bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNP-based pathway enrichment analysis for genome-wide association studies
Authors: Weng Lingjie , Macciardi Fabio , Subramanian Aravind , Guffanti Guia , Potkin Steven G , Yu Zhaoxia , Xie Xiaohui 
Published: April 2011

Abstract

Background
Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS) to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs), have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs.

Results
We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1) for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one) SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2) ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one from European-American (EA) and the other from African-American (AA). In the EA data set, we found 22 pathways with nominal P-value less than or equal to 0.001 and corresponding false discovery rate (FDR) less than 5%. In the AA data set, we found 11 pathways by controlling the same nominal P-value and FDR threshold. Interestingly, 8 of these pathways overlap with those found in the EA sample. We have implemented our method in a JAVA software package, called SNP Set Enrichment Analysis (SSEA), which contains a user-friendly interface and is freely available at http://cbcl.ics.uci.edu/SSEA.

Conclusions
The SNP-based pathway enrichment method described here offers a new alternative approach for analysing GWAS data. By applying it to schizophrenia GWAS studies, we show that our method is able to identify statistically significant pathways, and importantly, pathways that can be replicated in large genetically distinct samples.
Complications of childbirth and maternal deaths in Kinshasa hospitals: testimonies from women and their families
Authors: Kabali Eugénie , Gourbin Catherine , De Brouwere Vincent 
Published: April 2011

Abstract

Background
Maternal mortality in Kinshasa is high despite near universal availability of antenatal care and hospital delivery. Possible explanations are poor-quality care and by delays in the uptake of care. There is, however, little information on the circumstances surrounding maternal deaths. This study describes and compares the circumstances of survivors and non survivors of severe obstetric complications.

Method
Semi structured interviews with 208 women who survived their obstetric complication and with the families of 110 women who died were conducted at home by three experienced nurses under the supervision of EK. All the cases were identified from twelve referral hospitals in Kinshasa after admission for a serious acute obstetric complication. Transcriptions of interviews were analysed with N-Vivo 2.0 and some categories were exported to SPSS 14.0 for further quantitative analysis.

Results
Testimonies showed that despite attendance at antenatal care, some women were not aware of or minimized danger signs and did not seek appropriate care. Cost was a problem; 5 deceased and 4 surviving women tried to avoid an expensive caesarean section by delivering in a health centre, although they knew the risk. The majority of surviving mothers (for whom the length of stay was known) had the caesarean section on the day of admission while only about a third of those who died did so. Ten women died before the required caesarean section or blood transfusion could take place because they did not bring the money in time. Negligence and lack of staff competence contributed to the poor quality of care. Interviews revealed that patients and their families were aware of the problem, but often powerless to do anything about it.

Conclusion
Our findings suggest that women with serious obstetric complications have a greater chance of survival in Kinshasa if they have cash, go directly to a functioning referral hospital and have some leverage when dealing with health care staff
Association of high sensitive C-reactive protein (hsCRP) with established cardiovascular risk factors in the Indian population
Authors: Jeemon Panniyammakal , Prabhakaran Dorairaj , Ramakrishnan Lakhmy , Gupta Ruby , Ahmed F , Thankappan KR , Kartha CC , Chaturvedi Vivek , Reddy KS ,   the Sentinel Surveillance in Industrial Populations Study Group
Published: April 2011

Abstract

Introduction
Inflammation, the key regulator of C-reactive protein (CRP) synthesis, plays a pivotal role in atherothrombotic cardiovascular disease.

Methods
High sensitivity CRP (hsCRP) analysis was carried out in randomly selected 600 individuals from the sentinel surveillance study in Indian industrial population (SSIP). The hsCRP was measured quantitatively by turbid metric test using kits from SPINREACT, Spain. We analyzed the association between hsCRP and traditional CVD risk factors in this sub-sample.

Results
Complete risk factor data and CRP levels were available from 581/600 individuals. One half (51.2%) of the study subjects were males. Mean age of the study group was 39.2 ± 11.2 years. The Pearson correlation coefficients were in the range of 0.12 for SBP (p = 0.004) to 0.55 for BMI (p < 0.001). The linear regression coefficients ranged from 0.01 for SBP, PG and TC (p < 0.001) to 0.55 for logeTAG (p < 0.001) after adjustment for age, sex and education. The mean of logehsCRP significantly increased (P < 0.001) from individuals with ≤1 risk factors (-0.50) to individuals with three or more risk factors (0.60). In the multivariate model, the odds ratios for elevated CRP (CRP ≥ 2.6 mg/dl) were significantly elevated only in females in comparison to males (1.63, 95% CI; 1.02-2.58), overweight individuals in comparison to normal weight individuals (3.90, 95% CI; 2.34-6.44, p < 0.001), and abdominal obese individuals (1.62, 95% CI; 1.02-2.60, p = 0.04) in comparison to non-obese individuals.

Conclusion
Clinical measurements of adiposity (body mass index and abdominal obesity) correlate well and can be surrogate for systemic inflammatory state of individuals.
Activation of the Galanin Receptor 2 in the Periphery Reverses Nerve Injury-Induced Allodynia
Authors: Hulse Richard P , Wynick David , Donaldson Lucy F 
Published: April 2011

Background: Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain. Results: Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord. Conclusions: These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.
De novo assembly of potential linear artificial chromosome constructs capped with expansive telomeric repeats
Authors: Lin Li , Koo Dal-Hoe , Zhang Wenli , St Peter Joseph , Jiang Jiming 
Published: April 2011

Abstract

Background
Artificial chromosomes (ACs) are a promising next-generation vector for genetic engineering. The most common methods for developing AC constructs are to clone and combine centromeric DNA and telomeric DNA fragments into a single large DNA construct. The AC constructs developed from such methods will contain very short telomeric DNA fragments because telomeric repeats can not be stably maintained in Escherichia coli.

Results
We report a novel approach to assemble AC constructs that are capped with long telomeric DNA. We designed a plasmid vector that can be combined with a bacterial artificial chromosome (BAC) clone containing centromeric DNA sequences from a target plant species. The recombined clone can be used as the centromeric DNA backbone of the AC constructs. We also developed two plasmid vectors containing short arrays of plant telomeric DNA. These vectors can be used to generate expanded arrays of telomeric DNA up to several kilobases. The centromeric DNA backbone can be ligated with the telomeric DNA fragments to generate AC constructs consisting of a large centromeric DNA fragment capped with expansive telomeric DNA at both ends.

Conclusions
We successfully developed a procedure that circumvents the problem of cloning and maintaining long arrays of telomeric DNA sequences that are not stable in E. coli. Our procedure allows development of AC constructs in different eukaryotic species that are capped with long and designed sizes of telomeric DNA fragments.
Effect of the dual endothelin receptor antagonist bosentan on untreatable skin ulcers in a patient with diabetes: a case report
Authors: Álvarez Reyes Fátima , Luna Gómez Cristina , Brito Suárez Manuel 
Published: April 2011

AbstractIntroductionRefractory skin ulcers are a major burden in patients with diabetes. Their pathogenesis is multifactorial, and data increasingly implicate endothelin as a mediator of diabetic macro- and microvasculopathy. Here we describe the first reported case of an endothelin receptor antagonist being used to successfully treat refractory skin ulcers in a patient with diabetes.Case presentationAn 85-year-old Caucasian man with a 30-year history of type 2 diabetes developed multiple skin ulcerations, including a right heel ulcer. Despite appropriate treatment, the ulcer showed little improvement and the risk of amputation was high. The patient was treated with the dual endothelin receptor antagonist bosentan. After three weeks of treatment, major improvements were observed, and after 21 weeks, all ulcers had healed. No abnormalities were observed during monitoring of blood pressure, erythrocyte sedimentation rate or serum aminotransferase levels.ConclusionIn patients with refractory ulceration associated with diabetes, bosentan may be of real benefit, especially in terms of amputation prevention. This case supports the proposed role for endothelin in the pathogenesis of skin ulceration in diabetes and is suggestive of a potential benefit of bosentan in this patient type. This case report is of interest to diabetologists and dermatologists.
A comparison of ankle foot orthoses with foot abduction orthoses to prevent recurrence following correction of idiopathic clubfoot by the Ponseti method
Authors: Janicki J. A. , Wright J. G. , Weir S. , Narayanan U. G. 
Published: April 2011

The Ponseti method of clubfoot management requires a period of bracing in order to maintain correction. This study compared the effectiveness of ankle foot orthoses and Denis Browne boots and bar in the prevention of recurrence following successful initial management. Between 2001 and 2003, 45 children (69 feet) with idiopathic clubfeet achieved full correction following Ponseti casting with or without a tenotomy, of whom 17 (30 clubfeet) were braced with an ankle foot orthosis while 28 (39 clubfeet) were prescribed with Denis Browne boots and bar. The groups were similar in age, gender, number of casts and tenotomy rates. The mean follow-up was 60 months (50 to 72) in the ankle foot orthosis group and 47 months (36 to 60) in the group with boots and bars. Recurrence requiring additional treatment occurred in 25 of 30 (83%) of the ankle foot orthosis group and 12 of 39 (31%) of the group with boots and bars (p < 0.001). Additional procedures included repeat tenotomy (four in the ankle foot orthosis group and five in the group treated with boot and bars), limited posterior release with or without tendon transfers (seven in the ankle foot orthosis group and two in the group treated with boots and bars), posteromedial releases (nine in the orthosis group) and midfoot osteotomies (five in the orthosis group, p < 0.001). Following initial correction by the Ponseti method, children managed with boots and bars had far fewer recurrences than those managed with ankle foot orthoses. Foot abduction appears to be important to maintain correction of clubfeet treated by the Ponseti method, and this cannot be achieved with an ankle foot orthosis.
A new uncemented hydroxyapatite-coated femoral component for the treatment of femoral neck fractures
Authors: Sköldenberg O. G. , Salemyr M. O. , Bodén H. S. , Lundberg A. , Ahl T. E. , Adolphson P. Y. 
Published: April 2011

Our aim in this pilot study was to evaluate the fixation of, the bone remodelling around, and the clinical outcome after surgery of a new, uncemented, fully hydroxyapatite-coated, collared and tapered femoral component, designed specifically for elderly patients with a fracture of the femoral neck. We enrolled 50 patients, of at least 70 years of age, with an acute displaced fracture of the femoral neck in this prospective single-series study. They received a total hip replacement using the new component and were followed up regularly for two years. Fixation was evaluated by radiostereometric analysis and bone remodelling by dual-energy x-ray absorptiometry. Hip function and the health-related quality of life were assessed using the Harris hip score and the EuroQol-5D. Up to six weeks post-operatively there was a mean subsidence of 0.2 mm (−2.1 to +0.5) and a retroversion of a mean of 1.2° (−8.2° to +1.5°). No component migrated after three months. The patients had a continuous loss of peri-prosthetic bone which amounted to a mean of 16% (−49% to +10%) at two years. The mean Harris hip score was 82 (51 to 100) after two years. The two-year results from this pilot study indicate that this new, uncemented femoral component can be used for elderly patients with osteoporotic fractures of the femoral neck.
Ice-cream cone reconstruction of the pelvis: a new type of pelvic replacement
Authors: Fisher N. E. , Patton J. T. , Grimer R. J. , Porter D. , Jeys L. , Tillman R. M. , Abudu A. , Carter S. R. 
Published: April 2011

Endoprosthetic replacement of the pelvis is one of the most challenging types of limb-salvage surgery, with a high rate of complications. In an attempt to reduce this and build greater versatility into the reconstruction process, a new type of pelvic endoprosthesis was developed in 2003, based on the old McKee-Farrar prosthesis. This study reviews the outcomes in 27 patients who had an ice-cream cone pelvic prosthesis inserted at two different specialist bone tumour centres in the United Kingdom over the past six years. The indications for treatment included primary bone tumours in 19 patients and metastatic disease in two, and six implants were inserted following failure of a previous pelvic reconstruction. Most of the patients had a P2+P3 resection as classified by Enneking, and most had resection of the ilium above the sciatic notch. The mean age of the patients at operation was 49 years (13 to 81). Complications occurred in ten patients (37.0%), of which dislocation was the most common, affecting four patients (14.8%). A total of three patients (11.1%) developed a deep infection around the prosthesis but all were successfully controlled by early intervention and two patients (7.4%) developed a local recurrence, at the same time as widespread metastases appeared. In one patient the prosthesis was removed for severe pain. This method of treatment is still associated with high morbidity, but early results are promising. Complications are diminishing with increasing experience.
Distal femoral physeal growth arrest secondary to a cemented proximal femoral endoprosthetic replacement
Authors: Gaston C. L. , Tillman R. M. , Grimer R. J. 
Published: April 2011

We report a case of spontaneous physeal growth arrest of the distal femur in a nine-year-old child with Ewing’s sarcoma of the proximal femur treated with chemotherapy and endoprosthetic replacement. Owing to the extent of disuse osteoporosis at the time of surgery, the entire intramedullary canal up to the distal femoral physis was filled with cement. Three years later, the femur remained at its pre-operative length of 19 cm. Pre-operative calculations of further growth failed to account for the growth arrest, and the initial expandable growing prosthesis inserted has been revised to a longer one in order to address the leg-length discrepancy. To our knowledge, this is the only reported case of distal femoral physeal growth arrest following cemented endoprosthetic replacement of the proximal femur.
Das Portal VD 18: Konzeption und Realisierung. Mit einer Einleitung von Heiner Schnelling
Authors: Schmidt Mirjam 
Published: April 2011

Zusammenfassung
Gefördert von der Deutschen Forschungsgemeinschaft arbeiten seit November 2009 fünf Bibliotheken in Kooperation mit dem Institut für Historisch-Kulturwissenschaftliche Informationsverarbeitung der Universität zu Köln am Verzeichnis der im deutschen Sprachraum erschienenen Drucke des 18. Jahrhunderts (VD 18): die Staatsbibliothek zu Berlin – Preußischer Kulturbesitz, die Sächsische Landesbibliothek – Staats- und Universitätsbibliothek Dresden, die Niedersächsische Staats-und Universitätsbibliothek Göttingen, die Universitäts- und Landesbibliothek in Halle, die Bayerische Staatsbibliothek in München. Neben der nationalbibliographischen Verzeichnung sind Digitalisierung und vertiefte Erschließung der Drucke zentrale Elemente des Projekts. Um diesen Mehrwert unter einer einheitlichen Oberfläche verfügbar zu machen, wurde an der ULB Halle im Rahmen eines sechsmonatigen Projektes an der konzeptionellen Entwicklung einer Portallösung für das VD 18 gearbeitet.
Cigarette smoking and progesterone and androgen metabolites in premenopausal women
Authors: Dušková Michaela , Šimůnková Kateřina , Hill Martin , Velíková Marta , Kubátová Jana , Hruškovičová Hana , Pospíšilová Hana , Rácz Beáta , Cirmanová Veronika , Králíková Eva , Stárka Luboslav 
Published: April 2011

Abstract

Background: Smoking represents the most widespread substance dependence in the world. Several studies show nicotine’s ability to alter women hormonal homeostasis. Women smokers have higher testosterone and lower estradiol levels throughout life compared to women non-smokers. This negatively affects women’s reproductive function. Furthermore, alteration of neuroactive and neuroprotective steroids occurs in women smokers, and this plays an important role in the activity of the central nervous system, cognition, mental condition, and degree of substance dependence.

Methods: We monitored the effect of smoking discontinuation on steroid spectrum in 40 premenopausal women heavy smokers. These women were examined before they began to discontinue smoking, and after 6, 12, 24 and 48 weeks of abstinence. In each examination, blood was collected to determine steroid spectrum, LH, FSH, and SHBG; basic anthropometric data were also measured using GC-MS or immunoanalysis. Repeated-measures analysis of variance (ANOVA) model was used for evaluation of the data.

Results: Given the small number of women who persisted in not smoking, only the data after 6 weeks could be analyzed. No changes were found in C21 steroids, and a slight increase in androgens occurred after the discontinuation of smoking.

Conclusion: Chronic smoking causes hyperandrogenism in fertile women; after smoking discontinuation, it increases further. Longer-term monitoring is necessary to show the effect of smoking discontinuation on steroid spectrum.
Effect of Aluminum Coating by Magnetron Sputtering on Corrosion Resistance of AZ31B Alloy
Authors: Zhang Jin , Yang Dong-Hua 
Published: April 2011

Abstract
In this study, aluminum coatings were prepared by dc magnetron sputtering on AZ31B magnesium alloy. The influence of sputtering parameters (include sputtering current, argon pressure, and deposition time) on corrosion behavior was investigated by potentiodynamic polarization tests in 3.5 % NaCl solution. The corrosion morphology was examined in detail by scanning electron microscopy and optical microscopy, respectively. It was found that the corrosion current density of magnesium alloy with aluminum coating was 2–3 orders of magnitude less than that of bare alloy. The corrosion potential with aluminum coating had been positive shift. The corrosion resistance of the coatings was strongly affected by its structure and residual stress, which depended on the process condition. Severe corrosion will occur after the aluminum coating is damaged due to the interaction of galvanic corrosion and other corrosion forms.