bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine and CHK1 Inhibition Potentiate EGFR-Directed Radioimmunotherapy against Pancreatic Ductal Adenocarcinoma
Authors: Al-Ejeh Fares , Pajic Marina , Shi Wei , Kalimutho Murugan , Miranda Mariska , Nagrial Adnan M. , Chou Angela , Biankin Andrew V. , Grimmond Sean M. ,   for the Australian Pancreatic Cancer Genome Initiative, Brown Michael P. , Khanna Kum Kum 
Published: May 2014

Abstract
Purpose: To develop effective combination therapy against pancreatic ductal adenocarcinoma (PDAC) with a combination of chemotherapy, CHK1 inhibition, and EGFR-targeted radioimmunotherapy.
Experimental Design: Maximum tolerated doses were determined for the combination of gemcitabine, the CHK1 inhibitor PF-477736, and Lutetium-177 (177Lu)–labeled anti-EGFR antibody. This triple combination therapy was investigated using PDAC models from well-established cell lines, recently established patient-derived cell lines, and fresh patient-derived xenografts. Tumors were investigated for the accumulation of 177Lu-anti-EGFR antibody, survival of tumor-initiating cells, induction of DNA damage, cell death, and tumor tissue degeneration.
Results: The combination of gemcitabine and CHK1 inhibitor PF-477736 with 177Lu-anti-EGFR antibody was tolerated in mice. This triplet was effective in established tumors and prevented the recurrence of PDAC in four cell line–derived and one patient-derived xenograft model. This exquisite response was associated with the loss of tumor-initiating cells as measured by flow cytometric analysis and secondary implantation of tumors from treated mice into treatment-naïve mice. Extensive DNA damage, apoptosis, and tumor degeneration were detected in the patient-derived xenograft. Mechanistically, we observed CDC25A stabilization as a result of CHK1 inhibition with consequent inhibition of gemcitabine-induced S-phase arrest as well as a decrease in canonical (ERK1/2 phosphorylation) and noncanonical EGFR signaling (RAD51 degradation) as a result of EGFR inhibition.
Conclusions: Our study developed an effective combination therapy against PDAC that has potential in the treatment of PDAC. Clin Cancer Res; 20(12); 3187–97. ©2014 AACR.
Dynamic Interactions between Cancer Cells and the Embryonic Microenvironment Regulate Cell Invasion and Reveal EphB6 as a Metastasis Suppressor
Authors: Bailey Caleb M. , Kulesa Paul M. 
Published: May 2014

Abstract
Metastatic dissemination drives the high mortality associated with melanoma. However, difficulties in visualizing in vivo cell dynamics during metastatic invasion have limited our understanding of these cell behaviors. Recent evidence has revealed that melanoma cells exploit portions of their ancestral embryonic neural crest emigration program to facilitate invasion. What remains to be determined is how embryonic microenvironmental signals influence invasive melanoma cell behavior, and whether these signals are relevant to human disease. To address these questions, we interrogated the role of the neural crest microenvironment in dictating the spatiotemporal pattern of melanoma cell invasion in the chick embryo using 2-photon time-lapse microscopy. Results reveal that both permissive and inhibitory neural crest microenvironmental signals regulate the timing and direction of melanoma invasion to coincide with the neural crest migration pattern. These cues include bidirectional signaling mediated through the ephrin family of receptor tyrosine kinases. We demonstrate that EphB6 reexpression forces metastatic melanoma cells to deviate from the canonical migration pattern observed in the chick embryo transplant model. Furthermore, EphB6-expressing melanoma cells display significantly reduced metastatic potential in a chorioallantoic membrane (CAM) metastasis assay. These data on melanoma invasion in the embryonic neural crest and CAM microenvironments identify EphB6 as a metastasis suppressor in melanoma, likely acting at the stage of intravasation.
Implications: This article links cellular metastasis to behaviors observed in the ancestrally related embryonic neural crest and demonstrates the powerful influence of the embryonic microenvironment in regulating cell migratory behavior. Mol Cancer Res; 12(9); 1303–13. ©2014 AACR.
Electrocardiographic T Wave and its Relation With Ventricular Repolarization Along Major Anatomical Axes
Authors: Meijborg Veronique M.F. , Conrath Chantal E. , Opthof Tobias , Belterman Charly N.W. , de Bakker Jacques M.T. , Coronel Ruben 
Published: May 2014

Background—
The genesis of the electrocardiographic T wave is incompletely understood and subject to controversy. We have correlated the ventricular repolarization sequence with simultaneously recorded T waves.

Methods and Results—

Nine pig hearts were Langendorff-perfused (atrial pacing, cycle length 650 ms). Local activation and repolarization times were derived from unipolar electrograms sampling the ventricular myocardium. Dispersion of repolarization time was determined along 4 anatomic axes: left ventricle (LV)–right ventricle (RV), LV:apico-basal, LV:anterior-posterior, and LV:transmural. The heart was immersed in a fluid-filled bucket containing 61 electrodes to determine T
p
(T
peak
in lead of maximum integral), T
p
T
e
(T
p
to T
end
), and T
p
T
e
_total (first T
peak
in any lead to last T
end
in any lead). Repolarization was nonlinearly distributed in time. RT
25
(time at which 25% of sites were repolarized, 288±26 ms) concurred with T
p
. T
p
T
e
was 38±8 ms, and T
p
T
e
_total was 75±9 ms. T
p
T
e
_total correlated with dispersion of repolarization time in the entire heart (73±18 ms), but not with dispersion of repolarization times along individual axes (LV–RV, 66±17 ms; LV:apico-basal, 51±18 ms; LV:anterior-posterior, 51±27 ms; mean LV:transmural, 14±7 ms; all n=9).

Conclusions—

We provide a correlation between local repolarization and T wave in a pseudo-ECG. Repolarization differences along all anatomic axes contribute to the T wave. T
p
T
e
_total represents total dispersion of repolarization. At T
p
, ≈25% of ventricular sites have been repolarized.
Northern Hemisphere Glacier and Ice Cap Surface Mass Balance and Contribution to Sea Level Rise
Authors: Mernild Sebastian H. , Liston Glen E. , Hiemstra Christopher A. 
Published: May 2014

Abstract
Mass changes and mass contribution to sea level rise from glaciers and ice caps (GIC) are key components of the earth’s changing sea level. GIC surface mass balance (SMB) magnitudes and individual and regional mean conditions and trends (1979–2009) were simulated for all GIC having areas greater or equal to 0.5 km2 in the Northern Hemisphere north of 25°N latitude (excluding the Greenland Ice Sheet). Recent datasets, including the Randolph Glacier Inventory (RGI; v. 2.0), the NOAA Global Land One-km Base Elevation Project (GLOBE), and the NASA Modern-Era Retrospective Analysis for Research and Applications (MERRA) products, together with recent SnowModel developments, allowed relatively high-resolution (1-km horizontal grid; 3-h time step) simulations of GIC surface air temperature, precipitation, sublimation, evaporation, surface runoff, and SMB. Simulated SMB outputs were calibrated against 1422 direct glaciological annual SMB observations of 78 GIC. The overall GIC mean annual and mean summer air temperature, runoff, and SMB loss increased during the simulation period. The cumulative GIC SMB was negative for all regions. The SMB contribution to sea level rise was largest from Alaska and smallest from the Caucasus. On average, the contribution to sea level rise was 0.51 ± 0.16 mm sea level equivalent (SLE) yr−1 for 1979–2009 and ~40% higher 0.71 ± 0.15 mm SLE yr−1 for the last decade, 1999–2009.
Process-Oriented Diagnosis of East Pacific Warm Pool Intraseasonal Variability
Authors: Maloney Eric D. , Jiang Xianan , Xie Shang-Ping , Benedict James J. 
Published: May 2014

Abstract
June–October east Pacific warm pool intraseasonal variability (ISV) is assessed in eight atmospheric general circulation simulations. Complex empirical orthogonal function analysis is used to document the leading mode of 30–90-day precipitation variability in the models and Tropical Rainfall Measuring Mission observations. The models exhibit a large spread in amplitude of the leading mode about the observed amplitude. Little relationship is demonstrated between the amplitude of the leading mode and the ability of models to simulate observed north-northeastward propagation.
Several process-oriented diagnostics are explored that attempt to distinguish why some models produce superior ISV. A diagnostic based on the difference in 500–850-hPa averaged relative humidity between the top 5% and the bottom 10% of precipitation events exhibits a significant correlation with leading mode amplitude. Diagnostics based on the vertically integrated moist entropy budget also demonstrate success at discriminating models with strong and weak variability. In particular, the vertical component of gross moist stability exhibits a correlation with amplitude of −0.9, suggesting that models in which convection and associated divergent circulations are less efficient at discharging moisture from the column are better able to sustain strong ISV.
Several other diagnostics are tested that show no significant relationship with leading mode amplitude, including the warm pool mean surface zonal wind, the strength of surface flux feedbacks, and 500–850-hPa averaged relative humidity for the top 1% of rainfall events. Vertical zonal wind shear and 850-hPa zonal wind do not appear to be good predictors of model success at simulating the observed northward propagation pattern.
Convectively Induced Secondary Circulations in Fine-Grid Mesoscale Numerical Weather Prediction Models
Authors: Ching J. , Rotunno R. , LeMone M. , Martilli A. , Kosovic B. , Jimenez P. A. , Dudhia J. 
Published: May 2014

AbstractMesoscale numerical weather prediction models using fine-grid [O(1) km] meshes for weather forecasting, environmental assessment, and other applications capture aspects of larger-than-grid-mesh size, convectively induced secondary circulations (CISCs) such as cells and rolls that occur in the convective planetary boundary layer (PBL). However, 1-km grid spacing is too large for the simulation of the interaction of CISCs with smaller-scale turbulence. The existence of CISCs also violates the neglect of horizontal gradients of turbulent quantities in current PBL schemes. Both aspects—poorly resolved CISCs and a violation of the assumptions behind PBL schemes—are examples of what occurs in Wyngaard’s “terra incognita,” where horizontal grid spacing is comparable to the scale of the simulated motions. Thus, model CISCs (M-CISCs) cannot be simulated reliably. This paper describes how the superadiabatic layer in the lower convective PBL together with increased horizontal resolution allow the critical Rayleigh number to be exceeded and thus allow generation of M-CISCs like those in nature; and how the M-CISCs eventually neutralize the virtual temperature stratification, lowering the Rayleigh number and stopping their growth. Two options for removing M-CISCs while retaining their fluxes are 1) introducing nonlocal closure schemes for more effective removal of heat from the surface and 2) restricting the effective Rayleigh number to remain subcritical. It is demonstrated that CISCs are correctly handled by large-eddy simulation (LES) and thus may provide a way to improve representation of them or their effects. For some applications, it may suffice to allow M-CISCs to develop, but account for their shortcomings during interpretation.
Operation Airway
Authors: Rogers Derek J. , Collins Corey , Carroll Ryan , Yager Phoebe , Cummings Brian , Raol Nikhila , Setlur Jennifer , Maturo Stephen , Tremblay Sarah , Quinones Ernesto , Noviski Natan , Hartnick Christopher J. 
Published: May 2014

Objective: This study aimed to describe the development and implementation of the first sustainable, multidisciplinary, pediatric airway surgical mission in an underserved country. Methods: This prospective, qualitative study was conducted for the first 4 Operation Airway missions in Quito, Ecuador. The major goals of the missions were to assist children with aerodigestive abnormalities, create a sustainable program where the local team could independently provide for their own patient population, develop an educational curriculum and training program for the local team, and cultivate a collaborative approach to provide successful multidisciplinary care. Results: Twenty patients ages 4 months to 21 years were included. Twenty-three bronchoscopies, 5 salivary procedures, 2 tracheostomies, 1 T-tube placement, 1 tracheocutaneous fistula closure, 2 open granuloma excisions, and 6 laryngotracheal reconstructions (LTRs) were performed. All LTR patients were decannulated. A new type of LTR (1.5 stage) was developed to meet special mission circumstances. Two videofluoroscopic swallow studies and 40 bedside swallow evaluations were performed. One local pediatric otolaryngologist, 1 pediatric surgeon, 3 anesthesiologists, 7 intensivists, 16 nurses, and 2 speech-language pathologists have received training. More than 25 hours of lectures were given, and a website was created collaboratively for educational and informational dissemination ( http://www.masseyeandear.org/specialties/pediatrics/pediatric-ent/airway/OperationAirway/ ). Conclusion: We demonstrated the successful creation of the first mission stemming from a teaching institution with the goal of developing a sustainable, autonomous surgical airway program.
Psychological flexibility and nonjudgemental acceptance in voice hearers: relationships with omnipotence and distress
Authors: Morris Eric MJ , Garety Philippa , Peters Emmanuelle 
Published: May 2014

Objective: The psychological flexibility model has been hypothesized as a transdiagnostic, process-oriented approach to understanding various clinical disorders and problems, including chronic pain, anxiety, and substance misuse. In this study we investigated the model’s applicability to the experience of hearing distressing voices. Methods: Fifty people experiencing persisting auditory hallucinations were administered the Kentucky Inventory of Mindfulness Skills, Acceptance and Action Questionnaire, Beliefs about Voices Questionnaire-Revised, Thought Control Questionnaire, and the Beck Anxiety and Depression Inventories. We predicted that psychological flexibility, mindful action, and nonjudgemental acceptance would be negatively associated with distress, disability, and behavioural responses to voice hearing and would have additional explanatory power when included with appraisals of voices and thought-control strategies (as predicted by cognitive models of auditory hallucinations). Results: The results showed differential contributions between measures of psychological flexibility and nonjudgemental acceptance. Psychological flexibility accounted for a significant proportion of the variance in regression-based models of depression and anxiety, while nonjudgemental acceptance contributed to the prediction of emotional and behavioural resistance to voices, in addition to appraisals of voices and use of thought-control strategies. However, this was not found for distress associated with voice hearing, life disruption, and engagement with voices, which were explained solely by cognitive variables. Conclusions: The study results suggest that psychological flexibility and nonjudgemental acceptance are related to general emotional well being and resistance response styles to voices, but not to specific dimensions of voice hearing.
Premature atrial contraction as a predictor of postoperative atrial fibrillation
Authors: Hashimoto Makoto , Yamauchi Akihiko , Inoue Satomi 
Published: May 2014

Background Postoperative atrial fibrillation occurs in 20%–60% of patients after cardiac surgery. Recently, premature atrial contraction has been considered an initiator of atrial fibrillation. This study evaluated whether the frequency of premature atrial contractions predicts the occurrence of postoperative atrial fibrillation. Methods The subjects of this study were 70 patients with no history of atrial fibrillation who had undergone a 24-h Holter electrocardiogram before off-pump coronary artery bypass. Their records were reviewed and postoperative electrocardiograms and telemetry strips were analyzed for postoperative atrial fibrillation. Results Postoperative atrial fibrillation was documented in 22 (31.4%) patients. The frequency of preoperative premature atrial contractions was significantly higher in the postoperative atrial fibrillation group (4128 ± 7186 vs. 69 ± 221 beats/24 h, p < 0.001). The incidence of postoperative atrial fibrillation increased with the frequency of preoperative premature atrial contractions which occurred in 60% of patients in the upper 50th percentile group of preoperative premature atrial contractions. Multivariate logistic regression analysis revealed the upper 50th percentile group of preoperative premature atrial contractions (odds ratio = 67; 95% confidence interval: 5.51–838; p = 0.001) to be an independent predictor of postoperative atrial fibrillation. Conclusion A high frequency of preoperative premature atrial contractions is a strong independent predictor of postoperative atrial fibrillation in off-pump coronary artery bypass.
Extraction of mediastinal teratoma contents for complete thoracoscopic resection
Authors: Tsubochi Hiroyoshi , Endo Shunsuke , Nakano Tomoyuki , Minegishi Kentaro , Tetsuka Kenji , Hasegawa Tsuyoshi 
Published: May 2014

Objectives Video-assisted thoracic surgery is widely applied for resection of mediastinal tumors. The mediastinal mature teratoma, however, is usually operated on via an open approach because it is generally large, making it difficult to dissect under a thoracoscopic view and remove it from the thoracic cavity. We attempted to extract intracystic material during video-assisted thoracic surgery to facilitate dissection and removal of the tumor from the thoracic cavity. Methods From January 1998 to April 2013, 13 patients (9 women, 4 men; mean age 33 years, range 17–54 years) with mediastinal mature teratomas were operated on via video-assisted thoracic surgery. Intracystic contents of the tumor were aspirated before dissection or after the teratoma was dissected and placed in the retrieval pouch. Results None of the patients required conversion to an open procedure. Operating time was 95–184 min (mean 132 min). Blood loss during the operation amounted to 10–300 mL (mean 78 mL). The tumor size ranged from 5 to 12 cm (mean 8 cm). In all cases, the tumors were confirmed pathologically to be mature cystic teratomas with no malignant components. During and after follow-up, all patients continue to do well without recurrence. Conclusion Extraction of intracystic contents enabled thoracoscopic resection of large mature mediastinal teratomas.
Indications, contraindications and performance: European Guidelines for Sclerotherapy in Chronic Venous Disorders
Authors: Rabe E , Pannier F ,   for the Guideline Group
Published: May 2014

Aim Sclerotherapy is the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. The treated veins may be intradermal, subcutaneous, and/or transfascial as well as superficial and deep in venous malformations. The aim of this guideline is to give evidence-based recommendations for liquid and foam sclerotherapy. Methods This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7th – 10th May 2012 in Mainz. The conference was organized by the German Society of Phlebology. Results This guideline focuses on the two sclerosing drugs which are licensed in the majority of the European countries, Polidocanol (POL) and Sodium tetradecyl sulphate (STS). Other sclerosants are not discussed in detail. In this paper the recommendations concerning indications, contraindications, concentrations, volumes and technique of liquid and foam sclerotherapy of varicose veins and venous malformations are reviewed.
Compression for the management of venous leg ulcers: which material do we have?
Authors: Partsch Hugo 
Published: May 2014

Compression therapy is the most important basic treatment modality in venous leg ulcers. The review focusses on the materials which are used: 1. Compression bandages, 2. Compression stockings, 3. Self-adjustable Velcro-devices, 4. Compression pumps, 5. Hybrid devices. Compression bandages, usually applied by trained staff, provide a wide spectrum of materials with different elastic properties. To make bandaging easier, safer and more effective, most modern bandages combine different material components. Self-management of venous ulcers has become feasible by introducing double compression stockings (“ulcer kits”) and self-adjustable Velcro devices. Compression pumps can be used as adjunctive measures, especially for patients with restricted mobility. The combination of sustained and intermittent compression (“hybrid device”) is a promising new tool. The interface pressure corresponding to the dosage of compression therapy determines the hemodynamic efficacy of each device. In order to reduce ambulatory venous hypertension compression pressures of more than 50 mm Hg in the upright position are desirable. At the same time pressure should be lower in the resting position in order to be tolerated. This prerequisite may be fulfilled by using inelastic, short stretch material including multicomponent bandages and cohesive surfaces, all characterized by high stiffness. Such materials do not give way when calf muscles contract during walking which leads to high peaks of interface pressure (“massaging effect”).
Timing and duration of compression therapy after deep vein thrombosis
Authors: Bouman AC , Cate-Hoek AJ ten 
Published: May 2014

After deep vein thrombosis (DVT) 20-50%, of patients develop post thrombotic syndrome (PTS). Up till now, there is no effective treatment for PTS and prevention is therefore of major importance. Compression therapy after DVT, with elastic compression stockings (ECS), is the only available preventive measure for PTS. However, the usefulness, timing, and duration of compression therapy are matters of debate. The effect of early compression on the long-term development of PTS is still unclear as studies performed so far have conflicting outcomes.16–19 The effectiveness of ECS therapy initiated in the sub-acute phase was assessed in three large randomized controlled trials. Kahn et al could not reproduce the large risk reduction found in the trials by Brandjes and Prandoni et al.20–22 Also for the optimal duration of ECS therapy, a certain conclusion has yet to be drawn. Therefore identification of patients who most likely will benefit from ECS therapy as well as the optimal ECS treatment strategy remain subjects for further study.