bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia
Authors: Slager Susan L. , Skibola Christine F. , Di Bernardo Maria Chiara , Conde Lucia , Broderick Peter , McDonnell Shannon K. , Goldin Lynn R. , Croft Naomi , Holroyd Amy , Harris Shelley , Riby Jacques , Serie Daniel J. , Kay Neil E. , Call Timothy G. , Bracci Paige M. , Halperin Eran , Lanasa Mark C. , Cunningham Julie M. , Leis Jose F. , Morrison Vicki A. , Spector Logan G. , Vachon Celine M. , Shanafelt Tait D. , Strom Sara S. , Camp Nicola J. , Weinberg J. Brice , Matutes Estella , Caporaso Neil E. , Wade Rachel , Dyer Martin J. S. , Dearden Claire , Cerhan James R. , Catovsky Daniel , Houlston Richard S. 
Published: June 2012

Abstract
We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10−16). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.
Impaired surfactant protein B synthesis in infants with congenital diaphragmatic hernia
Authors: Cogo Paola E. , Simonato Manuela , Danhaive Olivier , Verlato Giovanna , Cobellis Giovanna , Savignoni Francesco , Peca Donatella , Baritussio Aldo , Carnielli Virgilio P. 
Published: June 2012

Pulmonary hypoplasia and hypertension account for significant morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH). Whether CDH is associated with surfactant dysfunction remains controversial. Therefore, we measured disaturated phosphatidylcholine (DSPC) and surfactant protein (SP)-B concentration in tracheal aspirates and their synthesis rate in infants with CDH compared to infants without lung disease.2H2O as a precursor of DSPC and 1-13C-leucine as a precursor of SP-B were administered to 13 infants with CDH and eight controls matched for gestational age. DSPC and SP-B were isolated from tracheal aspirates, and their fractional synthesis rate was derived from2H and13C enrichment curves obtained by mass spectrometry. DSPC and SP-B amounts in tracheal aspirates were also measured.In infants with CDH, SP-B fractional synthesis rate and amount were 62±27% and 57±22% lower, respectively, than the value found in infants without lung disease (p<0.01 and p<0.05, respectively). There were no significant group differences in DSPC fractional synthesis rate and amount.Infants with CDH have a lower rate of synthesis of SP-B and less SP-B in tracheal aspirates. In these infants, partial SP-B deficiency could contribute to the severity of respiratory failure and its correction might represent a therapeutic goal.
Universal HIV testing in London tuberculosis clinics: a cluster randomised controlled trial
Authors: Roy Anjana , Anaraki Sudy , Hardelid Pia , Catchpole Mike , Rodrigues Laura C. , Lipman Marc , Perkins Samantha , Roche Anita , Stagg Helen R. , Figueroa Jose , Abubakar Ibrahim 
Published: June 2012

We assessed whether implementation of a combination of interventions in London tuberculosis clinics raised the levels of HIV test offers, acceptance and coverage.A stepped-wedge cluster randomised controlled trial was conducted across 24 clinics. Interventions were training of clinical staff and provision of tailor-made information resources with or without a change in clinic policy from selective to universal HIV testing. The primary outcome was HIV test acceptance amongst those offered a test, before and after the intervention; the secondary outcome was an offer of HIV testing. Additionally, the number and proportion of HIV tests among all clinic attendees (coverage) was assessed.1,315 patients were seen in 24 clinics. The offer and coverage of testing rose significantly in clinics without (p = 0.002 and p = 0.004, respectively) and with an existing policy of universal testing (p = 0.02 and p = 0.04, respectively). However, the level of HIV test acceptance did not increase in 18 clinics without routine universal testing (p = 0.76) or the six clinics with existing universal testing (p = 0.40).The intervention significantly increased the number of HIV tests offered and proportion of participants tested, although acceptance did not change significantly. However, the magnitude of increase is modest due to the high baseline coverage.
Association between preterm birth and intrauterine growth retardation and child asthma
Authors: Källén Bengt , Finnström Orvar , Nygren Karl-Gösta , Otterblad Olausson Petra 
Published: June 2012

An association between preterm birth and an increased risk of childhood asthma has been demonstrated, but the importance of intrauterine growth retardation on asthma risk is unclear.Using data from Swedish health registers, infant characteristics and childhood asthma were studied. Analyses were made using Mantel–Haenszel methodology with adjustment for year of birth, maternal age, parity, smoking in early pregnancy and maternal body mass index. Preterm birth, birth weight and birth weight for gestational week were analysed and childhood asthma was evaluated from prescriptions of anti-asthmatic drugs. Neonatal respiratory problems and treatment for them were studied as mediating factors.Both short gestational duration and intrauterine growth retardation appeared to be risk factors and seemed to act separately. The largest effect was seen from short gestational duration. Use of mechanical ventilation in the newborn period and bronchopulmonary dysplasia were strong risk factors. A moderately increased risk was also seen in infants born large for gestational age.We conclude that preterm birth is a stronger risk factor for childhood asthma than intrauterine growth disturbances; however, the latter also affects the risk, and is also seen in infants born at term.
Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding
Authors: Lang Irene M. , Pesavento Raffaele , Bonderman Diana , Yuan Jason X-J. 
Published: June 2012

All available evidence today indicates that chronic thromboembolic pulmonary hypertension (CTEPH) is primarily caused by venous thromboembolism, as opposed to primary pulmonary vascularin situthrombosis. Both the initial magnitude of clot and pulmonary embolism (PE) recurrence may contribute to the development of CTEPH. Only few specific thrombophilic factors, such as phospholipid antibodies, lupus anticoagulant and elevated factor VIII, are statistically associated with CTEPH.A mechanistic view of CTEPH as a disease caused by obliteration of central pulmonary arteries by pulmonary emboli is too simplistic. Based on available data one may speculate that PE may be followed by a pulmonary vascular remodelling process modified by infection, immune phenomena, inflammation, circulating and vascular-resident progenitor cells, thyroid hormone replacement or malignancy. Both plasmatic factors (hypercoagulation, “sticky” red blood cells, high platelet counts and uncleavable fibrinogens) and a misguided vascular remodelling process contribute to major vessel and small vessel obliteration. Endothelial dysfunction and endothelial–mesenchymal transition may be important, but their precise roles remain obscure. There exists no animal model for CTEPH; therefore, experimentation in the future must include human tissues and clinical data in parallel.
On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies
Authors: Petersen Ann-Kristin , Krumsiek Jan , Wägele Brigitte , Theis Fabian J , Wichmann H-Erich , Gieger Christian , Suhre Karsten 
Published: June 2012

Abstract

Background
Genome-wide association studies (GWAS) with metabolic traits and metabolome-wide association studies (MWAS) with traits of biomedical relevance are powerful tools to identify the contribution of genetic, environmental and lifestyle factors to the etiology of complex diseases. Hypothesis-free testing of ratios between all possible metabolite pairs in GWAS and MWAS has proven to be an innovative approach in the discovery of new biologically meaningful associations. The p-gain statistic was introduced as an ad-hoc measure to determine whether a ratio between two metabolite concentrations carries more information than the two corresponding metabolite concentrations alone. So far, only a rule of thumb was applied to determine the significance of the p-gain.

Results
Here we explore the statistical properties of the p-gain through simulation of its density and by sampling of experimental data. We derive critical values of the p-gain for different levels of correlation between metabolite pairs and show that B/(2*α) is a conservative critical value for the p-gain, where α is the level of significance and B the number of tested metabolite pairs.

Conclusions
We show that the p-gain is a well defined measure that can be used to identify statistically significant metabolite ratios in association studies and provide a conservative significance cut-off for the p-gain for use in future association studies with metabolic traits.
Linkage disequilibrium and inbreeding estimation in Spanish Churra sheep
Authors: García-Gámez Elsa , Sahana Goutam , Gutiérrez-Gil Beatriz , Arranz Juan-Jose 
Published: June 2012

AbstractBackgroundGenomic technologies, such as high-throughput genotyping based on SNP arrays, have great potential to decipher the genetic architecture of complex traits and provide background information concerning genome structure in domestic animals, including the extent of linkage disequilibrium (LD) and haplotype blocks. The objective of this study was to estimate LD, the population evolution (past effective population size) and the level of inbreeding in Spanish Churra sheep.ResultsA total of 43,784 SNPs distributed in the ovine autosomal genome was analyzed in 1,681 Churra ewes. LD was assessed by measuringr2between all pairs of loci. For SNPs up to 10 kb apart, the averager2was 0.329; for SNPs separated by 200–500 kb the averager2was 0.061. When SNPs are separated by more than 50 Mbp, the averager2is the same as between non-syntenic SNP pairs (0.003). The effective population size has decreased through time, faster from 1,000 to 100 years ago and slower since the selection scheme started (15–25 generations ago). In the last generation, four years ago, the effective population size was estimated to be 128 animals. Inbreeding coefficients, although differed depending on the estimation approaches, were generally low and showed the same trend, which indicates that since 2003, inbreeding has been slightly increasing in the studied resource population.ConclusionsThe extent of LD in Churra sheep persists over much more limited distances than reported in dairy cattle and seems to be similar to other ovine populations. Churra sheep show a wide genetic base, with a long-term viable effective population size that has been slightly decreasing since selection scheme began in 1986. The genomic dataset analyzed provided useful information for identifying low-level inbreeding in the sample, whereas based on the parameters reported here, a higher marker density than that analyzed here will be needed to successfully conduct accurate mapping of genes underlying production traits and genomic selection prediction in this sheep breed. Although the Ovine Assembly development is still in a draft stage and future refinements will provide a more accurate physical map that will improve LD estimations, this work is a first step towards the understanding of the genetic architecture in sheep.
A high-resolution map of the Nile tilapia genome: a resource for studying cichlids and other percomorphs
Authors: Guyon Richard , Rakotomanga Michaelle , Azzouzi Naoual , Coutanceau Jean Pierre , Bonillo Celine , D’Cotta Helena , Pepey Elodie , Soler Lucile , Rodier-Goud Marguerite , D’Hont Angelique , Conte Matthew A , van Bers Nikkie EM , Penman David J , Hitte Christophe , Crooijmans Richard PMA , Kocher Thomas D , Ozouf-Costaz Catherine , Baroiller Jean Francois , Galibert Francis 
Published: June 2012

AbstractBackgroundThe Nile tilapia (Oreochromis niloticus) is the second most farmed fish species worldwide. It is also an important model for studies of fish physiology, particularly because of its broad tolerance to an array of environments. It is a good model to study evolutionary mechanisms in vertebrates, because of its close relationship to haplochromine cichlids, which have undergone rapid speciation in East Africa. The existing genomic resources for Nile tilapia include a genetic map, BAC end sequences and ESTs, but comparative genome analysis and maps of quantitative trait loci (QTL) are still limited.ResultsWe have constructed a high-resolution radiation hybrid (RH) panel for the Nile tilapia and genotyped 1358 markers consisting of 850 genes, 82 markers corresponding to BAC end sequences, 154 microsatellites and 272 single nucleotide polymorphisms (SNPs). From these, 1296 markers could be associated in 81 RH groups, while 62 were not linked. The total size of the RH map is 34,084 cR3500and 937,310 kb. It covers 88% of the entire genome with an estimated inter-marker distance of 742 Kb. Mapping of microsatellites enabled integration to the genetic map. We have merged LG8 and LG24 into a single linkage group, and confirmed that LG16-LG21 are also merged. The orientation and association of RH groups to each chromosome and LG was confirmed by chromosomal in situ hybridizations (FISH) of 55 BACs. Fifty RH groups were localized on the 22 chromosomes while 31 remained small orphan groups. Synteny relationships were determined between Nile tilapia, stickleback, medaka and pufferfish.ConclusionThe RH map and associated FISH map provide a valuable gene-ordered resource for gene mapping and QTL studies. All genetic linkage groups with their corresponding RH groups now have a corresponding chromosome which can be identified in the karyotype. Placement of conserved segments indicated that multiple inter-chromosomal rearrangements have occurred between Nile tilapia and the other model fishes. These maps represent a valuable resource for organizing the forthcoming genome sequence of Nile tilapia, and provide a foundation for evolutionary studies of East African cichlid fishes.
Biological characterization and selection criteria of adjuvant chemotherapy for early breast cancer: experience from the Italian observational NEMESI study
Authors: Clavarezza Matteo , Mustacchi Giorgio , Casadei Gardini Andrea , Del Mastro Lucia , De Matteis Andrea , Riccardi Ferdinando , Adamo Vincenzo , Aitini Enrico , Amoroso Domenico , Marchetti Paolo , Gori Stefania , Carrozza Francesco , Maiello Evaristo , Giotta Francesco , Dondi Davide , Venturini Marco 
Published: June 2012

Abstract

Background
International treatment guidelines recommend administration of adjuvant chemotherapy in early breast cancer based on clinical, prognostic and predictive parameters.

Methods
An observational study (NEMESI) was conducted in 63 Italian oncology centres in patients with early breast cancer. Age, performance status, concomitant disease, menopausal status, histology, tumor dimension (pT), axillary lymph node status (pN), grading (G), estrogen and progesterone receptor (ER and PgR), proliferative index (ki67 or MIB-1), human epidermal growth factor receptor 2 (HER2) and type of adjuvant treatment were recorded. The primary objective of the study was to define parameters influencing the decision to prescribe adjuvant chemotherapy and the type of chemotherapy.

Results
Data for 1894 patients were available. 69.0% postmenopausal, 67.0% pT1, 22.3% pTmic/pT1a/pT1b, 61.0% pN0, 48.7% luminal A, 18.1% luminal B, 16.1% HER2 positive, 8.7% triple negative, 8.4% unknown. 57.8% received adjuvant chemotherapy: 38.1% of luminal A, 67.3% luminal B, 88.2% HER2-positive, 97.6% triple negative. Regimens administered: 9.1% CMF-like, 48.8% anthracyclines, 38.4% anthracyclines plus taxanes, 3.7% taxanes alone. Increasing pT/pN and, marginally, HER2-positive were associated with the prescription of anthracyclines plus taxanes. Suboptimal schedules (CMF-like or AC/EC or FEC-75) were prescribed in 37.3% receiving chemotherapy, even in HER2-positive and triple negative disease (36.5% and 34.0%, respectively).

Conclusions
This study showed an overprescription of adjuvant chemotherapy for early breast cancer, particularly referred to luminal A. pT, pN and, marginally, HER2 were the principal determinants for the choice of chemotherapy type. Suboptimal chemotherapy regimens were adopted in at least one third of HER2-positve and triple negative.
A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006
Authors: Chen Cynthia , Naidoo Nasheen , Yang Qian , Hartman Mikael , Verkooijen Helena M , Loy En Yun , Bouchardy Christine , Chia Kee Seng , Chia Sin Eng 
Published: June 2012

Abstract

Background
Prostate cancer is the most commonly diagnosed malignancy in men in Sweden and Geneva, and the third most common in men in Singapore. This population-based study describes trends in the incidence and mortality rates of prostate cancer in Singapore, Sweden and Geneva (Switzerland) from 1973 to 2006 and explores possible explanations for these different trends.

Methods
Data from patients diagnosed with prostate cancer were extracted from national cancer registries in Singapore (n = 5,172), Sweden (n = 188,783) and Geneva (n = 5,755) from 1973 to 2006. Trends of incidence and mortality were reported using the Poisson and negative binomial regression models. The age, period and birth-cohort were tested as predictors of incidence and mortality rates of prostate cancer.

Results
Incidence rates of prostate cancer increased over all time periods for all three populations. Based on the age-period-cohort analysis, older age and later period of diagnosis were associated with a higher incidence of prostate cancer, whereas older age and earlier period were associated with higher mortality rates for prostate cancer in all three countries.

Conclusions
This study demonstrated an overall increase in incidence rates and decrease in mortality rates in Singapore, Sweden and Geneva. Both incidence and mortality rates were much lower in Singapore. The period effect is a stronger predictor of incidence and mortality of prostate cancer than the birth-cohort effect.
Effect of inhibition of the Ubiquitin-Proteasome System and Hsp90 on growth and survival of Rhabdomyosarcoma cells in vitro
Authors: Peron Marica , Bonvini Paolo , Rosolen Angelo 
Published: June 2012

AbstractBackgroundThe ubiquitin-proteasome system (UPS) and the heat shock response (HSR) are two critical regulators of cell homeostasis, as their inhibition affects growth and survival of normal cells, as well as stress response and invasiveness of cancer cells. We evaluated the effects of the proteasome inhibitor Bortezomib and of 17-DMAG, a competitive inhibitor of Hsp90, in rhabdomyosarcoma (RMS) cells, and analyzed the efficacy of single-agent exposures with combination treatments.MethodsTo assess cytotoxicity induced by Bortezomib and 17-DMAG in RMS cells, viability was measured by MTT assay after 24, 48 and 72 hours. Western blotting and immunofluorescence analyses were carried out to elucidate the mechanisms of action. Apoptosis was measured by FACS with Annexin-V-FITC and Propidium Iodide.ResultsBortezomib and 17-DMAG, when combined at single low-toxic concentrations, enhanced growth inhibition of RMS cells, with signs of autophagy that included intensive cytoplasmic vacuolization and conversion of cytosolic LC3-I protein to its autophagosome-associated form. Treatment with lysosomal inhibitor chloroquine facilitates apoptosis, whereas stimulation of autophagy by rapamycin prevents LC3-I conversion and cell death, suggesting that autophagy is a resistance mechanism in RMS cells exposed to proteotoxic drugs. However, combination treatment also causes caspase-dependent apoptosis, PARP cleavage and Annexin V staining, as simultaneous inhibition of both UPS and HSR systems limits cytoprotective autophagy, exacerbating stress resulting from accumulation of misfolded proteins.ConclusionThe combination of proteasome inhibitor Bortezomib with Hsp90 inhibitor 17-DMAG, appears to have important therapeutic advantages in the treatment of RMS cells compared with single-agent exposure, because compensatory survival mechanisms that occur as side effects of treatment may be prevented.
The greatest risk for low-back pain among newly educated female health care workers; body weight or physical work load?
Authors: Jensen Jette Nygaard , Holtermann Andreas , Clausen Thomas , Mortensen Ole Steen , Carneiro Isabella Gomes , Andersen Lars Louis 
Published: June 2012

Abstract

Background
Low back pain (LBP) represents a major socioeconomic burden for the Western societies. Both life-style and work-related factors may cause low back pain. Prospective cohort studies assessing risk factors among individuals without prior history of low back pain are lacking. This aim of this study was to determine risk factors for developing low back pain (LBP) among health care workers.

Methods
Prospective cohort study with 2,235 newly educated female health care workers without prior history of LBP. Risk factors and incidence of LBP were assessed at one and two years after graduation.

Results
Multinomial logistic regression analyses adjusted for age, smoking, and psychosocial factors showed that workers with high physical work load had higher risk for developing LBP than workers with low physical work load (OR 1.8; 95% CI 1.1–2.8). In contrast, workers with high BMI were not at a higher risk for developing LBP than workers with a normal BMI.

Conclusion
Preventive initiatives for LBP among health care workers ought to focus on reducing high physical work loads rather than lowering excessive body weight.