bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mutation in the interferon regulatory element of HBV may influence the response of interferon treatment in chronic hepatitis B patients
Authors: Lu Jia-Jie , Chen En-Qiang , Yang Jia-Hong , Zhou Tao-You , Liu Li , Tang Hong 
Published: January 2012

Abstract

Background
A functional interferon regulatory element (IRE) has been found in the EnhI/X promoter region of hepatitis B virus (HBV) genome. The purpose of this study is to compare the gene order of responder and non-responder to interferon therapy in patients with chronic hepatitis B (CHB), so as to evaluate the relationship between IRE mutation and the response to interferon treatment for CHB patients.

Results
Synthetic therapeutic effect is divided into complete response (CR), partial response (PR) and non-response (NR). Among the 62 cases included in this study, 40 cases (64.5%) were in the response group (CR and PR) and 22 (35.5%) cases were in the NR group. Wild type sequence of HBV IRE TTTCACTTTC were found in 35 cases (56.5%), and five different IRE gene sequences. included TTTtACTTTC, TTTCAtTTTC, TTTtAtTTTC, TTTtACTTTt and cTTtACcTTC, were found in 22 cases (35.5%), 1 case (1.6%), 1 case (1.6%), 2 cases (3.2%) and 1 case (1.6%) respectively. There were 41.9%cases (26/62) with forth base C→T mutation, consisted of 32.5% (13/40) cases in response group and 59.1% (13/22) cases in NR group. Among the 35 cases with IRE sequences, there were 67.5% (27/40) cases in response group and 36.4% (8/22) in NR group, and the difference in IRE sequences between two groups was statistic significantly (P = 0.027). The result suggested that there is likely relationship between the forth base mutation (C→T) of IRE region and the response of HBV to Interferon therapy, and this mutation may partially decrease the inhibition effect of interferon on HBV.

Conclusion
The forth base C→T mutation in IRE element of HBV may partially influence the response of Interferon treatment in CHB patients.
Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience
Authors: Zielinski Stephanie M , Viveiros Helena , Heetveld Martin J , Swiontkowski Marc F , Bhandari Mohit , Patka Peter , Van Lieshout Esther MM 
Published: January 2012

Abstract

Background
Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance.

Methods
Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates.

Results
Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217).

Conclusions
In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy.

Trial Registration
ClinicalTrials.gov: NCT00761813
Opposite effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) over-expression and knockdown on colorectal liver metastases
Authors: Bandapalli Obul R , Paul Eva , Schirmacher Peter , Brand Karsten 
Published: January 2012

Abstract

Background
Tissue inhibitors of metalloproteinases (TIMPs) and the corresponding metalloproteinases are integral parts of the protease network and have been shown to be involved in cancer development and metastasis. Paradoxically, for TIMP-1, tumor promoting as well as tumor inhibitory effects have been observed.

Methods
To address this paradox, we utilized the BALB/c/CT26 mouse model that reliably leads to liver metastasis after splenic tumor cell injection and variegated the type of target cells for therapeutic intervention and the modalities of gene transfer. Since we have observed before that over-expression of TIMP-1 in liver host cells leads to efficient tumor growth inhibition in this model, we now examined whether targeting the tumor cells themselves will have a similar effect.

Results
In concordance with the earlier results, TIMP-1 over-expression in tumor cells led to a dramatic reduction of tumor growth as well. To evaluate any influence of treatment modality, we further examined whether TIMP-1 knockdown in the same animal model would have the opposite effect on tumor growth than TIMP-1 over-expression. Indeed, TIMP-1 knockdown led to a marked increase in tumor burden.

Conclusion
These data indicate that in the BALB/c/CT26 model, the modification of TIMP-1 has concordant effects irrespective of the type of target cell or the technique of modulation of TIMP-1 activity, and that TIMP-1 is unequivocally tumor inhibitory in this model.
Enhancers and silencers: an integrated and simple model for their function
Authors: Kolovos Petros , Knoch Tobias A , Grosveld Frank G , Cook Peter R , Papantonis Argyris 
Published: January 2012

Abstract
Regulatory DNA elements such as enhancers, silencers and insulators are embedded in metazoan genomes, and they control gene expression during development. Although they fulfil different roles, they share specific properties. Herein we discuss some examples and a parsimonious model for their function is proposed. All are transcription units that tether their target promoters close to, or distant from, transcriptional hot spots (or 'factories').
Effect of prostaglandin E2 injection on the structural properties of the rat patellar tendon
Authors: Ferry Scott T , Afshari Hessam M , Lee Justin A , Dahners Laurence E , Weinhold Paul S 
Published: January 2012

Abstract

Background
Increased tendon production of the inflammatory mediator prostaglandin E2 (PGE2) has been suggested to be a potential etiologic agent in the development of tendinopathy. Repeated injection of PGE2 into tendon has been proposed as a potential animal model for studying treatments for tendinopathy. In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit PGE2 production and are commonly prescribed in treating tendinopathy have been shown to impair the healing of tendon after acute injury in animal models. The contradictory literature suggests the need to better define the functional effects of PGE2 on tendon. Our objective was to characterize the effects of PGE2 injection on the biomechanical and biochemical properties of tendon and the activity of the animals. Our hypothesis was that weekly PGE2 injection to the rat patellar tendon would lead to inferior biomechanical properties.

Methods
Forty rats were divided equally into four groups. Three groups were followed for 4 weeks with the following peritendinous injection procedures: No injection (control), 4 weekly injections of saline (saline), 4 weekly injections of 800 ng PGE2 (PGE2-4 wks). The fourth group received 4 weekly injections of 800 ng PGE2 initially and was followed for a total of 8 weeks. All animals were injected bilaterally. The main outcome measurements included: the structural and material properties of the patellar tendon under tensile loading to failure, tendon collagen content, and weekly animal activity scores.

Results
The ultimate load of PGE2-4 wks tendons at 4 weeks was significantly greater than control or saline group tendons. The stiffness and elastic modulus of the PGE2 injected tendons at 8 weeks was significantly greater than the control or saline tendons. No differences in animal activity, collagen content, or mean fibril diameter were observed between groups.

Conclusions
Four weekly peritendinous injections of PGE2 to the rat patellar tendon were not found to be an effective model of clinical tendinopathy. In contrast, improved structural and material properties of the patellar tendon were found after PGE2 injection. While PGE2 has been thought to have a contributory role in the development of tendinopathy and anti-inflammatory medications remain a common treatment, our results suggest a positive role of PGE2 in tendon remodeling in some circumstances.
Randomized Trial Using Gonadotropin-Releasing Hormone Agonist Triptorelin for the Preservation of Ovarian Function During (Neo)Adjuvant Chemotherapy for Breast Cancer
Authors: Munster Pamela N. , Moore Amy P. , Ismail-Khan Roohi , Cox Charles E. , Lacevic Mensura , Gross-King Margaret , Xu Ping , Carter W. Bradford , Minton Susan E. 
Published: January 2012

Purpose Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. Patients and Methods Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. Results Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. Conclusion When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.
Synthesis, quality control and biological evaluation of tris[(1,10-phenanthroline)[153Sm]samarium(III)]trithiocyanate complex as a therapeutic agent
Authors: Naseri Zohreh , Hakimi Amir , Jalilian A. R. , Nemati Kharat A. , Shirvani-Arani Simindokht , Bahrami-Samani A. , Ghannadi-Maragheh M. 
Published: January 2012

Abstract
Therapeutic radiopharmaceuticals are designed to deliver high doses of radiation to selected target organs or tissues with an aim of minimizing unwanted radiation to surrounding healthy tissue. In this work, [tris(1,10-phenanthroline) [153Sm]samarium(III)]trithiocyanate (153Sm-TPTTC) was developed for possible therapeutic properties. The cold compound, i.e.
natSm-TPTTC was prepared and characterized by IR, UV, mass and 1H-NMR spectroscopy. 153Sm-TPTTC was prepared in two steps using [153Sm]SmCl3, obtained by neutron activation of an enriched 152Sm sample. Stability tests, partition coefficient determination, toxicity tests and biodistribution studies of the complex in wild-type and fibrosarcoma-bearing mice were determined. The radiolabeled complex was prepared in high radiochemical purity (> 99% precipitation method) and specific activity of 278 GBq/mmol and demonstrated significant stability at 4, 25 and 37 ºC (in presence of human serum). Initial complex biodistribution data showed significant liver accumulation in wild-type mice and significant tumor accumulation in fibrosarcoma-bearing mice with tumor:blood and tumor:muscle ratios of 3.55 (2 h) and 38.26 (96 h) respectively. 153Sm-TPTTC properties suggest an efficient tumor targeting agent with high tumor-avidity. Further investigation on the therapeutic properties must be conducted.
Coprecipitation of europium with barium sulphate
Authors: Bouhlassa S. , Salhamen F. 
Published: January 2012

Abstract
The distribution behaviour of the trivalent europium ion at a micro-component scale, between barium sulphate and aqueous solution, was studied at ambient temperature. Experiments were carried out using radioactive tracers. Results indicate an enrichment of the micro component in the solid phase relative to the solution. The effects of the concentrations of the micro and macro-elements on the coprecipitation have been examined. Europium distribution coefficient D
Eu increases from 1.1 ± 0.2 to 3.2 ± 0.4 when initial europium concentration decreases from more than 17 × 10−5 to 1.4 × 10−5 M, in sulphuric media with SO4
2− in excess or C
Ba2+
/C
SO4
2−
< 1. The excess of barium in opposite, results in a decreasing D
Eu. The coprecipitation of europium with barium sulphate as a heterovalent solid-solution is described by heterogeneous model obeying the Doerner and Hoskins logarithmic partition law. The weaker partition coefficients lower than unity (λ = 0.25 when C
Eu(III) ≈ 1.4 × 10−5 M and λ = 0.13 when C
Ba2+
/CSO4
2−
< 1 and 17.8 × 10−5 ≤ C
Eu(III) ≤ 153.5 × 10−5 M) lead to crystals increasingly enriched in the trace element.
Genome-Wide Survey of Large Rare Copy Number Variants in Alzheimer’s Disease Among Caribbean Hispanics
Authors: Ghani Mahdi , Pinto Dalila , Lee Joseph H , Grinberg Yakov , Sato Christine , Moreno Danielle , Scherer Stephen W , Mayeux Richard , St. George-Hyslop Peter , Rogaeva Ekaterina 
Published: January 2012

AbstractRecently genome-wide association studies have identified significant association between Alzheimer’s disease (AD) and variations in CLU, PICALM, BIN1, CR1, MS4A4/MS4A6E, CD2AP, CD33, EPHA1, and ABCA7. However, the pathogenic variants in these loci have not yet been found. We conducted a genome-wide scan for large copy number variation (CNV) in a dataset of Caribbean Hispanic origin (554 controls and 559 AD cases that were previously investigated in a SNP-based genome-wide association study using Illumina HumanHap 650Y platform). We ran four CNV calling algorithms to obtain high-confidence calls for large CNVs (&gt;100 kb) that were detected by at least two algorithms. Global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications, total or average CNV size; or number of genes affected by CNVs. However, we observed a nominal association between AD and a ∼470 kb duplication on chromosome 15q11.2 (P = 0.037). This duplication, encompassing up to five genes (TUBGCP5, CYFIP1, NIPA2, NIPA1, and WHAMML1) was present in 10 cases (2.6%) and 3 controls (0.8%). The dosage increase of CYFIP1 and NIPA1 genes was further confirmed by quantitative PCR. The current study did not detect CNVs that affect novel AD loci identified by recent genome-wide association studies. However, because the array technology used in our study has limitations in detecting small CNVs, future studies must carefully assess novel AD genes for the presence of disease-related CNVs.
Use of Cumulative Poisson Probability Distribution as an Estimator of the Recombination Rate in an Expanding Population: Example of theMacaca fascicularisMajor Histocompatibility Complex
Authors: Blancher Antoine , Aarnink Alice , Savy Nicolas , Takahata Naoyuki 
Published: January 2012

AbstractWe describe a method to estimate the rate of recombination per generation from the genotypes of a large individual sample of an expanding population, for which the founding event is dated. The approach is illustrated with an application to estimating the major histocompatibility complex (MHC) recombination rate in the Mauritian macaque population. We genotyped 750 macaques by means of 17 microsatellites across the MHC region and reconstructed the seven most frequent haplotypes assumed to represent the founding haplotypes (Hrec(0)) as well as the 31% recombinant haplotypes (Hrec(h)) resulting from a variable number “h” of recombinations between the founding haplotypes. The relative frequencies of the various classes of haplotypes (Hrec(0) and Hrec(h)) follow a Poisson distribution. By using a maximum likelihood method, we calculated the mean of the Poisson distribution that best fits the data. By dividing this mean by the number of generations (50−100) from the date of the population founding, we deduced that rate of recombination in the MHC is approximately 0.004 to 0.008 in the Mauritian macaque population. When the founding date of the population is precisely known, our method presents a useful alternative to the coalescent method.
Natural Genetic Variation for Growth and Development Revealed by High-Throughput Phenotyping inArabidopsis thaliana
Authors: Zhang Xu , Hause Ronald J , Borevitz Justin O 
Published: January 2012

AbstractLeaf growth and development determines a plant’s capacity for photosynthesis and carbon fixation. These morphological traits are the integration of genetic and environmental factors through time. Yet fine dissection of the developmental genetic basis of leaf expansion throughout a growing season is difficult, due to the complexity of the trait and the need for real time measurement. In this study, we developed a time-lapse image analysis approach, which traces leaf expansion under seasonal light variation. Three growth traits, rosette leaf area, circular area, and their ratio as compactness, were measured and normalized on a linear timescale to control for developmental heterogeneity. We found high heritability for all growth traits that changed over time. Our study highlights a cost-effective, high-throughput phenotyping approach that facilitates the dissection of genetic basis of plant shoot growth and development under dynamic environmental conditions.
Linkage and Physical Mapping of Sex Region on LG23 of Nile Tilapia (Oreochromis niloticus)
Authors: Eshel O , Shirak A , Weller J I , Hulata G , Ron M 
Published: January 2012

AbstractEvidence supports that sex determination (SD) in tilapia is controlled by major genetic factors that may interact with minor genetic as well as environmental factors, thus implying that SD should be analyzed as a quantitative trait. Quantitative trait loci (QTL) for SD in Oreochromis niloticus were previously detected on linkage groups (LG) 1 and 23. Twenty-one short single repeats (SSR) of &gt;12 TGs and one single nucleotide polymorphism were identified using the unpublished tilapia genome sequence on LG23. All markers showed two segregating alleles in a mapping family that was obtained by a cross between O. niloticus male (XY) and sex-reversed female (ΔXY) yielding 29 females (XX) and 61 males (XY and YY). Interval mapping analysis mapped the QTL peak between SSR markers ARO172 and ARO177 with a maximum F value of 78.7 (P &lt; 7.6 × 10−14). Twelve adjacent markers found in this region were homozygous in females and either homozygous for the alternative allele or heterozygous in males. This segment was defined as the sex region (SR). The SR encompasses 1.5 Mbp on a single tilapia scaffold (no. 101) harboring 51 annotated genes. Among 10 candidate genes for SD that were tested for gene expression, anti-Müllerian hormone (Amh), which is located in the center of the SR, showed the highest overexpression in male vs. female embryos at 3 to 7 days postfertilization.
Chromosome Y Regulates Survival Following Murine Coxsackievirus B3 Infection
Authors: Case Laure K , Toussaint Leon , Moussawi Mohamad , Roberts Brian , Saligrama Naresha , Brossay Laurent , Huber Sally A , Teuscher Cory 
Published: January 2012

AbstractCoxsackievirus B3 (CVB3) contributes to the development of myocarditis, an inflammatory heart disease that predominates in males, and infection is a cause of unexpected death in young individuals. Although gonadal hormones contribute significantly to sex differences, sex chromosomes may also influence disease. Increasing evidence indicates that Chromosome Y (ChrY) genetic variants can impact biological functions unrelated to sexual differentiation. Using C57BL/6J (B6)-ChrY consomic mice, we show that genetic variation in ChrY has a direct effect on the survival of CVB3-infected animals. This effect is not due to potential Sry-mediated differences in prenatal testosterone exposure or to differences in adult testosterone levels. Furthermore, we show that ChrY polymorphism influences the percentage of natural killer T cells in B6-ChrY consomic strains but does not underlie CVB3-induced mortality. These data underscore the importance of investigating not only the hormonal regulation but also ChrY genetic regulation of cardiovascular disease and other male-dominant, sexually dimorphic diseases and phenotypes.
Social-Emotional Screening for Infants and Toddlers in Primary Care
Authors: Briggs Rahil D. , Stettler Erin M. , Silver Ellen Johnson , Schrag Rebecca D. A. , Nayak Meghna , Chinitz Susan , Racine Andrew D. 
Published: January 2012

BACKGROUND AND OBJECTIVES:
Recommendations in pediatrics call for general developmental screening of young children; however, research suggests social-emotional development, in particular, is important as an initial indicator of general well-being versus risk. We aim to describe a program designed to identify the social-emotional status of young children in the pediatric setting by using the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) as a universal screening tool, and to assess the effect of interventions by a colocated psychologist on changes in ASQ:SE scores over time.

METHODS:
In a prospective cohort design we analyzed scores on ASQ:SE surveys completed on children 6 to 36 months of age, to determine if children were at risk for problems in social-emotional development. The probability of remaining at risk over time was then compared between subjects receiving intervention by the psychologist, and those who declined intervention. Logit specifications were used in multivariate comparisons to control for a set of covariates.

RESULTS:
Three thousand one hundred and sixty-nine children were screened; 711 (22.4%) scored at or above the risk cutoff. Among the 711 at-risk children, 170 were rescreened. At the time of rescreening, those children who received intervention from the psychologist showed significant improvement on ASQ:SE scores compared with those who declined intervention (P = .01).

CONCLUSIONS:
Universal social-emotional screening in a busy pediatric practice is challenging. Significant percentages of children can be identified as being at risk for social-emotional problems, and colocation of a psychologist promotes the ability to effectively address young children’s social-emotional development within their medical home.