bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and design of the Pan African Pulmonary hypertension Cohort (PAPUCO) study: implementing a contemporary registry on pulmonary hypertension in Africa
Authors: Thienemann Friedrich , Dzudie Anastase , Mocumbi Ana O , Blauwet Lori , Sani Mahmoud U , Karaye Kamilu M , Ogah Okechukwu S , Mbanze Irina , Mbakwem Amam , Udo Patience , Tibazarwa Kemi , Ibrahim Ahmed S , Burton Rosie , Damasceno Albertino , Stewart Simon , Sliwa Karen 
Published: October 2014

IntroductionPulmonary hypertension (PH) is a devastating, progressive disease with increasingly debilitating symptoms and usually shortened overall life expectancy due to a narrowing of the pulmonary vasculature and consecutive right heart failure. Little is known about PH in Africa, but limited reports suggest that PH is more prevalent in Africa compared with developed countries due to the high prevalence of risk factors in the region.Methods and analysisA multinational multicentre registry-type cohort study was established and tailored to resource-constraint settings to describe disease presentation, disease severity and aetiologies of PH, comorbidities, diagnostic and therapeutic management, and the natural course of PH in Africa. PH will be diagnosed by specialist cardiologists using echocardiography (right ventricular systolic pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure), usually accompanied by shortness of breath, fatigue, peripheral oedema and other cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per guidelines (European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines). Additional investigations such as a CT scan, a ventilation/perfusion scan or right heart catheterisation will be performed at the discretion of the treating physician. Functional tests include a 6 min walk test and the Karnofsky Performance Score. The WHO classification system for PH will be applied to describe the different aetiologies of PH. Several substudies have been implemented within the registry to investigate specific types of PH and their outcome at up to 24 months. Data will be analysed by an independent institution following a data analyse plan.Ethics and disseminationAll local ethics committees of the participating centres approved the protocol. The data will be disseminated through peer-reviewed journals at national and international conferences and public events at local care providers.
Screening for gonorrhoea using samples collected through the English National Chlamydia Screening Programme and risk of false positives: a national survey of Local Authorities
Authors: Field Nigel , Kennedy Iain , Folkard Kate , Duffell Stephen , Town Katy , Ison Catherine A , Hughes Gwenda 
Published: October 2014

ObjectivesTo investigate use of dual tests forChlamydia trachomatisandNeisseria gonorrhoeaeon samples collected through the National Chlamydia Screening Programme (NCSP) in England.Design and settingDuring May–July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15–24 years.Main outcome measures(1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%.Results64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450–4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17–67%.ConclusionsOver half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed.
Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma
Authors: Kim Jung Ho , Kim Kyung-Ju , Bae Jeong Mo , Rhee Ye-Young , Cho Nam-Yun , Lee Hye Seung , Kang Gyeong Hoon 
Published: October 2014

AimsCrohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) is associated with a favourable prognosis and microsatellite instability-high (MSI-H) status. However, there is a lack of consensus on optimal criteria for CLR assessment. The aim of this study was to comparatively validate traditional and novel assessment criteria for CLR.MethodsCLR status in 212 MSI-H CRCs was assessed independently by two pathologists using three different criteria: (1) traditional semiquantitative criteria (Graham–Appelman criteria), (2) the largest lymphoid aggregate (LA) size-based criteria (Ueno criteria) and (3) LA density-based criteria (Väyrynen–Mäkinen criteria).ResultsAmong the three criteria, the Väyrynen–Mäkinen criteria-based CLR assessment showed the best interobserver agreement (κ value, 0.71; intraclass correlation coefficient, 0.76). Pathologically, intense CLR (grade 2) by Graham–Appelman criteria, active CLR (largest LA size ≥1 mm) by Ueno criteria and high-density CLR (≥0.38 LAs/mm) by Väyrynen–Mäkinen criteria significantly correlated with an early cancer stage (stage I/II). In Kaplan–Meier analysis, both CLR statuses determined by Ueno criteria and Väyrynen–Mäkinen criteria were associated with significant differences in disease-free survival in MSI-H CRC patients (p=0.005 and p=0.001, respectively). In multivariable analysis, both active CLR and high-density CLR proved to be independent favourable prognostic factors in MSI-H CRC (HR, 0.47; 95% CI 0.24 to 0.9 for active CLR and HR, 0.5; 95% CI 0.28 to 0.89 for high-density CLR).ConclusionsOur study confirms that the two recently suggested criteria (Ueno criteria and Väyrynen–Mäkinen criteria) for CLR assessment are fairly reproducible methods and can serve as superior prognosticators in CRC.
Bioactive Prolactin Levels and Risk of Breast Cancer: A Nested Case–Control Study
Authors: Tworoger Shelley S. , Rice Megan S. , Rosner Bernard A. , Feeney Yvonne B. , Clevenger Charles V. , Hankinson Susan E. 
Published: October 2014

Abstract
Background: Prolactin is a lactogenic hormone associated with breast cancer risk in prospective studies, which used immunoassays. The immunoassay captures multiple isoforms and may not fully reflect the biologic activity of prolactin relevant to breast carcinogenesis.
Methods: We considered plasma bioactive prolactin levels measured by the Nb2 lymphoma cell bioassay, which is sensitive to the somatolactogenic activity of prolactin and growth hormone, within a nested case–control study of invasive breast cancer in the Nurses' Health Studies (NHS/NHSII). We also considered associations with breast cancer risk factors.
Results: We had bioassay measures on 1,329 cases and 1,329 controls. Bioassay levels were inversely associated with parity (4+ vs. 0 children = −18%, P = 0.01), body mass index (30+ vs. &lt;22 kg/m2 = −16%, P &lt; 0.01), and age at menopause (53+ vs. 48 years = −18%, P = 0.03) and positively with family history of breast cancer (yes vs. no = 14%, P &lt; 0.01). The relative risk (RR) comparing the top versus bottom quartile of bioassay levels was 1.19 [95% confidence intervals (CI), 0.94–1.51; Ptrend = 0.18]. The association was suggestively stronger for postmenopausal (RR = 1.36; 95% CI, 0.93–1.98; Ptrend = 0.12) versus premenopausal women (RR = 0.99; 95% CI, 0.71–1.37; Ptrend = 0.71). There was an association for cases diagnosed &lt;4 years after blood draw (RR = 2.66; 95% CI, 1.45–4.89; Ptrend &lt; 0.01), but not for cases diagnosed later. We did not observe differential associations by estrogen receptor status or other tumor characteristics.
Conclusions: Our results show similar associations for prolactin levels measured by bioassay and by immunoassay with both breast cancer risk factors and risk.
Impact: Future work examining risk prediction model of breast cancer can use the immunoassay to accurately characterize risk. Cancer Epidemiol Biomarkers Prev; 24(1); 73–80. ©2014 AACR.
Dual Disruption of DNA Repair and Telomere Maintenance for the Treatment of Head and Neck Cancer
Authors: Lajud Shayanne A. , Nagda Danish A. , Yamashita Taku , Zheng Jun , Tanaka Nobuaki , Abuzeid Waleed M. , Civantos Alyssa , Bezpalko Orysia , O'Malley Bert W. , Li Daqing 
Published: October 2014

AbstractPurpose: Poly(ADP-ribose) polymerases (PARP) and the Mre11, Rad50, and Nbs1 (MRN) complex are key regulators of DNA repair, and have been recently shown to independently regulate telomere length. Sensitivity of cancers to PARPi is largely dependent on the BRCAness of the cells. Unfortunately, the vast majority of cancers are BRCA-proficient. In this study, therefore, we investigated whether a targeted molecular “hit” on the MRN complex, which is upstream of BRCA, can effectively sensitize BRCA-proficient head and neck squamous cell carcinoma (HNSCC) to PARP inhibitor (PARPi).Experimental Design: Human HNSCC cell lines and a mouse model with HNSCC xenografts were used in this study. In vitro and in vivo studies were conducted to evaluate the effects and underlying mechanisms of dual molecular disruption of PARP and the MRN complex, using a pharmacologic inhibitor and a dominant-negative Nbs1 expression vector, respectively.Results: Our findings demonstrate that downregulation of the MRN complex disrupts homologous recombination, and, when combined with PARPi, leads to accumulation of lethal DNA double-strand breaks. Moreover, we show that PARPi and MRN complex disruption induces significantly shortening telomere length. Together, our results demonstrate that dual disruption of these pathways causes significant cell death in BRCA-proficient tumor cells both in vitro and in vivo.Conclusion: Our study, for the first time, elucidates a novel mechanism for MRN complex and PARP inhibition beyond DNA repair, demonstrating the feasibility of a dual disruption approach that extends the utility of PARPi to the treatment of BRCA-proficient cancers. Clin Cancer Res; 20(24); 6465–78. ©2014 AACR.
A Phase I Dose Escalation and Expansion Study of the Anticancer Stem Cell Agent Demcizumab (Anti-DLL4) in Patients with Previously Treated Solid Tumors
Authors: Smith David C. , Eisenberg Peter D. , Manikhas Georgy , Chugh Rashmi , Gubens Matthew A. , Stagg Robert J. , Kapoun Ann M. , Xu Lu , Dupont Jakob , Sikic Branimir 
Published: October 2014

Abstract
Purpose: This phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of demcizumab (OMP-21M18), a humanized IgG2 mAb targeting the Notch ligand DLL4 in adult patients with advanced malignancies.
Experimental Design: Standard 3+3 design, with demcizumab 0.5, 1, 2.5, or 5 mg/kg weekly or 2.5, 5, or 10 mg/kg every other week, with an expansion cohort at 10 mg/kg every other week. Dose-limiting toxicities (DLT) were assessed during the first 28 days.
Results: Fifty-five patients received demcizumab (15 weekly, 18 every other week, 21 expansion cohort, 1 loading dose). No more than one DLT was seen at any dose level. The MTD was not reached for either schedule. Treatment-related adverse events occurring in &gt;10% of patients were hypertension or blood pressure increased (47%), fatigue (31%), anemia (22%), headache (20%), nausea (13%), hypoalbuminemia (11%), dizziness (11%), and dyspnea (11%). One patient dosed at 2.5 mg/kg developed reversible right-sided heart failure after 63 days on treatment and 4 dosed at 10 mg/kg developed congestive heart failure after ≥98 days on treatment. Five patients were hospitalized with bleeding episodes (2 episodes of tumor-associated bleeding). Sixteen of 25 (64%) evaluable patients at 10 mg/kg had evidence of stabilization of disease or response.
Conclusion: Demcizumab was generally well tolerated at doses ≤5 mg weekly with disease stabilization and decreases in tumor size demonstrating antitumor activity. Hypertension was the most common adverse event that was clearly related to treatment. Prolonged administration was associated with an increased risk of congestive heart failure. Clin Cancer Res; 20(24); 6295–303. ©2014 AACR.
miR-154* and miR-379 in the DLK1-DIO3 MicroRNA Mega-Cluster Regulate Epithelial to Mesenchymal Transition and Bone Metastasis of Prostate Cancer
Authors: Gururajan Murali , Josson Sajni , Chu Gina Chia-Yi , Lu Chia-Lun , Lu Yi-Tsung , Haga Christopher L. , Zhau Haiyen E. , Liu Chunyan , Lichterman Jake , Duan Peng , Posadas Edwin M. , Chung Leland W.K. 
Published: October 2014

AbstractPurpose: MicroRNAs in the delta-like 1 homolog–deiodinase, iodothyronine 3 (DLK1-DIO3) cluster have been shown to be critical for embryonic development and epithelial to mesenchymal transition (EMT). DLK1-DIO3 cluster miRNAs are elevated in the serum of patients with metastatic cancer. However, the biologic functions of these miRNAs in the EMT and metastasis of cancer cells are poorly understood. We previously demonstrated the oncogenic and metastatic role of miR-409-3p/5p, a member of this cluster, in prostate cancer. In this study, we defined the role of miR-154* and miR-379, two key members of this cluster, in prostate cancer progression and bone metastasis in both cell line models and clinical specimens.Experimental Design: Genetic manipulation of miR-154* and miR-379 was performed to determine their role in tumor growth, EMT, and bone metastasis in mouse models. We determined the expression of miR-154* in prostate cancer clinical samples and bone metastasis samples using in situ hybridization and quantum dot labeling.Results: Elevated expression of miR-154* and miR-379 was observed in bone metastatic prostate cancer cell lines and tissues, and miR-379 expression correlated with progression-free survival of patients with prostate cancer. Intracardiac inoculation (to mimic systemic dissemination) of miR-154* inhibitor-treated bone metastatic ARCaPM prostate cancer cells in mice led to decreased bone metastasis and increased survival.Conclusion: miR-154* and miR-379 play important roles in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding has particular translational importance because miRNAs in the DLK1-DIO3 cluster can be attractive biomarkers and possible therapeutic targets to treat bone metastatic prostate cancer. Clin Cancer Res; 20(24); 6559–69. ©2014 AACR.
Prospective Blinded Study of BRAFV600E Mutation Detection in Cell-Free DNA of Patients with Systemic Histiocytic Disorders
Authors: Hyman David M. , Diamond Eli L. , Vibat Cecile Rose T. , Hassaine Latifa , Poole Jason C. , Patel Minal , Holley Veronica R. , Cabrilo Goran , Lu Timothy T. , Arcila Maria E. , Chung Young Rock , Rampal Raajit , Lacouture Mario E. , Rosen Neal , Meric-Bernstam Funda , Baselga José , Kurzrock Razelle , Erlander Mark G. , Janku Filip , Abdel-Wahab Omar 
Published: October 2014

Abstract
Patients with Langerhans cell histiocytosis (LCH) and Erdheim–Chester disease (ECD) have a high frequency of BRAFV600E mutations and respond to RAF inhibitors. However, detection of mutations in tissue biopsies is particularly challenging in histiocytoses due to low tumor content and stromal contamination. We applied a droplet-digital PCR assay for quantitative detection of the BRAFV600E mutation in plasma and urine cell-free (cf) DNA and performed a prospective, blinded study in 30 patients with ECD/LCH. There was 100% concordance between tissue and urinary cfDNA genotype in treatment-naïve samples. cfDNA analysis facilitated identification of previously undescribed KRASG12S-mutant ECD and dynamically tracked disease burden in patients treated with a variety of therapies. These results indicate that cfDNA BRAFV600E mutational analysis in plasma and urine provides a convenient and reliable method of detecting mutational status and can serve as a noninvasive biomarker to monitor response to therapy in LCH and ECD.
Significance: Patients with BRAFV600E-mutant histiocytic disorders have remarkable responses to RAF inhibition, but mutation detection in tissue in these disorders is challenging. Here, we identify that analysis of plasma and urinary cfDNA provides a reliable method to detect the BRAFV600E mutation and monitor response to therapy in these disorders. Cancer Discov; 5(1); 64–71. ©2014 AACR.
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Cymatosirella Dąbek, Witkowski &amp; Sabbe gen. nov., a new marine benthic diatom genus (Bacillariophyta) belonging to the family Cymatosiraceae
Authors: DĄBEK PRZEMYSŁAW , SABBE KOEN , WITKOWSKI ANDRZEJ , ARCHIBALD COLIN , KURZYDŁOWSKI KRZYSZOF J. , ZGŁOBICKA IZABELA 
Published: October 2014

We present a new marine benthic diatom genus Cymatosirella gen. nov. The genus belongs to the family Cymatosiraceae and has been assigned to the subfamily Extubocelluloideae on the basis of ultrastructural cell wall features. It has isovalvate cells with undulate valves and is characterized by the absence of tubular processes and the occurrence of hollow spines which are observed for the first time in the Cymatosiraceae. The new genus contains four species, two of which are transferred from the genus Cymatosira, viz. Cymatosirella capensis comb. nov. and Cymatosirella minutissima comb. nov., and two which are new to science, viz. Cymatosirella benguelensis sp. nov. and Cymatosirella taylorii sp. nov. Cymatosirella capensis is chosen as the generitype. The new genus includes a group of very small taxa inhabiting the intertidal zone of the Atlantic Ocean with three species in South Africa and one in Europe. C. capensis was originally described by Giffen from Langebaan Lagoon (a shallow marine inlet in the southern part of Saldanha Bay, Western Cape Province), on the basis of light microscopy only, and has to date only been illustrated by line drawings. C. minutissima, so far only known from the Westerschelde estuary (The Netherlands), has previously been documented in more detail using both light and electron microscopy. Here, we present the results of detailed light and electron microscopical investigations of C. capensis, both from its original type material and from recently collected samples from the type locality and neighboring littoral areas in the Western Cape Province, and of the new species C. benguelensis and C. taylorii, also from Western Cape localities. All species are compared with similar small taxa belonging to the Cymatosiraceae, subfamily Extubocelluloideae.
Hydrometeorological Analysis and Remote Sensing of Extremes: Was the July 2012 Beijing Flood Event Detectable and Predictable by Global Satellite Observing and Global Weather Modeling Systems?
Authors: Zhang Yu , Hong Yang , Wang Xuguang , Gourley Jonathan J. , Xue Xianwu , Saharia Manabendra , Ni Guangheng , Wang Gaili , Huang Yong , Chen Sheng , Tang Guoqiang 
Published: October 2014

Abstract
Prediction, and thus preparedness, in advance of flood events is crucial for proactively reducing their impacts. In the summer of 2012, Beijing, China, experienced extreme rainfall and flooding that caused 79 fatalities and economic losses of $1.6 billion. Using rain gauge networks as a benchmark, this study investigated the detectability and predictability of the 2012 Beijing event via the Global Hydrological Prediction System (GHPS), forced by the NASA Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis at near–real time and by the deterministic and ensemble precipitation forecast products from the NOAA Global Forecast System (GFS) at several lead times. The results indicate that the disastrous flooding event was detectable by the satellite-based global precipitation observing system and predictable by the GHPS forced by the GFS 4 days in advance. However, the GFS demonstrated inconsistencies from run to run, limiting the confidence in predicting the extreme event. The GFS ensemble precipitation forecast products from NOAA for streamflow forecasts provided additional information useful for estimating the probability of the extreme event. Given the global availability of satellite-based precipitation in near–real time and GFS precipitation forecast products at varying lead times, this study demonstrates the opportunities and challenges that exist for an integrated application of GHPS. This system is particularly useful for the vast ungauged regions of the globe.
Effects of Radial-Based Noise Power Estimation on Spectral Moment Estimates
Authors: Ivić Igor R. , Krause Jane C. , Boydstun Olen E. , Daniel Amy E. , Free Alan D. , Zittel Walter D. 
Published: October 2014

AbstractA radar antenna intercepts thermal radiation from various sources, including the ground, the sun, the sky, precipitation, and man-made radiators. In the radar receiver, this external radiation produces noise that constructively adds to the receiver internal noise and results in the overall system noise. Consequently, the system noise power is dependent on the antenna position and needs to be estimated accurately. Inaccurate noise power measurements may lead to a reduction of coverage if the noise power is overestimated or to radar data images cluttered by noise speckles if the noise power is underestimated. Moreover, when an erroneous noise power is used at low to moderate signal-to-noise ratios, estimators can produce biased meteorological variables. Therefore, to obtain the best quality of radar products, it is desirable to compute meteorological variables using the noise power measured at each antenna position. An effective technique that achieves this by estimating the noise power in real time from measured powers at each scan direction and in parallel with weather data collection has been proposed. Herein, the effects of such radial-based noise power estimation on spectral moment estimates are investigated.