bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel and spatial analysis of syphilis in Shenzhen, China, to inform spatially targeted control measures
Authors: Wu Xiaobing , Tucker Joseph D , Hong Fuchang , Messina Jane , Lan Lina , Hu Yufeng , Feng Tiejian , Emch Michael E , Liu Xiaoli , Zhang Chunlai , Wen Lizhang 
Published: March 2012

ObjectivesThe present study investigates the varied spatial distribution of syphilis cases in Shenzhen, China, and explores the individual-, neighbourhood- and district-level factors affecting the distribution.MethodsThis study uses spatial analysis and multi-level generalised estimating equations to explore the spatial distribution of reported syphilis cases among individuals in Shenzhen, Guangdong Province, China. The spatial distribution of primary/secondary and latent cases was investigated using the Moran's I-statistic. Primary/secondary syphilis cases were compared with all syphilis cases using a three-level model with individual (n=6496), neighbourhood (n=55) and district (n=6) levels.ResultsA total of 6496 syphilis cases were reported in 2009 with 35.8% primary and secondary syphilis cases. Both primary/secondary syphilis cases (Moran's I value=0.33, p<0.01) and latent syphilis cases (Moran's I value=0.19, p<0.01) showed significant spatial clustering at the neighbourhood level. Adjusting for the number of reporting hospitals, the best model found that the following characteristics were associated with primary/secondary syphilis infection: individuals who are younger in age (p=0.003), male (p<0.001), migrant labourers (p=0.047) and those who live in districts with a higher gross domestic product (p<0.001).ConclusionsThere is substantial clustering of primary and secondary syphilis cases at the neighbourhood level in Shenzhen, suggesting the need for greater STD health service provision in these clustered neighbourhoods. Spatially targeted syphilis control measures may be useful to optimise testing, treatment and partner services.
Suppression of the Epithelial–Mesenchymal Transition by Grainyhead-like-2
Authors: Cieply Benjamin , Riley Philip , Pifer Phillip M. , Widmeyer Joseph , Addison Joseph B. , Ivanov Alexey V. , Denvir James , Frisch Steven M. 
Published: March 2012

Abstract
Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial–mesenchymal transitions (EMT) occurring in wound-healing processes and the cancer stem cell–like compartment of tumors, including TGF-β dependence, we investigated the role of the Grainyhead gene, Grainyhead-like-2 (GRHL2) in oncogenic EMT. GRHL2 was downregulated specifically in the claudin-low subclass breast tumors and in basal-B subclass breast cancer cell lines. GRHL2 suppressed TGF-β–induced, Twist-induced or spontaneous EMT, enhanced anoikis sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated in part by suppression of ZEB1 expression via direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription and it upregulated mir-200b/c as well as the TGF-β receptor antagonist, BMP2. Finally, ectopic expression of GRHL2 in MDA-MB-231 breast cancer cells triggered an MET and restored sensitivity to anoikis. Taken together, our findings define a major role for GRHL2 in the suppression of oncogenic EMT in breast cancer cells. Cancer Res; 72(9); 2440–53. ©2012 AACR.
Experimental investigation and finite element analysis of welding induced residual stresses
Authors: Mollicone Pierluigi , Gray Thomas GF , Camilleri Duncan 
Published: March 2012

Welding is one of the most important metal joining techniques due to its advantages in relation to speed and versatility. One of the unwanted effects of gas metal arc welding is residual stress, that arises due to the inherent temperature loadings and can lead to structural integrity or assembly problems. Experimental investigation of these effects is highly desirable but often costly, especially in large-scale construction such as shipbuilding. It is therefore of interest to exploit the potential of computational analysis techniques, such as finite element analysis, for the assessment of these effects. The use of finite element analysis in this context is however not straightforward, due to the complex nature of the problem. The work presented here deals with an experimentally validated modelling strategy applied to two weld joint configurations: butt and fillet welded plates. Simulation techniques are presented which are aimed at predicting residual stresses. These are validated against measurements carried out using the hole drilling method for residual stress determination. Results show a good qualitative and quantitative match in simulated and experimentally measured values, which back up the modelling techniques adopted.
Extracellular ATP induces P2X7-dependent nicotinamide phosphoribosyltransferase release in LPS-activated human monocytes
Authors: Schilling Erik , Hauschildt Sunna 
Published: March 2012

Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in NAD biosynthesis, has recently been identified as a novel mediator of innate immunity. In the present study, we report that treatment of LPS-primed monocytes with ATP greatly enhanced the secretion of NAMPT in a time- and concentration-dependent manner without displaying any cytotoxic effect. NAMPT release was suppressed by pretreatment with the P2X7 receptor (P2X7R) inhibitors oxidized ATP (oxATP) and KN-62, indicating the engagement of P2X7Rs. Furthermore, P2X7R was found to be involved in mediating cell permeability caused by the addition of ATP. To define a role of endogenous ATP in NAMPT secretion, LPS-primed monocytes were incubated in the presence of oxATP and KN-62, as well as the ATP-hydrolyzing enzymes apyrase and hexokinase. With the exception of oxATP, neither substance led to a decrease in NAMPT release, suggesting that autocrine/paracrine ATP is unlikely to be responsible for the LPS-induced release of NAMPT. In conclusion, the enhanced release of NAMPT by extracellular ATP described here indicates the requirement of a second stimulus for the efficient secretion of NAMPT. This mode of secretion, which also applies to IL-1β, might represent a general mechanism for the release of leaderless secretory proteins at locally restricted sites.
Coffee cysteine proteinases and related inhibitors with high expression during grain maturation and germination
Authors: Lepelley Maud , Amor Mohamed Ben , Martineau Nelly , Cheminade Gerald , Caillet Victoria , McCarthy James 
Published: March 2012

Abstract

Background
Cysteine proteinases perform multiple functions in seeds, including participation in remodelling polypeptides and recycling amino acids during maturation and germination. Currently, few details exist concerning these genes and proteins in coffee. Furthermore, there is limited information on the cysteine proteinase inhibitors which influence the activities of these proteinases.

Results
Two cysteine proteinase (CP) and four cysteine proteinase inhibitor (CPI) gene sequences have been identified in coffee with significant expression during the maturation and germination of coffee grain. Detailed expression analysis of the cysteine proteinase genes CcCP1 and CcCP4 in Robusta using quantitative RT-PCR showed that these transcripts accumulate primarily during grain maturation and germination/post germination. The corresponding proteins were expressed in E. coli and purified, but only one, CcCP4, which has a KDDL/KDEL C-terminal sequence, was found to be active after a short acid treatment. QRT-PCR expression analysis of the four cysteine proteinase inhibitor genes in Robusta showed that CcCPI-1 is primarily expressed in developing and germinating grain and CcCPI-4 is very highly expressed during the late post germination period, as well as in mature, but not immature leaves. Transcripts corresponding to CcCPI-2 and CcCPI-3 were detected in most tissues examined at relatively similar, but generally low levels.

Conclusions
Several cysteine proteinase and cysteine proteinase inhibitor genes with strong, relatively specific expression during coffee grain maturation and germination are presented. The temporal expression of the CcCP1 gene suggests it is involved in modifying proteins during late grain maturation and germination. The expression pattern of CcCP4, and its close identity with KDEL containing CP proteins, implies this proteinase may play a role in protein and/or cell remodelling during late grain germination, and that it is likely to play a strong role in the programmed cell death associated with post-germination of the coffee grain. Expression analysis of the cysteine proteinase inhibitor genes suggests that CcCPI-1 could primarily be involved in modulating the activity of grain CP activity; while CcCPI-4 may play roles modulating grain CP activity and in the protection of the young coffee seedlings from insects and pathogens. CcCPI-2 and CcCPI-3, having lower and more widespread expression, could be more general "house-keeping" CPI genes.
Potential application of serological tests on fluids from carcasses: detection of antibodies against Toxoplasma gondii and Sarcoptes scabiei in red foxes (Vulpes vulpes)
Authors: Jakubek Eva-Britt , Mattsson Roland , Mörner Torsten , Mattsson Jens G , Gavier-Widén Dolores 
Published: March 2012

Abstract

Background
Serological surveys for disease investigation of wild animal populations require obtaining blood samples for analysis, which has logistic, ethic and economic difficulties. Applying serological test to fluids collected from dead animals is an alternative. The aim of this study was to assess if antibodies could be detected in two types of fluids collected from 56 carcasses of red foxes (Vulpes vulpes): pleural fluid and lung extract.

Findings
In 22 (39%) foxes antibodies against Sarcoptes scabiei were detected in both fluid types by ELISA and Western blot. In 46 (82%) foxes, antibodies against Toxoplasma gondii were detected in pleural fluid and in 41 (73%) in lung extract applying a Toxo-screen test (DAT). Antibodies were still detectable in the same fluids kept at room temperature for 28 days, although in fewer foxes (16 and 14 foxes tested for T. gondii in lung extract and pleural fluid respectively; and 1 and 4 tested for S. scabiei in lung extract and pleural fluid respectively.

Conclusions
These results indicate the potential utility of using fluids from carcasses for antibody screening of wild animals at the population level.
A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System
Authors: Meijers Björn , Laleman Wim , Vermeersch Pieter , Nevens Frederik , Wilmer Alexander , Evenepoel Pieter 
Published: March 2012

Abstract
Introduction
The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens.

Methods
We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis.

Results
Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events.

Conclusions
Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.
Domestic violence: its relevance to psychiatry
Authors: Howard Louise M. 
Published: March 2012

SummaryDomestic violence is a major public health problem because it is common and associated with physical and mental health morbidity. It is more common in psychiatric patients but is underdetected by mental health professionals. Routine enquiry increases detection but needs to be introduced in the context of comprehensive training, and only where referral and care pathways have been developed. High-risk patients should be referred to multi-agency risk assessment conferences for multidisciplinary assessment and safe management.
Comorbid anxiety and depression: bête noire or quick fix?
Authors: Andreescu Carmen , Lenze Eric J. 
Published: March 2012

SummaryThe common territory shared by anxiety and depression has always been a contentious subject. Research in favour of anxious depression as a potentially treatment-relevant subtype has been limited by diagnostic dilemmas and crude measurement. The most recent evidence from genetics, neuropeptide systems and functional neuroimaging suggests a valid diagnostic construct.
Doctors' health: stigma and the professional discomfort in seeking help
Authors: Garelick Antony I. 
Published: March 2012

SummaryI describe the needs for and impediments in provision of psychological support services for doctors. Morbidity and the resistance in the profession to addressing their own health needs are discussed. I also explore the principles of bespoke services for doctors, with particular emphasis on overcoming stigma and facilitating therapeutic engagement. I argue that triage is an inappropriate service model of care for doctors.
Economic and Clinical Impact of a Pharmacy Resident at a Large Academic Medical Center
Authors: Daghstani Alia A. , Patel Nilam P. 
Published: March 2012

Purpose To define the financial impact of a pharmacy residency program at a large academic medical center, to assess physician evaluation of pharmacy residents on patient rounds, and to describe the role of the pharmacy resident. Methods One pharmacy resident recorded all interventions during a 4-month period. Interventions were classified as cost-saving or cost-avoiding and were evaluated as such. The cost-savings and cost-avoidance of interventions, along with the costs of alternative weekend coverage and Medicare reimbursement, were summed to determine the financial impact of residency positions. To calculate costs associated with pharmacy residency programs, resident stipend and benefits as well as cost of preceptor teaching and preparation time were added together. Various daily activities were logged to describe the role of the pharmacy resident. To assess physician evaluation of including pharmacy resident on rounds, a short, optional survey was administered to members of the medical team. Results Over the 4-month study period, a total of 347 interventions were made by the pharmacy resident. The total cost-savings and cost-avoidance for interventions during the study period was $110,601. When comparing the costs and benefits of the residency program, there was a net benefit of $55,821 during the study period. Based on survey results, physician evaluation of the inclusion of pharmacy residents on rounds was positive. The resident provided pharmaceutical care to a mean of 15 patients daily, required about 1 hour of preceptor teaching time daily, and provided 7 inservices during the 4-month period. Conclusion Pharmacy residency programs have a positive financial impact. Pharmacy residents are thought by physicians to be helpful, and they enhance patient care when included on rounds.
Role of Mediator in Regulating Pol II Elongation and Nucleosome Displacement in Saccharomyces cerevisiae
Authors: Kremer Selena B , Kim Sunyoung , Jeon Jeong Ok , Moustafa Yara W , Chen Apeng , Zhao Jing , Gross David S 
Published: March 2012

Abstract
Mediator is a modular multisubunit complex that functions as a critical coregulator of RNA polymerase II (Pol II) transcription. While it is well accepted that Mediator plays important roles in the assembly and function of the preinitiation complex (PIC), less is known of its potential roles in regulating downstream steps of the transcription cycle. Here we use a combination of genetic and molecular approaches to investigate Mediator regulation of Pol II elongation in the model eukaryote, Saccharomyces cerevisiae. We find that ewe (expressionwithout heat shockelement) mutations in conserved Mediator subunits Med7, Med14, Med19, and Med21—all located within or adjacent to the middle module—severely diminish heat-shock–induced expression of the Hsf1-regulated HSP82 gene. Interestingly, these mutations do not impede Pol II recruitment to the gene’s promoter but instead impair its transit through the coding region. This implies that a normal function of Mediator is to regulate a postinitiation step at HSP82. In addition, displacement of histones from promoter and coding regions, a hallmark of activated heat-shock genes, is significantly impaired in the med14 and med21 mutants. Suggestive of a more general role, ewe mutations confer hypersensitivity to the anti-elongation drug 6-azauracil (6-AU) and one of them—med21—impairs Pol II processivity on a GAL1-regulated reporter gene. Taken together, our results suggest that yeast Mediator, acting principally through its middle module, can regulate Pol II elongation at both heat-shock and non–heat-shock genes.
Detecting Maternal-Effect Loci by Statistical Cross-Fostering
Authors: Wolf Jason , Cheverud James M 
Published: March 2012

AbstractGreat progress has been made in understanding the genetic architecture of phenotypic variation, but it is almost entirely focused on how the genotype of an individual affects the phenotype of that same individual. However, in many species the genotype of the mother is a major determinant of the phenotype of her offspring. Therefore, a complete picture of genetic architecture must include these maternal genetic effects, but they can be difficult to identify because maternal and offspring genotypes are correlated and therefore, partially confounded. We present a conceptual framework that overcomes this challenge to separate direct and maternal effects in intact families through an analysis that we call “statistical cross-fostering.” Our approach combines genotype data from mothers and their offspring to remove the confounding effects of the offspring’s own genotype on measures of maternal genetic effects. We formalize our approach in an orthogonal model and apply this model to an experimental population of mice. We identify a set of six maternal genetic effect loci that explain a substantial portion of variation in body size at all ages. This variation would be missed in an approach focused solely on direct genetic effects, but is clearly a major component of genetic architecture. Our approach can easily be adapted to examine maternal effects in different systems, and because it does not require experimental manipulation, it provides a framework that can be used to understand the contribution of maternal genetic effects in both natural and experimental populations.
Maximum Likelihood Estimation of Linkage Disequilibrium in Half-Sib Families
Authors: Gomez-Raya L 
Published: March 2012

AbstractMaximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ = 0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium.
The Role of Background Selection in Shaping Patterns of Molecular Evolution and Variation: Evidence from Variability on the Drosophila
X Chromosome
Authors: Charlesworth Brian 
Published: March 2012

Abstract
In the putatively ancestral population of Drosophila melanogaster, the ratio of silent DNA sequence diversity for X-linked loci to that for autosomal loci is approximately one, instead of the expected “null” value of 3/4. One possible explanation is that background selection (the hitchhiking effect of deleterious mutations) is more effective on the autosomes than on the X chromosome, because of the lack of crossing over in male Drosophila. The expected effects of background selection on neutral variability at sites in the middle of an X chromosome or an autosomal arm were calculated for different models of chromosome organization and methods of approximation, using current estimates of the deleterious mutation rate and distributions of the fitness effects of deleterious mutations. The robustness of the results to different distributions of fitness effects, dominance coefficients, mutation rates, mapping functions, and chromosome size was investigated. The predicted ratio of X-linked to autosomal variability is relatively insensitive to these variables, except for the mutation rate and map length. Provided that the deleterious mutation rate per genome is sufficiently large, it seems likely that background selection can account for the observed X to autosome ratio of variability in the ancestral population of D. melanogaster. The fact that this ratio is much less than one in D. pseudoobscura is also consistent with the model’s predictions, since this species has a high rate of crossing over. The results suggest that background selection may play a major role in shaping patterns of molecular evolution and variation.