bluuebunny/crossref_metadata_2025_split huggingface dataset:
GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology
Authors: Cota Ana Marcia M , Oliveira Joao Batista A , Petersen Claudia G , Mauri Ana L , Massaro Fabiana C , Silva Liliane FI , Nicoletti Andreia , Cavagna Mario , Baruffi Ricardo LR , Franco José G 
Published: April 2012

Abstract

Background
The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation.

Methods
A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed.

Results
Out of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist-treated groups (P ≫ 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P ≫ 0.05).

Conclusions
Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.
Mitogen Activated Protein Kinase Phosphatase-1 Prevents the Development of Tactile Sensitivity in a Rodent Model of Neuropathic Pain
Authors: Ndong Christian , Landry Russell P. , DeLeo Joyce A. , Romero-Sandoval Edgar Alfonso 
Published: April 2012

Background: Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK) family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs) limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results: We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs) as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide). Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced proinflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions: Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.
Lamina I NK1 Expressing Projection Neurones are Functional in Early Postnatal Rats and Contribute to the Setting up of Adult Mechanical Sensory Thresholds
Authors: Man Sharon HW , Géranton Sandrine M , Hunt Stephen P 
Published: April 2012

Background: A small proportion of lamina I neurons of the spinal cord project upon the hindbrain and are thought to engage descending pathways that modulate the behavioural response to peripheral injury. Early postnatal development of nociception in rats is associated with exaggerated and diffuse cutaneous reflexes with a gradual refinement of responses over the first postnatal weeks related to increased participation of inhibitory networks. This study examined the postnatal development of lamina I projection neurons from postnatal day 3 (P3) until P48. Results: At P3, a subset of lamina I neurons were found to express the neurokinin 1 (NK1) receptor. Using fluorogold retrograde tracing, we found that the NK1 positive neurons projected upon the parabrachial nucleus (PB) within the hindbrain. Using c-fos immunohistochemistry, we showed that lamina I and PB neurons in P3 rats responded to noxious stimulation of the periphery. Finally, ablation of lamina I neurons with substance-P saporin conjugates at P3 resulted in increased mechanical sensitivity from P45 onwards compared to control animals of the same age. Conclusions: These results suggest that the lamina I pathway is present and functional at least from P3 and required for establishing and fine-tuning mechanical sensitivity in adult rats.
Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial
Authors: Jäger Susanne , Müller Kai W , Ruckes Christian , Wittig Tobias , Batra Anil , Musalek Michael , Mann Karl , Wölfling Klaus , Beutel Manfred E 
Published: April 2012

Abstract

Background
In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy.

Methods/design
This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment.

Discussion
A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed.

Trial Registration
ClinicalTrials (NCT01434589)
A study of the effect of the FertilMate™ scrotum cooling patch on male fertility. SCOP trial (scrotal cooling patch) - study protocol for a randomised controlled trial
Authors: Osman M Waseem , Nikolopoulos llias , Haoula Zeina , Kannamannadiar Jayaprakasan , Atiomo William 
Published: April 2012

Abstract

Background
Male infertility is a significant contributor to the need for fertility treatment. Treatment currently involves correcting any identifiable adverse lifestyle factors in men with suboptimal sperm parameters, and if these measures are unsuccessful, assisted conception is offered, which can be quite expensive. Raised scrotal temperature is one of the least studied but easily corrected risk factors for male infertility. In a recent review of the literature, sperm count, motility and morphology improved with scrotal cooling devices. The devices used to achieve testicular cooling were, however, not practical for day-to-day use. A potentially more practical device for scrotal cooling has recently been developed. The Babystart® FertilMate™ Scrotum Cooling Patch is a hydrogel pad which allows for comfortable application. The aims of this study were to investigate whether exposing the scrotum to lower temperatures by means of these new patches could improve semen parameters, thereby improving fertility, and to assess the feasibility of a clinical trial.

Methods/design
This is a randomised controlled trial set in a university teaching hospital in the United Kingdom. The proposed sample size was 40 men with mild, moderate or severe oligoasthenospermia, of whom 20 would be randomised to wearing the scrotum cooling patch for 90 days and 20 men would be acting as controls and not wearing the patches. The primary outcome measure was the change in sperm concentration. Secondary outcome measures included the change in sperm volume, motility and morphology; endocrine parameters; metabolomic biomarkers; testicular volume and blood flow. Reasons for dropping out and non-compliance were also going to be noted and reported.

Discussion
The study started recruiting in October 2011 and as of November 2011 four men had been consented and were participating in the study. No operational challenges had been encountered at the time of the submission of this manuscript. Although the study also aimed to evaluate the feasibility of a definitive study, the change in sperm count after 90 days of wearing the scrotal cooling patches was made the primary outcome measure because a statistically significant improvement in sperm parameters with the scrotal patches would in itself be a definitive finding.

Trial registration
Current Controlled Trials ISRCTN94041896
The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: the bullous pemphigoid steroids and tetracyclines study
Authors: Bratton Daniel J , Nunn Andrew J , Wojnarowska Fenella , Kirtschig Gudula , Sandell Anna , Williams Hywel C 
Published: April 2012

Abstract

Background
The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool is intended to be used in the design phase of trials to help investigative teams design trials in-line with their purpose. Our team applied this tool to an ongoing trial (BLISTER) to determine whether the initial suggestion among some team members that the trial could be described as largely pragmatic was the consensus.

Methods
Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the trial.

Results
The trial team found that the design of the trial was closest to the pragmatic end of the pragmatic-explanatory continuum. The strongest consensus was found on the ‘flexibility of the comparison intervention’ and ‘practitioner adherence’ domains (SD = 13). The trial team appeared to disagree most on the ‘eligibility criteria’ (SD = 35) and ‘participant compliance’ (SD = 31) domains, although the large standard deviations were a result of a single outlier in the two domains.

Conclusion
The PRECIS tool can be used to retrospectively determine the pragmatism of a trial provided enough expertise and information on the trial is available. Illustrating the design of a trial on the PRECIS wheel can help research users more easily identify studies of interest. We hope our recommendations for applying this useful tool will encourage others to consider using it when designing, conducting and reporting studies.

Trial registration
Current Controlled Trials http://www.controlled-trials.com/ISRCTN13704604
Retracted: MyoD-dependent regulation of NF-κB activity couples cell-cycle withdrawal to myogenic differentiation
Authors: Parker Maura H , von Maltzahn Julia , Bakkar Nadine , Al-Joubori Ban , Ishibashi Jeff , Guttridge Denis , Rudnicki Michael A 
Published: April 2012

Abstract

Background
Mice lacking MyoD exhibit delayed skeletal muscle regeneration and markedly enhanced numbers of satellite cells. Myoblasts isolated from MyoD

-/-
myoblasts proliferate more rapidly than wild type myoblasts, display a dramatic delay in differentiation, and continue to incorporate BrdU after serum withdrawal.

Methods
Primary myoblasts isolated from wild type and MyoD

-/-
mutant mice were examined by microarray analysis and further characterized by cell and molecular experiments in cell culture.

Results
We found that NF-κB, a key regulator of cell-cycle withdrawal and differentiation, aberrantly maintains nuclear localization and transcriptional activity in MyoD

-/-
myoblasts. As a result, expression of cyclin D is maintained during serum withdrawal, inhibiting expression of muscle-specific genes and progression through the differentiation program. Sustained nuclear localization of cyclin E, and a concomitant increase in cdk2 activity maintains S-phase entry in MyoD

-/-
myoblasts even in the absence of mitogens. Importantly, this deficit was rescued by forced expression of IκBαSR, a non-degradable mutant of IκBα, indicating that inhibition of NF-κB is sufficient to induce terminal myogenic differentiation in the absence of MyoD.

Conclusion
MyoD-induced cytoplasmic relocalization of NF-κB is an essential step in linking cell-cycle withdrawal to the terminal differentiation of skeletal myoblasts. These results provide important insight into the unique functions of MyoD in regulating the switch from progenitor proliferation to terminal differentiation.
Straightforward thiol-mediated protein labelling with DTPA: Synthesis of a highly active 111In-annexin A5-DTPA tracer
Authors: Kratz Harald , Haeckel Akvile , Michel Roger , Schönzart Lena , Hanisch Uli , Hamm Bernd , Schellenberger Eyk 
Published: April 2012

Abstract

Background
Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes.

Methods
Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, without affecting the binding domain of cys-anxA5.

Results
The metal complexing capacity of anxA5-DTPA was investigated by labelling with 111In3+ and Eu3+. Binding of modified anxA5-DTPA to apoptotic cells was tested in competition experiments with a fluorescent anxA5 derivative (anxA5-FITC) using flow cytometry and compared with that of wildtype anxA5 or non-binding anxA5-DTPA (M1234-anxA5-DTPA). The binding affinity to apoptotic cells of the anxA5-DTPA conjugate does not differ from that of wildtype anxA5.

Conclusions
This two-step synthesis of annexin A5-DTPA resulted in biologically active anxA5-DTPA, which can be labelled with radionuclides for use in SPECT and PET imaging.
Thrombin induces heme oxygenase-1 expression in human synovial fibroblasts through protease-activated receptor signaling pathways
Authors: Liu Ju-Fang , Hou Sheng-Mou , Tsai Chun-Hao , Huang Chun-Yin , Yang Wei-Hung , Tang Chih-Hsin 
Published: April 2012

Abstract
Introduction
Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of osteoarthritis (OA). Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury. Here, we investigated the intracellular signaling pathways involved in thrombin-induced HO-1 expression in human synovial fibroblasts (SFs).

Methods
Thrombin-mediated HO-1 expression was assessed with quantitative real-time (q)PCR. The mechanisms of action of thrombin in different signaling pathways were studied by using Western blotting. Knockdown of protease-activated receptor (PAR) proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of Nrf2 to the HO-1 promoter. Transient transfection was used to examine HO-1 activity.

Results
Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of thrombin, and expression was higher than in normal SFs. OASFs stimulation with thrombin induced concentration- and time-dependent increases in HO-1 expression. Pharmacologic inhibitors or activators and genetic inhibition by siRNA of protease-activated receptors (PARs) revealed that the PAR1 and PAR3 receptors, but not the PAR4 receptor, are involved in thrombin-mediated upregulation of HO-1. Thrombin-mediated HO-1 expression was attenuated by thrombin inhibitor (PPACK), PKCδ inhibitor (rottlerin), or c-Src inhibitor (PP2). Stimulation of cells with thrombin increased PKCδ, c-Src, and Nrf2 activation.

Conclusion
Our results suggest that the interaction between thrombin and PAR1/PAR3 increases HO-1 expression in human synovial fibroblasts through the PKCδ, c-Src, and Nrf2 signaling pathways.
The renal urate transporter SLC17A1 locus: confirmation of association with gout
Authors: Hollis-Moffatt Jade E , Phipps-Green Amanda J , Chapman Brett , Jones Gregory T , van Rij Andre , Gow Peter J , Harrison Andrew A , Highton John , Jones Peter B , Montgomery Grant W , Stamp Lisa K , Dalbeth Nicola , Merriman Tony R 
Published: April 2012

Abstract
Introduction
Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets.

Methods
Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian.

Results
At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype.

Conclusion
We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.
Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel
Authors: Simonis Marieke , Atanur Santosh S , Linsen Sam , Guryev Victor , Ruzius Frans-Paul , Game Laurence , Lansu Nico , de Bruijn Ewart , van Heesch Sebastiaan , Jones Steven JM , Pravenec Michal , Aitman Tim J , Cuppen Edwin 
Published: April 2012

Abstract
Background
With the advent of next generation sequencing it has become possible to detect genomic variation on a large scale. However, predicting which genomic variants are damaging to gene function remains a challenge, as knowledge of the effects of genomic variation on gene expression is still limited. Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression.

Results
We generated a comprehensive inventory of genomic differences between the two founder strains of the rat HXB/BXH recombinant inbred panel: SHR/OlaIpcv and BN-Lx/Cub. We identified 3.2 million single nucleotide variants, 425,924 small insertions and deletions, 907 copy number changes and 1,094 large structural genetic variants. RNA-sequencing analyses on liver tissue of the two strains identified 532 differentially expressed genes and 40 alterations in transcript structure. We identified both coding and non-coding variants that correlate with differential expression and alternative splicing. Furthermore, structural variants, in particular gene duplications, show a strong correlation with transcriptome alterations.

Conclusions
We show that the panel is a good model for assessing the genetic basis of phenotypic heterogeneity and for providing insights into possible underlying molecular mechanisms. Our results reveal a high diversity and complexity underlying quantitative and qualitative transcriptional differences.
Data error quantification in spectral induced polarization imaging
Authors: Orozco Adrián Flores , Kemna Andreas , Zimmermann Egon 
Published: April 2012

Induced polarization (IP) imaging is being increasingly used in near-surface geophysical studies, particularly for hydrogeologic and environmental applications. However, the analysis of IP data error has received little attention, even though the importance of an adequate error parameterization has been demonstrated for electrical resistivity imaging. Based on the analysis of data sets measured in the frequency range from 1 Hz to 1 kHz, we proposed a model for the quantification of phase data errors in IP measurements. The analyzed data sets were collected on an experimental tank containing targets of different polarizability. Our study is based on the common practice that the discrepancy of measurements taken in normal and reciprocal configuration can be considered as a measure of data error. Statistical analysis of the discrepancies between normal and reciprocal measurements revealed that the phase error decreases with increasing resistance (i.e., signal strength). We proposed an inverse power-law model to quantify the phase error as a function of the measured resistances. We found that the adequate implementation of the proposed error model in an inversion scheme leads to improved IP imaging results in laboratory experiments. Application to a data set collected at the field-scale also demonstrated the superiority of the new model over previous assumptions.