bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary outcome switching among drug trials with and without principal investigator financial ties to industry: a cross-sectional study
Authors: Jones Christopher W , Misemer Benjamin S , Platts-Mills Timothy F , Ahn Rosa , Woodbridge Alexandra , Abraham Ann , Saba Susan , Korenstein Deborah , Madden Erin , Keyhani Salomeh 
Published: February 2018

ObjectivesTo determine the relationship between manufacturer-related financial ties among investigators of published drug trials and rates of discrepant registered and published primary trial outcomes.DesignCross-sectional study.SettingHuman subjects drug trials published in ‘core clinical’ MEDLINE journals in 2013.Primary and secondary outcome measuresThe primary study endpoint was the presence of a prospectively registered, clearly defined primary outcome that matched the published primary outcome for each included trial. Secondary outcomes included assessments of registration timing and quality, and the impact of outcome discrepancies between registration and publication on the statistical significance of the included trials.ResultsOf 192 included trials, 134 (70%) were positive and 58 (30%) were negative. Financial ties were present between first or last authors and drug manufacturers for 130 trials (68%), of which 78% were positive, versus 53% of trials with no financial ties that were positive. Clearly defined, prospectively registered outcomes that matched the published outcomes were present in just 76 of the 192 trials (40%). After adjusting for study start date and sample size, the observed relationship between investigator financial ties and the presence of a match between prospectively registered and published primary outcomes was of borderline statistical significance (OR 2.12, 95% CI 0.998 to 4.50). Studies with financial ties present were more likely than studies without ties to have been prospectively registered (78%vs48%, P<0.001) and were more likely to have prospectively registered a clearly defined primary outcome(62%vs35%, P<0.001).ConclusionsLess than half of the trials in this cohort were prospectively registered with a clear primary outcome that was consistent with the primary outcome reported in the published manuscript. The presence of investigator financial ties was associated with higher quality registration practices, though this association diminished after adjusting for factors that impact registration quality.
Outcome measures in coeliac disease trials: the Tampere recommendations
Authors: Ludvigsson Jonas F , Ciacci Carolina , Green Peter HR , Kaukinen Katri , Korponay-Szabo Ilma R , Kurppa Kalle , Murray Joseph A , Lundin Knut Erik Aslaksen , Maki Markku J , Popp Alina , Reilly Norelle R , Rodriguez-Herrera Alfonso , Sanders David S , Schuppan Detlef , Sleet Sarah , Taavela Juha , Voorhees Kristin , Walker Marjorie M , Leffler Daniel A 
Published: February 2018

ObjectiveA gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures.DesignBased on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed.ResultsWe comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease.ConclusionCareful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.
Trends and determinants of the Flynn effect in cognitive functioning among older individuals in 10 European countries
Authors: Hessel Philipp , Kinge Jonas M , Skirbekk Vegard , Staudinger Ursula M 
Published: February 2018

BackgroundAlthough cognitive performance levels in old age have increased in most countries, recent evidence documents a slowing down or even decline in cohort gains in highly developed countries. The aim of this study was to assess trends and determinants in secular cohort gains in cognitive functioning among older individuals and whether cohort gains are levelling off in most advanced countries.MethodsData for individuals aged between 50 and 84 years from the Survey of Health, Ageing and Retirement in Europe in 10 European countries between 2004 and 2013 (n=92 739) were used to assess country and age-specific changes in immediate word recall. Multivariate random intercept models were used to assess associations between secular cohort changes in immediate word recall, initial performance levels and changes in country-level socio-demographic characteristics.ResultsPerformance in immediate word recall improved in all countries between 2004 and 2013 (from 4.40 to 5.08 words, P<0.05). However, secular cohort gains were significantly smaller in countries with initially higher performance levels (coeff.=−0.554, 95% CI −0.682 to –0.426). Changes in socio-demographic and health conditions, including decreases in cardiovascular disease, physical activity and educational achievement, were associated with larger secular cohort gains.ConclusionsResults may either reflect that some countries are approaching the limits of cognitive plasticity, are slowing in their progress or that societal structures have not yet been optimised to improve cognitive abilities in midlife and beyond, or a combination of these interpretations.
Reference percentiles of FEV1 for the Canadian cystic fibrosis population: comparisons across time and countries
Authors: Kim Sang-Ook , Corey Mary , Stephenson Anne L , Strug Lisa J 
Published: February 2018

BackgroundForced expiratory volume in 1 s (FEV1) indicates lung health in cystic fibrosis (CF). FEV1 is commonly communicated as a per cent predicted of a healthy individual sharing the same age, sex, race and height. CF-specific reference equations are complementary and calibrate a patient’s FEV1 to that of their CF peers.Objectives(1) To derive Canadian CF-specific FEV1 reference percentiles (FEV1%iles), (2) characterize how they have changed over time and (3) compare the Canadian FEV1%iles to those for USA and European CF populations.MethodCF FEV1%iles are calculated using the Canadian CF Registry and quantile regression.ResultsThe Canadian FEV1%iles demonstrated better lung function in more recent time periods within Canada, especially below the 50% percentile and in males. When compared to USA and European FEV1%iles for the same time period, Canadian FEV1%iles were higher.ConclusionCF-specific FEV1%iles can provide useful information about changes in lung health. An online calculator (available at cfpercentile.research.sickkids.ca) makes these FEV1%iles accessible.
Jet modules for the centerless Virasoro-like algebra
Authors: Guo Xiangqian , Liu Genqiang 
Published: February 2018

In this paper, we studied the jet modules for the centerless Virasoro-like algebra which is the Lie algebra of the Lie group of the area-preserving diffeomorphisms of a [Formula: see text]-torus. The jet modules are certain natural modules over the Lie algebra of semi-direct product of the centerless Virasoro-like algebra and the Laurent polynomial algebra in two variables. We reduce the irreducible jet modules to the finite-dimensional irreducible modules over some infinite-dimensional Lie algebra and then characterize the irreducible jet modules with irreducible finite dimensional modules over [Formula: see text]. To determine the indecomposable jet modules, we use the technique of polynomial modules in the sense of [Irreducible representations for toroidal Lie algebras, J. Algebras 221 (1999) 188–231; Weight modules over exp-polynomial Lie algebras, J. Pure Appl. Algebra 191 (2004) 23–42]. Consequently, indecomposable jet modules are described using modules over the algebra [Formula: see text], which is the “positive part” of a Block type algebra studied first by [Some infinite-dimensional simple Lie algebras in characteristic [Formula: see text] related to those of Block, J. Pure Appl. Algebra 127(2) (1998) 153–165] and recently by [A [Formula: see text]-graded generalization of the Witt-algebra, preprint; Classification of simple Lie algebras on a lattice, Proc. London Math. Soc. 106(3) (2013) 508–564]).
FOXO Transcription Factors Both Suppress and Support Breast Cancer Progression
Authors: Hornsveld Marten , Smits Lydia M.M. , Meerlo Maaike , van Amersfoort Miranda , Groot Koerkamp Marian J.A. , van Leenen Dik , Kloet David E.A. , Holstege Frank C.P. , Derksen Patrick W.B. , Burgering Boudewijn M.T. , Dansen Tobias B. 
Published: February 2018

Abstract
FOXO transcription factors are regulators of cellular homeostasis and putative tumor suppressors, yet the role of FOXO in cancer progression remains to be determined. The data on FOXO function, particularly for epithelial cancers, are fragmentary and come from studies that focused on isolated aspects of cancer. To clarify the role of FOXO in epithelial cancer progression, we characterized the effects of inducible FOXO activation and loss in a mouse model of metastatic invasive lobular carcinoma. Strikingly, either activation or loss of FOXO function suppressed tumor growth and metastasis. We show that the multitude of cellular processes critically affected by FOXO function include proliferation, survival, redox homeostasis, and PI3K signaling, all of which must be carefully balanced for tumor cells to thrive.
Significance: FOXO proteins are not solely tumor suppressors, but also support tumor growth and metastasis by regulating a multitude of cellular processes essential for tumorigenesis. Cancer Res; 78(9); 2356–69. ©2018 AACR.
A DDX31/Mutant–p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer
Authors: Daizumoto Kei , Yoshimaru Tetsuro , Matsushita Yosuke , Fukawa Tomoya , Uehara Hisanori , Ono Masaya , Komatsu Masato , Kanayama Hiro-omi , Katagiri Toyomasa 
Published: February 2018

Abstract
The p53 and EGFR pathways are frequently altered in bladder cancer, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of muscle-invasive bladder cancer (MIBC) through its sequential interactions with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31-bound mutp53/SP1 enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin in advanced MIBC, leading to EGFR–Akt signaling activation. High expression of both cytoplasmic DDX31 and p53 proteins correlated with poor prognosis in patients with MIBC, and blocking the DDX31/NCL interaction resulted in downregulation of EGFR/Akt signaling, eliciting an in vivo antitumor effect against bladder cancer. These findings reveal that DDX31 cooperates with mutp53 and EGFR to promote progression of MIBC, and inhibition of DDX31/NCL formation may lead to potential treatment strategies for advanced MIBC.
Significance: DDX31 cooperates with mutp53 and EGFR to promote progression of muscle invasive bladder cancer. Cancer Res; 78(9); 2233–47. ©2018 AACR.
Targeted BiTE Expression by an Oncolytic Vector Augments Therapeutic Efficacy Against Solid Tumors
Authors: Speck Tobias , Heidbuechel Johannes P.W. , Veinalde Rūta , Jaeger Dirk , von Kalle Christof , Ball Claudia R. , Ungerechts Guy , Engeland Christine E. 
Published: February 2018

Abstract
Purpose: Immunotherapy with bispecific T-cell engagers has achieved striking success against hematologic malignancies, but efficacy against solid tumors has been limited. We hypothesized that oncolytic measles viruses encoding bispecific T-cell engagers (MV-BiTEs) represent a safe and effective treatment against solid tumors through local BiTE expression, direct tumor cell lysis and in situ tumor vaccination.
Experimental Design: To test this hypothesis, we generated MV-BiTEs from the Edmonston B vaccine strain to target two model antigens. Replicative and oncolytic potential were assessed by infection and cell viability assays, respectively. Functionality of virus-derived BiTEs was tested in vitro by complementary binding and cytotoxicity assays. In vivo efficacy of MV-BiTE was investigated using both syngeneic and xenograft mouse models of solid cancers.
Results: We verified secretion of functional BiTE antibodies by MV-BiTE-infected cells. Further, we demonstrated therapeutic efficacy of MV-BiTE against established tumors in fully immunocompetent mice. MV-BiTE efficacy was associated with increased intratumoral T-cell infiltration and induction of protective antitumor immunity. In addition, we showed therapeutic efficacy of MV-BiTE in xenograft models of patient-derived primary colorectal carcinoma spheroids with transfer of peripheral blood mononuclear cells.
Conclusions: MV-BiTE treatment was effective in two distinct models of solid tumors without signs of toxicity. This provides strong evidence for therapeutic benefits of tumor-targeted BiTE expression by oncolytic MV. Thus, this study represents proof of concept for an effective strategy to treat solid tumors with BiTEs. Clin Cancer Res; 24(9); 2128–37. ©2018 AACR.
A First-in-Human Study of the New Oral Selective Estrogen Receptor Degrader AZD9496 for ER+/HER2− Advanced Breast Cancer
Authors: Hamilton Erika P. , Patel Manish R. , Armstrong Anne C. , Baird Richard D. , Jhaveri Komal , Hoch Matthias , Klinowska Teresa , Lindemann Justin P.O. , Morgan Shethah R. , Schiavon Gaia , Weir Hazel M. , Im Seock-Ah 
Published: February 2018

Abstract
Purpose: AZD9496 is an oral nonsteroidal, small-molecule inhibitor of estrogen receptor alpha (ERα) and a potent and selective antagonist and degrader of ERα. This first-in-human phase I study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2− advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity.
Patients and Methods: Forty-five patients received AZD9496 [20 mg once daily (QD) to 600 mg twice daily (BID)] in a dose-escalation, dose-expansion “rolling 6” design. Safety, tolerability, and PK activity in each cohort were reviewed before escalating to the next dose. PK was determined by mass spectrometry. Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Objective tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Results: Most common causally related AEs were diarrhea (35.6%), fatigue (31.1%), and nausea (22.2%), and seven patients had grade ≥3 AEs. Three patients experienced a dose-limiting toxicity: one each at 150 mg BID (abnormal hepatic function), 400 mg BID (diarrhea and elevated liver function tests), and 600 mg BID (diarrhea), and all were reversible. The maximum tolerated dose was not reached. Partial response was confirmed in one patient, who also had decreased tumor marker Ca15.3. Four patients had stable disease at 12 months' follow-up.
Conclusions: AZD9496 is well tolerated with an acceptable safety profile, showing evidence of prolonged disease stabilization in heavily pretreated patients with ER+/HER2− advanced breast cancer. Clin Cancer Res; 24(15); 3510–8. ©2018 AACR.
See related commentary by Jordan, p. 3480
Shedding Light on IDH1 Mutation in Gliomas
Authors: Hollon Todd C. , Orringer Daniel A. 
Published: February 2018

Abstract
IDH mutation is of central importance in the diagnosis and treatment of gliomas. Fourier-transform infrared spectroscopy, in combination with a supervised machine-learning approach, can be used to detect metabolic alterations induced by IDH1 mutations in a fraction of the time of conventional techniques. Clin Cancer Res; 24(11); 2467–9. ©2018 AACR.
See related article by Uckermann et al., p. 2530
Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial
Authors: Pol Tymon , Held Claes , Westerbergh Johan , Lindbäck Johan , Alexander John H. , Alings Marco , Erol Cetin , Goto Shinya , Halvorsen Sigrun , Huber Kurt , Hanna Michael , Lopes Renato D. , Ruzyllo Witold , Granger Christopher B. , Hijazi Ziad 
Published: February 2018

Background
Dyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation.

Methods and Results

Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14 884 atrial fibrillation patients. Median length of follow‐up was 1.9 years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70 g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81;
P
<0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome (
P
=0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both
P
values ≥0.2448).

Conclusions
In patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00412984.
On the Need of Conviviality: Experiences of Religious Diversity of Nordic Youth
Authors: Vähäkangas Auli , Leis-Peters Annette 
Published: February 2018

Abstract
This article studies young people’s experiences of religious diversity in two Nordic localities in Finland and in Norway. In the Nordic discourse, the concept of conviviality gained importance through the lwf’s policy document Seeking Conviviality in 2013. Haugen’s three “Rs”, respect, relationality and reciprocity will be used as a starting point for the analysis of the experiences of young people. The aim of the study is to understand how young people experience religious diversity and what these experiences can contribute to Haugen’s reformulation of conviviality. The results show that conviviality tends to be more easily discussed than practised. They indicate that living in the same neighbourhood with youth from other religious traditions helps to face religious diversity but that this coexistence does not in itself generate reciprocity. Rather, in order to really live together there is a need to get to know each other’s practices and values more deeply.
Meteorology's Educational Dilemma
Authors: Croft Paul J. , Binkley Mark S. 
Published: February 2018

Meteorology has seen unparalleled growth and change during the past 50 years. Rapid advances in theory, applications, and technology have demanded constant revision and updating of basic meteorology course material. This continued growth and expansion of basic knowledge and applications requires that older materials be replaced with new, that depth be replaced by breadth, or that fundamental pedagogical changes be made in instruction and curricular content. These choices are symptomatic of meteorology's current and future educational dilemma: How do we adequately prepare future meteorologists for their careers as the wealth of meteorological information, theory, and applications change?
Answering this question requires a brief consideration of the history and effectiveness of undergraduate meteorological education. Perhaps more importantly, it points to the need for a consensus within the field as to what constitutes appropriate undergraduate meteorological preparation. Only then may possible solutions be outlined and their merits, cost-effectiveness, and efficacy reviewed. Based on this assessment, a plan of action can be developed to ensure the field's growth and its ability to produce viable meteorologists. Seven options are outlined in this paper as possible solutions to the dilemma. Of these, we believe that a revision of the pedagogy of meteorology with regard to curriculum requirements, course content, certification, and methods of instruction may be the most appropriate.
Climatology of Hail Frequency and Size in China, 1980–2015
Authors: Li Xiaofei , Zhang Qinghong , Zou Tian , Lin Jipei , Kong Hoiio , Ren Zhihua 
Published: February 2018

AbstractThe hail day climatology from 1961 to 2005 was previously studied based on hundreds of surface stations in China. Recently, both hail occurrence and maximum hail diameter (MHD) data from more than 2000 surface stations were released by the National Meteorological Information Center of China. These data enable hail climatology to be explored using both hail frequency (HF), which is defined as annual mean hail occurrence, and MHD records from more stations over the entire country. Following quality control, hail data from 2254 stations were selected for the period of 1980–2015. In general, HF increased with station topography height, with a maximum of more than 30 events per year in the Tibetan Plateau and a minimum of less than 1 event per year in southern China, whereas the station mean MHD decreased with topography height. The highest peak of the 80th-percentile cumulative distribution function of the annual MHD cycle in southern China occurred in May but was delayed to July in the north. Severe hail (MHD ≥ 20 mm; 5.32% of all cases) mainly occurred along the edge of the plain, near the mountainsides, and was most likely to develop in the afternoon.