bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitotic Vulnerability in Triple-Negative Breast Cancer Associated with LIN9 Is Targetable with BET Inhibitors
Authors: Sahni Jennifer M. , Gayle Sylvia S. , Webb Bryan M. , Weber-Bonk Kristen L. , Seachrist Darcie D. , Singh Salendra , Sizemore Steven T. , Restrepo Nicole A. , Bebek Gurkan , Scacheri Peter C. , Varadan Vinay , Summers Matthew K. , Keri Ruth A. 
Published: August 2017

Abstract
Triple-negative breast cancers (TNBC) are highly aggressive, lack FDA-approved targeted therapies, and frequently recur, making the discovery of novel therapeutic targets for this disease imperative. Our previous analysis of the molecular mechanisms of action of bromodomain and extraterminal protein inhibitors (BETi) in TNBC revealed these drugs cause multinucleation, indicating BET proteins are essential for efficient mitosis and cytokinesis. Here, using live cell imaging, we show that BET inhibition prolonged mitotic progression and induced mitotic cell death, both of which are indicative of mitotic catastrophe. Mechanistically, the mitosis regulator LIN9 was a direct target of BET proteins that mediated the effects of BET proteins on mitosis in TNBC. Although BETi have been proposed to function by dismantling super-enhancers (SE), the LIN9 gene lacks an SE but was amplified or overexpressed in the majority of TNBCs. In addition, its mRNA expression predicted poor outcome across breast cancer subtypes. Together, these results provide a mechanism for cancer selectivity of BETi that extends beyond modulation of SE-associated genes and suggest that cancers dependent upon LIN9 overexpression may be particularly vulnerable to BETi. Cancer Res; 77(19); 5395–408. ©2017 AACR.
Preclinical Evaluation of Intravesical Cisplatin Nanoparticles for Non–Muscle-Invasive Bladder Cancer
Authors: Kates Max , Date Abhijit , Yoshida Takahiro , Afzal Umara , Kanvinde Pranjali , Babu Taarika , Sopko Nikolai A. , Matsui Hotaka , Hahn Noah M. , McConkey David J. , Baras Alexander , Hanes Justin , Ensign Laura , Bivalacqua Trinity J. 
Published: August 2017

Abstract
Purpose: Prior clinical trials evaluating cisplatin for non–muscle-invasive bladder cancer (NMIBC) were stopped due to local and systemic toxicity. Currently, there is still a need for improved intravesical therapies, and nanoparticle-based CDDP may be efficacious without the toxicity of free cisplatin observed in the past.
Experimental Design: Cisplatin nanoparticles (CDDP NPs) were developed using biocompatible poly(l-aspartic acid sodium salt; PAA), both with and without low and high grafting density of methoxy-polyethylene glycol (PEG). In vitro cytotoxicity studies confirmed activity of CDDP NPs and CDDP solution against a papillary bladder cancer cell line. Local toxicity was assessed by three weekly intravesical administrations of CDDP formulations. CDDP NPs and CDDP solution were evaluated for bladder absorption in murine models 1 and 4 hours after intravesical administration. In vivo efficacy was evaluated in an immunocompetent carcinogen model of NMIBC.
Results: CDDP NPs showed decreased local toxicity, as assessed by bladder weight, compared with CDDP solution. Furthermore, &gt;2 μg/mL of platinum was observed in mouse serum after intravesical administration of CDDP solution, whereas serum platinum was below the limit of quantification after intravesical administration of CDDP NPs. CDDP NPs provided significantly increased (P &lt; 0.05) drug levels in murine bladders compared with CDDP solution for at least 4 hours after intravesical administration. In vivo, CDDP NPs reduced cancer cell proliferation compared with untreated controls, and was the only treatment group without evidence of invasive carcinoma.
Conclusions: Cisplatin-loaded PAA NPs have the potential to improve intravesical treatment of NMIBC while reducing local and systemic side effects. Clin Cancer Res; 23(21); 6592–601. ©2017 AACR.
Inter-Rater Reliability and Downstream Financial Implications of Electrocardiography Screening in Young Athletes
Authors: Dhutia Harshil , Malhotra Aneil , Yeo Tee Joo , Ster Irina Chis , Gabus Vincent , Steriotis Alexandros , Dores Helder , Mellor Greg , García-Corrales Carmen , Ensam Bode , Jayalapan Viknesh , Ezzat Vivienne Anne , Finocchiaro Gherardo , Gati Sabiha , Papadakis Michael , Tome-Esteban Maria , Sharma Sanjay 
Published: August 2017

Background—
Preparticipation screening for cardiovascular disease in young athletes with electrocardiography is endorsed by the European Society of Cardiology and several major sporting organizations. One of the concerns of the ECG as a screening test in young athletes relates to the potential for variation in interpretation. We investigated the degree of variation in ECG interpretation in athletes and its financial impact among cardiologists of differing experience.

Methods and Results—
Eight cardiologists (4 with experience in screening athletes) each reported 400 ECGs of consecutively screened young athletes according to the 2010 European Society of Cardiology recommendations, Seattle criteria, and refined criteria. Cohen κ coefficient was used to calculate interobserver reliability. Cardiologists proposed secondary investigations after ECG interpretation, the costs of which were based on the UK National Health Service tariffs. Inexperienced cardiologists were more likely to classify an ECG as abnormal compared with experienced cardiologists (odds ratio, 1.44; 95% confidence interval, 1.03–2.02). Modification of ECG interpretation criteria improved interobserver reliability for categorizing an ECG as abnormal from poor (2010 European Society of Cardiology recommendations; κ=0.15) to moderate (refined criteria; κ=0.41) among inexperienced cardiologists; however, interobserver reliability was moderate for all 3 criteria among experienced cardiologists (κ=0.40–0.53). Inexperienced cardiologists were more likely to refer athletes for further evaluation compared with experienced cardiologists (odds ratio, 4.74; 95% confidence interval, 3.50–6.43) with poorer interobserver reliability (κ=0.22 versus κ=0.47). Interobserver reliability for secondary investigations after ECG interpretation ranged from poor to fair among inexperienced cardiologists (κ=0.15–0.30) and fair to moderate among experienced cardiologists (κ=0.21–0.46). The cost of cardiovascular evaluation per athlete was $175 (95% confidence interval, $142–$228) and $101 (95% confidence interval, $83–$131) for inexperienced and experienced cardiologists, respectively.

Conclusions—
Interpretation of the ECG in athletes and the resultant cascade of investigations are highly physician dependent even in experienced hands with important downstream financial implications, emphasizing the need for formal training and standardized diagnostic pathways.
The checklist of photosynthetic euglenoids (order Euglenales) of the Czech Republic: ecology, taxonomy, distribution
Authors: JURÁŇ JOSEF 
Published: August 2017

This study brings results of a floristic survey of photosynthetic euglenoids. Data in this survey come from a floristic examination of more than 200 localities during the years 2008–2014 in combination with the literature data recorded from the end of 19th century to the present. In this work, 284 euglenoid taxa which belong to the genera Colacium (6 taxa), Cryptoglena (2 species), Discoplastis (1 species), Euglena (48 taxa), Euglenaformis (1 species), Euglenaria (3 species), Lepocinclis (36 taxa), Monomorphina (7 species), Phacus (71 taxa), Strombomonas (16 taxa) and Trachelomonas (93 taxa) are listed. Four categories of rarity were designed—common (52 taxa), rare (44 taxa), very rare (120 taxa) and data deficient (68 taxa). In checklist, ecological characteristics (colonized habitats, life strategy, level of rarity) of taxa are shown. Number of species is compared with several works from European countries (Hungary, Great Britain, Poland, Romania, Slovak Republic, Slovenia and Ukraine). Taxonomic notes and new combinations reflecting recent works based on molecular-morphology are made and discussed. Results of this study bring next part to the knowledge of the Czech Republic algal flora.
Toward Generalizing the Impact of Surface Heating, Stratification, and Terrain Geometry on the Daytime Heat Export from an Idealized Valley
Authors: Leukauf Daniel , Gohm Alexander , Rotach Mathias W. 
Published: August 2017

AbstractThe convective export of heat from different types of idealized valleys for fair-weather daytime conditions is studied with the Weather Research and Forecasting (WRF) Model. The goal is to test the hypothesis that the total export of heat over the course of the day depends on a so-called breakup parameter B. The breakup parameter is the ratio between the energy required to neutralize the initially stably stratified valley atmosphere and the total energy provided by the surface sensible heat flux. To achieve this goal, simulations with different surface heating, initial stability, and terrain geometry are performed. The fraction of the sensible heat provided at the surface that is exported at crest height over the course of the day depends exponentially on B. The effects of variations of the valley width, crest height, forcing amplitude, and initial stratification on the total export of heat can be described by this function. The complete neutralization of the stratification in the valley is never reached if B exceeds a critical value of about 0.65 for an initially constant stratification. For a valley geometry with linear slopes and sharp crests, up to 60% of the provided heat is exported for the strongest forcing and the weakest stability (i.e., B ≈ 0.1), whereas less than 5% is exported for B > 0.65. The minimum heat export for larger B is higher for rounded crests (10%) and for a deep residual layer that extends to above crest height (17%).
A New Mechanism of the Slow Eastward Propagation of Unstable Disturbances with Convection in the Tropics: Implications for the MJO
Authors: Hayashi Michiya , Itoh Hisanori 
Published: August 2017

Abstract
To understand the slow eastward propagation of the Madden–Julian oscillation (MJO), the authors propose a new mechanism of slow eastward propagation of an unstable disturbance [slow eastward-propagating disturbance (SED)] in the tropics assuming a simplified instability source. Two conditions are necessary over the convective region associated with the SED for this mechanism: (i) moderately negative gross moist stability (GMS) and (ii) strong stretching in the lower layer. The instability due to (i) needs to be moderate for causing a propagating convective disturbance. Under the structure of twin cyclonic vortices to the west and convection to the east, stretching of planetary vorticity associated with the convection produces cyclonic vorticity, which results in eastward propagation of the vortices. Equatorial β-plane dynamics explain the positional relation between the twin vortices and convection coherently: strong equatorial low-level westerly winds accompanying the vortices induce convergence and thus convection to the eastern side of the vortices. The SED may be considered an eastward-propagating large-scale “convective vortex” (LCV). Its dynamics is ascertained by parameter-sweep numerical experiments using a simple model with two cumulus parameterization schemes that can produce negative GMS in the convective region.
This propagation mechanism is based on dynamics and thus does not relate to the instability that may be sensitive to schemes for clouds, moisture, and radiation in realistic situations. Therefore, when an LCV is generated in the tropics under any circumstance, and strong stretching occurs, the LCV necessarily propagates eastward slowly because of the dynamics of the SED. Thus, this mechanism is applicable to the MJO.
Potential Vorticity Diagnostics to Quantify Effects of Latent Heating in Extratropical Cyclones. Part I: Methodology
Authors: Büeler Dominik , Pfahl Stephan 
Published: August 2017

Abstract
Extratropical cyclones develop because of baroclinic instability, but their intensification is often substantially amplified by diabatic processes, most importantly, latent heating (LH) through cloud formation. Although this amplification is well understood for individual cyclones, there is still need for a systematic and quantitative investigation of how LH affects cyclone intensification in different, particularly warmer and moister, climates. For this purpose, the authors introduce a simple diagnostic to quantify the contribution of LH to cyclone intensification within the potential vorticity (PV) framework. The two leading terms in the PV tendency equation, diabatic PV modification and vertical advection, are used to derive a diagnostic equation to explicitly calculate the fraction of a cyclone’s positive lower-tropospheric PV anomaly caused by LH. The strength of this anomaly is strongly coupled to cyclone intensity and the associated impacts in terms of surface weather. To evaluate the performance of the diagnostic, sensitivity simulations of 12 Northern Hemisphere cyclones with artificially modified LH are carried out with a numerical weather prediction model. Based on these simulations, it is demonstrated that the PV diagnostic captures the mean sensitivity of the cyclones’ PV structure to LH as well as parts of the strong case-to-case variability. The simple and versatile PV diagnostic will be the basis for future climatological studies of LH effects on cyclone intensification.
Adverse Events Following Cervical Disc Arthroplasty: A Systematic Review
Authors: Xu Jordan C. , Goel Chandni , Shriver Michael F. , Tanenbaum Joseph E. , Steinmetz Michael P. , Benzel Edward C. , Mroz Thomas E. 
Published: August 2017

Study Design: Systematic review. Objectives: Cervical arthroplasty is an increasingly popular treatment of cervical radiculopathy and myelopathy. An understanding of the potential adverse events (AEs) is important to help both clinicians and patients. We sought to provide a comprehensive systematic review of the AEs reported in all randomized controlled trials (RCTs) of cervical disc arthroplasty in an attempt to characterize the quality of reporting. Methods: We conducted a systematic review of MEDLINE and Web of Science for RCTs of cervical disc arthroplasty reporting AEs. We reported the most frequently mentioned AEs, including dysphagia/dysphonia, vascular compromise, dural injury, and infections. We recorded the presence of industry funding and scored the quality of collection methods and reporting of AEs. Results: Of the 3734 identified articles, 29 articles met full inclusion criteria. The quality of AE reporting varied significantly between studies, and a combined meta-analysis was not feasible. The 29 articles covered separate 19 RCTs. Eight studies were US Food and Drug Administration (FDA) investigational device exemption (IDE) trials. Rates were recorded for the following AEs: dysphagia/dysphonia (range = 1.3% to 27.2%), vascular compromise (range = 1.1% to 2.4%), cervical wound infection (range = 1.2% to 22.5%), and cerebrospinal fluid leak (range = 0.8% to 7.1%). Conclusions: There is a lack of consistency in reporting of AEs among RCTs of cervical arthroplasty. FDA IDE trials scored better in AE event reporting compared to other studies. Standardized definitions for AEs and standardized data collection methodology are needed to improve future studies.
Platelet dense granules begin to selectively accumulate mepacrine during proplatelet formation
Authors: Hanby Hayley A. , Bao Jialing , Noh Ji-Yoon , Jarocha Danuta , Poncz Mortimer , Weiss Mitchell J. , Marks Michael S. 
Published: August 2017

Key PointsCompartments labeled by the vital dense granule dye mepacrine are distinct from acidic structures in platelets but not in megakaryocytes. Distinct hypoacidic mepacrine-labeled structures first appear during megakaryocyte differentiation to proplatelets.
The role of the multidisciplinary team in the management of deep infiltrating endometriosis
Authors: Ugwumadu Lilian , Chakrabarti Rima , Williams-Brown Elaine , Rendle John , Swift Ian , John Babbin , Allen-Coward Heather , Ofuasia Emmanuel 
Published: August 2017

AbstractThe multidisciplinary team (MDT) is considered good practice in the management of chronic conditions and is now a well-established part of clinical care in the NHS. There has been a recent drive to have MDTs in the management of women with severe endometriosis requiring complex surgery as a result of recommendations from the European Society for Human Reproduction and Embryology (ESHRE) and British Society for Gynaecological Endoscopy (BSGE). The multidisciplinary approach to the management of patients with endometriosis leads to better results in patient outcomes; however, there are potentially a number of barriers to its implementation and maintenance. This paper aims to review the potential benefits, disadvantages and barriers of the multidisciplinary team in the management of severe endometriosis.
The typically developing paediatric foot: how flat should it be? A systematic review
Authors: Uden Hayley , Scharfbillig Rolf , Causby Ryan 
Published: August 2017

AbstractBackgroundAll typically developing children are born with flexible flat feet, progressively developing a medial longitudinal arch during the first decade of their lives. Whilst the child's foot is expected to be flat, there is currently no consensus as to how flat this foot should be. Furthermore, whilst feet are observed to decrease in flatness with increasing age, it is not known how flat they should be at each age increment. The objective of this systematic review is to define the postural characteristics of the ‘typically’ developing paediatric foot.MethodsThe PRISMA protocol was applied to compare all data currently published describing the typical development of the paediatric foot. The Epidemiological Appraisal Instrument (EAI) was used to assess the risk of bias of the included studies.ResultsThirty four epidemiological papers pertaining to the development of the paediatric foot were graphically compared. Sixteen different foot posture assessments were identified of which footprint based measures were the most reported outcome.ConclusionFirstly, the use of the term normal in relation to foot posture is misleading in the categorisation of the paediatric foot, as indeed a flat foot posture is a normal finding at specific ages. Secondly, the foot posture of the developing child is indeed age dependent and has been shown to change over time. Thirdly, no firm conclusion could be reached as to which age the foot posture of children ceases to develop further, as no two foot measures are comparable, therefore future research needs to consider the development of consensus recommendations as to the measurement of the paediatric foot, using valid and reliable assessment tools.
Chemostratigraphic and depositional characterization of the Niobrara Formation: Techniques for assessing lateral heterogeneity, CEMEX Quarry, Lyons, Colorado, Denver-Julesburg Basin
Authors: O’Neal Denton , Sonnenberg Stephen 
Published: August 2017

The Late Cretaceous (89–82 Ma) Niobrara Formation is the primary target for unconventional horizontal well activity in the Denver Basin. With an abundance of horizontal activity, the question of well-length scale lateral heterogeneity becomes paramount addressing steering practices, completion, and ultimately well performance. We have incorporated detailed core description, high-resolution chemostratigraphy, and petrophysical logs from four near-surface cores taken at the CEMEX Lyons Quarry to assess lateral heterogeneity. Cores were originally intended to determine the geochemistry and areal extent of the Fort Hays Limestone Member of the Niobrara Formation, CEMEX’s primary target for cement production. However, due to the cores’ proximity to one another (91.4–609.6 m [300–2000 ft]) and the presence of not only the Fort Hays Limestone but also the petroliferous chalks and marls of the Lower Smoky Hill Member (including the D Chalk, C Marl, and a portion of the C Chalk), the data set can also be used as a proxy to model changes along a pseudohorizontal wellbore. Observations include lateral bentonite discontinuity, trace element and organic carbon variations, and distinct changes in sedimentary structures. Well-length sedimentological and stratigraphic changes may have unique implications for unconventional oil and gas development.
Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer—PROSELICA
Authors: Eisenberger Mario , Hardy-Bessard Anne-Claire , Kim Choung Soo , Géczi Lajos , Ford Daniel , Mourey Loïc , Carles Joan , Parente Phillip , Font Albert , Kacso Gabriel , Chadjaa Mustapha , Zhang Wenping , Bernard John , de Bono Johann 
Published: August 2017

Purpose Cabazitaxel 25 mg/m2 (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m2 (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25. To claim noninferiority of C20 (maintenance of ≥ 50% of the OS benefit of C25 v mitoxantrone in TROPIC) with 95% confidence level, the upper boundary of the CI of the hazard ratio (HR) for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary end points included progression-free survival, prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety. Results Overall, 1,200 patients were randomly assigned (C20, n = 598; C25, n = 602). Baseline characteristics were similar in both arms. Median OS was 13.4 months for C20 and 14.5 months for C25 (HR, 1.024). The upper boundary of the HR CI was 1.184 (less than the 1.214 noninferiority margin). Significant differences were observed in favor of C25 for PSA response (C20, 29.5%; C25, 42.9%; nominal P < .001) and time to PSA progression (median: C20, 5.7 months; C25, 6.8 months; HR for C20 v C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between cohorts. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. Conclusion The efficacy of cabazitaxel in postdocetaxel patients with mCRPC was confirmed. The noninferiority end point was met; C20 maintained ≥ 50% of the OS benefit of C25 versus mitoxantrone in TROPIC. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.
Cellular and molecular mechanisms coordinating pancreas development
Authors: Bastidas-Ponce Aimée , Scheibner Katharina , Lickert Heiko , Bakhti Mostafa 
Published: August 2017

ABSTRACT
The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer.