bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical Simulation of 2010 Pakistan Flood in the Kabul River Basin by Using Lagged Ensemble Rainfall Forecasting
Authors: Ushiyama Tomoki , Sayama Takahiro , Tatebe Yuya , Fujioka Susumu , Fukami Kazuhiko 
Published: September 2013

Abstract
Lagged ensemble forecasting of rainfall and rainfall–runoff–inundation (RRI) forecasting were applied to the devastating flood in the Kabul River basin, the first strike of the 2010 Pakistan flood. The forecasts were performed using the Global Forecast System of the National Centers for Environmental Prediction (NCEP-GFS) and were provided four times daily. Dynamical downscaling was also applied to the forecasts by the Weather Research and Forecasting Model (WRF), a regional model. The forecasts of the rainfall and inundation area were verified by comparing rain gauge–corrected Global Satellite Mapping of Precipitation (GSMaP) data and the observed indicator of an inundation map based on Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data. The GFS predicted a sign of heavy rainfall in northern Pakistan 4 days ahead of the onset. However, most of the forecasts predicted it in wrong places, and only those performed after the rainfall onset predicted it in the accurate location. Downscaling corrected the locations of the misplaced GFS forecasts and also underestimated or overestimated rainfall amount derived from GFS. Finally, downscaled forecasts predicted a reliable amount of rainfall in the Kabul River basin 1 day ahead of the rainfall onset and predicted a high probability of heavy rainfall 3 days ahead. Lagged ensemble forecasts of discharge and inundation distribution based on GFS rainfall predicted the probability of the actual discharge and inundation distribution, but in low reliability. The reliability substantially improved when downscaled rainfall was used. The reliability of the flood alert system combining NCEP-GFS, dynamical downscaling by WRF, and the RRI model was at an acceptable level in this study.
CT Measured Normative Cartilage Growth in Children Requiring Costochondral Grafting
Authors: Andreoli Steven M. , Mills Jared C. , Kilpatrick Lauren A. , White David R. , Patel Krishna G. 
Published: September 2013

ObjectiveCareful operative timing is required for children undergoing microtia repair using autologous costochondral grafting. This operation is performed as early as age 6 in efforts to treat children before school matriculation while allowing for sufficient rib growth. There remains a paucity of data regarding cartilaginous growth of the ribs and synchondrosis routinely harvested during microtia repair. This study employs CT imaging to generate normative costochondral growth characteristics in children.Study DesignA population‐based study was performed.SettingTertiary care children's hospital.Subjects and MethodsChest CTs were reviewed in 360 children ages 3 to 20 years. Measurements included: length of ribs 6, 7, and 8 and the height and width of the synchondrosis between ribs 6 and 7. Growth charts are presented for gender and laterality.ResultsAt age 6: ribs 6, 7, and 8 measure 5.96 ± 0.69, 7.79 ± 0.84, and 6.33 ± 1.01 cm, respectively. In adulthood the mean length of ribs 6, 7, and 8 are 8.29 ± 1.00, 11.10 ± 1.19, and 8.95 ± 1.99 cm, respectively. The vertical height of the synchondrosis at years 6 and 20 are 2.42 ± 0.39 and 3.59 ± 0.53 cm, respectively. Ribs 6, 7, and 8 as well as the synchondrosis grow in a nearly linear fashion.ConclusionsCartilaginous growth of ribs 6 to 8 during early childhood is nearly linear. Synchondrosis height approaches adult auricle width at 8 years. Rib size is consistently larger in males and on the left side. These data are useful for the pediatric otolaryngologist and facial plastics and reconstructive surgeon performing microtia surgery.
Sturge-Weber syndrome with late onset hemiplegic migraine-like attacks and progressive unilateral cerebral atrophy
Authors: Planche Vincent , Chassin Olivier , Leduc Louise , Regnier Wendy , Kelly Antony , Colamarino Renato 
Published: September 2013

Background Sturge-Weber syndrome (SWS) is an uncommon etiology of hemiplegic migraine-like (HM-like) attacks, associated with epilepsy and mental retardation. Case We report the case of a 40-year-old woman with SWS who has been suffering from HM-like episodes since she was 24, with no history of seizure or mental retardation. Susceptibility weighted imaging (SWI)-MRI and CT scans have shown bilateral calcifications of the choroidal plexuses, a developmental venous anomaly with dilated transmedullary veins and a left parieto-occipital leptomeningeal angioma. 18F-Fluorodeoxyglucose (FDG)-PET/CT revealed a diffuse left-hemisphere hypometabolism. The comparison between the MRI performed at the age of 24 and the one performed at the age of 40 highlighted a progressive unilateral fronto-temporo-parietal atrophy. Surprisingly, even now, cognitive functions of this patient are relatively preserved. Lamotrigine permitted an improvement of HM-like attacks. Discussion Explanations for this minimally symptomatic form of SWS may be the absence of seizure, the importance of her deep venous drainage, the absence of cortical calcification and white matter impairment in the affected hemisphere, and, paradoxically, the severely asymmetric cortical metabolism. Furthermore, this case reinforces the hypothesis that alteration of cerebral hemodynamics could precipitate the cortical spreading depression giving rise to migraine with aura. Conclusion We propose to consider SWS as a cause of apparently isolated hemiplegic migraine and lamotrigine as a preventive medication in HM-like attacks.
High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis
Authors: Fürst Daniel , Müller Carlheinz , Vucinic Vladan , Bunjes Donald , Herr Wolfgang , Gramatzki Martin , Schwerdtfeger Rainer , Arnold Renate , Einsele Hermann , Wulf Gerald , Pfreundschuh Michael , Glass Bertram , Schrezenmeier Hubert , Schwarz Klaus , Mytilineos Joannis 
Published: September 2013

Key Points
HLA mismatches at the allele and antigen level (possibly with the exception of HLA-DQB1) should be treated equally in donor selection. HLA mismatches at >1 locus (including HLA-DQB1) have additive detrimental effects.
Effector T cells require fatty acid metabolism during murine graft-versus-host disease
Authors: Byersdorfer Craig A. , Tkachev Victor , Opipari Anthony W. , Goodell Stefanie , Swanson Jacob , Sandquist Stacy , Glick Gary D. , Ferrara James L. M. 
Published: September 2013

Key PointsT cells activated during GVHD increase their dependence upon fatty acid oxidation. This dependence is not observed following acute activation or during normal immune reconstitution, suggesting novel therapeutic targets.
Redox signaling in pathophysiology of hypertension
Authors: Majzunova Miroslava , Dovinova Ima , Barancik Miroslav , Chan Julie YH 
Published: September 2013

Abstract
Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.
Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats
Authors: Smeding Lonneke , Kuiper Jan Willem , Plötz Frans B , Kneyber Martin CJ , Groeneveld AB Johan 
Published: September 2013

Abstract

Background
Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.

Materials and methods
N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.

Results
Instillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.

Conclusions
Injurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.
Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses
Authors: Pitta Denise da Rocha , Sarian Luis Otávio , Barreta Amilcar , Campos Elisabete Aparecida , de Angelo Andrade Liliana Lucci , Fachini Ana Maria Dias , Campbell Leonardo Martins , Derchain Sophie 
Published: September 2013

Abstract

Background
This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound.

Methods
This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae.

Results
Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI.

Conclusion
Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.
Molecular dynamics simulations on the Tre1 G protein-coupled receptor: exploring the role of the arginine of the NRY motif in Tre1 structure
Authors: Pruitt Margaret M , Lamm Monica H , Coffman Clark R 
Published: September 2013

Abstract

Background
The arginine of the D/E/NRY motif in Rhodopsin family G protein-coupled receptors (GPCRs) is conserved in 96% of these proteins. In some GPCRs, this arginine in transmembrane 3 can form a salt bridge with an aspartic acid or glutamic acid in transmembrane 6. The Drosophila melanogaster GPCR Trapped in endoderm-1 (Tre1) is required for normal primordial germ cell migration. In a mutant form of the protein, Tre1sctt, eight amino acids RYILIACH are missing, resulting in a severe disruption of primordial germ cell development. The impact of the loss of these amino acids on Tre1 structure is unknown. Since the missing amino acids in Tre1sctt include the arginine that is part of the D/E/NRY motif in Tre1, molecular dynamics simulations were performed to explore the hypothesis that these amino acids are involved in salt bridge formation and help maintain Tre1 structure.

Results
Structural predictions of wild type Tre1 (Tre1+) and Tre1sctt were subjected to over 250 ns of molecular dynamics simulations. The ability of the model systems to form a salt bridge between the arginine of the D/E/NRY motif and an aspartic acid residue in transmembrane 6 was analyzed. The results indicate that a stable salt bridge can form in the Tre1+ systems and a weak salt bridge or no salt bridge, using an alternative arginine, is likely in the Tre1sctt systems.

Conclusions
The weak salt bridge or lack of a salt bridge in the Tre1sctt systems could be one possible explanation for the disrupted function of Tre1sctt in primordial germ cell migration. These results provide a framework for studying the importance of the arginine of the D/E/NRY motif in the structure and function of other GPCRs that are involved in cell migration, such as CXCR4 in the mouse, zebrafish, and chicken.
Cytostatic versus cytocidal profiling of quinoline drug combinations via modified fixed-ratio isobologram analysis
Authors: Gorka Alexander P , Jacobs Lauren M , Roepe Paul D 
Published: September 2013

Abstract

Background
Drug combination therapy is the frontline of malaria treatment. There is an ever-accelerating need for new, efficacious combination therapies active against drug resistant malaria. Proven drugs already in the treatment pipeline, such as the quinolines, are important components of current combination therapy and also present an attractive test bank for rapid development of new concepts.

Methods
The efficacy of several drug combinations versus chloroquine-sensitive and chloroquine-resistant strains was measured using both cytostatic and cytocidal potency assays.

Conclusions
These screens identify quinoline and non-quinoline pairs that exhibit synergy, additivity, or antagonism using the fixed-ratio isobologram method and find tafenoquine – methylene blue combination to be the most synergistic. Also, interestingly, for selected pairs, additivity, synergy, or antagonism defined by quantifying IC50 (cytostatic potency) does not necessarily predict similar behaviour when potency is defined by LD50 (cytocidal potency). These data further support an evolving new model for quinoline anti-malarials, wherein haem and haemozoin are the principle target for cytostatic activity, but may not be the only target relevant for cytocidal activity.
Organization of Plasmodium falciparum spliceosomal core complex and role of arginine methylation in its assembly
Authors: Hossain Manzar , Sharma Shweta , Korde Reshma , Kanodia Shivani , Chugh Monika , Rawat Khushboo , Malhotra Pawan 
Published: September 2013

Abstract

Background
Splicing and alternate splicing are the two key biological processes that result in the generation of diverse transcript and protein isoforms in Plasmodium falciparum as well as in other eukaryotic organisms. Not much is known about the organization of splicing machinery and mechanisms in human malaria parasite. Present study reports the organization and assembly of Plasmodium spliceosome Sm core complex.

Methods
Presence of all the seven Plasmodium Sm-like proteins in the intra-erythrocytic stages was assessed based on the protein(s) expression analysis using immuno-localization and western blotting. Localization/co-localization studies were performed by immunofluorescence analysis on thin parasite smear using laser scanning confocal microscope. Interaction studies were carried out using yeast two-hybrid analysis and validated by in vitro pull-down assays. PfPRMT5 (arginine methyl transferase) and PfSmD1 interaction analysis was performed by pull-down assays and the interacting proteins were identified by MALDI-TOF spectrometry.

Results
PfSm proteins are expressed at asexual blood stages of the parasite and show nucleo-cytoplasmic localization. Protein-protein interaction studies showed that PfSm proteins form a heptameric complex, typical of spliceosome core complex as shown in humans. Interaction of PfSMN (survival of motor neuron, tudor domain containing protein) or PfTu-TSN (Tudor domain of Tudor Staphylococcal nuclease) with PfSmD1 proteins was found to be methylation dependent. Co-localization by immunofluorescence and co-immunoprecipitation studies suggested an association between PfPRMT5 and PfSmD1, indicating the role of arginine methylation in assembly of Plasmodium spliceosome complex.

Conclusions

Plasmodium Sm-like proteins form a heptameric ring-like structure, although the arrangement of PfSm proteins slightly differs from human splicing machinery. The data shows the interaction of PfSMN with PfSmD1 and this interaction is found to be methylation dependent. PfPRMT5 probably exists as a part of methylosome complex that may function in the cytoplasmic assembly of Sm proteins at asexual blood stages of P. falciparum.
YB-1 dependent oncolytic adenovirus efficiently inhibits tumor growth of glioma cancer stem like cells
Authors: Mantwill Klaus , Naumann Ulrike , Seznec Janina , Girbinger Vroni , Lage Hermann , Surowiak Pawel , Beier Dagmar , Mittelbronn Michel , Schlegel Jürgen , Holm Per Sonne 
Published: September 2013

Abstract

Background
The brain cancer stem cell (CSC) model describes a small subset of glioma cells as being responsible for tumor initiation, conferring therapy resistance and tumor recurrence. In brain CSC, the PI3-K/AKT and the RAS/mitogen activated protein kinase (MAPK) pathways are found to be activated. In consequence, the human transcription factor YB-1, knowing to be responsible for the emergence of drug resistance and driving adenoviral replication, is phosphorylated and activated. With this knowledge, YB-1 was established in the past as a biomarker for disease progression and prognosis. This study determines the expression of YB-1 in glioblastoma (GBM) specimen in vivo and in brain CSC lines. In addition, the capacity of Ad-Delo3-RGD, an YB-1 dependent oncolytic adenovirus, to eradicate CSC was evaluated both in vitro and in vivo.

Methods
YB-1 expression was investigated by immunoblot and immuno-histochemistry. In vitro, viral replication as well as the capacity of Ad-Delo3-RGD to replicate in and, in consequence, to kill CSC was determined by real-time PCR and clonogenic dilution assays. In vivo, Ad-Delo3-RGD-mediated tumor growth inhibition was evaluated in an orthotopic mouse GBM model. Safety and specificity of Ad-Delo3-RGD were investigated in immortalized human astrocytes and by siRNA-mediated downregulation of YB-1.

Results
YB-1 is highly expressed in brain CSC lines and in GBM specimen. Efficient viral replication in and virus-mediated lysis of CSC was observed in vitro. Experiments addressing safety aspects of Ad-Delo3-RGD showed that (i) virus production in human astrocytes was significantly reduced compared to wild type adenovirus (Ad-WT) and (ii) knockdown of YB-1 significantly reduced virus replication. Mice harboring othotopic GBM developed from a temozolomide (TMZ)-resistant GBM derived CSC line which was intratumorally injected with Ad-Delo3-RGD survived significantly longer than mice receiving PBS-injections or TMZ treatment.

Conclusion
The results of this study supported YB-1 based virotherapy as an attractive therapeutic strategy for GBM treatment which will be exploited further in multimodal treatment concepts.
Identical effects of VEGF and serum-deprivation on phenotype and function of adipose-derived stromal cells from healthy donors and patients with ischemic heart disease
Authors: Follin Bjarke , Tratwal Josefine , Haack-Sørensen Mandana , Elberg Jens Jørgen , Kastrup Jens , Ekblond Annette 
Published: September 2013

Abstract

Background
Adipose-derived stromal cells (ASCs) stimulated with vascular endothelial growth factor (VEGF) and serum-deprived, are applied in the first in-man double-blind placebo-controlled MyStromalCell Trial, as a novel therapeutic option for treatment of ischemic heart disease (IHD). This in vitro study explored the effect of VEGF and serum deprivation on endothelial differentiation capacity of ASCs from healthy donors and IHD patients.

Methods
ASCs stimulated with rhVEGFA165 in serum-deprived medium for one to three weeks were compared with ASCs in serum-deprived (2% fetal bovine serum) or complete medium (10% fetal bovine serum). Expression of VEGF receptors, endothelial and stem cell markers was measured using qPCR, flow cytometry and immunocytochemistry. In vitro tube formation and proliferation was also measured.

Results
ASCs from VEGF-stimulated and serum-deprived medium significantly increased transcription of transcription factor FOXF1, endothelial marker vWF and receptor VEGFR1 compared with ASCs from complete medium. ASCs maintained stem cell characteristics in all conditions. Tube formation of ASCs occurred in VEGF-stimulated and serum-deprived medium. The only difference between healthy and patient ASCs was a variation in proliferation rate.

Conclusions
ASCs from IHD patients and healthy donors proved equally inclined to differentiate in endothelial direction by serum-deprivation, however with no visible additive effect of VEGF stimulation. The treatment did not result in complete endothelial differentiation, but priming towards endothelial lineage.