bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Oncometabolite 2-Hydroxyglutarate Is a Potential Surrogate Biomarker in Patients with Isocitrate Dehydrogenase-Mutant Intrahepatic Cholangiocarcinoma
Authors: Borger Darrell R. , Goyal Lipika , Yau Thomas , Poon Ronnie T. , Ancukiewicz Marek , Deshpande Vikram , Christiani David C. , Liebman Hannah M. , Yang Hua , Kim Hyeryun , Yen Katharine , Faris Jason E. , Iafrate A. John , Kwak Eunice L. , Clark Jeffrey W. , Allen Jill N. , Blaszkowsky Lawrence S. , Murphy Janet E. , Saha Supriya K. , Hong Theodore S. , Wo Jennifer Y. , Ferrone Cristina R. , Tanabe Kenneth K. , Bardeesy Nabeel , Straley Kimberly S. , Agresta Sam , Schenkein David P. , Ellisen Leif W. , Ryan David P. , Zhu Andrew X. 
Published: January 2014

Abstract
Purpose: Mutations in the IDH1 and IDH2 (IDH1/2) genes occur in approximately 20% of intrahepatic cholangiocarcinoma and lead to accumulation of 2-hydroxyglutarate (2HG) in the tumor tissue. However, it remains unknown whether IDH1/2 mutations can lead to high levels of 2HG circulating in the blood and whether serum 2HG can be used as a biomarker for IDH1/2 mutational status and tumor burden in intrahepatic cholangiocarcinoma.
Experimental Design: We initially measured serum 2HG concentration in blood samples collected from 31 patients with intrahepatic cholangiocarcinoma in a screening cohort. Findings were validated across 38 resected patients with intrahepatic cholangiocarcinoma from a second cohort with tumor volume measures. Circulating levels of 2HG were evaluated relative to IDH1/2 mutational status, tumor burden, and a number of clinical variables.
Results: Circulating levels of 2HG in the screening cohort were significantly elevated in patients with IDH1/2-mutant (median, 478 ng/mL) versus IDH1/2–wild-type (median, 118 ng/mL) tumors (P &lt; 0.001). This significance was maintained in the validation cohort (343 ng/mL vs. 55 ng/mL, P &lt; 0.0001) and levels of 2HG directly correlated with tumor burden in IDH1/2-mutant cases (P &lt; 0.05). Serum 2HG levels ≥170 ng/mL could predict the presence of an IDH1/2 mutation with a sensitivity of 83% and a specificity of 90%. No differences were noted between the allelic variants IDH1 or IDH2 in regard to the levels of circulating 2HG.
Conclusions: This study indicates that circulating 2HG may be a surrogate biomarker of IDH1 or IDH2 mutation status in intrahepatic cholangiocarcinoma and that circulating 2HG levels may correlate directly with tumor burden. Clin Cancer Res; 20(7); 1884–90. ©2014 AACR.
Mutational Landscape of the Essential Autophagy Gene BECN1 in Human Cancers
Authors: Laddha Saurabh V. , Ganesan Shridar , Chan Chang S. , White Eileen 
Published: January 2014

Abstract
Evidence suggests that the catabolic process of macroautophagy (autophagy hereafter) can either suppress or promote cancer. The essential autophagy gene ATG6/BECN1 encoding the Beclin1 protein has been implicated as a haploinsufficient tumor suppressor in breast, ovarian, and prostate cancers. The proximity of BECN1 to the known breast and ovarian tumor suppressor breast cancer 1, early onset, BRCA1, on chromosome 17q21, has made this determination equivocal. Here, the mutational status of BECN1 was assessed in human tumor sequencing data from The Cancer Genome Atlas (TCGA) and other databases. Large deletions encompassing both BRCA1 and BECN1, and deletions of only BRCA1 but not BECN1, were found in breast and ovarian cancers, consistent with BRCA1 loss being a primary driver mutation in these cancers. Furthermore, there was no evidence for BECN1 mutation or loss in any other cancer, casting doubt on whether BECN1 is a tumor suppressor in most human cancers.
Implications: Contrary to previous reports, BECN1 is not significantly mutated in human cancer and not a tumor-suppressor gene, as originally thought.
Visual Overview: http://mcr.aacrjournals.org/content/early/2014/04/01/1541-7786.MCR-13-0614/F1.large.jpg. Mol Cancer Res; 12(4); 485–90. ©2014 AACR.
Platelet degranulation and glycoprotein IIbIIIa opening are not related to bleeding phenotype in severe haemophilia A patients
Authors: Schutgens Roger E. G. , Fischer Kathelijn , de Groot Philip G. , Roest Mark , van Bladel Esther R. 
Published: January 2014

SummaryRecently we reported data suggesting that platelets could compensate for the bleeding phenotype in severe haemophilia A (HA). The aim of this study was to confirm these results in a larger population with a detailed characterisation of clinical phenotype. Patients with diagnostic severe HA (FVIII:C <1%) were scored for clinical phenotype by integrating data on age at first joint bleed, joint damage, bleeding frequency and FVIII consumption. Phenotype was defined as onset of joint bleeding-score + arthropathy-score + joint bleeding-score + (2* treatment intensity-score). After a washout period of three days, blood was collected for measurement of basal level of platelet activation, platelet reactivity, endothelial cell activation and presence of procoagulant phospholipids in plasma. Thirty-three patients with severe HA were included, 13 patients with a mild, 12 patients with an average and eight patients with a severe clinical phenotype. No relevant differences in basal level of platelet activation, platelet reactivity, endothelial cell activation and procoagulant phospholipids between all three groups were observed. The mean annual FVIII consumption per kg did not correlate with the platelet P-selectin expression and glycoprotein (GP)IIbIIIa activation on platelets. In conclusion, variability in clinical phenotype in patients with diagnostic severe HA is not related to platelet activation or reactivity, measured as platelet degranulation and platelet GPIIbIIIa opening.
A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism
Authors: Tschepe Merle , Seeber Valerie , Zwiener Isabella , Kuhnert Katherina , Schäfer Katrin , Hasenfuß Gerd , Konstantinides Stavros , Lankeit Mareike , Dellas Claudia 
Published: January 2014

SummaryWe tested whether heart-type fatty acid binding protein (H-FABP) measured by a fully-automated immunoturbidimetric assay in comparison to ELISA provides additive prognostic value in patients with pulmonary embolism (PE), and validated a fast prognostic score in comparison to the ESC risk prediction model and the simplified Pulmonary Embolism Severity Index (sPESI). We prospectively examined 271 normotensive patients with PE; of those, 20 (7%) had an adverse 30-day outcome. H-FABP levels determined by immunoturbidimetry were higher (median, 5.2 [IQR; 2.7–9.8] ng/ml) than those by ELISA (2.9 [1.1–5.4] ng/ml), but Bland-Altman plot demonstrated a good agreement of both assays. The area under the curve for H-FABP was greater for immunoturbidimetry than for ELISA (0.82 [0.74–0.91] vs 0.78 [0.68–0.89]; P=0.039). H-FABP measured by immunoturbidimetry (but not by ELISA) provided additive prognostic information to other predictors of 30-day outcome (OR, 12.4 [95% CI, 1.6–97.6]; P=0.017). When H-FABP determined by immunoturbidimetry was integrated into a novel prognostic score (H-FABP, Syncope, and Tachycardia; FAST score), the score provided additive prognostic information by multivariable analysis (OR, 14.2 [3.9–51.4]; p<0.001; c-index, 0.86) which were superior to information obtained by the ESC model (c-index, 0.62; net reclassification improvement (NRI), 0.39 [0.21–0.56]; P<0.001) or the sPESI (c-index, 0.68; NRI, 0.24 [0.05–0.43]; P=0.012). In conclusion, determination of H-FABP by immunoturbidimetry provides prognostic information superior to that of ELISA and, if integrated in the FAST score, appears more suitable to identify patients with an adverse 30-day outcome compared to the ESC model and sPESI.
Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis
Authors: Engelberger Rolf P. , Fahrni Jennifer , Willenberg Torsten , Baumann Frederic , Spirk David , Diehm Nicolas , Do Dai-Do , Baumgartner Iris , Kucher Nils 
Published: January 2014

SummaryPatients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the postthrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute iliofemoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0–6%) and 6 minor bleedings (7%; 95%CI, 3–14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74–94%) and 96% (95% CI, 88–99%), respectively. At three months, 88% (95% CI, 78–94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81–99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with iliofemoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.
Abelisauridae (Dinosauria: Theropoda) from the Late Jurassic of Portugal and dentition-based phylogeny as a contribution for the identification of isolated theropod teeth
Authors: Hendrickx Christophe , Mateus Octávio 
Published: January 2014

Theropod dinosaurs form a highly diversified clade, and their teeth are some of the most common components of the Mesozoic dinosaur fossil record. This is the case in the Lourinhã Formation (Late Jurassic, Kimmeridgian-Tithonian) of Portugal, where theropod teeth are particularly abundant and diverse. Four isolated theropod teeth are here described and identified based on morphometric and anatomical data. They are included in a cladistic analysis performed on a data matrix of 141 dentition-based characters coded in 60 taxa, as well as a supermatrix combining our dataset with six recent datamatrices based on the whole theropod skeleton. The consensus tree resulting from the dentition-based data matrix reveals that theropod teeth provide reliable data for identification at approximately family level. Therefore, phylogenetic methods will help identifying theropod teeth with more confidence in the future. Although dental characters do not reliably indicate relationships among higher clades of theropods, they demonstrate interesting patterns of homoplasy suggesting dietary convergence in (1) alvarezsauroids, therizinosaurs and troodontids; (2) coelophysoids and spinosaurids; (3) compsognathids and dromaeosaurids; and (4) ceratosaurids, allosauroids and megalosaurids. Based on morphometric and cladistic analyses, the biggest tooth from Lourinhã is referred to a mesial crown of the megalosaurid Torvosaurus tanneri, due to the elliptical cross section of the crown base, the large size and elongation of the crown, medially positioned mesial and distal carinae, and the coarse denticles. The smallest tooth is identified as Richardoestesia, and as a close relative of R. gilmorei based on the weak constriction between crown and root, the “eight-shaped” outline of the base crown and, on the distal carina, the average of ten symmetrically rounded denticles per mm, as well as a subequal number of denticles basally and at mid-crown. Finally, the two medium-sized teeth belong to the same taxon and exhibit pronounced interdenticular sulci between distal denticles, hooked distal denticles for one of them, an irregular enamel texture, and a straight distal margin, a combination of features only observed in abelisaurids. They provide the first record of Abelisauridae in the Jurassic of Laurasia and one of the oldest records of this clade in the world, suggesting a possible radiation of Abelisauridae in Europe well before the Upper Cretaceous.
The Interannual Variability of Tropical Precipitation and Interhemispheric Energy Transport
Authors: Donohoe Aaron , Marshall John , Ferreira David , Armour Kyle , McGee David 
Published: January 2014

Abstract
The interannual variability of the location of the intertropical convergence zone (ITCZ) is strongly (R = 0.75) correlated with the atmospheric heat transport across the equator (AHTEQ) over the satellite era (1979–2009). A 1° northward displacement of the ITCZ is associated with 0.34 PW of anomalous AHTEQ from north to south. The AHTEQ and precipitation anomalies are both associated with an intensification of the climatological Hadley cell that is displaced north of the equator. This relationship suggests that the tropical precipitation variability is driven by a hemispheric asymmetry of energy input to the atmosphere at all latitudes by way of the constraint that AHTEQ is balanced by a hemispheric asymmetry in energy input to the atmosphere.
A 500-yr coupled model simulation also features strong interannual correlations between the ITCZ location and AHTEQ. The interannual variability of AHTEQ in the model is associated with a hemispheric asymmetry in the top of the atmosphere radiative anomalies in the tropics with the Northern Hemisphere gaining energy when the ITCZ is displaced northward. The surface heat fluxes make a secondary contribution to the interannual variability of AHTEQ despite the fact that the interannual variability of the ocean heat transport across the equator (OHTEQ) is comparable in magnitude to that in AHTEQ. The OHTEQ makes a minimal impact on the atmospheric energy budget because the vast majority of the interannual variability in OHTEQ is stored in the subsurface ocean and, thus, the interannual variability of OHTEQ does not strongly impact the atmospheric circulation.
On the Warm Water Volume and Its Changing Relationship with ENSO
Authors: Bunge Lucia , Clarke Allan J. 
Published: January 2014

Abstract
The interannual, equatorial Pacific, 20°C isotherm depth variability since 1980 is dominated by two empirical orthogonal function (EOF) modes: the “tilt” mode, having opposite signs in the eastern and western equatorial Pacific and in phase with zonal wind forcing and El Niño–Southern Oscillation (ENSO) indices, and a second EOF mode of one sign across the Pacific. Because the tilt mode is of opposite sign in the eastern and western equatorial Pacific while the second EOF mode is of one sign, the second mode has been associated with the warm water volume (WWV), defined as the volume of water above the 20°C isotherm from 5°S to 5°N, 120°E to 80°W. Past work suggested that the WWV led the tilt mode by about 2–3 seasons, making it an ENSO predictor. But after 1998 the lead has decreased and WWV-based predictions of ENSO have failed. The authors constructed a sea level–based WWV proxy back to 1955, and before 1973 it also exhibited a smaller lead. Analysis of data since 1980 showed that the decreased WWV lead is related to a marked increase in the tilt mode contribution to the WWV and a marked decrease in second-mode EOF amplitude and its contribution. Both pre-1973 and post-1998 periods of reduced lead were characterized by “mean” La Niña–like conditions, including a westward displacement of the anomalous wind forcing. According to recent theory, and consistent with observations, such westward displacement increases the tilt mode contribution to the WWV and decreases the second-mode amplitude and its WWV contribution.
Wind Retrieval Algorithms for the IWRAP and HIWRAP Airborne Doppler Radars with Applications to Hurricanes
Authors: Guimond Stephen R. , Tian Lin , Heymsfield Gerald M. , Frasier Stephen J. 
Published: January 2014

Abstract
Algorithms for the retrieval of atmospheric winds in precipitating systems from downward-pointing, conically scanning airborne Doppler radars are presented. The focus is on two radars: the Imaging Wind and Rain Airborne Profiler (IWRAP) and the High-Altitude IWRAP (HIWRAP). The IWRAP is a dual-frequency (C and Ku bands), multibeam (incidence angles of 30°–50°) system that flies on the NOAA WP-3D aircraft at altitudes of 2–4 km. The HIWRAP is a dual-frequency (Ku and Ka bands), dual-beam (incidence angles of 30° and 40°) system that flies on the NASA Global Hawk aircraft at altitudes of 18–20 km.
Retrievals of the three Cartesian wind components over the entire radar sampling volume are described, which can be determined using either a traditional least squares or variational solution procedure. The random errors in the retrievals due to the airborne radar geometry and noise in the Doppler velocities are evaluated using both an error propagation analysis with least squares theory and a numerical simulation of a hurricane. These analyses show that the vertical and along-track wind errors have strong across-track dependence with values ranging from 0.25 m s−1 at nadir to 2.0 and 1.0 m s−1 at the swath edges, respectively. The average across-track wind errors are ~2.5 m s−1 or 7% of the hurricane wind speed. For typical rotated figure-four flight patterns through hurricanes, the zonal and meridional wind speed errors are ~1.5–2.0 m s−1. Evaluations of both retrieval methods show that the variational procedure is generally preferable to the least squares procedure.
Examples of measured data retrievals from IWRAP during an eyewall replacement cycle in Hurricane Isabel (2003) and from HIWRAP during the development of Tropical Storm Matthew (2010) are shown. Comparisons of IWRAP-measured data retrievals at nadir to flight-level data show errors of ~2.0 m s−1 for vertical winds and ~4.0 m s−1 for horizontal wind speed (~7% of the hurricane wind speed). Additional sources of error, such as hydrometeor fall speed uncertainties and a small height offset in the comparisons, are likely responsible for the larger vertical wind errors when compared to the simulated error analyses.
Calibration of Limited-Area Ensemble Precipitation Forecasts for Hydrological Predictions
Authors: Diomede Tommaso , Marsigli Chiara , Montani Andrea , Nerozzi Fabrizio , Paccagnella Tiziana 
Published: January 2014

Abstract
The main objective of this study is to investigate the impact of calibration for limited-area ensemble precipitation forecasts, to be used for driving discharge predictions up to 5 days in advance. A reforecast dataset, which spans 30 years, based on the Consortium for Small Scale Modeling Limited-Area Ensemble Prediction System (COSMO-LEPS) was used for testing the calibration strategy. Three calibration techniques were applied: quantile-to-quantile mapping, linear regression, and analogs. The performance of these methodologies was evaluated in terms of statistical scores for the precipitation forecasts operationally provided by COSMO-LEPS in the years 2003–07 over Germany, Switzerland, and the Emilia-Romagna region (northern Italy). The calibration provided a beneficial impact for the ensemble forecast over Switzerland and Germany; whereas, it resulted as less effective for Emilia-Romagna. The analog-based method seemed to be preferred because of its capability of correct position errors and spread deficiencies. A suitable spatial domain for the analog search can help to handle model spatial errors as systematic errors. However, the performance of the analog-based method may degrade in cases where a limited training dataset is available. The quantile-to-quantile mapping and linear regression methods were less effective, mainly because the forecast–analysis relation was not so strong for the available training dataset. The verification of the calibration process was then performed by coupling ensemble precipitation forecasts with a distributed rainfall–runoff model. This test was carried out for a medium-sized catchment located in Emilia-Romagna, showing a beneficial impact of the analog-based method on the reduction of missed events for discharge predictions.
Validation of ICHD-3 beta diagnostic criteria for 13.7 Tolosa-Hunt syndrome: Analysis of 77 cases of painful ophthalmoplegia
Authors: Zhang Xingwen , Zhou Zhibing , Steiner Timothy J , Zhang Wei , Liu Ruozhuo , Dong Zhao , Wang Xiaolin , Wang Rongfei , Yu Shengyuan 
Published: January 2014

Background Three editions of International Classification of Headache Disorders (ICHD) diagnostic criteria for Tolosa-Hunt syndrome (THS) have been published in 1998, 2004 and 2013; in ICHD-3 beta, there have been considerable changes. The validity of these new diagnostic criteria remains to be established. Methods We retrospectively identified 77 patients with non-traumatic painful ophthalmoplegia (PO) admitted between 2003 and 2013. We reviewed patients’ age at onset and gender, time courses between onset of pain and development of cranial nerve palsy, the cranial nerves involved, imaging findings, therapeutic efficacy of steroid treatment and recurrence of attacks. Results THS was the most frequent type of PO (46/77). In THS patients, the third cranial nerve was most commonly involved (76.3%). The median time interval between pain and cranial nerve palsy was two days, although in five patients (10.9%) the interval ranged from 16 to 30 days. Definitely abnormal MRI findings were found in 24 patients (52.2%). Conclusions It is essential to rule out other causes of PO in diagnosing THS, with MRI playing a crucial role in differential diagnosis. It may be helpful to understand and master the entity of THS for researchers and clinicians to adjust the gradation and ranking of the diagnostic criteria.