bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of sustained response to low‐dose pegylated interferon alpha‐2b plus ribavirin in patients with genotype 1b and high hepatitis C virus level using viral reduction within 2 weeks after therapy initiation
Authors: Tamai Hideyuki , Shingaki Naoki , Shiraki Tatsuya , Tukuda Hiroshi , Mori Yoshiyuki , Moribata Kosaku , Enomoto Shotaro , Deguchi Hisanobu , Ueda Kazuki , Inoue Izumi , Maekita Takao , Iguchi Mikitaka , Yanaoka Kimihiko , Oka Masashi , Ichinose Masao 
Published: September 2011

Aim:  Continuation of pegylated interferon (PEG‐IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low‐dose PEG‐IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated.Methods:  A total of 106 patients with a high viral load of genotype‐1b hepatitis C virus (HCV) underwent low‐dose PEG‐IFN plus ribavirin therapy. PEG‐IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600–800 mg/day) were administered for 48 weeks.Results:  Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR‐contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1‐log or greater HCV‐RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2‐log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively.Conclusion:  Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low‐dose PEG‐IFN plus ribavirin therapy.
Cost‐effective variable selection in habitat surveys
Authors: Braun Douglas C. , Reynolds John D. 
Published: September 2011

Summary1. Researchers usually expect to understand the ecological systems better when they examine more variables. However, we cannot measure everything because time and money are limited, so we need to make difficult choices. Decisions are complicated by the fact that variables are often either uninformative or highly correlated, leading to diminishing returns on information with new variables. Correlated variables and diminishing returns on information per variable can be explicitly incorporated with costs of data collection to design cost‐effective survey programmes.2. We develop a step‐by‐step quantitative protocol to evaluate the cost‐effectiveness of survey designs under different cost scenarios to help scientists and managers design cost‐effective surveys. We illustrate this protocol using a case study that relates physical stream habitat variables to variation in sockeye salmon spawning populations.3. We present our protocol by comparing linear regression models containing different combinations of variables representing different survey designs. The steps of the protocol are to (i) eliminate redundant variables, (ii) calculate costs scenarios, (iii) calculate survey performance metrics and (iv) identify and compare a subset of survey designs that maximize effectiveness at a given cost. Survey designs are compared by their ranked performance using R2, AICc, average cost‐effectiveness ratio and incremental cost‐effectiveness ratio.4. Our case study shows diminishing returns on the information provided by the addition of more variables as survey costs increase. The protocol supports the design of cost‐effective monitoring programmes and leads to a general discussion relating changing environmental conditions to survey costs, including the need for clear and measurable objectives, which allow scientific information to be translated into management options.
RNA-Mediated Reciprocal Regulation between Two Bacterial Operons Is RNase III Dependent
Authors: Johnson Christopher M. , Haemig Heather H. A. , Chatterjee Anushree , Wei-Shou Hu , Weaver Keith E. , Dunny Gary M. 
Published: September 2011

ABSTRACT

In bacteria, RNAs regulate gene expression and function via several mechanisms. An RNA may pair with complementary sequences in a target RNA to impact transcription, translation, or degradation of the target. Control of conjugation of pCF10, a pheromone response plasmid of
Enterococcus faecalis
, is a well-characterized system that serves as a model for the regulation of gene expression in bacteria by intercellular signaling. The
prgQ
operon, whose products mediate conjugation, is negatively regulated by two products of the
prgX
operon, Anti-Q, a small RNA, and PrgX, the transcriptional repressor of the
prgQ
promoter. Here we show that Qs, an RNA from the 5′ end of the
prgQ
operon, represses expression of PrgX by targeting
prgX
mRNA for cleavage by RNase III. Our results demonstrate that the
prgQ
and
prgX
operons each use RNAs to negatively regulate gene expression from the opposing operon by different mechanisms. Such reciprocal regulation between two operons using RNAs has not been previously demonstrated. Furthermore, these results show that Qs is an unusually versatile RNA, serving three separate functions in the regulation of conjugation. Understanding the potential versatility of RNAs and their various roles in gene regulatory networks will allow us to better understand how cells regulate complex behavior.

IMPORTANCE
Bacteria use RNA to regulate gene expression by a variety of mechanisms. The
prgQ
and
prgX
operons of pCF10, a conjugative plasmid of
Enterococcus faecalis
, have been shown to negatively regulate one another by a variety of mechanisms. One of these mechanisms involves Anti-Q, a small RNA from the
prgX
operon that prevents gene expression from the
prgQ
operon. In this work, we find that Qs, an RNA from the
prgQ
operon, negatively regulates gene expression from the
prgX
operon. These findings have a number of implications. (i) The Anti-Q and Qs RNAs act by different mechanisms, highlighting the variety of ways in which bacteria can regulate gene expression using RNAs. (ii) Reciprocal regulation between operons mediated by small RNAs has not been previously described, deepening our understanding of how bacteria regulate complex behavior. (iii) Additional roles for Qs have been described, demonstrating the versatility of this RNA.
Hydrogen peroxide decomposition in bicarbonate solution catalyzed by ferric citrate*This article has a companion paper in this issue (doi: 10.1139/v11-080).
Authors: Attiogbe Francis K. , Francis Raymond C. 
Published: September 2011

The peroxymonocarbonate mono- and di-anions (HCO4–and CO42–) are known to be generated from H2O2/HCO3–. They are promising oxidants for wood pulp bleaching, but peroxide decomposition catalyzed by ferric complexes can be significant for pulps whose lignin is highly reactive. Dicarboxylates from lignin peroxidation are believed to be the ferric chelators in the pH 8.5 range that is optimum for H2O2/HCO3–. This investigation aimed to see if HCO3–addition caused destabilization of the peroxygen system owing to its partial conversion to HCO4–. This anionic peracid is a much stronger oxidant than H2O2and could lead to a higher rate of Fe(II) oxidation to Fe(III) and (or) Fe(IV). For most free radical chain mechanisms, an increase in Fe(II) oxidation results in a higher rate of peroxide decomposition. Based on the kinetic data that were obtained and theoretical analyses, it was concluded that HCO4–did not significantly destabilize the peroxygen system when citrate was used as a model chelator for Fe(III). Increasing the [HCO3–] fourfold from 0.025 to 0.10 mol/L caused the decomposition rate to increase by only 20%.
Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial
Authors: Goodin Douglas S , Hartung Hans-Peter , O’Connor Paul , Filippi Massimo , Arnason Barry , Comi Giancarlo , Cook Stuart , Jeffery Douglas , Kappos Ludwig , Bogumil Timon , Knappertz Volker , Sandbrink Rupert , Beckmann Karola , White Rick , Petkau John , Pohl Christoph 
Published: September 2011

Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFNβ-1b) on clinical and radiographic outcomes is controversial. Objective: To assess NAb impact in the BEYOND study. Methods: 2244 patients were randomized (2:2:1) to receive IFNβ-1b, either 250 or 500 µg, or glatiramer acetate, 20 mg, and observed for 2–3.5 years. NAb titers were determined every 6 months. A titer ≥20 NU/ml was considered NAb positive. Efficacy was compared between NAb-positive and NAb-negative patients, using comprehensive statistical analyses, taking into account the delayed appearance of NAbs, the time-dependent changes in the relapse rate, spontaneous reversions to NAb-negative status, NAb-titer level, and also adjusting for baseline factors. Results: In the IFNβ-1b 250 µg group, NAb-positive titers were detected (≥ once) in 319 patients (37.0%); of these, 112 (35.1%) reverted to NAb-negative status. In the IFNβ-1b 500 µg group, 340 patients (40.7%) became NAb-positive and 119 (35.0%) reverted to NAb-negative status. In both IFNβ groups, especially the 250 µg arm, NAb-positive status was not associated with a convincing impact on any clinical outcome measure by any statistical analysis. By contrast, in both IFNβ groups, NAbs were associated with a very consistent deleterious impact on most MRI outcomes. Conclusion: There was a notable dissociation between the impact of NAbs on MRI and clinical outcomes. On MRI measures, the impact was consistent and convincing, whereas on clinical measures a negative impact of NAbs was not found. The basis for this clinico-radiographic paradox is unknown but it suggests that the relationship between NAbs and the therapeutic effects of IFNβ-1b is complex.
Temporal trends of disability progression in multiple sclerosis: findings from British Columbia, Canada (1975–2009)
Authors: Shirani Afsaneh , Zhao Yinshan , Kingwell Elaine , Rieckmann Peter , Tremlett Helen 
Published: September 2011

Background: Recent natural history studies suggest that multiple sclerosis (MS) is a more slowly progressing disease than previously thought. These observations are from studies separated by time, geography and methodological approach. Objectives: We investigated whether MS disease progression has changed over time in British Columbia, Canada. Methods: The British Columbia MS database was queried for relapsing-onset MS patients with symptom onset from 1975 to <1995, first assessed within 15 years from onset and with at least two Expanded Disability Status Scale (EDSS) scores. Latest follow-up was to 2009. Patients were grouped by 5-year onset intervals (1975 to <1980, 1980 to <1985, 1985 to <1990, 1990 to <1995). Outcome was defined as time to reach sustained and confirmed EDSS 6 within 15 years of disease duration. Kaplan–Meier analysis was used to compare: the proportion of patients reaching EDSS 6 (primary analysis) and the time to EDSS 6 (secondary analysis) across the time-period groups. Results: A total of 2236 relapsing-onset MS patients (73.4% female; mean age at onset: 32.3 ± 8.8 years) were included. No significant temporal trend was found in the proportion of patients reaching EDSS 6 within 15 years from onset (28.5%, 26.4%, 27.7%, 22.3% for intervals 1975 to <1980, 1980 to <1985, 1985 to <1990, 1990 to <1995, respectively; p = 0.09) or in survival curves for time to reach the outcome ( p = 0.14). Conclusions: Rates of disease progression remained relatively stable over two decades of MS onset in British Columbia, Canada. Our results suggest that differences in disease progression findings between natural history studies may be related to factors other than time period.
An overview of cancer/testis antigens expression in classical Hodgkin's lymphoma (cHL) identifies MAGE-A family and MAGE-C1 as the most frequently expressed antigens in a set of Brazilian cHL patients
Authors: Inaoka Riguel J , Jungbluth Achim A , Baiocchi Otávio CG , Assis Mariane CG , Hanson Nicole C , Frosina Denise , Tassello Jodie , Bortoluzzo Adriana B , Alves Antonio C , Colleoni Gisele WB 
Published: September 2011

AbstractBackgroundCancer/testis antigens are considered potential targets for immunotherapy due to their tumor-associated expression pattern. Although recent studies have demonstrated high expression of CT45 in classical Hodgkin's lymphomas (cHL), less is known about the expression pattern of other families of CTAs in cHL. We aim to evaluate the expression of MAGE-A family, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO1 and GAGE family in cHL and to correlate their expression with clinical and prognostic factors in cHL.MethodsTissue microarray was generated from 38 cHL archival cases from Pathology Department of Universidade Federal de Sao Paulo. Immunohistochemistry (IHC) was done using the following panel of antibodies: MAGE-A family (MA454, M3H67, 57B and 6C1), GAGE (#26), NY-ESO-1 (E978), MAGE-C1/CT7 (CT7-33) and MAGE-C2/CT10 (CT10#5).ResultsWe found CTA expression in 21.1% of our cHL series. Among the tested CTAs, only MAGE-A family 7/38 (18.4%) and MAGE-C1/CT7 5/38 (13.2%) were positive in our cHL samples. We found higher CTA positivity in advanced stage (28.6%) compared to early stage (11.8%) disease, but this difference was not statistically significant. Analysis of other clinicopathological subgroups of cHL including histological subtypes, EBV status and response to treatment also did not demonstrate statistical significant differences in CTA expression.ConclusionWe found CTA expression in 21.1% of cHL samples using our panel. Our preliminary findings suggest that from all CTAs included in this study, MAGE-A family and MAGE-C1/CT7 are the most interesting ones to be explored in further studies.
Implementing knowledge into practice for improved neonatal survival; a cluster-randomised, community-based trial in Quang Ninh province, Vietnam
Authors: Wallin Lars , Målqvist Mats , Nga Nguyen T , Eriksson Leif , Persson Lars-Åke , Hoa Dinh P , Huy Tran Q , Duc Duong M , Ewald Uwe 
Published: September 2011

Abstract

Background
Globally, almost 4 million newborns die during the first 4 weeks of life every year. By increased use of evidence-based knowledge in the healthcare system a large proportion of these neonatal deaths could be prevented. But there is a severe lack of knowledge on effective methods for successful implementation of evidence into practice, particularly in low- and middle-income countries. Recent studies have demonstrated promising results with increased survival among both mothers and newborns using community-based approaches. In Vietnam evidence-based guidelines on reproductive health were launched in 2003 and revised in 2009. The overall objective of the current project is to evaluate if a facilitation intervention on the community level, with a problem-solving approach involving local representatives if the healthcare system and the community, results in improvements of neonatal health and survival.

Methods/Design
The study, which has been given the acronym NeoKIP (Neonatal Health - Knowledge Into Practice), took place in 8 districts composed by 90 communes in a province in northern Vietnam, where neonatal mortality rate was 24/1000 in 2005. A cluster randomised design was used, allocating clusters, as defined as a commune and its correponding Commune Health Center (CHC) to either intervention or control arm. The facilitation intervention targeted staff at healthcare centres and key persons in the communes. The facilitator role was performed by lay women (Women's Union representatives) using quality improvement techniques to initiate and sustain improvement processes targeting identified problem areas. The intervention has been running over 3 years and data were collected on the facilitation process, healthcare staff knowledge in neonatal care and their behaviour in clinical practice, and reproductive and perinatal health indicators. Primary outcome is neonatal mortality.

Discussion
The intervention is participatory and dynamic, focused on developing a learning process and a problem-solving cycle. The study recognises the vital role of the local community as actors in improving their own and their newborns' health, and applies a bottom-up approach where change will be accomplished by an increasing awareness at and demand from grass root level. By utilising the existing healthcare structure this intervention may, if proven successful, be well suited for scaling up.

Trial registration
Current Controlled Trials ISRCTN44599712
Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination
Authors: Jiang Cheng-Gang , Lv Ling , Liu Fu-Rong , Wang Zhen-Ning , Liu Fu-Nan , Li Yan-Shu , Wang Chun-Yu , Zhang Hong-Yan , Sun Zhe , Xu Hui-Mian 
Published: September 2011

Abstract

Background
Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown.

Results
In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P < 0.05). Patients with positive CTGF expression had significantly lower cumulative postoperative 5 year survival rate than those with negative CTGF expression (22.9% versus 48.1%, P < 0.001). We demonstrated that knockdown of CTGF expression significantly inhibited cell growth of gastric cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines.

Conclusions
These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.
An implicit iterative algorithm with errors for two families of generalized asymptotically nonexpansive mappings
Authors: Agarwal Ravi P , Qin Xiaolong , Kang Shin Min 
Published: September 2011

AbstractIn this paper, an implicit iterative algorithm with errors is considered for two families of generalized asymptotically nonexpansive mappings. Strong and weak convergence theorems of common fixed points are established based on the implicit iterative algorithm.Mathematics Subject Classification (2000) 47H09 · 47H10 · 47J25
The use of LiDCO based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: Neck of femur optimisation therapy - targeted stroke volume (NOTTS): study protocol for a randomized controlled trial
Authors: Wiles Matthew D , Whiteley William JD , Moran Chris G , Moppett Iain K 
Published: September 2011

AbstractBackgroundApproximately 70,000 patients/year undergo surgery for repair of a fractured hip in the United Kingdom. This is associated with 30-day mortality of 9% and survivors have a considerable length of acute hospital stay postoperatively (median 26 days). Use of oesophageal Doppler monitoring to guide intra-operative fluid administration in hip fracture repair has previously been associated with a reduction in hospital stay of 4-5 days. Most hip fracture surgery is now performed under spinal anaesthesia. Oesophageal Doppler monitoring may be unreliable in the presence of spinal anaesthesia and most patients would not tolerate the probes. An alternative method of guiding fluid administration (minimally-invasive arterial pulse contour analysis) has been shown to reduce length of stay in high-risk surgical patients but has never been studied in hip fracture surgery.MethodsSingle-centre randomised controlled parallel group trial. Randomisation by website using computer generated concealed tables. Setting: University hospital in UK. Participants: 128 patients with acute primary hip fracture listed for operative repair under spinal anaesthesia and aged > 65 years. Intervention: Stroke volume guided intra-operative fluid management. Continuous measurement of SV recorded by a calibrated cardiac output monitor (LiDCOplus). Maintenance fluid and 250 ml colloid boluses given to achieve sustained 10% increases in stroke volume. Control group: fluid administration at the responsible (blinded) anaesthetist's discretion. The intervention terminates at the end of the surgical procedure and post-operative fluid management is at the responsible anaesthetist's discretion. Primary outcome: length of acute hospital stay is determined by a blinded team of clinicians. Secondary outcomes include number of complications and total cost of care.Funding NIHR/RfPB: PB-PG-0407-13073.Trial registration numberTrial registration: Current Controlled TrialsISRCTN88284896.
How funding structures for HIV/AIDS research shape outputs and utilization: a Swiss case study
Authors: Frey Kathrin , Kübler Daniel 
Published: September 2011

BackgroundResearch policy in the field of HIV has changed substantially in recent decades in Switzerland. Until 2004, social science research on HIV/AIDS was funded by specialized funding agencies. After 2004, funding of such research was “normalized” and integrated into the Swiss National Science Foundation as the main funding agency for scientific research in Switzerland. This paper offers a longitudinal analysis of the relationship between the changing nature of funding structures on the one hand and the production and communication of policy‐relevant scientific knowledge in the field of HIV on the other hand.MethodsThe analysis relies on an inventory of all social sciences research projects on HIV in Switzerland that were funded between 1987 and 2010, including topics covered and disciplines involved, as well as financial data. In addition, in‐depth interviews were conducted with 18 stakeholders.ResultsThe analysis highlights that the pre‐2004 funding policy ensured good coverage of important social science research themes. Specific incentives and explicit promotion of social science research related to HIV gave rise to a multidisciplinary, integrative and health‐oriented approach. The abolition of a specific funding policy in 2004 was paralleled by a drastic reduction in the number of social science research projects submitted for funding, and a decline of public money dedicated to such research. Although the public administration in charge of HIV policy still acknowledges the relevance of findings from social sciences for the development of prevention, treatment and care, HIV‐related social science research does not flourish under current funding conditions.ConclusionsThe Swiss experience sheds light on the difficulties of sustaining social science research and multidisciplinary approaches related to HIV without specialized funding agencies. Future funding policy might not necessarily require specialized agencies, but should better take into account research dynamics and motivations in the field of social sciences.