bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases
Authors: Lotsari Johanna E , Gylling Annette , Abdel-Rahman Wael M , Nieminen Taina T , Aittomäki Kristiina , Friman Marjukka , Pitkänen Reino , Aarnio Markku , Järvinen Heikki J , Mecklin Jukka-Pekka , Kuopio Teijo , Peltomäki Päivi 
Published: June 2012

Abstract
Introduction
Breast carcinoma is the most common cancer in women, but its incidence is not increased in Lynch syndrome (LS) and studies on DNA mismatch repair deficiency (MMR) in LS-associated breast cancers have arrived at conflicting results. This study aimed to settle the question as to whether breast carcinoma belongs to the LS tumor spectrum.

Methods
MMR status and epigenetic profiles were determined for all available breast carcinomas identified among 200 LS families from a nation-wide registry (23 tumors from mutation carriers and 18 from non-carriers). Sporadic breast carcinomas (n = 49) and other cancers (n = 105) from MMR gene mutation carriers were studied for comparison.

Results
The proportion of breast carcinomas that were MMR-deficient based on absent MMR protein, presence of microsatellite instability, or both was significantly (P = 0.00016) higher among breast carcinomas from mutation carriers (13/20, 65%) compared to non-carriers (0/14, 0%). While the average age at breast carcinoma diagnosis was similar in carriers (56 years) and non-carriers (54 years), it was lower for MMR-deficient versus proficient tumors in mutation carriers (53 years versus 61 years, P = 0.027). Among mutation carriers, absent MMR protein was less frequent in breast carcinoma (65%) than in any of seven other tumor types studied (75% to 100%). Tumor suppressor promoter methylation patterns were organ-specific and similar between breast carcinomas from mutation carriers and non-carriers.

Conclusions
Breast carcinoma from MMR gene mutation carriers resembles common breast carcinoma in many respects (for example, general clinicopathological and epigenetic profiles). MMR status makes a distinction: over half are MMR-deficient typical of LS spectrum tumors, while the remaining subset which is MMR-proficient may develop differently. The results are important for appropriate surveillance in mutation carriers and may be relevant for LS diagnosis in selected cases.
SWAN: Subset-quantile Within Array Normalization for Illumina Infinium HumanMethylation450 BeadChips
Authors: Maksimovic Jovana , Gordon Lavinia , Oshlack Alicia 
Published: June 2012

AbstractDNA methylation is the most widely studied epigenetic mark and is known to be essential to normal development and frequently disrupted in disease. The Illumina HumanMethylation450 BeadChip assays the methylation status of CpGs at 485,577 sites across the genome. Here we present Subset-quantile Within Array Normalization (SWAN), a new method that substantially improves the results from this platform by reducing technical variation within and between arrays. SWAN is available in the minfi Bioconductor package.
Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
Authors: Barrenäs Fredrik , Chavali Sreenivas , Alves Alexessander Couto , Coin Lachlan , Jarvelin Marjo-Riitta , Jörnsten Rebecka , Langston Michael A , Ramasamy Adaikalavan , Rogers Gary , Wang Hui , Benson Mikael 
Published: June 2012

Abstract
Background
Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases.

Results
We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined small interfering RNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases.

Conclusions
Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.
Human cytomegalovirus induction of a unique signalsome during viral entry into monocytes mediates distinct functional changes: a strategy for viral dissemination
Authors: Chan Gary , Nogalski Maciej T , Stevenson Emily V , Yurochko Andrew D 
Published: June 2012

Abstract
Review on the viral entry process of HCMV and the potential role of receptor-ligand interactions in modulating monocyte biology.
HCMV pathogenesis is a direct consequence of the hematogenous dissemination of the virus to multiple host organ sites. The presence of infected monocytes in the peripheral blood and organs of individuals exhibiting primary HCMV infection have long suggested that these blood sentinels are responsible for mediating viral spread. Despite monocytes being “at the right place at the right time”, their short lifespan and the lack of productive viral infection in these cells complicate this scenario of a monocyte-driven approach to viral dissemination by HCMV. However, our laboratory has provided evidence that HCMV infection is able to induce a highly controlled polarization of monocytes toward a unique and long-lived proinflammatory macrophage, which we have demonstrated to be permissive for viral replication. These observations suggest that HCMV has evolved as a distinct mechanism to induce select proinflammatory characteristics that provide infected monocytes with the necessary tools to mediate viral spread following a primary infection. In the absence of viral gene products during the early stages of infection, the process by which HCMV “tunes” the inflammatory response in infected monocytes to promote viral spread and subsequently, viral persistence remains unclear. In this current review, we focus on the viral entry process of HCMV and the potential role of receptor-ligand interactions in modulating monocyte biology. Specifically, we examine the signaling pathways initiated by the distinct combination of cellular receptors simultaneously engaged and activated by HCMV during viral entry and how the acquisition of this distinct signalsome results in a nontraditional activation of monocytes leading to the induction of the unique, functional attributes observed in monocytes following HCMV infection.
C1q and phagocytosis: the perfect complement to a good meal
Authors: Galvan Manuel D , Greenlee-Wacker Mallary C , Bohlson Suzanne S 
Published: June 2012

Abstract
Review on the role for C1q in enhancement of phagocytosis, specifically focusing on C1q-mediated clearance of apoptotic cells.
Complement component C1q is a member of a family of soluble proteins called defense collagens, which are important in host defense and apoptotic cell clearance. Failure to efficiently clear apoptotic cells in the absence of C1q is associated with autoimmunity. Here, we review the literature describing a central role for C1q in the enhancement of phagocyte function and focus specifically on C1q in apoptotic cell clearance. In addition, we highlight our recent findings demonstrating that C1q elicits a macrophage phenotype that is tailored specifically for clearance of apoptotic cells.
Association of KRAS G13D Tumor Mutations With Outcome in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab
Authors: Tejpar Sabine , Celik Ilhan , Schlichting Michael , Sartorius Ute , Bokemeyer Carsten , Van Cutsem Eric 
Published: June 2012

Purpose We investigated in the first-line setting our previous finding that patients with chemorefractory KRAS G13D–mutated metastatic colorectal cancer (mCRC) benefit from cetuximab treatment. Methods Associations between tumor KRAS mutation status (wild-type, G13D, G12V, or other mutations) and progression-free survival (PFS), survival, and response were investigated in pooled data from 1,378 evaluable patients from the CRYSTAL and OPUS studies. Multivariate analysis correcting for differences in baseline prognostic factors was performed. Results Of 533 patients (39%) with KRAS-mutant tumors, 83 (16%) had G13D, 125 (23%) had G12V, and 325 (61%) had other mutations. Significant variations in treatment effects were found for tumor response (P = .005) and PFS (P = .046) in patients with G13D-mutant tumors versus all other mutations (including G12V). Within KRAS mutation subgroups, cetuximab plus chemotherapy versus chemotherapy alone significantly improved PFS (median, 7.4 v 6.0 months; hazard ratio [HR], 0.47; P = .039) and tumor response (40.5% v 22.0%; odds ratio, 3.38; P = .042) but not survival (median, 15.4 v 14.7 months; HR, 0.89; P = .68) in patients with G13D-mutant tumors. Patients with G12V and other mutations did not benefit from this treatment combination. Patients with KRAS G13D–mutated tumors receiving chemotherapy alone experienced worse outcomes (response, 22.0% v 43.2%; odds ratio, 0.40; P = .032) than those with other mutations. Effects were similar in the separate CRYSTAL and OPUS studies. Conclusion The addition of cetuximab to first-line chemotherapy seems to benefit patients with KRAS G13D–mutant tumors. Relative treatment effects were similar to those in patients with KRAS wild-type tumors but with lower absolute values.
Mediators of a long-term movement abnormality in a Drosophila melanogaster model of classic galactosemia
Authors: Ryan Emily L. , DuBoff Brian , Feany Mel B. , Fridovich-Keil Judith L. 
Published: June 2012

Summary
Despite neonatal diagnosis and life-long dietary restriction of galactose, many patients with classic galactosemia grow to experience significant long-term complications. Among the more common are speech, cognitive, behavioral, ovarian, and neurological/movement difficulties. Despite decades of research, the pathophysiology of these long-term complications remains obscure, hindering prognosis and attempts at improved intervention. As a first step to overcome this roadblock we have begun to explore long-term outcomes in our previously reported GALT-null Drosophila melanogaster model of classic galactosemia. Here we describe the first of these studies. Using a countercurrent device, a simple climbing assay, and a startle response test to characterize and quantify an apparent movement abnormality, we explored the impact of cryptic GALT expression on phenotype, tested the role of sub-lethal galactose exposure and galactose-1-phosphate (gal-1P) accumulation, tested the impact of age, and searched for potential anatomical defects in brain and muscle. We found that about 2.5% residual GALT activity was sufficient to reduce outcome severity. Surprisingly, sub-lethal galactose exposure and gal-1P accumulation during development showed no effect on adult phenotype. Finally, despite the apparent neurological or neuromuscular nature of the complication we found no clear morphological differences between mutants and controls in brain or muscle, suggesting that the defect is subtle and/or may be physiologic rather than structural. Combined, our results confirm that, like human patients, GALT-null Drosophila experience significant long-term complications that occur independent of galactose exposure, and serve as a proof of principle demonstrating utility of the GALT-null Drosophila model as a tool to explore genetic and environmental modifiers of long-term outcome in GALT deficiency.
Symmorphosis and the insect respiratory system: a comparison between flight and hopping muscle
Authors: Snelling Edward P. , Seymour Roger S. , Runciman Sue , Matthews Philip G. D. , White Craig R. 
Published: June 2012

SummaryWeibel and Taylor's theory of symmorphosis predicts that the structural components of the respiratory system are quantitatively adjusted to satisfy, but not exceed, an animal's maximum requirement for oxygen. We test this in the respiratory system of the adult migratory locust Locusta migratoria by comparing the aerobic capacity of hopping and flight muscle with the morphology of the oxygen cascade. Maximum oxygen uptake by flight muscle during tethered-flight is 967 ± 76 μmol h-1 g-1 (body mass-specific, ± 95% CI), whereas the hopping muscles consume a maximum of 158 ± 8 during jumping. The 6.1-fold difference in aerobic capacity between the two muscles is matched by a 6.4-fold difference in tracheole lumen volume, which is 3.5×108 ± 1.2×108 μm3 g-1 in flight muscle and 5.5×107 ± 1.8×107 in the hopping muscles, a 6.4-fold difference in tracheole inner cuticle surface area, which is 3.2×109 ± 1.1×109 μm2 g-1 in flight muscle and 5.0×108 ± 1.7×108 in the hopping muscles, and a 6.8-fold difference in tracheole radial diffusing capacity, which is 113 ± 47 μmol kPa-1 h-1 g-1 in flight muscle and 16.7 ± 6.5 in the hopping muscles. However, there is little congruence between the 6.1-fold difference in aerobic capacity and the 19.8-fold difference in mitochondrial volume, which is 3.2×1010 ± 3.9×109 μm3 g-1 in flight muscle and only 1.6×109 ± 1.4×108 in the hopping muscles. Therefore, symmorphosis is upheld in the design of the tracheal system, but not in relation to the amount of mitochondria, which might be due to other factors operating on the molecular level.
Characterizing emergency admissions of patients with sickle cell crisis in NHS brent: observational study
Authors: Green Stuart A , Aljuburi Ghida , Majeed Azeem , Okoye Ogo , Amobi Carole , Banarsee Ricky , Phekoo Karen J 
Published: June 2012

Objectives To characterize emergency admissions for patients with sickle cell crisis in NHS Brent and to determine which patients and practices may benefit most from primary care intervention. Design Observational study Setting Emergency departments attended by residents of the London borough of Brent Participants Patients with sickle cell disease registered with a general practitioner (GP) in the borough of Brent Main outcome measures Analysis of admissions between January 2008 and July 2010 that included length of stay (average and <2 days versus ≥2 days) by age group and registered GP practice. Results Thirty six percent of sickle cell disease admission spells resulted in a length of stay of less than two days. Seventy four percent of total bed days are associated with patients with more than one admission during the period of analysis, i.e. multiple admissions. Two general practices in Brent were identified as having the highest number of patients admitted to the emergency department for sickle cell crisis and may benefit most from primary care intervention. Discussion Patients with short length of stay and multiple admissions may be potentially amenable to primary care intervention. The practices which have the highest numbers of sickle cell disease patients who frequently seek emergency care will be earmarked for an education intervention designed to help further engage general practitioners in the care and management of their sickle cell patients.
The influence of process and patient factors on the recall of consent information in mentally competent patients undergoing surgery for neck of femur fractures
Authors: Khan SK , Karuppaiah K , Bajwa AS 
Published: June 2012

INTRODUCTION Informed consent is an ethical and legal prerequisite for major surgical procedures. Recent literature has identified ‘poor consent’ as a major cause of litigation in trauma cases. We aimed to investigate the patient and process factors that influence consent information recall in mentally competent patients (abbreviated mental test score [AMTS] ≥6) presenting with neck of femur (NOF) fractures. METHODS A prospective study was conducted at a tertiary unit. Fifty NOF patients (cases) and fifty total hip replacement (THR) patients (controls) were assessed for process factors (adequacy and validity of consent) as well as patient factors (comprehension and retention) using consent forms and structured interview proformas. RESULTS The two groups were matched for ASA (American Society of Anesthesiologists) grade and AMTS. The consent forms were adequate in both groups but scored poorly for validity in the NOF group. Only 26% of NOF patients remembered correctly what surgery they had while only 48% recalled the risks and benefits of the procedure. These results were significantly poorer than in THR patients (p=0.0001). CONCLUSIONS This study confirms that NOF patients are poor at remembering the information conveyed to them at the time of consent when compared with THR patients despite being intellectually and physiologically matched. We suggest using pre-printed consent forms (process factors), information sheets and visual aids (patient factors) to improve retention and recall.
Parenting Young Children with and Without Fragile X Syndrome
Authors: Sterling Audra , Barnum Leah , Skinner Debra , Warren Steven F. , Fleming Kandace 
Published: June 2012

AbstractThe purpose of this study was to examine maternal parenting styles across age-matched siblings using a within-family design, in which one child has Fragile X syndrome. Thirteen families participated; children were aged 16 to 71 months. Mothers completed several videotaped activities with each child separately as well as an interview. Mothers used a consistent, responsive style with both children, using the same degree of positive affect and warmth. Differences included using more behavior management strategies with the child with Fragile X and a conversational style of interaction with the sibling. Differences in approaches suggest the mothers adapted to the developmental differences between the children. The interview data supported these findings; mothers were aware of the changes made to accommodate the developmental differences.
Vaccine-Related Beliefs and Practices of Parents of Children with Autism Spectrum Disorders
Authors: Bazzano Alicia , Zeldin Ari , Schuster Erica , Barrett Christopher , Lehrer Danise 
Published: June 2012

AbstractAlthough the assertion of a link between vaccines and autism has been scientifically rejected, the theory continues to be popular and may influence the attitudes of parents of children with autism spectrum disorders. The authors sought to assess how often parents change or discontinue their child's vaccine schedule after autism spectrum disorder diagnosis and whether beliefs about the etiology of autism affect their decision to do so. The authors surveyed 197 (43%) of 460 eligible parents of children under 18 years of age with autism spectrum disorders who were enrolled in a state-funded agency that provides services to those with developmental disabilities in western Los Angeles County. Half of the parents discontinued or changed vaccination practices, and this was associated with a belief that vaccines contributed to autism spectrum disorders, indicating a potential subset of undervaccinated children. Educational tools should be designed to assist physicians when talking to parents of children with autism spectrum disorders about vaccination.
A New Method for Numerical Analysis of Reinforced Soil
Authors: Jie Yu-xin , Zhang Bin , Li Guang-xin 
Published: June 2012

AbstractThere are two general approaches to the analysis of reinforced soil. One is to deal with the soil and the reinforcement separately, assuming that they interact with each other through friction on the interface between them. The other is to consider the reinforced soil as an anisotropic homogeneous composite, such that the forces of interaction between soil and reinforcement material become internal, something that does not appear in calculations of the stress and deformation of the composite. In this paper, a new method is proposed for the analysis of reinforced soil. The basic principle of this method is that only the soil skeleton is taken into account, while the reinforcing effect is considered as an equivalent additional stress acting on the soil skeleton in the direction of the reinforcement bedding. The existing constitutive model for soil can be directly used in this method without having to formulate new models. The procedures involved in the determination of the equivalent additional stress and other relevant parameters are also presented in the paper. Examples show that the new method can reasonably describe the stress–strain relationship of fiber-reinforced soil and soil structures reinforced with layers of reinforcement.
Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy
Authors: Barbosa Edna J L , Glad Camilla A M , Nilsson Anna G , Filipsson Nyström Helena , Götherström Galina , Svensson Per-Arne , Vinotti Isabela , Bengtsson Bengt-Åke , Nilsson Staffan , Boguszewski Cesar Luiz , Johannsson Gudmundur 
Published: June 2012

ObjectiveGH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults.Design and methodsIn 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations.ResultsAt baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations;CETPSNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C;APOESNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, andCETPSNP rs1800775 with higher LDL-C; andAPOE/C1/C4/C2cluster SNP rs35136575 with lower serum TG. After treatment,APOBSNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C andPPARGSNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI.ConclusionsIn GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in theAPOBandPPARGgenes.