bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex Patterns of Altered MicroRNA Expression during the Adenoma-Adenocarcinoma Sequence for Microsatellite-Stable Colorectal Cancer
Authors: Bartley Angela N. , Yao Hui , Barkoh Bedia A. , Ivan Cristina , Mishra Bal M. , Rashid Asif , Calin George A. , Luthra Rajyalakshmi , Hamilton Stanley R. 
Published: September 2011

Abstract
Purpose: MicroRNAs are short noncoding RNAs that regulate gene expression and are over- or underexpressed in most tumors, including colorectal adenocarcinoma. MicroRNAs are potential biomarkers and therapeutic targets and agents, but limited information on microRNAome alterations during progression in the well-known adenoma-adenocarcinoma sequence is available to guide their usage.
Experimental Design: We profiled 866 human microRNAs by microarray analysis in 69 matched specimens of microsatellite-stable adenocarcinomas, adjoining precursor adenomas including areas of high- and low-grade dysplasia, and nonneoplastic mucosa.
Results: We found 230 microRNAs that were significantly differentially expressed during progression, including 19 not reported previously. Altered microRNAs clustered into two major patterns of early (type I) and late (type II) differential expression. The largest number (n = 108) was altered at the earliest step from mucosa to low-grade dysplasia (subtype IA) prior to major nuclear localization of β-catenin, including 36 microRNAs that had persistent differential expression throughout the entire sequence to adenocarcinoma. Twenty microRNAs were intermittently altered (subtype IB), and six were transiently altered (subtype IC). In contrast, 33 microRNAs were altered late in high-grade dysplasia and adenocarcinoma (subtype IIA), and 63 in adenocarcinoma only (subtype IIB). Predicted targets in 12 molecular pathways were identified for highly altered microRNAs, including the Wnt signaling pathway leading to low-grade dysplasia. β-catenin expression correlated with downregulated microRNAs.
Conclusions: Our findings suggest that numerous microRNAs play roles in the sequence of molecular events, especially early events, resulting in colorectal adenocarcinoma. The temporal patterns and complexity of microRNAome alterations during progression will influence the efficacy of microRNAs for clinical purposes. Clin Cancer Res; 17(23); 7283–93. ©2011 AACR.
Efficacy of Low Interatrial Septum and Right Atrial Appendage Pacing for Prevention of Permanent Atrial Fibrillation in Patients With Sinus Node Disease
Authors: Verlato Roberto , Botto Giovanni Luca , Massa Riccardo , Amellone Claudia , Perucca Antonello , Bongiorni Maria Grazia , Bertaglia Emanuele , Ziacchi Vigilio , Piacenti Marcello , Del Rosso Attilio , Russo Giovanni , Baccillieri Maria Stella , Turrini Pietro , Corbucci Giorgio 
Published: September 2011

Background—
The role of pacing sites and atrial electrophysiology on the progression of atrial fibrillation (AF) to the permanent form in patients with sinus node dysfunction (SND) has never been investigated. The aim of the study was to investigate the relationship between atrial electrophysiology and the efficacy of atrial pacing at the low interatrial septum (IAS) or at the right atrial appendage (RAA) to prevent persistent/permanent AF in patients with SND.

Methods and Results—

The Electrophysiology-Guided Pacing Site Selection (EPASS) Study was a prospective, controlled, randomized study. Atrial refractoriness, basal and incremental conduction times from the RAA to the coronary sinus ostium were measured before implantation, and the difference (ΔCTos) was calculated. Patients with ΔCTos ≥50 ms (study group) and those with ΔCTos <50 ms (control group) were randomly assigned to RAA or IAS with algorithms for continuous atrial stimulation “on.” The primary end point was time to development of permanent or persistent AF within a 2-year follow-up in the study group, IAS versus RAA. Data were analyzed by intention to treat. One hundred two patients (77±7 years, 44 mol/L) were enrolled, 69 (68%) in the study group and 33 (32%) in the control group. Of these, 97 ended the study, respectively, randomly assigned: 29 IAS versus 36 RAA and 18 IAS versus 14 RAA. After a mean follow-up of 15±7 (median, 17) months, 11 (16.6%) patients in the study group met the primary end point: 2 IAS versus 9 RAA (log rank=3.93,
P
=0.047).

Conclusions—
In patients with SND and intra-atrial conduction delay, low IAS pacing was superior to RAA pacing in preventing progression to persistent or permanent AF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00239226.
Radiofrequency Catheter Ablation and Antiarrhythmic Drug Therapy
Authors: Pappone Carlo , Vicedomini Gabriele , Augello Giuseppe , Manguso Francesco , Saviano Massimo , Baldi Mario , Petretta Andrea , Giannelli Luigi , Calovic Zarko , Guluta Vladimir , Tavazzi Luigi , Santinelli Vincenzo 
Published: September 2011

Background—
Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AADs) >1 year after randomization is important for clinical decision-making.

Methods and Results—

A total of 198 patients (age, 56±10 years) with paroxysmal atrial fibrillation were randomly assigned to RFA (99 patients) or to AADs (99 patients). We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis. Cardiac rhythm was assessed with daily transtelephonic transmissions. Quality of life was also analyzed. At 4 years, among the 99 patients first assigned to RFA, the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients (27.3%). Among the 99 patients randomly assigned to AADs, 87 (87.9%) crossed over to undergo RFA and 4 years after random assignment only 12 (12.1%) were in sinus rhythm with AAD alone without ablation. Despite the high level of crossovers, at 4 years the intention-to-treat analysis showed that 72.7% of patients in the ablation arm and 56.5% of those initially randomly assigned to AADs were free of recurrent atrial fibrillation/atrial tachycardia (
P
=0.017). During the follow-up, 19.2% of AAD patients progressed to persistent atrial fibrillation before switching to RFA. RFA significantly improved quality of life (
P
<0.001), whereas before crossing over to RFA, patients receiving AADs showed poorer quality of life. Except for new left atrial tachycardia, there were no serious complications caused by RFA.

Conclusions—
With follow-up extended to 4 years after randomly assigned, ablation remains superior to antiarrhythmic drug in these patients with paroxysmal atrial fibrillation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00340314.
Changes in Secondary Sexual Characters of Males of Thor Floridanus (Decapoda, Hippolytidae), Infested by Bopyrinella Thorii (Isopoda, Bopyridae)
Authors: Romero-Rodríguez J. , Román-Contreras R. 
Published: September 2011

Abstract
This study describes changes in the secondary sexual characters of Thor floridanus Kingsley, 1878 males, caused by the isopod Bopyrinella thorii (Richardson, 1904). Of 380 specimens of T. floridanus examined, the females were more often infested (n = 313) than the males (n = 41), and had a wider size range (0.7-2.85 mm POCL) compared to the males (0.9-2.32 mm POCL); no ovigerous females of T. floridanus were found. In 25 males the appendix masculina was reduced in size, the endopod of the second pleopod was barely ornamented, and the flexor margin of the propod of the third pereiopod was similar to that of the female of the species; all those males were classified as “feminized”. Those individuals were infested mainly by pairs of mature parasites, and 75% of the “primary” males carried cryptoniscus larvae, suggesting that the “feminization” of the males is caused by the parasite, as a result of the sexual development of hosts and parasites.
Land Tax alā l-misāa and muqāsama: Legal Theory and the Balance of Social Forces in Early Medieval Iraq (6th-8th Centuries C.E.)
Authors: Campopiano Michele 
Published: September 2011

AbstractThe article argues that any analysis of tax policies must be grounded in the given society’s ‘mode of production’. This is demonstrated through analysis of the political relationship between the Abbasid state and the landlords, and the reasons why certain prominent Muslim jurists between 750 and ca. 900. promoted muqāsama in the Sawād of Iraq. These jurists’ tax policy is explained with reference to Haldon’s concept of the tributary mode of production. It is concluded that according to the jurists, muqāsama favoured a redistribution of surpluses between the state and the landowners which could strengthen relations between the Abbasid state and the powerful landlords in Iraq.
Numerical Experiments of an Advanced Radiative Transfer Model in the U.S. Navy Operational Global Atmospheric Prediction System
Authors: Liu Ming , Kim Young-Joon , Zhao Qingyun 
Published: September 2011

AbstractA high-order accurate radiative transfer (RT) model developed by Fu and Liou has been implemented into the Navy Operational Global Atmospheric Prediction System (NOGAPS) to improve the energy budget and forecast skill. The Fu–Liou RT model is a four-stream algorithm (with a two-stream option) integrating over 6 shortwave bands and 12 longwave bands. The experimental 10-day forecasts and analyses from data assimilation cycles are compared with the operational output, which uses a two-stream RT model of three shortwave and five longwave bands, for both winter and summer periods. The verifications against observations of radiosonde and surface data show that the new RT model increases temperature accuracy in both forecasts and analyses by reducing mean bias and root-mean-square errors globally. In addition, the forecast errors also grow more slowly in time than those of the operational NOGAPS because of accumulated effects of more accurate cloud–radiation interactions. The impact of parameterized cloud effective radius in estimating liquid and ice water optical properties is also investigated through a sensitivity test by comparing with the cases using constant cloud effective radius to examine the temperature changes in response to cloud scattering and absorption. The parameterization approach is demonstrated to outperform that of constant radius by showing smaller errors and better matches to observations. This suggests the superiority of the new RT model relative to its operational counterpart, which does not use cloud effective radius. An effort has also been made to improve the computational efficiency of the new RT model for operational applications.
Fuzzy adaptive observer-based projective synchronization for nonlinear systems with input nonlinearity
Authors: Boulkroune Abdesselem , M’saad Mohammed 
Published: September 2011

In this paper, a projective synchronization problem of master-slave chaotic systems is investigated. More specifically, a fuzzy adaptive slave chaotic system subject to both sector nonlinearities and dead-zone in the input channel is proposed using only the measurable output of the master system thanks to a suitable observer. The asymptotical projective synchronization between the master and slave systems is achieved by an adequate fuzzy adaptive variable-structure control system. The underlying parameter adaptation design as well as the asymptotical synchronization and stability analysis are carried out using a Lyapunov based approach. The distinctive feature of the control design is that the uncertainties function and the gain reduction tolerances of the dead-zone are no longer required to be known thanks to the parameter adaptation capability of the control system. The proposed synchronization scheme is extended to two classes of the master-slave chaotic systems with time-delays. By using the Lyapunov-Krasovskii approach, some stability conditions relating to these classes are derived. Simulation results are given to show the effectiveness of the proposed projective synchronization scheme.
Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts
Authors: Blau Olga , Baldus Claudia Dorothea , Hofmann Wolf-Karsten , Thiel Gundula , Nolte Florian , Burmeister Thomas , Türkmen Seval , Benlasfer Ouidad , Schümann Elke , Sindram Annette , Molkentin Mara , Mundlos Stefan , Keilholz Ulrich , Thiel Eckhard , Blau Igor Wolfgang 
Published: September 2011

AbstractMesenchymal stromal cells (MSCs) are an essential cell type of the hematopoietic microenvironment. Concerns have been raised about the possibility that MSCs undergo malignant transformation. Several studies, including one from our own group, have shown the presence of cytogenetic abnormalities in MSCs from leukemia patients. The aim of the present study was to compare genetic aberrations in hematopoietic cells (HCs) and MSCs of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients. Cytogenetic aberrations were detected in HCs from 25 of 51 AML patients (49%) and 16 of 43 MDS patients (37%). Mutations of the FLT3 and NPM1 genes were detected in leukemic blasts in 12 (23%) and 8 (16%) AML patients, respectively. Chromosomal aberrations in MSCs were detected in 15 of 94 MDS/AML patients (16%). No chromosomal abnormalities were identified in MSCs of 36 healthy subjects. We demonstrate herein that MSCs have distinct genetic abnormalities compared with leukemic blasts. We also analyzed the main characteristics of patients with MSCs carrying chromosomal aberrations. In view of these data, the genetic alterations in MSCs may constitute a particular mechanism of leukemogenesis.
Clinical pharmacogenomic testing of KRAS, BRAF and EGFRmutations by high resolution melting analysis and ultra-deep pyrosequencing
Authors: Borràs Emma , Jurado Ismael , Hernan Imma , Gamundi María José , Dias Miguel , Martí Isabel , Mañé Begoña , Arcusa Àngels , Agúndez José AG , Blanca Miguel , Carballo Miguel 
Published: September 2011

Abstract

Background
Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices.

Methods
We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform.

Results
We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations.

Conclusions
HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.
Increased Atherosclerosis in Mice Deficient in Perilipin1
Authors: Langlois Dominique , Forcheron Fabien , Li Jacques-Yuan , del Carmine Peggy , Neggazi Samia , Beylot Michel 
Published: September 2011

Abstract

Background
Perilipin1, a lipid droplet associated protein has an important role in the regulation of lipolysis and lipid storage in adipocytes. Perilipin1 is also expressed in foam cells of atheroma plaques and could therefore play a role in the accumulation of lipids in arterial wall and in the development of atherosclerosis. The aim of the study was to investigate this possible role of perilipin1 in atherogenesis.

Methods
Mice deficient in perilipin1 (Plin1-/-) were crossed with Ldlr-/- mice. Ldlr-/- and Plin1-/- Ldlr-/- mice received an atherogenic diet during 10 or 20 weeks. Blood pressure and plasma lipids concentrations were measured. Aortas were collected at the end of the atherogenic diet periods for quantification of atheroma lesions (en face method), histological and immunohistological studies

Results

Ldlr-/- and Plin1-/- Ldlr-/- mice had comparable blood pressure and plasma lipids levels. Plin1-/- Ldlr-/- mice had a lower body weight and decreased adiposity. The atherosclerotic lesion area in Plin1-/-Ldlr-/- mice was moderately increased after 10 weeks of atherogenic diet (ns) and significantly higher after 20 weeks (p < 0.01). Histology of atheroma plaques was comparable with no sign of increased inflammation in Plin1-/- Ldlr-/- mice.

Conclusion
Perilipin1 ablation in mice results in increased atherosclerosis independently of modifications of risk factors such as raised blood pressure or plasma lipids levels. These data strongly support an atheroprotective role for perilipin1.
Intravenous leiomyomatosis of the uterus with extension to the right heart
Authors: Lou Yu-Feng , Shi Xin-Ping , Song Ze-Zhou 
Published: September 2011

Abstract
A 42-year-old woman admitted with debilitation and engorgement both lower extremities. Transthoracic two-dimensional echocardiography, abdominal ultrasound and computerized tomography revealed a lobulated pelvic mass, a mass within right internal iliac vein, both common iliac vein, as well as the inferior vena cava, extending into the right atrium. In addition, echocardiography and abdominal ultrasound showed the tumor of right atrium and inferior vena cave has no stalk and has well-demarcated borders with the wall of right atrium and inferior vena cave. Hence, the presumptive diagnosis of IVL was made by echocardiography and abdominal ultrasound and the presumptive diagnosis of sarcoma with invasion in right internal iliac vein, both common iliac vein, the inferior vena cava, as well as the right atrium was made by multi-detector-row computerized tomography. The patient underwent a one-stage combined multidisciplinary thoraco-abdominal operation under general anaesthetic. Subsequently the pathologic report confirmed IVL.
Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease
Authors: Diedrich Madeleine , Kitada Tohru , Nebrich Grit , Koppelstaetter Andrea , Shen Jie , Zabel Claus , Klose Joachim , Mao Lei 
Published: September 2011

Abstract
Parkinson's disease (PD) is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO), in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS) pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia nigra. Taken together, the delicate balance between oxidative protection and mitophagy capacity in different brain regions could contribute to brain region-specific pathological patterns in PD.
Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study
Authors: Johansson Jessica , Landgren Magnus , Fernell Elisabeth , Vumma Ravi , Åhlin Arne , Bjerkenstedt Lars , Venizelos Nikolaos 
Published: September 2011

Abstract

Background
The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for synthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin. A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport.

Methods
Fibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine, tryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (V

max
) and affinity constant (K

m
) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test.

Results
The ADHD group had significantly decreased V

max
(p = 0.039) and K

m
(increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher V

max
of alanine transport (p = 0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of the kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group.

Conclusions
Tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.