bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1
Authors: Li Min , Riddle Suzette , Zhang Hui , D’Alessandro Angelo , Flockton Amanda , Serkova Natalie J. , Hansen Kirk C. , Moldovan Radu , McKeon B. Alexandre , Frid Maria , Kumar Sushil , Li Hong , Liu Hongbing , Caánovas Angela , Medrano Juan F. , Thomas Milton G. , Iloska Dijana , Plecitá-Hlavatá Lydie , Ježek Petr , Pullamsetti Soni , Fini Mehdi A. , El Kasmi Karim C. , Zhang QingHong , Stenmark Kurt R. 
Published: August 2016

Background:
Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1).

Methods:

RNA sequencing, quantitative polymerase chain reaction,
13
C–nuclear magnetic resonance, fluorescence-lifetime imaging, mass spectrometry–based metabolomics, and tracing experiments with U-
13
C-glucose were used to assess glycolytic reprogramming and to measure the NADH/NAD
+
ratio in bovine and human adventitial fibroblasts and mouse lung tissues. Immunohistochemistry was used to assess CtBP1 expression in the whole-lung tissues. CtBP1 siRNA and the pharmacological inhibitor 4-methylthio-2-oxobutyric acid (MTOB) were used to abrogate CtBP1 activity in cells and hypoxic mice.

Results:

We found that adventitial fibroblasts from calves with severe hypoxia-induced PH and humans with idiopathic pulmonary arterial hypertension (PH-Fibs) displayed aerobic glycolysis when cultured under normoxia, accompanied by increased free NADH and NADH/NAD
+
ratios. Expression of the NADH sensor CtBP1 was increased in vivo and in vitro in fibroblasts within the pulmonary adventitia of humans with idiopathic pulmonary arterial hypertension and animals with PH and cultured PH-Fibs, respectively. Decreasing NADH pharmacologically with MTOB or genetically blocking CtBP1 with siRNA upregulated the cyclin-dependent genes (p15 and p21) and proapoptotic regulators (NOXA and PERP), attenuated proliferation, corrected the glycolytic reprogramming phenotype of PH-Fibs, and augmented transcription of the anti-inflammatory gene
HMOX1
. Chromatin immunoprecipitation analysis demonstrated that CtBP1 directly binds the
HMOX1
promoter. Treatment of hypoxic mice with MTOB decreased glycolysis and expression of inflammatory genes, attenuated proliferation, and suppressed macrophage numbers and remodeling in the distal pulmonary vasculature.

Conclusions:
CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target.
Atrial Fibrillation in Transient Ischemic Attack Versus Ischemic Stroke
Authors: Buchwald Fredrik , Norrving Bo , Petersson Jesper 
Published: August 2016

Background and Purpose—
Compared with ischemic stroke (IS), the association of atrial fibrillation (AF) with transient ischemic attack (TIA) is less well established. We aimed to assess the proportion of AF in patients with TIA, and these patients’ characteristics and secondary preventive treatment in comparison to patients with IS.

Methods—
Hospital-based data on TIA and IS events, registered from July 2011 to June 2013, were obtained from the Swedish Stroke Register (Riksstroke). A time-based TIA definition (duration of symptoms <24 hours) was applied. AF was registered as present when previously known or diagnosed at the time of assessment.

Results—
AF was present in 2779 of 14 980 (18.6%) patients with TIA and 13 258 of 44 173 (30.0%) patients with IS. The proportion of AF increased with age, reaching 32.9% in TIA and 46.6% in IS patients ≥85 years. Both in TIA and IS, age, hypertension, a history of stroke, and TIA, and being a nonsmoker were associated with the presence of AF. In contrast to IS, AF was less common in female than in male patients with TIA. At discharge, 64.2% of TIA and 50.0% of IS patients with AF were treated with oral anticoagulants. Proportions of AF patients treated with oral anticoagulants decreased substantially with increasing age.

Conclusions—
AF is highly prevalent not only in IS but also in TIA patients, with proportions steeply increasing with age. In both TIA and IS, a substantial proportion of patients with AF were discharged without anticoagulant therapy.
Low-Frequency Currents from Deep Moorings in the Southern Bay of Bengal
Authors: Wijesekera H. W. , Teague W. J. , Wang D. W. , Jarosz E. , Jensen T. G. , Jinadasa S. U. P. , Fernando H. J. S. , Hallock Z. R. 
Published: August 2016

AbstractHigh-resolution currents and hydrographic fields were measured at six deep-water moorings in the southern Bay of Bengal (BoB) by the Naval Research Laboratory as part of an international effort focused on the dynamics of the Indian Ocean. Currents, temperature, and salinity were sampled over the upper 500 m for 20 months between December 2013 and August 2015. One of the major goals is to understand the space–time scales of the currents and physical processes that contribute to the exchange of water between the BoB and the Arabian Sea. The observations captured Southwest and Northeast Monsoon Currents, seasonally varying large eddies including a cyclonic eddy, the Sri Lanka dome (SLD), and an anticyclonic eddy southeast of the SLD. The observations further showed intraseasonal oscillations with periods of 30–70 days, near-inertial currents, and tides. Monthly averaged velocities commonly exceeded 50 cm s−1 near the surface, and extreme velocities exceeded 150 cm s−1 during the southwest monsoon. Tides were small and dominated by the M2 component with velocities of about 3 cm s−1. The average transport into the BoB over the measurement period was 2 Sv (1 Sv ≡ 106 m3 s−1) but likely exceeded 15 Sv during summer of 2014. This study suggests the water exchange away from coastal boundaries, in the interior of the BoB, may be largely influenced by the location and strength of the two eddies that modify the path of the Southwest Monsoon Current. In addition, there is a pathway below 200 m for transport of water into the BoB throughout the year.
Polynomial Chaos–Based Bayesian Inference of K-Profile Parameterization in a General Circulation Model of the Tropical Pacific
Authors: Sraj Ihab , Zedler Sarah E. , Knio Omar M. , Jackson Charles S. , Hoteit Ibrahim 
Published: August 2016

AbstractThe authors present a polynomial chaos (PC)–based Bayesian inference method for quantifying the uncertainties of the K-profile parameterization (KPP) within the MIT general circulation model (MITgcm) of the tropical Pacific. The inference of the uncertain parameters is based on a Markov chain Monte Carlo (MCMC) scheme that utilizes a newly formulated test statistic taking into account the different components representing the structures of turbulent mixing on both daily and seasonal time scales in addition to the data quality, and filters for the effects of parameter perturbations over those as a result of changes in the wind. To avoid the prohibitive computational cost of integrating the MITgcm model at each MCMC iteration, a surrogate model for the test statistic using the PC method is built. Because of the noise in the model predictions, a basis-pursuit-denoising (BPDN) compressed sensing approach is employed to determine the PC coefficients of a representative surrogate model. The PC surrogate is then used to evaluate the test statistic in the MCMC step for sampling the posterior of the uncertain parameters. Results of the posteriors indicate good agreement with the default values for two parameters of the KPP model, namely the critical bulk and gradient Richardson numbers; while the posteriors of the remaining parameters were barely informative.
Fontan circulation over 30 years. What should we learn from those patients?
Authors: Sakamoto Takahiko , Nagashima Mitsugi , Hiramatsu Takeshi , Matsumura Goki , Park In-Sam , Yamazaki Kenji 
Published: August 2016

Background This study aimed to evaluate Fontan circulation which was observed over 30 years. Methods Forty patients who underwent a Fontan operation between 1974 and 1986 and survived (group S, n = 20) or died in the late period (group LD, n = 20) were evaluated. The median age at operation was 10 years (range 2–32 years). The diagnoses were tricuspid atresia in 21, single ventricle in 9, and others in 10. The Fontan procedure was a right atrium-pulmonary artery graft in 2, atriopulmonary connection in 28, and right atrium-right ventricle anastomosis in 10 (Björk in 4, graft in 6). Results Causes of late death were congestive heart failure in 6, sudden death in 4, arrhythmia in 4, and others in 6. Sixteen patients underwent reoperation 23.3 ± 6.5 years after Fontan. Cardiac catheterization was performed at 1 month and 12 years. There were no significant differences in central venous pressure, ventricular ejection fraction, or pulmonary vascular resistance between the two groups. However, changes in ventricular end-diastolic volume suggested volume and pressure overload in group LD. In group S, the latest chest radiographs showed cardiothoracic ratio 51.3% ± 7.6%, oxygen saturation 94% ± 2%, brain natriuretic peptide 153 ± 111 pg ċ mL−1, and Holter monitoring revealed sinus rhythm in 10 patients. New York Heart Association class was I in 12 patients, II in 6, and III in 2. Conclusions For long-term Fontan survival, timely total cavopulmonary connection conversion and medication to decrease ventricular volume and pressure load might be important.
Targeted tumor MRI with gadobutrol-loaded anti-HER2 immunoliposomes
Authors: Chen Weicui , Liu Bo , Chen Jun , Liu Guoqing , Liu Xian 
Published: August 2016

Background Immunoliposomes have been used to deliver MR contrast agents to cancer tissue by targeting tumor associated antigens, thus enabling the visualization of biological processes at the cellular level. Purpose To develop and evaluate the feasibility of specific HER2 targeted liposomal MR contrast agent. Material and Methods Gd-loaded anti-HER2 immunolipomes (Gd-ILs) and non-targeted PEGylated liposomes (Gd-NTLs) were prepared and characterized. Tumor bearing animals were randomized into three groups: Gd- ILs, Gd- NTLs and gadobutrol. Animals were imaged prior and 5, 15, 60, 120 and 180 min after i.v. injection of different contrast agents. The signal intensity enhancement percentage, signal- to- noise ratio and contrast- to –noise ratio was used to qualify tumor enhancement of different groups. After imaging, tumors were excised for histological examination. Results In vivo dynamic MR images, the specific targeted contrast agent bound to tumor tissue and result in a gradual and persisting enhancement for at least 3 hours in mice bearing tumor xenografts, reaching a maximum of 87.7% enhancement after 120 min post-injection. Gd-ILs demonstrated superior tumor enhancement over control non target contrast agent and gadobutrol in HER2 overexpressing tumors at 60, 120 and 180 min post- injection. The SNR and CNR of Gd-ILs in the tumors were significantly greater than that of Gd-NTLs at 60, 120, 180 min post- injection. Conclusion The results indicate the feasibility of Gd-ILs providing prolonged circulation, specific tumor enhancement and cancer cell recognition as targeted contrast agent.
Anatomic variations of lower extremity venous system in varicose vein patients: demonstration by three-dimensional CT venography
Authors: Kim Rihyeon , Lee Whal , Park Eun-Ah , Yoo Jin Young , Chung Jin Wook 
Published: August 2016

Background Understanding the anatomy of the lower extremity veins is essential for successful varicose vein treatment. Computed tomography (CT) venography may be used to obtain a comprehensive overview and detailed information regarding this. Purpose To describe anatomic variations of the lower extremity venous system in patients with varicose veins, using three-dimensional (3D) CT venography. Material and Methods A total of 810 limbs in 405 patients with suspected varicose veins were prospectively referred to undertake CT venography and included in our study population retrospectively. The CT venography images were evaluated by consensus of two cardiovascular radiologists. Anatomical variations of the lower extremity venous system and their incidence were analyzed. Specifically, the number of tributaries at saphenofemoral junction, relative location of the great saphenous vein (GSV) with respect to the common femoral artery bifurcation, pattern of saphenopopliteal junction, and end of thigh extension from the small saphenous vein (SSV) were assessed. Results The most frequent number of tributaries joining the GSV was four (44.4%, 360/810). Only 0.7% (6/810) of the limbs demonstrated unusual location of the GSV between the bifurcated superficial and deep femoral arteries. The most common pattern of veins at the saphenopopliteal junction was a larger caliber of saphenopopliteal junction than thigh extension from SSV (43.8%, 355/810), end of which joining the femoral vein directly (41.0%, 288/703). Conclusion CT venography with 3D reconstruction can be used to understand the anatomy of lower extremity veins and how their variations contribute to varicose veins.
Comparison of handheld ultrasound and automated breast ultrasound in women recalled after mammography screening
Authors: Hellgren Roxanna , Dickman Paul , Leifland Karin , Saracco Ariel , Hall Per , Celebioglu Fuat 
Published: August 2016

Background Automated breast volume scanner (ABVS) is an ultrasound (US) device with a wide scanner that sweeps over a large area of the breast and the acquired transverse images are sent to a workstation for reconstruction and review. Whether ABVS is as reliable as handheld US is, however, still not established. Purpose To compare the sensitivity and specificity of ABVS to handheld breast US for detection of breast cancer, in the situation of recall after mammography screening. Material and Methods A total of 113 women, five with bilateral suspicious findings, undergoing handheld breast US due to a suspicious mammographic finding in screening, underwent additional ABVS. The methods were assessed for each breast and each detected lesion separately and classified into two categories: breasts with mammographic suspicion of malignancy and breasts with a negative mammogram. Results Twenty-six cancers were found in 25 women. In the category of breasts with a suspicious mammographic finding (n = 118), the sensitivity of both handheld US and ABVS was 88% (22/25). The specificity of handheld US was 93.5% (87/93) and ABVS was 89.2% (83/93). In the category of breasts with a negative mammography (n = 103), the sensitivity of handheld US and ABVS was 100% (1/1). The specificity of handheld US was 100% (102/102) and ABVS was 94.1% (96/102). Conclusion ABVS can potentially replace handheld US in the investigation of women recalled from mammography screening due to a suspicious finding. Due to the small size of our study population, further investigation with larger study populations is necessary before the implementation of such practice.
Impact of urethral catheterization on uroflow during pressure-flow study
Authors: Zhu Bi Song , Jiang Hui Chuan , Li Yuan 
Published: August 2016

Objective To investigate the impact of urethral catheterization on uroflow by comparing urodynamic parameters of free uroflowmetry versus pressure-flow study in adult patients with benign prostatic hyperplasia, female stress incontinence, lumbosacral spinal injury or spina bifida. Methods Each patient was required to perform pressure-flow study immediately following free uroflowmetry. Maximum flow rate (Qmax), average flow rate (Qave), voided volume (VV), Tmax (time to Qmax) and post-voiding residual urine (PVR) were compared between the two tests. Results Out of 120 patients, transurethral catheterization significantly impacted uroflow. In male patients with benign prostatic hyperplasia ( n = 50), Qmax, Qave and Tmax were significantly different between free uroflow and pressure-flow study. In patients with female stress incontinence ( n = 30), there were no statistically significant between-test differences in VV and Tmax, but Qmax, Qave and PVR were significantly different. In patients with spinal injury or spina bifida ( n = 40), Qmax, Qave and VV were significantly different between free uroflow and pressure-flow study. Conclusion Urethral catheterization adversely impacts uroflow in patients with benign prostatic hyperplasia, female stress incontinence, spinal injury or spina bifida. Free uroflowmetry should be performed before pressure-flow study.
Miracle drug: Brazil approves never-tested cancer medicine
Authors: Kuchenbecker Ricardo S , Mota Daniel M 
Published: August 2016

Background Brazil recently approved synthetic phosphoetanolamine, a popularly dubbed ‘cancer pill’, a substance that has been shown to kill cancer cells in lab animal models but was not yet formally accessed in humans, and thus despite the existence of any evidence of its efficacy and safety. Methods The authors describe the recent decision of Brazil to aprove phosphoetanolamine in the context of growing ‘judicialization’ to promote access to medicines and thus reinforcing a growing sense of legal uncertainty. Results The approval of phosphoetanolamine despite the existence of any evidence of its efficacy and safety represents to the authors one of the saddest and surrealistic episodes in Brazil’s recent public health history. Brazil’s current economic crisis is fueling the ‘judicialization’ to promote access to medicines and thus reinforcing a growing sense of legal uncertainty in the context of rising economic constrains and a progressive failing state. The authors state that the Phosphoetanolamine’s approval bill violates current legal prohibition of commercialisation of drugs without the Brazilian national drug regulatory agency’s approval and thus may represent a potential menace to Brazil’s pharmacogovernance and the country’s governance to health technology assessment at the Brazilian national health systems. Conclusion Phosphoetanolamine’s approval illustrates that the combination of flawed decision making, economic crisis and political interference may threaten weak governance mechanisms for drug regulation and health technology assessment and thus representing an extra burden in the sustainability of universal access-based national health systems.
Arterial Clamping Increases Central Renal Cryoablation Efficacy: An Animal Study
Authors: Nonboe Lasse L. , Nielsen Tommy K. , Høyer Søren , Graumann Ole , Frøkiær Jørgen , Borre Michael 
Published: August 2016

Introduction: The minimally invasive treatment of small renal masses with cryoablation has become increasingly widespread during the past 15 years. Studies with long-term follow-up are beginning to emerge, showing good oncological control, however, tumors with a central and endophytic location seem to possess an increased risk of treatment failure. Such tumors are likely to be subjected to a high volume of blood giving thermal protection to the cancerous cells. Arterial clamping during freezing might reduce this effect but at the same time subject the kidney to ischemia. The aim of this study was to evaluate the effect of renal artery clamping during cryoablation in a porcine survival model. Methods: Ten Danish Landrace pigs (approximately 40 kg) underwent bilateral laparoscopic cryoablation with clamping of the right renal artery during freezing. The cryoablation consisted of a standard double-freeze cycle of 10-minute freeze followed by 8 minutes of thaw. Arterial clamping subjected the right kidney to 2 cycles of ischemia (10 minutes) with perfusion in between. After surgery, the animals were housed for 14 days prior to computed tomography perfusions scans, radioisotope renography, and bilateral nephrectomy. Results: No perioperative or postoperative complications were experienced. Mean differential renal function was 44% (95% confidence interval: 42-46) in the clamped right kidney group and 56% (95% confidence interval: 54-58) in the nonclamped left kidney group, P < .05. The ±5% technical inaccuracy is not accounted for in the results. Mean maximum temperature between freeze cycles was 5.13°C (95% confidence interval: −0.1 to 10.3) in the clamped right kidney group and 22.7°C (95% confidence interval: −16.6 to 28.8) in the nonclamped left kidney group, P < .05. Mean cryolesion volume, estimated on computed tomography perfusion, was 12.4 mL (95% confidence interval: 10.35-14.4) in the clamped right kidney group and 6.85 mL (95% confidence interval: 5.57-8.14) in the nonclamped left kidney group, P < .05. Pathological examination shows a higher degree of vital cells in the intermediate zone of the cryolesions in the nonclamped left kidneys when compared with the clamped right kidneys. Conclusion: Arterial clamping increases cryolesion size by approximately 80%, and pathologic examinations suggest a decreased risk of vital cells in the intermediate zone. The clamped kidneys showed no sign of injury from the limited ischemic insult. This study was limited by being a nontumor model.
The interaction between fibrinogen and zymogen FXIII-A2B2 is mediated by fibrinogen residues γ390-396 and the FXIII-B subunits
Authors: Byrnes James R. , Wilson Clare , Boutelle Anthony M. , Brandner Chase B. , Flick Matthew J. , Philippou Helen , Wolberg Alisa S. 
Published: August 2016

Key PointsFibrinogen γ-chain residues 390 to 396 bind FXIII-A2B2 and mediate its activation in a FXIII-B subunit-dependent mechanism. Excess FXIII-B2 in plasma circulates bound to fibrinogen.
Occupancy of human EPCR by protein C induces β-arrestin-2 biased PAR1 signaling by both APC and thrombin
Authors: Roy Ram Vinod , Ardeshirylajimi Abdolreza , Dinarvand Peyman , Yang Likui , Rezaie Alireza R. 
Published: August 2016

Key PointsThrombin and APC elicit paradoxical signaling responses through cleavage of PAR1 at different sites. EPCR occupancy mediates β-arrestin-2 biased protective PAR1 signaling by both proteases via recruiting GRK5 and Dvl-2.
Identification of DNA-binding proteins using multi-features fusion and binary firefly optimization algorithm
Authors: Zhang Jian , Gao Bo , Chai Haiting , Ma Zhiqiang , Yang Guifu 
Published: August 2016

Abstract
Background
DNA-binding proteins (DBPs) play fundamental roles in many biological processes. Therefore, the developing of effective computational tools for identifying DBPs is becoming highly desirable.

Results
In this study, we proposed an accurate method for the prediction of DBPs. Firstly, we focused on the challenge of improving DBP prediction accuracy with information solely from the sequence. Secondly, we used multiple informative features to encode the protein. These features included evolutionary conservation profile, secondary structure motifs, and physicochemical properties. Thirdly, we introduced a novel improved Binary Firefly Algorithm (BFA) to remove redundant or noisy features as well as select optimal parameters for the classifier. The experimental results of our predictor on two benchmark datasets outperformed many state-of-the-art predictors, which revealed the effectiveness of our method. The promising prediction performance on a new-compiled independent testing dataset from PDB and a large-scale dataset from UniProt proved the good generalization ability of our method. In addition, the BFA forged in this research would be of great potential in practical applications in optimization fields, especially in feature selection problems.

Conclusions
A highly accurate method was proposed for the identification of DBPs. A user-friendly web-server named iDbP (identification of DNA-binding Proteins) was constructed and provided for academic use.