bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary outcomes reporting in trials of paediatric type 1 diabetes mellitus: a systematic review
Authors: Khanpour Ardestani Samaneh , Karkhaneh Mohammad , Yu Hai Chuan , Hydrie Muhammad Zafar Iqbal , Vohra Sunita 
Published: December 2017

ObjectiveOur objective was to systematically review randomised clinical trials (RCTs) of paediatric type 1 diabetes mellitus (T1DM) to assess reporting of (1) primary outcome, (2) outcome measurement properties and (3) presence or absence of adverse events.MethodsElectronic searches in MEDLINE, EMBASE, CINAHL, Cochrane SR and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were undertaken. The search period was between 2001 and 2017. English-language RCTs on children younger than 21 years with T1DM were selected. We excluded studies of diagnostic or screening tools, multiple phase studies, protocols, and follow-up or secondary analysis of data.ResultsOf 11 816 unique references, 231 T1DM RCTs were included. Of total 231 included studies, 117 (50.6%) trials failed to report what their primary outcome was. Of 114 (49.4%) studies that reported primary outcome, 88 (77.2%) reported one and 26 (22.8%) more than one primary outcomes. Of 114 studies that clearly stated their primary outcome, 101 (88.6%) used biological/physiological measurements and 13 (11.4%) used instruments (eg, questionnaires, scales, etc) to measure their primary outcome; of these, 12 (92.3%) provided measurement properties or related citation. Of the 231 included studies, 105 (45.5%) reported that adverse events occurred, 39 (16.9%) reported that no adverse events were identified and 87 (37.7%) did not report on the presence or absence of adverse events.ConclusionDespite tremendous efforts to improve reporting of clinical trials, clear reporting of primary outcomes of RCTs for paediatric T1DM is still lacking. Adverse events due to DM interventions were often not reported in the included trials. Transparent reporting of primary outcome, validity of measurement tools and adverse events need to be improved in paediatric T1DM trials.
Evaluation of a federally funded mass media campaign and smoking cessation in pregnant women: a population-based study in three states
Authors: England Lucinda , Tong Van T , Rockhill Karilynn , Hsia Jason , McAfee Tim , Patel Deesha , Rupp Katelin , Conrey Elizabeth J , Valdivieso Claudia , Davis Kevin C 
Published: December 2017

ObjectivesIn 2012, theCenters for Disease Control and Prevention initiated a national anti-smoking campaign,Tips from Former Smokers(Tips). As a result of the campaign, quit attempts among smokers increased in the general population by 3.7 percentage points. In the current study, we assessed the effects ofTipson smoking cessation in pregnant women.MethodsWe used 2009–2013 certificates of live births in three US states: Indiana, Kentucky and Ohio. Smoking cessation by the third trimester of pregnancy was examined among women who smoked in the 3 months prepregnancy. Campaign exposure was defined as overlap between the airing ofTips2012 (March 19–June 10) and the prepregnancy and pregnancy periods. Women who delivered beforeTips2012 were not exposed. Adjusted logistic regression was used to determine whether exposure toTipswas independently associated with smoking cessation.ResultsCessation rates were stable during 2009–2011 but increased at the timeTips2012 aired and remained elevated. Overall, 32.9% of unexposed and 34.7% of exposed smokers quit by the third trimester (p<0.001). Exposure toTips2012 was associated with increased cessation (adjusted OR: 1.07, 95% CI 1.05 to 1.10).ConclusionsExposure to a national anti-smoking campaign for a general audience was associated with smoking cessation in pregnant women.
Frequency of equivocation in surgical meta-evidence: a review of systematic reviews within IBD literature
Authors: Delaney John D , Holbrook John T , Dewar Robert K , Laws Patrick J , Engel Alexander F 
Published: December 2017

ObjectiveTo assess the level of equivocation among level 1 evidence in ulcerative colitis and Crohn’s disease and determine whether any predisposing factors are present.MethodMEDLINE, Embase, CINHAL and Cochrane were searched from 2006 to 2017. Papers were scored using AMSTAR and categorised into surgical (S), medical (M) or medical and surgical (MS) groups. The ability of each paper to make a recommendation and conclusiveness in doing so was recorded.Results278 papers were assessed. 82% (n=227) could make a recommendation, 18% (n=51) could not. There was a significant difference in ability to provide a recommendation between S and M (P=0.003) but not MS and M (P=0.022) nor S and MS (P=0.79). Where a recommendation was made, S papers were more likely to be tempered than M papers (P=0.014) but not MS papers (P=0.987).ConclusionsSurgical meta-evidence within the inflammatory bowel disease domain is more than twice as likely as medical meta-evidence to be unable to provide a recommendation for clinical practice. Where a recommendation was made, surgical reviews were twice as likely to temper their conclusion.
Accrual monitoring in cardiovascular trials
Authors: Baldi Ileana , Gregori Dario , Desideri Alessandro , Berchialla Paola 
Published: December 2017

ObjectiveTo provide brief guidance on how to design accrual monitoring activities in a clinical trial protocol.SettingTwo completed clinical trials that did not achieve the planned sample size, the Cost of Strategies After Myocardial Infarction (COSTAMI) trial and the Biventricular Pacing After Cardiac Surgery (BiPACS) trial.DesignA Bayesian monitoring tool, the constant accrual model, is applied retrospectively to accrual data from each case study to illustrate how the tool could be used to identify problems with accrual early in the trial period and to frame the conditions in which the approach can be used in practice.ResultsAfter 312 days and 155 patients enrolled in the COSTAMI trial, accrual could be classified as ‘off target’ on the basis of statistical criteria outlined in the protocol. As for the BiPACS trial, after 2 years, it was already evident that the accrual was ‘considerably off target’.ConclusionsPrompt awareness of a high risk of accrual failure could trigger different interventions to overcome protocol-related, patient-related or investigator-related barriers to recruitment or ultimately contribute to an early stopping decision due to recruitment futility.Accrual prediction models should be included as standard tools for routine monitoring activities in cardiovascular research. Among them, methods relying on the Bayesian approach are particularly attractive, as they can naturally update past evidence when actual accrual data becomes available.
Inactivation of Cancer-Associated-Fibroblasts Disrupts Oncogenic Signaling in Pancreatic Cancer Cells and Promotes Its Regression
Authors: Dauer Patricia , Zhao Xianda , Gupta Vineet K. , Sharma Nikita , Kesh Kousik , Gnamlin Prisca , Dudeja Vikas , Vickers Selwyn M. , Banerjee Sulagna , Saluja Ashok 
Published: December 2017

Abstract
Resident fibroblasts that contact tumor epithelial cells (TEC) can become irreversibly activated as cancer-associated-fibroblasts (CAF) that stimulate oncogenic signaling in TEC. In this study, we evaluated the cross-talk between CAF and TEC isolated from tumors generated in a mouse model of KRAS/mut p53-induced pancreatic cancer (KPC mice). Transcriptomic profiling conducted after treatment with the anticancer compound Minnelide revealed deregulation of the TGFβ signaling pathway in CAF, resulting in an apparent reversal of their activated state to a quiescent, nonproliferative state. TEC exposed to media conditioned by drug-treated CAFs exhibited a decrease in oncogenic signaling, as manifested by downregulation of the transcription factor Sp1. This inhibition was rescued by treating TEC with TGFβ. Given promising early clinical studies with Minnelide, our findings suggest that approaches to inactivate CAF and prevent tumor–stroma cross-talk may offer a viable strategy to treat pancreatic cancer.
Significance: In an established mouse model of pancreatic cancer, administration of the promising experimental drug Minnelide was found to actively deplete reactive stromal fibroblasts and to trigger tumor regression, with implications for stromal-based strategies to attack this disease. Cancer Res; 78(5); 1321–33. ©2018 AACR.
Oncogenic RAS-Induced Perinuclear Signaling Complexes Requiring KSR1 Regulate Signal Transmission to Downstream Targets
Authors: Basu Sandip K. , Lee Sook , Salotti Jacqueline , Basu Srikanta , Sakchaisri Krisada , Xiao Zhen , Walia Vijay , Westlake Christopher J. , Morrison Deborah K. , Johnson Peter F. 
Published: December 2017

Abstract
The precise characteristics that distinguish normal and oncogenic RAS signaling remain obscure. Here, we show that oncogenic RAS and BRAF induce perinuclear relocalization of several RAS pathway proteins, including the kinases CK2 and p-ERK1/2 and the signaling scaffold KSR1. This spatial reorganization requires endocytosis, the kinase activities of MEK-ERK and CK2, and the presence of KSR1. CK2α colocalizes with KSR1 and Rab11, a marker of recycling endosomes, whereas p-ERK associates predominantly with a distinct KSR1-positive endosomal population. Notably, these perinuclear signaling complexes (PSC) are present in tumor cell lines, mouse lung tumors, and mouse embryonic fibroblasts undergoing RAS-induced senescence. PSCs are also transiently induced by growth factors (GF) in nontransformed cells with delayed kinetics (4–6 hours), establishing a novel late phase of GF signaling that appears to be constitutively activated in tumor cells. PSCs provide an essential platform for RAS-induced phosphorylation and activation of the prosenescence transcription factor C/EBPβ in primary MEFs undergoing senescence. Conversely, in tumor cells, C/EBPβ activation is suppressed by 3′UTR-mediated localization of Cebpb transcripts to a peripheral cytoplasmic domain distinct from the PSC region. Collectively, our findings indicate that sustained PSC formation is a critical feature of oncogenic RAS/BRAF signaling in cancer cells that controls signal transmission to downstream targets by regulating selective access of effector kinases to substrates such as C/EBPβ.
Significance: In addressing the long-standing question of the difference between normal and oncogenic RAS pathway signaling, this study shows that oncogenic RAS specifically triggers constitutive endocytosis-dependent movement of effector kinases to a perinuclear region, thereby creating connections to unique downstream targets such as the core prosenescence and the inflammatory regulatory transcription factor C/EBPβ. Cancer Res; 78(4); 891–908. ©2017 AACR.
Achieving the Zenith of Education: Human Rights Based Transformation of Higher Education in Sri Lanka
Authors: Perera Binendri 
Published: December 2017

As a country that has ratified core international human rights treaties, Sri Lanka has an international obligation to ensure that its higher education sector meets the standards set out in those treaties. However, due to a lack of normative recognition accorded at constitutional, legislative and policy levels, attempts at conformity with the aforementioned standards have been ad hoc and reactive. Consequently, whereas quality assurance mechanisms pertaining to state institutions are still in formative stages, private educational institutions have sprung up in the country without any effective scrutiny as to quality. The main method of challenging the standards of private institutions has been to reject the graduates from the said institutions.
This article explores the parameters of higher education as a state obligation under international human rights law, whereby the state is required simultaneously to be a provider of higher education and a facilitator of other providers to ensure that availability, accessibility, acceptability and adaptability of higher education are upheld. Establishment of a mechanism equipped to make human rights based transformations to the higher education sector of Sri Lanka is suggested to redress the deficiencies in setting standards for private higher educational institutions by the state.
Association of Socioeconomic Status, Race and Insurance Status with Chronic Rhinosinusitis Patient‐Reported Outcome Measures
Authors: Bergmark Regan W. , Hoehle Lloyd P. , Chyou Darius , Phillips Katie M. , Caradonna David S. , Gray Stacey T. , Sedaghat Ahmad R. 
Published: December 2017

ObjectiveDisparities in health and health care access are widely prevalent. However, disparities among patients with chronic rhinosinusitis (CRS) are poorly understood. We investigated if CRS severity at presentation according to socioeconomic factors.Study DesignCross‐sectional study.SettingTertiary rhinology center.Subjects and MethodsThree hundred prospectively recruited patients presenting with CRS were included. Outcome variables included CRS symptomatology, as reflected by the 22‐item Sinonasal Outcome Test (SNOT‐22); general health status, as reflected by the EuroQol 5‐dimensional visual analog scale (EQ‐5D VAS); and CRS‐related antibiotic and systemic corticosteroid use. Race/ethnicity, zip code income bracket, education level, and insurance status were used as predictor variables. Regression, controlling for clinical and demographic characteristics, was used to determine associations between predictor and outcome variables.ResultsMean SNOT‐22 score was 33.8 (SD, 23.2), and mean EQ‐5D VAS score was 74.2 (SD, 18.9). On multivariable analysis, presenting SNOT‐22 and EQ‐5D VAS scores were not associated with nonwhite patient race/ethnicity (P =. 634 and P =. 866), education (P =. 106 and P =. 586), or the percentage of households in zip code with incomes <$50,000 per year (P =. 917 and P =. 979, respectively). SNOT‐22 scores did not differ by insurance type, but patients receiving Medicare reported worse general health status. Use of oral antibiotics or oral steroids for CRS was not associated with predictor variables.ConclusionPatients with CRS presented to a tertiary rhinology center with similar metrics for CRS severity and pre‐presentation medical management regardless of race/ethnicity, education status, or zip code income level. Patients with Medicare had worse general health status. Further research should investigate potential disparities in diagnosis of CRS, specialist referral, and treatment outcomes.
A North American perspective of content and quality of websites in the English language on childhood-onset lupus erythematosus
Authors: Cutler C , Peng T , Stinson J , Tucker L , Boneparth A , Klein Gitelman M , Moorthy L Nandini 
Published: December 2017

Objective The objective of this article is to examine the quality, content, and readability of information and resources in the English language and accessible on the internet by pediatric patients with systemic lupus erythematosus (SLE) and their families in North America. Methods Keywords relevant to SLE were generated by an undergraduate student, a first-year medical student, and a third-year pediatric resident, and a search was conducted across five commonly used search engines. Quality of information found was evaluated independently by an undergraduate student, a graduate student, a first-year medical student, and a third-year pediatric resident using the DISCERN tool. Two pediatric rheumatologists assessed website accuracy and completeness. Readability of websites was determined using the Flesch-Kincaid grade level and Reading Ease score. Results Out of 2000 websites generated in the search, only 34 unique websites met inclusion criteria. Only 16 of these websites had DISCERN scores above 50% (fair quality). Overall quality of website information was fair with mean ±standard deviation (SD) DISCERN quality score of 44 ± 7 (range: 30–56). Only nine websites of 34 had DISCERN scores above 50 (>66%, indicating greater quality) and were further assessed for completeness. Flesch-Kincaid grade level was 11 ± 1 (mean±SD) and reading ease score was 39 ± 10 (mean±SD, range of 11–61). Conclusion Our study highlights the need for more complete, readable information regarding the unique needs of pediatric patients with childhood-onset SLE and their families.
Does Race Affect Outcomes in Triple Negative Breast Cancer?
Authors: Sachdev Jasgit C. , Ahmed Saira , Mirza Muhammad M. , Farooq Aamer , Kronish Lori , Jahanzeb Mohammad 
Published: December 2017

Background There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population. Methods Patients with Stage I-III TNBC were identified from our breast database. Event free survival (EFS) and Breast cancer specific survival (BCSS) were the primary outcome measures. Cox proportional hazards models were fitted for EFS and BCSS. Results Of the 124 patients, 71% were AA. No significant association between race and stage ( P = 0.21) or menopausal status ( P = 0.15) was observed. Median age at diagnosis was significantly lower for AA versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received standard neo/adjuvant chemotherapy, with no significant difference in duration and type of chemotherapy between the races. With a median follow up of 23 months, 28% of AA vs. 19% of CA women had an event ( P = 0.37). 3 year EFS and BCSS trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs. 76%, P = 0.13 respectively) with a similar trend noted on multiple variable modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women ≥50 years at diagnosis had a significantly worse BCSS than the CA women in that age group ( P = 0.012). Conclusion Older AA women with TNBC have a significantly worse breast cancer specific survival than their CA counterparts. Overall, there is a trend towards lower survival for AA women compared to Caucasians despite uniformity of tumor phenotype and treatment. The high early event rate, irrespective of race, underscores the need for effective therapies for women with TNBC.
Recurrent Lumbar Disc Herniation: A Review
Authors: Shepard Nicholas , Cho Woojin 
Published: December 2017

Study Design: Narrative review. Objectives: To identify the risk factors and surgical management for recurrent lumbar disc herniation using a systematic review of available evidence. Methods: We conducted a review of PubMed, MEDLINE, OVID, and Cochrane Library databases using search terms identifying recurrent lumbar disc herniation and risk factors or surgical management. Abstracts of all identified articles were reviewed. Detailed information from articles with levels I to IV evidence was extracted and synthesized. Results: There is intermediate levels III to IV evidence detailing perioperative risk factors and the optimal surgical technique for recurrent lumbar disc herniations. Conclusions: Multiple risk factors including smoking, diabetes mellitus, obesity, intraoperative technique, and biomechanical factors may contribute to the development of recurrent disc disease. There is widespread variation regarding optimal surgical management for recurrent herniation, which often include revision discectomies with or without fusion via open and minimally invasive techniques.
Phenotypes of symptomatic airways disease in China and New Zealand
Authors: Fingleton James , Huang Kewu , Weatherall Mark , Guo Yanfei , Ivanov Stefan , Bruijnzeel Piet , Zhang Hong , Wang Wei , Beasley Richard , Wang Chen 
Published: December 2017

It is uncertain whether phenotypes of asthma and chronic obstructive pulmonary disease (COPD) vary between populations with different genetic and environmental characteristics. Here, our objective was to compare the phenotypes of airways disease in two separate populations.This was a cross-sectional observational study in adult populations from New Zealand and China. Participants aged 40–75 years who reported wheeze and breathlessness in the last 12 months were randomly selected from the general population and underwent detailed characterisation. Complete data for cluster analysis were available for 345 participants. Hierarchical cluster analysis was undertaken, based on 12 variables: forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio, bronchodilator reversibility, peak expiratory flow variability, transfer coefficient of the lung for carbon monoxide, exhaled nitric oxide fraction, total IgE, C-reactive protein, age of symptom onset, body mass index, health status and cigarette smoke exposure.Cluster analysis of the combined dataset described five phenotypes: “severe late-onset asthma/COPD overlap group”, “moderately severe early-onset asthma/COPD overlap group”, “moderate to severe asthma group with type 2 predominant disease”, and two groups with minimal airflow obstruction, differentiated by age of onset. Separate analyses by country showed similar patterns; however, a distinct obese/comorbid group was observed in the New Zealand population.Cluster analysis of adults with symptomatic airways disease suggests the presence of similar asthma/COPD overlap phenotypes within populations with different genetic and environmental characteristics, and an obese/comorbid phenotype in a Western population.
Endoscopic ultrasound fine-needle aspiration by experienced pulmonologists: a cusum analysis
Authors: Leong Paul , Deshpande Sheetal , Irving Louis B. , Bardin Philip G. , Farmer Michael W. , Jennings Barton R. , Steinfort Daniel P. 
Published: December 2017

Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described.A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves.A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed.Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions.