bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCR-ABL1 doubling times more reliably assess the dynamics of CML relapse compared with the BCR-ABL1 fold rise: implications for monitoring and management
Authors: Branford Susan , Yeung David T. , Prime Jodi A. , Choi Soo-Young , Bang Ju-hee , Park Jin Eok , Kim Dong-Wook , Ross David M. , Hughes Timothy P. 
Published: March 2012

AbstractRising BCR-ABL1 transcripts indicate potential loss of imatinib response in CML. We determined whether the BCR-ABL1 doubling time could distinguish nonadherence from resistance as the cause of lost response. Distinct groups were examined: (1) acquired clinical resistance because of blast crisis and/or BCR-ABL1 mutations; and (2) documented imatinib discontinuation/interruption. Short doubling times occurred with blast crisis (median, 9.0 days; range, 6.1-17.6 days; n = 12 patients), relapse after imatinib discontinuation in complete molecular response (median, 9.0 days; range, 6.9-26.5 days; n = 17), and imatinib interruption during an entire measurement interval (median, 9.4 days; range, 4.2-17.6 days; n = 12; P = .72). Whereas these doubling times were consistently short and indicated rapid leukemic expansion, fold rises were highly variable: 71-, 9.5-, and 10.5-fold, respectively. The fold rise depended on the measurement interval, whereas the doubling time was independent of the interval. Longer doubling times occurred for patients with mutations who maintained chronic phase (CP: median, 48 days; range, 17.3-143 days; n = 29; P < .0001). Predicted short and long doubling times were validated on an independent cohort monitored elsewhere. The doubling time revealed major differences in kinetics according to clinical context. Long doubling times observed with mutations in CP allow time for intervention. A short doubling time for a patient in CP should raise the suspicion of nonadherence.
Prognostic role of SOX11 in a population-based cohort of mantle cell lymphoma
Authors: Nygren Lina , Baumgartner Wennerholm Stefanie , Klimkowska Monika , Christensson Birger , Kimby Eva , Sander Birgitta 
Published: March 2012

Abstract
The prognostic role of the transcription factor SOX11 in mantle cell lymphoma (MCL) is controversial. We investigated prognostic markers in a population-based cohort of 186 MCL cases. Seventeen patients (9%) did not require any therapy within the first 2 years after diagnosis and were retrospectively defined as having an indolent disease. As expected, indolent MCL had less frequent B symptoms and extensive nodal involvement and 88% of these cases expressed SOX11. In our cohort 13 cases (7.5%) lacked nuclear SOX11 at diagnosis. SOX11− MCL had a higher frequency of lymphocytosis, elevated level of lactate dehydrogenase (LDH), and p53 positivity. The overall survival in the whole cohort, excluding 37 patients receiving autologous stem cell transplantation, was 3.1 year and in patients with indolent or nonindolent disease, 5.9 and 2.8 years, respectively (P = .004). SOX11− cases had a shorter overall survival, compared with SOX11+ cases, 1.5 and 3.2 years, respectively (P = .014). In multivariate analysis of overall survival, age > 65 (P = .001), Eastern Cooperative Oncology Group score ≥ 2 (P = .022), elevated LDH level (P = .001), and p53 expression (P = .001) remained significant, and SOX11 lost significance. We conclude that most indolent MCLs are SOX11+ and that SOX11 cannot be used for predicting an indolent disease course.
Genome-wide dynamic transcriptional profiling in clostridium beijerinckii NCIMB 8052 using single-nucleotide resolution RNA-Seq
Authors: Wang Yi , Li Xiangzhen , Mao Yuejian , Blaschek Hans P 
Published: March 2012

AbstractBackgroundClostridium beijerinckiiis a prominent solvent-producing microbe that has great potential for biofuel and chemical industries. Although transcriptional analysis is essential to understand gene functions and regulation and thus elucidate proper strategies for further strain improvement, limited information is available on the genome-wide transcriptional analysis forC. beijerinckii.ResultsThe genome-wide transcriptional dynamics ofC. beijerinckiiNCIMB 8052 over a batch fermentation process was investigated using high-throughput RNA-Seq technology. The gene expression profiles indicated that the glycolysis genes were highly expressed throughout the fermentation, with comparatively more active expression during acidogenesis phase. The expression of acid formation genes was down-regulated at the onset of solvent formation, in accordance with the metabolic pathway shift from acidogenesis to solventogenesis. The acetone formation gene (adc), as a part of thesoloperon, exhibited highly-coordinated expression with the othersolgenes. Out of the > 20 genes encoding alcohol dehydrogenase inC. beijerinckii, Cbei_1722 and Cbei_2181 were highly up-regulated at the onset of solventogenesis, corresponding to their key roles in primary alcohol production. Most sporulation genes inC. beijerinckii8052 demonstrated similar temporal expression patterns to those observed inB. subtilisandC. acetobutylicum, while sporulation sigma factor genessigEandsigGexhibited accelerated and stronger expression inC. beijerinckii8052, which is consistent with the more rapid forespore and endspore development in this strain. Global expression patterns for specific gene functional classes were examined using self-organizing map analysis. The genes associated with specific functional classes demonstrated global expression profiles corresponding to the cell physiological variation and metabolic pathway switch.ConclusionsThe results from this work provided insights for furtherC. beijerinckiistrain improvement employing system biology-based strategies and metabolic engineering approaches.
Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways
Authors: Yang Yao-Jong , Chuang Ching-Chun , Yang Hsiao-Bai , Lu Cheng-Chan , Sheu Bor-Shyang 
Published: March 2012

AbstractBackgroundH. pyloriinfection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improveH. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.ResultsChallenge withH. pyloriincreased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased afterH. pyloriinfection in a dose-dependent manner. A higher dose (MOI 100) ofL. acidophiluspre-treatment attenuated theH. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB.L. acidophilusalso inhibitedH. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway.L. acidophiluspre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting.ConclusionsH. pyloriinfection induces Smad7, NFκB, IL-8, and TNF-α productionin vitro. Higher doses ofL. acidophiluspre-treatment reduceH. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.
EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors
Authors: Florkowska Magdalena , Tymoszuk Piotr , Balwierz Aleksandra , Skucha Anna , Kochan Jakub , Wawro Mateusz , Stalinska Krystyna , Kasza Aneta 
Published: March 2012

Abstract

Background
Tristetraprolin (TTP) is a key mediator of processes such as inflammation resolution, the inhibition of autoimmunity and in cancer. It carries out this role by the binding and degradation of mRNA transcripts, thereby decreasing their half-life. Transcripts modulated by TTP encode proteins such as cytokines, pro-inflammatory agents and immediate-early response proteins. TTP can also modulate neoplastic phenotypes in many cancers. TTP is induced and functionally regulated by a spectrum of both pro- and anti-inflammatory cytokines, mitogens and drugs in a MAPK-dependent manner. So far the contribution of p38 MAPK to the regulation of TTP expression and function has been best described.

Results
Our results demonstrate the induction of the gene coding TTP (ZFP36) by EGF through the ERK1/2-dependent pathway and implicates the transcription factor ELK-1 in this process. We show that ELK-1 regulates ZFP36 expression by two mechanisms: by binding the ZFP36 promoter directly through ETS-binding site (+ 883 to +905 bp) and by inducing expression of EGR-1, which in turn increases ZFP36 expression through sequences located between -111 and -103 bp.

Conclusions
EGF activates TTP expression via ELK-1 and EGR-1 transcription factors.
Differential effects of environment on potato phenylpropanoid and carotenoid expression
Authors: Payyavula Raja S , Navarre Duroy A , Kuhl Joseph C , Pantoja Alberto , Pillai Syamkumar S 
Published: March 2012

AbstractBackgroundPlant secondary metabolites, including phenylpropanoids and carotenoids, are stress inducible, have important roles in potato physiology and influence the nutritional value of potatoes. The type and magnitude of environmental effects on tuber phytonutrients is unclear, especially under modern agricultural management that minimizes stress. Understanding factors that influence tuber secondary metabolism could facilitate production of more nutritious crops. Metabolite pools of over forty tuber phenylpropanoids and carotenoids, along with the expression of twenty structural genes, were measured in high-phenylpropanoid purple potatoes grown in environmentally diverse locations in North America (Alaska, Texas and Florida).ResultsPhenylpropanoids, including chlorogenic acid (CGA), were higher in samples from the northern latitudes, as was the expression of phenylpropanoid genes including phenylalanine ammonia lyase (PAL), which had over a ten-fold difference in relative abundance. Phenylpropanoid gene expression appeared coordinately regulated and was well correlated with metabolite pools, except for hydroxycinnamoyl-CoA:quinatehydroxcinnamoyl transferase (HQT; r = -0.24).In silicopromoter analysis identified two cis-acting elements in the HQT promoter not found in the other phenylpropanoid genes. Anthocyanins were more abundant in Alaskan samples and correlated with flavonoid genes includingDFR(r = 0.91),UFGT(r = 0.94) andF3H(r = 0.77). The most abundant anthocyanin was petunidin-3-coum-rutinoside-5-glu, which ranged from 4.7 mg g-1in Alaska to 2.3 mg g-1in Texas. Positive correlations between tuber sucrose and anthocyanins (r = 0.85), suggested a stimulatory effect of sucrose. Smaller variation was observed in total carotenoids, but marked differences occurred in individual carotenoids, which had over a ten-fold range. Violaxanthin, lutein or zeaxanthin were the predominant carotenoids in tubers from Alaska, Texas and Florida respectively. Unlike in the phenylpropanoid pathway, poor correlations occurred between carotenoid transcripts and metabolites.ConclusionAnalysis of tuber secondary metabolism showed interesting relationships among different metabolites in response to collective environmental influences, even under conditions that minimize stress. The variation in metabolites shows the considerable phenotypical plasticity possible with tuber secondary metabolism and raises questions about to what extent these pathways can be stimulated by environmental cues in a manner that optimizes tuber phytonutrient content while protecting yields. The differences in secondary metabolites may be sufficient to affect nutritional quality.
Usefulness of health registries when estimating vaccine effectiveness during the influenza A(H1N1)pdm09 pandemic in Norway
Authors: Guzmán Herrador Bernardo Rafael , Aavitsland Preben , Feiring Berit , Riise Bergsaker Marianne A , Borgen Katrine 
Published: March 2012

Abstract

Background
During the 2009-2010 pandemic in Norway, 12 513 laboratory-confirmed cases of pandemic influenza A(H1N1)pdm09, were reported to the Norwegian Surveillance System for Communicable Diseases (MSIS). 2.2 million persons (45% of the population) were vaccinated with an AS03-adjuvanted monovalent vaccine during the pandemic. Most of them were registered in the Norwegian Immunisation Registry (SYSVAK). Based on these registries, we aimed at estimating the vaccine effectiveness (VE) and describing vaccine failures during the pandemic in Norway, in order to evaluate the role of the vaccine as a preventive measure during the pandemic.

Methods
We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination.

Results
The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age.

Conclusions
Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations.
Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells
Authors: Jia Dongxuan , Entersz Ildiko , Butler Christine , Foty Ramsey A 
Published: March 2012

Abstract

Background
Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells.

Methods
Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA.

Results
We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment.

Conclusions
We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade.
Epidemiology and seasonality of respiratory viral infections in hospitalized children in Kuala Lumpur, Malaysia: a retrospective study of 27 years
Authors: Khor Chee-Sieng , Sam I-Ching , Hooi Poh-Sim , Quek Kia-Fatt , Chan Yoke-Fun 
Published: March 2012

Abstract

Background
Viral respiratory tract infections (RTI) are relatively understudied in Southeast Asian tropical countries. In temperate countries, seasonal activity of respiratory viruses has been reported, particularly in association with temperature, while inconsistent correlation of respiratory viral activity with humidity and rain is found in tropical countries. A retrospective study was performed from 1982-2008 to investigate the viral etiology of children (≤ 5 years old) admitted with RTI in a tertiary hospital in Kuala Lumpur, Malaysia.

Methods
A total of 10269 respiratory samples from all children ≤ 5 years old received at the hospital's diagnostic virology laboratory between 1982-2008 were included in the study. Immunofluorescence staining (for respiratory syncytial virus (RSV), influenza A and B, parainfluenza types 1-3, and adenovirus) and virus isolation were performed. The yearly hospitalization rates and annual patterns of laboratory-confirmed viral RTIs were determined. Univariate ANOVA was used to analyse the demographic parameters of cases. Multiple regression and Spearman's rank correlation were used to analyse the correlation between RSV cases and meteorological parameters.

Results
A total of 2708 cases were laboratory-confirmed using immunofluorescence assays and viral cultures, with the most commonly detected being RSV (1913, 70.6%), parainfluenza viruses (357, 13.2%), influenza viruses (297, 11.0%), and adenovirus (141, 5.2%). Children infected with RSV were significantly younger, and children infected with influenza viruses were significantly older. The four main viruses caused disease throughout the year, with a seasonal peak observed for RSV in September-December. Monthly RSV cases were directly correlated with rain days, and inversely correlated with relative humidity and temperature.

Conclusion
Viral RTIs, particularly due to RSV, are commonly detected in respiratory samples from hospitalized children in Kuala Lumpur, Malaysia. As in temperate countries, RSV infection in tropical Malaysia also caused seasonal yearly epidemics, and this has implications for prophylaxis and vaccination programmes.
Gender differences in alcohol-related non-consensual sex; cross-sectional analysis of a student population
Authors: Gunby Clare , Carline Anna , Bellis Mark A , Beynon Caryl 
Published: March 2012

Abstract

Background
Sexual offences are a global public health concern. Recent changes in the law in England and Wales have dramatically altered the legal landscape of sexual offences, but sexual assaults where the victim is voluntarily intoxicated by alcohol continue to have low conviction rates. Worldwide, students are high consumers of alcohol. This research aimed to compare male and female students in relation to their knowledge and attitudes about alcohol and sexual activity and to identify factors associated with being the victim of alcohol-related non-consensual sex.

Methods
1,110 students completed an online questionnaire. Drinking levels were measured using the Alcohol Use Disorder Identification Test. Non-consensual sexual experiences were measured using the Sexual Experience Survey. Univariate and multivariate analyses were undertaken using chi square and backwards stepwise logistic regression respectively.

Results
A third of respondents had experienced alcohol-related non-consensual sex. Male and female students differed in the importance they gave to cues in deciding if a person wished to have sex with them and their understanding of the law of consent. 82.2% of women who had experienced alcohol-related non-consensual sex were hazardous drinkers compared to 62.9% who drank at lower levels (P < 0.001). Differences existed between men and women, and between those who had and had not experienced alcohol-related non-consensual sex, in relation to assessments of culpability in scenarios depicting alcohol-related intercourse. A third of respondents believed that a significant proportion of rapes were false allegations; significantly more men than women responded in this way.

Conclusions
Alcohol-related coerced sexual activity is a significant occurrence among students; attitudinal and knowledge differences between males and females may explain this. Educational messages that focus upon what is deemed acceptable sexual behaviour, the law and rape myths are needed but are set against a backdrop where drunkenness is commonplace.
In vivo assessment of the host reactions to the biodegradation of the two novel magnesium alloys ZEK100 and AX30 in an animal model
Authors: Huehnerschulte Tim Andreas , Reifenrath Janin , von Rechenberg Brigitte , Dziuba Dina , Seitz Jan Marten , Bormann Dirk , Windhagen Henning , Meyer-Lindenberg Andrea 
Published: March 2012

AbstractBackgroundMost studies on biodegradable magnesium implants published recently use magnesium-calcium-alloys or magnesium-aluminum-rare earth-alloys.However, since rare earths are a mixture of elements and their toxicity is unclear, a reduced content of rare earths is favorable. The present study assesses the in vivo biocompatibility of two new magnesium alloys which have a reduced content (ZEK100) or contain no rare earths at all (AX30).Methods24 rabbits were randomized into 4 groups (AX30 or ZEK100, 3 or 6 months, respectively) and cylindrical pins were inserted in their tibiae. To assess the biodegradation μCT scans and histological examinations were performed.ResultsThe μCT scans showed that until month three ZEK100 degrades faster than AX30, but this difference is leveled out after 6 months. Histology revealed that both materials induce adverse host reactions and high numbers of osteoclasts in the recipient bone. The mineral apposition rates of both materials groups were high.ConclusionsBoth alloys display favorable degradation characteristics, but they induce adverse host reactions, namely an osteoclast-driven resorption of bone and a subsequent periosteal formation of new bone. Therefore, the biocompatibility of ZEK100 and AX30 is questionable and further studies, which should focus on the interactions on cellular level, are needed.