bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occurrence and determinants of selective reporting of clinical drug trials: design of an inception cohort study
Authors: van den Bogert Cornelis A , Souverein Patrick C , Brekelmans Cecile T M , Janssen Susan W J , van Hunnik Manon , Koëter Gerard H , Leufkens Hubertus G M , Bouter Lex M 
Published: July 2015

IntroductionResponsible conduct of research implies that results of clinical trials should be completely and adequately reported. This article describes the design of a cohort study that aims to investigate the occurrence and the determinants of selective reporting in an inception cohort of all clinical drug trials that were reviewed by the Dutch Institutional Review Boards (IRBs) in 2007. It also describes the characteristics of the study cohort.Methods and analysisIn 2007, Dutch IRBs reviewed 622 clinical drug trials. For each trial, we assessed the stages of progress. We discriminated five intermediate stages and five definite stages. Intermediate stages of progress are: approved by an IRB; started inclusion; completed as planned; terminated early; published as article. The definite stages of progress are: rejected by an IRB; never started inclusion; not published as article; completely reported; selectively reported. We will use univariate and multivariate Cox regression models to identify trial characteristics associated with non-publication. We will identify seven trial-specific discrepancy items, including the objectives, inclusion and exclusion criteria, end points, sample size, additional analyses, type of population analysis and sponsor acknowledgement. The percentage of trials with discrepancies between the protocol and the publication will be scored. We will investigate the association between trial characteristics and the occurrence of discrepancies.Ethics and disseminationNo IRB-approval is required for this study. Access to confidential research protocols was provided by the Central Committee on Research Involving Human Subjects. We plan to finish data collection in June 2015, and expect to complete data cleaning, analysis and manuscript preparation within the next 3 months. Hence, a first draft of an article containing the results is expected before the end of October 2015.
Efficacy of a minimal home-based psychoeducative intervention versus usual care for managing anxiety and dyspnoea in patients with severe chronic obstructive pulmonary disease: a randomised controlled trial protocol
Authors: Bove Dorthe Gaby , Overgaard Dorthe , Lomborg Kirsten , Lindhardt Bjarne Ørskov , Midtgaard Julie 
Published: July 2015

IntroductionIn its final stages, chronic obstructive pulmonary disease is a severely disabling condition that is characterised by dyspnoea, which causes substantial anxiety. Anxiety is associated with an impaired quality of life and increased hospital admissions. Untreated comorbid anxiety can have devastating consequences for both patients and their relatives. Non-pharmacological interventions, including cognitive–behavioural therapy, have been effective in managing anxiety and dyspnoea in patients with chronic obstructive pulmonary disease. However, the majority of existing interventions have tested the efficacy of relatively intensive comprehensive programmes and primarily targeted patients who have moderate pulmonary disease. We present the rationale and design for a trial that focused on addressing the challenges experienced by severe pulmonary disease populations. The trial investigates the efficacy of a minimal home-based psychoeducative intervention versus usual care for patients with severe chronic obstructive pulmonary disease.Methods and analysisThe trial is a randomised controlled trial with a 4-week and 3-month follow-up. 66 patients with severe chronic obstructive pulmonary disease and associated anxiety will be randomised 1:1 to either an intervention or control group. The intervention consists of a single psychoeducative session in the patient's home in combination with a telephone booster session. The intervention is based on a manual, with a theoretical foundation in cognitive–behavioural therapy and psychoeducation. The primary outcome is patient-reported anxiety as assessed by the Hospital and Anxiety and Depression Scale (HADS).Ethics and disseminationThis trial complies with the latest Declaration of Helsinki, and The Ethics Committee of the Capital Region of Denmark (number H-1-2013-092) was queried for ethical approval. Trial results will be disseminated in peer-reviewed publications and presented at scientific conferences.Trial registration numberNCT02366390.
Pyrvinium Targets CD133 in Human Glioblastoma Brain Tumor–Initiating Cells
Authors: Venugopal Chitra , Hallett Robin , Vora Parvez , Manoranjan Branavan , Mahendram Sujeivan , Qazi Maleeha A. , McFarlane Nicole , Subapanditha Minomi , Nolte Sara M. , Singh Mohini , Bakhshinyan David , Garg Neha , Vijayakumar Thusyanth , Lach Boleslaw , Provias John P. , Reddy Kesava , Murty Naresh K. , Doble Bradley W. , Bhatia Mickie , Hassell John A. , Singh Sheila K. 
Published: July 2015

Abstract
Purpose: Clonal evolution of cancer may be regulated by determinants of stemness, specifically self-renewal, and current therapies have not considered how genetic perturbations or properties of stemness affect such functional processes. Glioblastoma-initiating cells (GICs), identified by expression of the cell surface marker CD133, are shown to be chemoradioresistant. In the current study, we sought to elucidate the functional role of CD133 in self-renewal and identify compounds that can specifically target this CD133+ treatment-refractory population.
Experimental Design: Using gain/loss-of-function studies for CD133 we assessed the in vitro self-renewal and in vivo tumor formation capabilities of patient-derived glioblastoma cells. We generated a CD133 signature combined with an in silico screen to find compounds that target GICs. Self-renewal and proliferation assays on CD133-sorted samples were performed to identify the preferential action of hit compounds. In vivo efficacy of the lead compound pyrvinium was assessed in intracranial GIC xenografts and survival studies. Lastly, microarray analysis was performed on pyrvinium-treated GICs to discover core signaling events involved.
Results: We discovered pyrvinium, a small-molecule inhibitor of GIC self-renewal in vitro and in vivo, in part through inhibition of Wnt/β-catenin signaling and other essential stem cell regulatory pathways. We provide a therapeutically tractable strategy to target self-renewing, chemoradioresistant, and functionally important CD133+ stem cells that drive glioblastoma relapse and mortality.
Conclusions: Our study provides an integrated approach for the eradication of clonal populations responsible for cancer progression, and may apply to other aggressive and heterogeneous cancers. Clin Cancer Res; 21(23); 5324–37. ©2015 AACR.
Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay
Authors: Prat Aleix , Galván Patricia , Jimenez Begoña , Buckingham Wesley , Jeiranian H. Arthur , Schaper Carl , Vidal Maria , Álvarez Martina , Díaz Sherley , Ellis Catherine , Nuciforo Paolo , Ferree Sean , Ribelles Nuria , Adamo Barbara , Ramón y Cajal Santiago , Peg Vicente , Alba Emilio 
Published: July 2015

Abstract
Purpose: Most hormone receptor (HR)+/HER2− breast cancer patients respond unfavorably to neoadjuvant chemotherapy (NAC); however, genomic tests may identify those patients who are likely to benefit. Using the Prosigna assay, we first evaluated the technical performance of core needle biopsy (CNB) tissues. We then determined whether Prosigna risk of relapse (ROR) score and intrinsic subtype predicted response to NAC in HR+/HER2− patients using CNB samples.
Experimental Design: Using the NanoString's nCounter Dx analysis system and a development tissue sample set, we established tissue requirements and assay output variance. We then evaluated the concordance in subtype and correlation in ROR between CNBs and corresponding surgical resection specimens (SRS) in a second independent sample set. Finally, we analyzed 180 independent CNB samples from HR+/HER2− patients who were treated with NAC and correlated ROR and intrinsic subtype with pathologic response.
Results: Intra- and interbiopsy variabilities were 2.2 and 6.8 ROR units, respectively. Subtype concordance within multiple CNBs was high for the 4- and 3-subtype classifications (k = 0.885 and 0.889, respectively). Correlation in Prosigna ROR score observed between paired CNBs and SRS was high (r ≥ 0.90), and subtype concordance was also high for the 4- and 3-subtype classifications (kappa = 0.81 and 0.91, respectively). Prosigna results obtained from the HR+/HER2− patient samples showed that both ROR (P = 0.047) and intrinsic subtype (OR LumA vs. non-LumA = 0.341, P = 0.037) were significant predictors of response to NAC.
Conclusions: Prosigna ROR and intrinsic subtype are readily obtained from CNB samples in normal practice and reliably predict response to NAC in HR+/HER2− patients. Clin Cancer Res; 22(3); 560–6. ©2015 AACR.
Sex-Stratified Trends in Enrollment, Patient Characteristics, Treatment, and Outcomes Among Non–ST-Segment Elevation Acute Coronary Syndrome Patients
Authors: Kragholm Kristian , Halim Sharif A. , Yang Qinghong , Schulte Phillip J. , Hochman Judith S. , Melloni Chiara , Mahaffey Kenneth W. , Moliterno David J. , Harrington Robert A. , White Harvey D. , Armstrong Paul W. , Ohman E. Magnus , Van de Werf Frans , Tricoci Pierluigi , Alexander John H. , Giugliano Robert P. , Newby L. Kristin 
Published: July 2015

Background—
Adequate representation by sex in trials allows generalizability of results. We examined representation of women in clinical trials during a 17-year period in which inclusion criteria were broadened and federal mandates for representativeness were launched.

Methods and Results—
Using mixed models, we studied sex-stratified temporal trends in enrollment, clinical characteristics, treatment, and outcomes among 76 148 non–ST-segment elevation acute coronary syndrome patients using patient-level data merged from 11 phase III trials conducted from 1994 to 2010. Overall, 33.3% of patients were women, which changed minimally over time. Women were consistently 4 to 5 years older than men (median age 68 [interquartile range 61–75] versus 64 [interquartile range 56–72] years) and more frequently had diabetes mellitus, hypertension, and heart failure; men more frequently had prior myocardial infarction and revascularization. GRACE risk scores increased over time for both sexes with the inclusion of older patients with more comorbidities. Use of percutaneous coronary intervention, in-hospital and discharge angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, β-blockers, and lipid-lowering drugs also increased among both sexes. Kaplan–Meier estimates of 6-month mortality declined from 7.0% [95% confidence interval 6.5%–7.6%] to 4.5% [95% confidence interval 4.0%–5.0%] among women and 6.3% [95% confidence interval 6.0%–6.7%] to 3.1% [95% confidence interval 2.9%–3.4%] among men during the 17-year period.

Conclusions—
The relative proportion of women in non–ST-segment elevation acute coronary syndrome trials changed minimally over time. Nevertheless, in parallel with men, use of evidence-based care and outcomes improved significantly over time among women.
Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death
Authors: Cavender Matthew A. , Steg Ph. Gabriel , Smith Sidney C. , Eagle Kim , Ohman E. Magnus , Goto Shinya , Kuder Julia , Im Kyungah , Wilson Peter W.F. , Bhatt Deepak L. 
Published: July 2015

Background—
Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus.

Methods and Results—

The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19–1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26–1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30–1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18–1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17–2.77;
P
<0.001) and hospitalization for heart failure (adjusted odds ratio, 4.72; 95% CI, 4.22–5.29;
P
<0.001).

Conclusions—
Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population.
Influence of prey species and concentration on egg production efficiency and hatching success in Acartia tonsa Dana (Copepoda, Calanoida)
Authors: Wendt I. , Thor P. 
Published: July 2015

We measured ingestion rate (IR), egg production rate (EPR) and egg hatching success (EHS) at increasing prey concentrations and calculated egg production efficiency (EPE) and maintenance rate (MR) in the estuarine copepod Acartia tonsa fed three different algal diets. EPR and EHS were relatively more affected by prey species than by prey concentration. EPEs were constant among carbon concentrations (C) on a diet of Rhodomonas baltica (0.202 ± 0.055, mean ± SD) and Dunaliella tertiolecta (0.034 ± 0.015), but decreased significantly from 0.371 ± 0.062 (mean of two lowest prey concentrations) to 0.200 ± 0.019 at the highest concentration of Thalassiosira weissflogii. In general it seems that other requirements than C demand limit EPE and EHS in A. tonsa. The MR (IR when EPR = 0) was significantly higher on D. tertiolecta, which also yielded the lowest EPEs, and it seems that variations in maintenance requirements may have been instrumental in evoking EPE variations as well.
Descriptions of the postembryonic developmental stages of Hatschekia bifurcata Yamaguti & Yamasu, 1959 (Copepoda, Siphonostomatoida, Hatschekiidae)
Authors: Izawa Kunihiko 
Published: July 2015

A series of descriptions of postembryonic developmental stages of Hatschekia bifurcata Yamaguti & Yamasu, 1959 is presented based on free-living larvae reared from eggs detached from ovigerous females recovered from the branchial lamellae of Aulacocephalus temmincki Bleeker, 1855, as well as on copepodids I-VI from A. temmincki and Diploprion bifasciatum Cuvier, 1828 (Pisces, Perciformes, Serranidae). The number of naupliar stages preceding the infective copepodid I is three in this species as in H. multibarbatae Izawa, 2015. A diagnostic feature of the species, a hook-like ventral process on the fourth antennular segment of the female, is regarded as an enlarged seta and was found to appear after copepodid V. A correction in the previously given setation of leg 2 and a complemental description of the antennule of the adult female are made. The male of this species is herein described for the first time. The sexes become distinct at copepodid III, and then growth curves of both sexes diverge stage by stage, as in H. multibarbatae. Aulacocephalus temmincki is reported as a new host species for H. bifurcata.
China Rising
Authors: Curado Marcelo 
Published: July 2015

China’s economic rise has caused a radical change in the operating conditions of the capitalist system and opened a wide range of opportunities and challenges for Brazil’s development. The Brazilian productive structure is going through great changes, key among them being the loss of importance of the manufacturing industry in job creation and in total GDP, and the efforts of Brazilian capitalists to promote investment and innovation have fallen short. The latter is a key element for an understanding of Brazilian industry’s weak participation in the highly competitive international scene. These opportunities and challenges can only be adequately addressed by the maintenance and expansion of the planning efforts of the state. A ascensão econômica da China tem causado mudança radical nas condições de fun-cionamento do sistema capitalista e criou um vasto espectro de oportunidades e desafios ao desenvolvimento do Brasil. A estrutura produtiva brasileira vem passando por grandes transformações. Entre elas, uma das mais sérias tem sido a perda na capacidade da indústria manufatureira de gerar empregos e a queda de sua participação no PIB. Demais, nota-se que os esforços de capitalistas brasileiros para promover investimento e inovação têm sido pífios. Esse último problema constitui elemento-chave para compreender-se a participação fraca da indústria brasileira em um cenário international extremamente competitivo. As oportunidades e desafios mencionados só podem ser adequadamente tratados por meio da manutenção e expansão do planejamento estatal.
China and Cuba
Authors: Xianglin Mao , Hearn Adrian H. , Weiguang Liu 
Published: July 2015

Sino-Cuban relations have deepened rapidly since the beginning of the twenty-first century, propelled by both political ideology and economic interests. A shared commitment to socialism with “local characteristics” has enabled the pursuit of an unusually broad range of cooperative initiatives. These include Chinese investment in the Cuban nickel and oil sectors, educational and medical exchange programs, the development of tourism, and engagement with the Chinese diaspora on the island. Data from Chinese sources on these spheres of engagement reflect an attempt to address contemporary needs with a blend of state and market forces. The intensification of Sino-Cuban relations over the past decade poses no challenge to the United States; on the contrary, it opens new opportunities for trilateral cooperation. Las relaciones sino-cubanos se han profundizado rápidamente desde comienzos del siglo XXI, impulsadas tanto por ideología política como por intereses económicos. Un compromiso compartido al socialismo con “características locales” ha permitido la consecución de una gama inusualmente amplia de iniciativas cooperativas. Éstas incluyen la inversión china en sectores cubanos de níquel y petróleo, programas de intercambio educacionales y médicos, el fomento de turismo, y la interacción con la diáspora china en la isla. Datos de fuentes chinas sobre estos ámbitos de interacción reflejan un intento de abordar necesidades contemporáneas con una mezcla de fuerzas estatales y del mercado. La profundización de relaciones sino-cubanas en recientes décadas no presenta ningún desafío a los Estados Unidos; al contrario, abre nuevas oportunidades de cooperación trilateral.
Mexico, China, and the Politics of Trust
Authors: Hearn Adrian H. 
Published: July 2015

Described by political scientists as a necessary condition for efficiency, productivity, and prosperity, trust has become a precept of good governance with global reach. The concept is often marshaled to support a conservative political agenda of state retrenchment and market deregulation. Proponents of this agenda argue that the natural inclination of private actors to trust and cooperate with each other is undermined by government monitoring and compliance regulations. The evidence from Mexico points to an alternative conclusion: when carefully targeted, state support to private actors has strengthened rather than impeded trusting relationships between suppliers, customers, and investors. Commercial competition with China raises an urgent challenge for Mexico’s government: to broaden the scope of its assistance beyond a narrow set of elite firms to small and medium-sized enterprises, including those of the resident Chinese community. Considerado por politólogos como condición necesaria para la eficiencia, productividad y prosperidad, la confianza ha llegado a ser un precepto de buena gobernanza con alcance global. Se utiliza el concepto a menudo para respaldar una agenda política conservadora de recortes del estado y desregulación del mercado. Los defensores de tal agenda sostienen que la inclinación natural de actores privados de confiar y cooperar entre sí es socavada por la fiscalización gubernamental y las regulaciones de cumplimiento. La evidencia desde México apunta a una conclusión alternativa: seleccionado cuidadosamente, el apoyo estatal a actores privados ha fortalecido en vez de impedir las relaciones de confianza entre proveedores, clientes, e inversores. La competencia comercial con la China presenta un desafío urgente para el gobierno de México: de ampliar el alcance de su ayuda más allá de un conjunto reducido de compañías élites hacia pequeñas y medianas empresas, inclu-yendo las de la comunidad residente china.
Tourism and Political Choices of Indigenous Populations in Yucatán
Authors: Hawn Heather , Tison Jennifer 
Published: July 2015

Anthropologists and other social scientists have traditionally decried the effects of tourism on exotic cultures, but contemporary research reveals that this growing resource is being utilized by rational actors to achieve political and social gains. Study of the effects of tourism on the political choices of Maya in Yucatán suggests that tourism helps indigenous actors negotiate favorable terms with state and private actors. Further, the presence of tourists reorganizes the costs and benefits of behaviors such as protests or land invasions. Thus this extrainstitutional behavior is more prevalent in the largest tourist areas (Cancún, Mérida, and Chichén Itzá) and covert behaviors such as pilfering and sick-outs in nontourist areas. Tradicionalmente, los antropólogos y científicos sociales han condenado los efectos del turismo sobre culturas exóticas, pero la investigación contemporánea pone de manifiesto que este recurso creciente está siendo utilizado por actores racionales para lograr beneficios políticos y sociales. El estudio de los efectos del turismo sobre las preferencias políticas de los maya en Yucatán sugiere que el turismo ayuda a los actores indígenas a negociar términos favorables con actores estatales y privados. Además, la presencia de turistas reorganiza los costos y beneficios de conductas como protestas o invasiones de tierras. Entonces, esta conducta extra-institucional es más prevalente en las zonas turísticas más grandes (Cancún, Mérida y Chichén Itzá) y las conductas encubiertas como el rateo y las ausencias colectivas por enfermedad prevalecen en zonas no-turísticas.