bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matrix metalloproteinase-2 functional promoter polymorphism G1575A is associated with elevated circulatory MMP-2 levels and increased risk of cardiovascular disease in systemic lupus erythematosus patients
Authors: Bahrehmand F , Vaisi-Raygani A , Kiani A , Rahimi Z , Tavilani H , Navabi SJ , Shakiba E , Hassanzadeh N , Pourmotabbed T 
Published: February 2012

Matrix metalloproteinase-2 (MMP-2) is a zinc dependent endonuclease that degrades type IV collagen, the major structural component of basement membranes. MMP-2 functional promoter polymorphism G1575A affects circulating level of MMP-2 and may be considered an important genetic determinant of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients. In this study, association between MMP-2 1575A allele with serum MMP-2, neopterin and lipid-lipoprotein levels and with SLE and developing CVD was investigated. The present case–control study consisted of 109 SLE patients with and without CVD (mean age, 35.6 years) and 101 gender- and age-matched, unrelated, healthy controls (mean age, 37.1 years) from the population in the west of Iran. MMP-2 1575G/A polymorphism was detected by polymerase chain reaction (restriction fragment length polymorphism) PCR-RFLP, serum MMP-2, neopterin and lipid levels were determined by enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC) and enzyme assay, respectively. The presence of MMP-2 G1575A allele was found to be associated with SLE and developed CVD (OR = 1.78, p = 0.029 and OR = 3.43, p = 0.025, respectively). The SLE patients with MMP-2 A (G/A + A/A) allele had higher MMP-2 activity (301 ± 166 vs. 194 ± 35.5, p = 0.002), neopterin (29.4 ± 39.4 vs. 7.3 ± 4.6, p = 0.005), LDL-C (120 ± 25.7 vs. 87 ± 39.3, p = 0.045) and lower HDL-C (39.6 ± 11 vs. 45.9 ± 11.8, p = 0.031) levels than the control subjects. There was a significantly positive correlation between MMP-2 level with neopterin, total cholesterol and TG levels and negative correlation with HDL-C level in SLE patients with CVD. MMP-2 G1575A allele may be a risk factor for SLE. The carriers of this allele have high levels of MMP-2, neopterin, total cholesterol and TG and lower levels of HDL, thus, they are more likely to develop heart disease.
Women and Leadership in Higher Education
Authors: Madsen Susan R. 
Published: February 2012

The Problem. There continues to be concern about the need to develop more women leaders in all sectors and industries in most countries around the world. This includes the need for more women to be positioned to take on critical leadership roles within higher education. The Solution. This preface article highlights the Issue’s overall problem, purpose, the approach used, and its relevance to human resource development (HRD) and practice. It introduces relevant literature and provides a brief introduction of each Issue article. The Issue in general explores various topics that directly influence the career decisions, challenges, experiences, and opportunities of women in postsecondary settings. Each article shares results of research studies or conceptual frameworks and also outlines specific implications for practice. The Stakeholders. This Issue will provide researchers and practitioners in various fields of study with foundations and strategic frameworks to be used for more reflective teaching, research, and practice around the topic of women and leadership.
Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study
Authors: Lioure Bruno , Béné Marie C. , Pigneux Arnaud , Huynh Anne , Chevallier Patrice , Fegueux Nathalie , Blaise Didier , Witz Brigitte , Delain Martine , Cornillon Jérôme , Luquet Isabelle , Blanchet Odile , Cornillet-Lefebvre Pascale , Carré Martin , Hunault Mathilde , Larosa Fabrice , Lamy Thierry , Randriamalala Edouard , Ojeda-Uribe Mario , Berthou Christian , Fornecker Luc , Harousseau Jean-Luc , Bouscary Didier , Ifrah Norbert , Cahn Jean-Yves 
Published: February 2012

Abstract
The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients. This study was registered at clinicaltrials.gov as no. NCT01015196.
Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti-inflammatory response in macrophages
Authors: Hutchins Andrew Paul , Poulain Stéphane , Miranda-Saavedra Diego 
Published: February 2012

AbstractInflammation is a powerful response of the immune system against invading pathogens, and must be cancelled when unneeded or otherwise death inevitably follows. In macrophages, the anti-inflammatory response (AIR) is driven by STAT3 upon IL-10 signaling. The role of STAT3 is to stimulate the expression of specific genes that in-turn suppress the transcription of proinflammatory genes. Here we describe a systematic approach to identify the elusive STAT3-controlled effectors of the AIR. In vivo STAT3-binding sites were identified by ChIP-seq, coupled to expression analysis by RNA-seq, both in resting and IL-10–treated peritoneal macrophages. We report the genomic targets of STAT3 and show that STAT3's transcriptional program during the AIR is highly specific to IL-10–stimulated macrophages, that STAT3 is a positive transcriptional regulator, and we predict severalputative AIR factors that merit further investigation. This is the first in-depth study of the AIR by next-generation sequencing and provides an unprecedented degree of detail into this fundamental physiologic response.
Interobserver agreement in determining non-small cell lung cancer subtype in specimens acquired by EBUS-TBNA
Authors: Steinfort Daniel P. , Russell Prudence A. , Tsui Alpha , White Gordon , Wright Gavin , Irving Louis B. 
Published: February 2012

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) may diagnose suspected lung cancer. Determination of non-small cell lung cancer (NSCLC) subtype may guide therapy in select patients. Small-volume biopsies may be subject to significant interobserver variability in subtype determination.Three pathologists independently reviewed specimens from 60 patients who underwent EBUS-TBNA for diagnosis/staging of suspected/known NSCLC. Smear, haematoxylin and eosin (H&E) and immunohistochemistry (IHC) specimens were reviewed without reference to other specimen types obtained from the same patient. Final diagnoses, and degree of confidence in the diagnosis, were recorded for each specimen.Almost perfect agreement was seen for distinguishing between small cell lung cancer and NSCLC for all specimen types. Agreement in determination of NSCLC subtype for smear, H&E and IHC specimens was slight (κ=0.095, 95% CI -0.164–0.355), fair (κ=0.278, 95% CI 0.075–0.481) and moderate (κ=0.564, 95% CI 0.338–0.740), respectively. Perfect agreement was seen when all three observers were confident of diagnoses made on IHC specimens.Interobserver agreement in interpretation of EBUS-TBNA specimens is moderate for determination of NSCLC subtype. Agreement is highest following examination of IHC specimens. Clinicians should be aware of the degree of pathologist confidence in the tissue diagnosis prior to commencement of subtype-specific therapy for NSCLC.
Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial
Authors: Tønnesen Philip , Lauri Hans , Perfekt Roland , Mann Karl , Batra Anil 
Published: February 2012

A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving.This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (≥1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany.Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1%versus16.1%; relative success rate (RR) 1.62, 95% CI 1.09–2.41), week 24 (15.7%versus6.8%; RR 2.30, 95% CI 1.23–4.30), and week 52 (13.8%versus5.6%; RR 2.48, 95% CI 1.24–4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active sprayversus71.4% with placebo spray.Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo.
TB and MDR/XDR-TB in European Union and European Economic Area countries: managed or mismanaged?
Authors: Migliori G.B. , Sotgiu G. , D’Ambrosio L. , Centis R. , Lange C. , Bothamley G. , Cirillo D.M. , De Lorenzo S. , Guenther G. , Kliiman K. , Muetterlein R. , Spinu V. , Villar M. , Zellweger J.P. , Sandgren A. , Huitric E. , Manissero D. 
Published: February 2012

In spite of the growing awareness of emerging drug-resistantMycobacterium tuberculosis, the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/European Economic Area countries, with special focus on multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool.National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards.Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms.Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance.
Detrended fluctuation analysis of peak expiratory flow and exacerbation frequency in COPD
Authors: Donaldson Gavin C. , Seemungal Terence A.R. , Hurst John R. , Wedzicha Jadwiga A. 
Published: February 2012

We investigated whether exacerbation frequency in chronic obstructive pulmonary disease (COPD) was related to an exponent α which quantifies self-similarity in daily peak expiratory flow (PEF) and is calculated using detrended fluctuation analysis (DFA).We examined data from COPD patients who recorded an increase in respiratory symptoms and post-bronchodilator PEF on daily diary cards. We also investigated PEF data from a double-blind, placebo-controlled trial of the anti-cholinergic agent, tiotropium.In the observational study there were 308 patients with COPD (195 males; mean±sdage 68.3±8.4 yrs, forced expiratory volume in 1 s (FEV1) 1.12±0.46 L, FEV1% predicted 44.5±16.4%). The mean±sdα over the first year was 0.944±0.19 and it was positively related to the frequency of exacerbations per year (p=0.009). In the clinical trial, α was lower in COPD patients randomised to tiotropium, mean±sd0.87±0.21 (n=48) than on placebo, mean±sd0.95±0.19 (n=52; p=0.035). Power analysis showed that fewer patients would be required for clinical studies with α as the outcome measure than exacerbation frequency.DFA shows that daily PEF in COPD has long-term correlations which are related to exacerbation frequency. Monitoring of PEF and use of α may result in smaller COPD patient sample sizes in trials.
Peptide markers of aminoacyl tRNA synthetases facilitate taxa counting in metagenomic data
Authors: Persi Erez , Weingart Uri , Freilich Shiri , Horn David 
Published: February 2012

Abstract

Background
Taxa counting is a major problem faced by analysis of metagenomic data. The most popular method relies on analysis of 16S rRNA sequences, but some studies employ also protein based analyses. It would be advantageous to have a method that is applicable directly to short sequences, of the kind extracted from samples in modern metagenomic research. This is achieved by the technique proposed here.

Results
We employ specific peptides, deduced from aminoacyl tRNA synthetases, as markers for the occurrence of single genes in data. Sequences carrying these markers are aligned and compared with each other to provide a lower limit for taxa counts in metagenomic data. The method is compared with 16S rRNA searches on a set of known genomes. The taxa counting problem is analyzed mathematically and a heuristic algorithm is proposed. When applied to genomic contigs of a recent human gut microbiome study, the taxa counting method provides information on numbers of different species and strains. We then apply our method to short read data and demonstrate how it can be calibrated to cope with errors. Comparison to known databases leads to estimates of the percentage of novelties, and the type of phyla involved.

Conclusions
A major advantage of our method is its simplicity: it relies on searching sequences for the occurrence of just 4000 specific peptides belonging to the S61 subgroup of aaRS enzymes. When compared to other methods, it provides additional insight into the taxonomic contents of metagenomic data. Furthermore, it can be directly applied to short read data, avoiding the need for genomic contig reconstruction, and taking into account short reads that are otherwise discarded as singletons. Hence it is very suitable for a fast analysis of next generation sequencing data.
Phase I clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibtion
Authors: Hamilton Erika , Blackwell Kimberly , Hobeika Amy C , Clay Timothy M , Broadwater Gloria , Ren Xiu-Rong , Chen Wei , Castro Henry , Lehmann Frederic , Spector Neil , Wei Junping , Osada Takuya , Lyerly H Kim 
Published: February 2012

AbstractBackgroundPatients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when combined with lapatinib in murine models. We wished to test the clinical safety, immunogenicity, and activity of a HER2-based cancer vaccine, when combined with lapatinib.MethodsWe immunized women (n = 12) with metastatic, trastuzumab-refractory, HER2-overexpressing breast cancer with dHER2, a recombinant protein consisting of extracellular domain (ECD) and a portion of the intracellular domain (ICD) of HER2 combined with the adjuvant AS15, containing MPL, QS21, CpG and liposome. Lapatinib (1250 mg/day) was administered concurrently. Peripheral blood antibody and T cell responses were measured.ResultsThis regimen was well tolerated, with no cardiotoxicity. Anti-HER2-specific antibody was induced in all patients whereas HER2-specific T cells were detected in one patient. Preliminary analyses of patient serum demonstrated downstream signaling inhibition in HER2 expressing tumor cells. The median time to progression was 55 days, with the majority of patients progressing prior to induction of peak anti-HER2 immune responses; however, 300-day overall survival was 92% (95% CI: 77-100%).ConclusionsdHER2 combined with lapatinib was safe and immunogenic with promising long term survival in those with HER2-overexpressing breast cancers refractory to trastuzumab. Further studies to define the anticancer activity of the antibodies induced by HER2 vaccines along with lapatinib are underway.Trial registryClinicalTrials.govNCT00952692
Cryptorchidism in Mice with an Androgen Receptor Ablation in Gubernaculum Testis
Authors: Kaftanovskaya Elena M. , Huang Zaohua , Barbara Agustin M. , De Gendt Karel , Verhoeven Guido , Gorlov Ivan P. , Agoulnik Alexander I. 
Published: February 2012

Abstract
Androgens play a critical role in the development of the male reproductive system, including the positioning of the gonads. It is not clear, however, which developmental processes are influenced by androgens and what are the target tissues and cells mediating androgen signaling during testicular descent. Using a Cre-loxP approach, we have produced male mice (GU-ARKO) with conditional inactivation of the androgen receptor (Ar) gene in the gubernacular ligament connecting the epididymis to the caudal abdominal wall. The GU-ARKO males had normal testosterone levels but developed cryptorchidism with the testes located in a suprascrotal position. Although initially subfertile, the GU-ARKO males became sterile with age. We have shown that during development, the mutant gubernaculum failed to undergo eversion, a process giving rise to the processus vaginalis, a peritoneal outpouching inside the scrotum. As a result, the cremasteric sac did not form properly, and the testes remained in the low abdominal position. Abnormal development of the cremaster muscles in the GU-ARKO males suggested the participation of androgens in myogenic differentiation; however, males with conditional AR inactivation in the striated or smooth muscle cells had a normal testicular descent. Gene expression analysis showed that AR deficiency in GU-ARKO males led to the misexpression of genes involved in muscle differentiation, cell signaling, and extracellular space remodeling. We therefore conclude that AR signaling in gubernacular cells is required for gubernaculum eversion and outgrowth. The GU-ARKO mice provide a valuable model of isolated cryptorchidism, one of the most common birth defects in newborn boys.
Evaluation of Optimum Room Entry Times for Radiation Therapists after High Energy Whole Pelvic Photon Treatments
Authors: Ho Lavine , White Peter , Chan Edward , Chan Kim , Ng Janet , Tam Timothy 
Published: February 2012

Evaluation of Optimum Room Entry Times for Radiation Therapists after High Energy Whole Pelvic Photon Treatments: Lavine HO, et al. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong—ObjectivesLinear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists.MethodsTwo types of technique (anteriorposterior opposing and 3‐field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses Received by radiation therapists were estimated, and optimum room entry times were determined.ResultsThe highest gamma dose rates were approximately 7 μSv/h inside the treatment room, while the doses in the control room were close to background (~0 μSv/h) for all techniques. The highest personal dose Received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam‐off prior to room entry.ConclusionsThe potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered.
Hydrothermal Synthesis of Bioinert Oxide Film on Pure Ti: In Vitro and In Vivo Studies
Authors: Ueda Masato , Ikeda Masahiko , Langford Richard , Skepper Jeremy , Cameron Ruth E. , Best Serena M. 
Published: February 2012

ABSTRACTTitanium and its alloys have been employed in bone plates/screws, and these are often designed to be removed after recovery. Bone is known to bond to the surface of Ti alloys. This can lead to re-fracture of newly repaired bone during operations to remove the implants, however bone does not bond to Zr-based alloys. The inhibition of bone conduction on the surface of Zr-based alloys is thought to be due to the presence of a thin layer of zirconia (ZrO2) on the surface. The purpose of the present study was to synthesize bioinert films, including ZrO2 on pure Ti surfaces. In vitro apatite (HAp) formation and in vivo bone conduction in the tibiae of rats on the films were also investigated.Commercial purity Ti was chemically treated with aqueous H2O2/HNO3 at 353 K for 20 min. The disks were hydrothermally treated with aqueous ZrOCl2/NH3/C6H8O7 (citric acid) in an autoclave at 453 K for 12 h. Simulated body fluid (SBF) immersion test and implantation into tibiae of rats were carried out.In the hydrothermal treatment with aqueous ZrOCl2/NH3, the surface product was anatase-type TiO2. On the other hand, when citric acid was added the surface of Ti was covered homogeneously with a TiO2–ZrO2 composite film though the amount of ZrO2 was very small. HAp began to form on the non-modified Ti and TiO2 surfaces after 6 days and 4 days immersion in Hank’s solution, respectively. On the surfaces of TiO2–ZrO2, the presence of precipitates was confirmed after 6-8 days. The HAp formation was suppressed on the surfaces of TiO2–ZrO2.The present TiO2-ZrO2 surface also showed significantly lower bone-implant contact ratio in cortical bone compared with TiO2.