymph node metastasis and liver metastasis of nasopharyngeal carcinoma cells, whereas silencing SPINK6 exhibited opposing effects. SPINK6 enhanced epithelial–mesenchymal transition by activating EGFR and the downstream AKT pathway. Inhibition of EGFR with a neutralizing antibody or erlotinib reversed SPINK6-induced nasopharyngeal carcinoma cell migration and invasion. Erlotinib also inhibited SPINK6-induced metastasis in vivo. Notably, SPINK6 bound to the EGFR extracellular domain independent of serine protease–inhibitory activity. Overall, our results identified a novel EGFR-activating mechanism in which SPINK6 has a critical role in promoting nasopharyngeal carcinoma metastasis, with possible implications as a prognostic indicator in nasopharyngeal carcinoma patients. Cancer Res; 77(2); 579–89. ©2016 AACR.
Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences
Authors: Valla Marit , Vatten Lars Johan , Engstrøm Monica Jernberg , Haugen Olav Anton , Akslen Lars Andreas , Bjørngaard Johan Håkon , Hagen Anne Irene , Ytterhus Borgny , Bofin Anna Mary , Opdahl Signe 
Published: September 2016

Abstract
Background: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886–1977.
Methods: A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886–1928 and 1929–1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs.
Results: Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2−) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50–54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8–6.9 and 2.5; 95% CI, 1.2–5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3–0.5), Luminal B (HER2−; HR 0.5; 95% CI, 0.3–0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2–0.9).
Conclusions: We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2−) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype.
Impact: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625–34. ©2016 AACR.
Is Pelvic Inflammatory Disease a Risk Factor for Ovarian Cancer?
Authors: Rasmussen Christina B. , Jensen Allan , Albieri Vanna , Andersen Klaus K. , Kjaer Susanne K. 
Published: September 2016

Abstract
Background: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive, and only few cohort studies have been conducted.
Methods: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978–2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype.
Results: For ovarian cancer overall, we observed no association with PID (HR, 1.05; 95% CI, 0.92–1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR, 1.19; 1.00–1.41; P = 0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer.
Conclusions: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes.
Impact: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies. Cancer Epidemiol Biomarkers Prev; 26(1); 104–9. ©2016 AACR.