bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role and regulation of phosphatidylinositol 3-kinase β in platelet integrin α2β1 signaling
Authors: Consonni Alessandra , Cipolla Lina , Guidetti Gianni , Canobbio Ilaria , Ciraolo Elisa , Hirsch Emilio , Falasca Marco , Okigaki Mitsuhiko , Balduini Cesare , Torti Mauro 
Published: November 2011

Abstract
Integrin α2β1–mediated adhesion of human platelets to monomeric type I collagen or to the GFOGER peptide caused a time-dependent activation of PI3K and Akt phosphorylation. This process was abrogated by pharmacologic inhibition of PI3Kβ, but not of PI3Kγ or PI3Kα. Moreover, Akt phosphorylation was undetectable in murine platelets expressing a kinase-dead mutant of PI3Kβ (PI3KβKD), but occurred normally in PI3KγKD platelets. Integrin α2β1 failed to stimulate PI3Kβ in platelets from phospholipase Cγ2 (PLCγ2)–knockout mice, and we found that intracellular Ca2+ linked PLCγ2 to PI3Kβ activation. Integrin α2β1 also caused a time-dependent stimulation of the focal kinase Pyk2 downstream of PLCγ2 and intracellular Ca2+. Whereas activation of Pyk2 occurred normally in PI3KβKD platelets, stimulation of PI3Kβ was strongly reduced in Pyk2-knockout mice. Neither Pyk2 nor PI3Kβ was required for α2β1–mediated adhesion and spreading. However, activation of Rap1b and inside-out stimulation of integrin αIIbβ3 were reduced after inhibition of PI3Kβ and were significantly impaired in Pyk2-deficient platelets. Finally, both PI3Kβ and Pyk2 significantly contributed to thrombus formation under flow. These results demonstrate that Pyk2 regulates PI3Kβ downstream of integrin α2β1, and document a novel role for Pyk2 and PI3Kβ in integrin α2β1 promoted inside-out activation of integrin αIIbβ3 and thrombus formation.
MLVA genotyping of Chinese human Brucella melitensisbiovar 1, 2 and 3 isolates
Authors: Jiang Hai , Fan Mengguang , Chen Jingdiao , Mi Jingchuan , Yu Ruiping , Zhao Hongyan , Piao Dongri , Ke Changwen , Deng Xiaoling , Tian Guozhong , Cui Buyun 
Published: November 2011

Abstract

Background
Since 1950, Brucella melitensis has been the predominant strain associated with human brucellosis in China. In this study we investigated the genotypic characteristics of B. melitensis isolates from China using a multiple-locus variable-number tandem-repeat analysis (MLVA) and evaluated the utility of MLVA with regards to epidemiological trace-back investigation.

Results
A total of 105 B. melitensis strains isolated from throughout China were divided into 69 MLVA types using MLVA-16. Nei's genetic diversity indices for the various loci ranged between 0.00 - 0.84. 12 out 16 loci were the low diversity with values < 0.2 and the most discriminatory markers were bruce16 and bruce30 with a diversity index of > 0.75 and containing 8 and 7 alleles, respectively. Many isolates were single-locus or double-locus variants of closely related B. melitensis isolates from different regions, including the north and south of China. Using panel 1, the majority of strains (84/105) were genotype 42 clustering to the 'East Mediterranean' B. melitensis group. Chinese B. melitensis are classified in limited number of closely related genotypes showing variation mainly at the panel 2B loci.

Conclusion
The MLVA-16 assay can be useful to reveal the predominant genotypes and strain relatedness in endemic or non-endemic regions of brucellosis. However it is not suitable for biovar differentiation of B. melitensis. Genotype 42 is widely distributed throughout China during a long time. Bruce 16 and bruce 30 in panel 2B markers are most useful for typing Chinese isolates.
SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in Drosophila melanogaster
Authors: Waldholm Johan , Wang Zhi , Brodin David , Tyagi Anu , Yu Simei , Theopold Ulrich , Farrants Ann Kristin Östlund , Visa Neus 
Published: November 2011

Abstract

Background
The SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA.

Results
We have investigated whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of depleting individual SWI/SNF subunits on pre-mRNA processing throughout the genome, and we have identified a subset of transcripts that are affected by depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion of different subunits targets a subset of common transcripts suggests that the SWI/SNF complex is responsible for the effects observed on pre-mRNA processing when knocking down Brm. We have also depleted Brm in larvae and we have shown that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo.

Conclusions
We have shown that SWI/SNF can modulate alternative pre-mRNA processing, not only in cultured cells but also in vivo. The effect is restricted to and specific for a subset of transcripts. Our results provide novel insights into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic diversity in higher eukaryotes.
Retrospective study of necrotizing fasciitis and characterization of its associated Methicillin-resistant Staphylococcus aureusin Taiwan
Authors: Changchien Chih-Hsuan , Chen Ying-Ying , Chen Shu-Wun , Chen Wan-Lin , Tsay Jwu-Guh , Chu Chishih 
Published: November 2011

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a prevalent pathogen of necrotizing fasciitis (NF) in Taiwan. A four-year NF cases and clinical and genetic differences between hospital acquired (HA)- and community-acquired (CA)-MRSA infection and isolates were investigated.

Methods
A retrospective study of 247 NF cases in 2004-2008 and antimicrobial susceptibilities, staphylococcal chromosomal cassette mec (SCCmec) types, pulsed field gel electrophoresis (PFGE) patterns, virulence factors, and multilocus sequence typing (MLST) of 16 NF-associated MRSA in 2008 were also evaluated.

Results
In 247 cases, 42 microbial species were identified. S. aureus was the major prevalent pathogen and MRSA accounted for 19.8% of NF cases. Most patients had many coexisting medical conditions, including diabetes mellitus, followed by hypertension, chronic azotemia and chronic hepatic disease in order of decreasing prevalence. Patients with MRSA infection tended to have more severe clinical outcomes in terms of amputation rate (p < 0.05) and reconstruction rate (p = 0.001) than those with methicillin-sensitive S. aureus or non-S. aureus infection. NF patients infected by HA-MRSA had a significantly higher amputation rate, comorbidity, C-reactive protein level, and involvement of lower extremity than those infected by CA-MRSA. In addition to over 90% of MRSA resistant to erythromycin and clindamycin, HA-MRSA was more resistant than CA-MRSA to trimethoprim-sulfamethoxazole (45.8% vs. 4%). ST59/pulsotype C/SCCmec IV and ST239/pulsotype A/SCCmec III isolates were the most prevalent CA- and HA-MRSA, respectively in 16 isolates obtained in 2008. In contrast to the gene for γ-hemolysin found in all MRSA, the gene for Panton-Valentine leukocidin was only identified in ST59 MRSA isolates. Other three virulence factors TSST-1, ETA, and ETB were occasionally identified in MRSA isolates tested.

Conclusion
NF patients with MRSA infection, especially HA-MRSA infection, had more severe clinical outcomes than those infected by other microbial. The prevalent NF-associated MRSA clones in Taiwan differed distinctly from the most predominant NF-associated USA300 CA-MRSA clone in the USA. Initial empiric antimicrobials with a broad coverage for MRSA should be considered in the treatment of NF patients in an endemic area.
Accuracy of physical activity assessment during pregnancy: an observational study
Authors: Smith Katie M , Foster Randal C , Campbell Christina G 
Published: November 2011

Abstract

Background
Prenatal physical activity may improve maternal and infant health and lower future disease risk for both mother and baby; however, very few physical activity assessment methods have been validated for use during pregnancy. The purpose of this study was to evaluate the accuracy of a subjective physical activity record (PAR) and an objective activity monitor, against a reference standard to quantify moderate and vigorous physical activity (MVPA) in pregnant women. The reference standard was based on participant interviews to determine if a woman was an exerciser and confirmed with information obtained from the PAR and a heart rate monitor.

Methods
Fifty-two pregnant women completed a physical activity record (PAR) and wore a SenseWear® Mini Armband (SWA) activity monitor over a 7-day period at 18 weeks gestation. Total minutes spent in MVPA were totaled from both modalities and evaluated against the reference standard using contingency analysis and Pearson's chi-square test to evaluate the number of women meeting minimum prenatal physical activity recommendations (at least 3, 30 minute sessions of exercise per week). Both modalities were also tested individually and collectively to assess their ability as indicators of activity using empirically determined cut-offs as indicated by receiver-operator characteristic curves. These experimentally-derived criteria were also tested with Pearson's chi-square test.

Results
According to the reference standard, 13 of 52 participants (25%) met the criterion of 3, 30 minute sessions of volitional, moderate-intensity activity. When compared to the reference standard, both the PAR and SWA overestimated exercise status; 42 (81%) and 52 (100%) participants, respectively, achieved 90 minutes of MVPA (P < 0.0001 for both comparisons). Single-modality predictors of MVPA did not show a significant correlation. A composite predictor of MVPA offered the most favorable option for sensitivity and specificity (true positives, n = 8 and true negatives, n = 36) using cut-offs of 280 and 385 minutes/week for the PAR and SWA, respectively.

Conclusion
Compared to the reference standard, time spent in MVPA obtained from the PAR or SWA overestimated the prevalence of women meeting prenatal exercise recommendations. The most accurate predictor of women meeting current prenatal exercise guidelines was identified by using the PAR and SWA collectively.
Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer
Authors: Hwang Jun-Eul , Kim Ha-Na , Kim Dae-Eun , Choi Hyun-Jung , Jung Sung-Hoon , Shim Hyun-Jeong , Bae Woo-Kyun , Hwang Eu-Chang , Cho Sang-Hee , Chung Ik-Joo 
Published: November 2011

Abstract

Background
There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS), and overall survival (OS) in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy.

Methods
We reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS), C-reactive protein (CRP), albumin, Glasgow prognostic score (GPS), and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 mg/dL) were assigned a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were assigned a GPS of 1, and patients with a normal CRP and albumin were assigned a score of 0. To evaluate the factors that affected PFS and OS, univariate and multivariate analyses were performed.

Results
According to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, P = 0.035), bone metastasis (HR 1.74, 95% CI 1.14-2.65, P = 0.009), and CRP elevation (HR 1.64, 95% CI 1.28-2.09, P = 0.001). The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, P = 0.037), bone metastasis (HR 1.61, 95% CI 1.08-2.39, P = 0.017), and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, P = 0.001).

Conclusions
The results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.
Insulin resistance increases the occurrence of new cardiovascular events in patients with manifest arterial disease without known diabetes. The SMART study
Authors: Verhagen Sandra N , Wassink Annemarie MJ , van der Graaf Yolanda , Gorter Petra M , Visseren Frank LJ ,   the SMART Study Group
Published: November 2011

Abstract

Background
Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome. Metabolic syndrome is associated with an increased cardiovascular risk in patients with manifest arterial disease. We investigated whether insulin resistance is associated with an increased risk for cardiovascular events in patients with manifest arterial disease without known diabetes and whether this can be explained by the components of the metabolic syndrome or by inflammation.

Methods
Prospective cohort study in 2611 patients with manifest arterial disease without known diabetes. Homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. The relation of HOMA-IR with cardiovascular events (vascular death, myocardial infarction or stroke) and all cause mortality was assessed with Cox regression analysis. In additional models adjustments were performed for the single components constituting the metabolic syndrome and for inflammation.

Results
HOMA-IR increases with the number of metabolic syndrome components (mean HOMA-IR ± SD in groups with 0, 1, 2, 3, 4 and 5 metabolic syndrome components: 1.4 ± 0.7; 1.8 ± 1.2; 2.4 ± 1.5; 3.1 ± 1.8; 4.0 ± 2.6; and 5.6 ± 3.6 respectively). High HOMA-IR was independently associated with an increased risk of cardiovascular events (tertile 2 vs. 1 HR 1.92; 95%CI 1.20-3.08) (tertile 3 vs.1 HR 1.78; 95%CI 1.10-2.89) and with all cause mortality (tertile 2 vs. 1 HR 1.80; 95%CI 1.04-3.10) (tertile 3 vs.1 HR 1.56; 95%CI 0.88-2.75). These relations were not influenced by the individual components of metabolic syndrome or by inflammation.

Conclusions
In patients with manifest arterial disease without known diabetes, insulin resistance increases with the number of metabolic syndrome components, and elevated insulin resistance increases the risk of new cardiovascular events.
High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction
Authors: Arena Christopher B , Sano Michael B , Rossmeisl John H , Caldwell John L , Garcia Paulo A , Rylander Marissa Nichole , Davalos Rafael V 
Published: November 2011

Abstract

Background
Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.

Methods
A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.

Results
No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.

Conclusions
H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.
HBV inhibits apoB production via the suppression of MTP expression
Authors: Wang Fu-Bing , Zhu Cheng-liang , Liu Xinghui , Gao Guo-sheng 
Published: November 2011

Abstract

Background
Liver dominates the production and secretion of apolipoprotein B (apoB) and evidence shows that liver malfunction induced by hepatitis B virus (HBV) infection could lead to apolipoprotein metabolism disorders. The present study was undertaken to assess the effects of HBV on apoB expression.

Methods
Clinical examination: serum apoB levels in patients with chronic HBV infection and in healthy individuals were measured by immunoturbidimetry using biochemical analyzer Olympus 5400. Cell study: mRNA and protein expression levels of apoB in HepG2 and HepG2.2.15 cells were measured by RT-PCR and Western blot. Alternatively, HBV infectious clone pHBV1.3 or control plasmid pBlue-ks were tranfected into HepG2 cells, and mRNA and protein expression levels of apoB, as well as the microsomal triglyceride transfer protein (MTP) in tranfected HepG2 cells were also measured by RT-PCR and western blot.

Results
Serum apoB level was much lower in chronic HBV patients as compared to healthy individuals (P < 0.05). Expression of apoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells. Similarly, expression of apoB mRNA and protein was lower in pHBV1.3 transfected HepG2 cells than in pBlue-ks transfected HepG2 cells. Expression of MTP mRNA and protein in pHBV1.3 transfected HepG2 cells was reduced in a dose-dependent fashion.

Conclusion
HBV infection plays an inhibitory effect on apoB expression.
Retroperitoneoscopic laparo-endoscopic single-site radical nephrectomy (RLESS-RN): initial experience with a homemade port
Authors: Chung Shiu-Dong , Huang Chao-Yuan , Tsai Yao-Chou , Chueh Shih-Chieh , Hung Shun-Fa , Wang Shuo-Meng , Liao Chun-Hou , Yu Hong-Jeng 
Published: November 2011

Abstract
We successfully performed 6 LESS radical nephrectomy via the retroperitoneal approach (RLESS) using the Alexis wound retractor as a single access with conventional laparoscopic instruments. The results demonstrated that our RLESS technique of radical nephrectomy is a safe and feasible procedure for management of localized renal cancer.
Prevention of abdominal wound infection (PROUD trial, DRKS00000390): study protocol for a randomized controlled trial
Authors: Heger Ulrike , Voss Sabine , Knebel Phillip , Doerr-Harim Colette , Neudecker Jens , Schuhmacher Christoph , Faist Eugen , Diener Markus K , Kieser Meinhard , Seiler Christoph M , Büchler Markus W 
Published: November 2011

Abstract

Background
Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating.

Methods/Design
The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available.

Discussion
The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity.

Trial Registration
The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390).