bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype–Environment Interactions in Microsatellite Stable/Microsatellite Instability-Low Colorectal Cancer: Results from a Genome-Wide Association Study
Authors: Figueiredo Jane C. , Lewinger Juan Pablo , Song Chi , Campbell Peter T. , Conti David V. , Edlund Christopher K. , Duggan Dave J. , Rangrej Jagadish , Lemire Mathieu , Hudson Thomas , Zanke Brent , Cotterchio Michelle , Gallinger Steven , Jenkins Mark , Hopper John , Haile Robert , Newcomb Polly , Potter John , Baron John A. , Marchand Loic Le , Casey Graham 
Published: May 2011

AbstractBackground: Genome-wide association studies (GWAS) have led to the identification of a number of common susceptibility loci for colorectal cancer (CRC); however, none of these GWAS have considered gene–environment (G × E) interactions. Therefore, it is unclear whether current hits are modified by environmental exposures or whether there are additional hits whose effects are dependent on environmental exposures.Methods: We conducted a systematic search for G × E interactions using genome wide data from the Colon Cancer Family Registry that included 1,191 cases of microsatellite stable (MSS) or microsatellite instability–low (MSI-L) CRC and 999 controls genotyped using either the Illumina Human1M or Human1M-Duo BeadChip. We tested for interactions between genotypes and 14 environmental factors using 3 methods: a traditional case–control test, a case-only test, and the recently proposed 2-step method by Murcray and colleagues. All potentially significant findings were replicated in the ARCTIC Study.Results: No G × E interactions were identified that reached genome-wide significance by any of the 3 methods. When analyzing previously reported susceptibility loci, 7 significant G × E interactions were found at a 5% significance level. We investigated these 7 interactions in an independent sample and none of the interactions were replicated.Conclusions: Identifying G × E interactions will present challenges in a GWAS setting. Our power calculations illustrate the need for larger sample sizes; however, as CRC is a heterogeneous disease, a tradeoff between increasing sample size and heterogeneity needs to be considered.Impact: The results from this first genome-wide analysis of G × E in CRC identify several challenges, which may be addressed by large consortium efforts. Cancer Epidemiol Biomarkers Prev; 20(5); 758–66. ©2011 AACR.
International Approaches to Advancing Biospecimen Science
Authors: Moore Helen M. , Compton Carolyn C. , Alper Joseph , Vaught Jimmie B. 
Published: May 2011

Abstract
Biospecimen quality is affected by a number of preanalytical factors that may or may not be obvious to the investigator. These factors are introduced through multiple biospecimen collection, processing, and storage procedures, which can differ dramatically within and between medical institutions and biorepositories. Biospecimen Science is the emerging field of study that is attempting to quantify and control such variability. A variety of efforts are under way around the world to establish research programs, evidence-based biospecimen protocols, and standards to improve the overall quality of biospecimens for research. Cancer Epidemiol Biomarkers Prev; 20(5); 729–32. ©2011 AACR.
Are P2Y12 reaction unit (PRU) and % inhibition index equivalent for the expression of P2Y12 inhibition by the VerifyNow® assay? Role of haematocrit and haemoglobin levels
Authors: Voisin Sophie , Bongard Vanina , Tidjane Mohammed A. , Lhermusier Thibault , Carrié Didier , Sié Pierre 
Published: May 2011

SummaryThe results of the whole blood VerifyNow® P2Y12 assay can be expressed as platelet reaction units (PRU) or % inhibition index (%inh), but an optimal cut-off for the assessment of high on-treatment platelet reactivity (HPR) predictive of clinical events has been validated only for PRU. The aim of the study was to study the influence of haematological variables, such as platelet and leukocyte counts or haematocrit / haemoglobin, within the limits indicated by the manufacturer for assay validity, on the results of the test. We performed a comparison of PRU and %inh in a series 186 samples obtained from a clinical trial on patients under dual antiplatelet therapy. The results show that PRU significantly decreases with increasing haematocrit / haemoglobin, whereas %inh does not, due to a parallel change in PRU and iso-TRAP baseline value. PRU and % inhibition index are not equivalent for the definition of HPR, because of their different sensitivities to haematocrit / haemoglobin.
Glenohumeral Osteoarthritis after Arthroscopic Bankart Repair for Anterior Instability
Authors: Franceschi Francesco , Papalia Rocco , Del Buono Angelo , Vasta Sebastiano , Maffulli Nicola , Denaro Vincenzo 
Published: May 2011

Background Few data on shoulder arthropathy in patients undergoing arthroscopic repair for glenohumeral instability are available. Hypothesis Arthroscopic stabilization of Bankart lesions does not prevent the development of postoperative glenohumeral osteoarthritis. Study Design Case series; Level of evidence, 4. Methods Clinical (Rowe and Constant scores) and radiographic preoperative and postoperative data from 60 patients who underwent arthroscopic Bankart repair were compared. Osteoarthritis was graded preoperatively and postoperatively with the Buscayret classification grading system. The average age at surgery was 27.6 years, and follow-up averaged 8.0 years. Results The postoperative incidence of osteoarthritis in patients with no preoperative degenerative changes was 21.8% (12 of 55 patients). The incidence of degenerative joint disease of the glenohumeral joint showed evidence of a statistically significant association with older age at first dislocation and at surgery, increased length of time from the first episode to surgery, increased number of preoperative dislocations, increased length of time from the initial dislocation until surgery, increased number of anchors used at surgery, and more degenerated labrum at surgery. A higher number of preoperative dislocations, a greater length of follow-up, and reduced external rotation in abduction influenced Rowe and Constant scores. Conclusion The number of anchors used and the state of the labrum are the most important factors associated with a higher risk of radiographic degenerative changes. Longer follow-up investigations are needed to draw meaningful conclusions.
Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis
Authors: Sombekke MH , van der Voort LF , Kragt JJ , Nielsen JM , Guzel H , Visser A , Oudejans CBM , Crusius JBA , Peña A Salvador , Vrenken H , Polman CH , Killestein J 
Published: May 2011

Background: The interleukin 7 receptor (IL7R) has been recognized as a susceptibility gene for Multiple Sclerosis (MS). Analysis of rs6897932 (the most strongly MS-associated single nucleotide polymorphism (SNP)), showed effects of genotype on the relative expression of membrane-bound to total amount of IL7R mRNA. Objective: We assessed the relevance of IL7R on MS phenotype (including clinical and magnetic resonance imaging (MRI) parameters) at DNA and mRNA level in Dutch patients with MS. Methods: The genotype of rs6897932 was analyzed in 697 patients with MS and 174 healthy controls. The relevance of genotype and carriership of the C allele on MS phenotype (disease activity and severity, using clinical and MRI parameters) was assessed. In addition, relative gene expression of membrane-bound to total IL7R mRNA was analyzed with respect to disease phenotype in a subgroup of 95 patients with early relapsing MS. Results: In particular, homozygosity for the risk allele is a risk factor for MS in our population (ORCC vs CT and TT = 1.65 (95% CI: 1.18–2.30), two-sided p = 0.004). However, no effect of genotype or the relative expression of membrane-bound IL7R (presence of exon 6–7) to total amount of IL7R mRNA (presence of exon 4–5) was found on MS phenotype. Discussion: Homozygosity for the IL7R exon 6 rs6897932 C allele is associated with a higher risk for MS in our Dutch population. No effect was found of genotype or mRNA expression on disease phenotype.
Intracortical lesions by 3T magnetic resonance imaging and correlation with cognitive impairment in multiple sclerosis
Authors: Nelson Flavia , Datta Sushmita , Garcia Nereyda , Rozario Nigel L , Perez Francisco , Cutter Gary , Narayana Ponnada A , Wolinsky Jerry S 
Published: May 2011

Background: Accurate classification of multiple sclerosis (MS) lesions in the brain cortex may be important in understanding their impact on cognitive impairment (CI). Improved accuracy in identification/classification of cortical lesions was demonstrated in a study combining two magnetic resonance imaging (MRI) sequences: double inversion recovery (DIR) and T1-weighted phase-sensitive inversion recovery (PSIR). Objective: To evaluate the role of intracortical lesions (IC) in MS-related CI and compare it with the role of mixed (MX), juxtacortical (JX), the sum of IC + MX and with total lesions as detected on DIR/PSIR images. Correlations between CI and brain atrophy, disease severity and disease duration were also sought. Methods: A total of 39 patients underwent extensive neuropsychological testing and were classified into normal and impaired groups. Images were obtained on a 3T scanner and cortical lesions were assessed blind to the cognitive status of the subjects. Results: Some 238 cortical lesions were identified (130 IC, 108 MX) in 82% of the patients; 39 JX lesions were also identified. Correlations between CI and MX lesions alone ( p = 0.010) and with the sum of IC + MX lesions ( p = 0.030) were found. A correlation between severity of CI and Expanded Disability Status Scale was also seen ( p = 0.009). Conclusion: Cortical lesions play an important role in CI. However, our results suggest that lesions that remain contained within the cortical ribbon do not play a more important role than ones extending into the adjacent white matter; furthermore, the size of the cortical lesion, and not the tissue-specific location, may better explain their correlation with CI.
GenDrux: A biomedical literature search system to identify gene expression-based drug sensitivity in breast cancer
Authors: Crasto Chiquito , Luo Dajie , Yu Feliciano , Forero Andres , Chen Dongquan 
Published: May 2011

Abstract

Background
This paper describes the development of a web-based tool, GenDrux, which extracts and presents (over the Internet) information related to the disease-gene-drug nexus. This information is archived from the relevant biomedical literature using automated methods. GenDrux is designed to alleviate the difficulties of manually processing the vast biomedical literature to identify disease-gene-drug relationships. GenDrux will evolve with the literature without additional algorithmic modifications.

Results
GenDrux, a pilot system, is developed in the domain of breast cancer and can be accessed at http://www.microarray.uab.edu/drug_gene.pl. GenDrux can be queried based on drug, gene and/or disease name. From over 8,000 relevant abstracts from the biomedical literature related to breast cancer, we have archived a corpus of more than 4,000 articles that depict gene expression-drug activity relationships for breast cancer and related cancers. The archiving process has been automated.

Conclusions
The successful development, implementation, and evaluation of this and similar systems when created may provide clinicians with a tool for literature management, clinical decision making, thus setting the platform for personalized therapy in the future.
AP-1 protein induction during monopoiesis favors C/EBP: AP-1 heterodimers over C/EBP homodimerization and stimulates FosB transcription
Authors: Hong SunHwa , Skaist Alyza M , Wheelan Sarah J , Friedman Alan D 
Published: May 2011

ABSTRACTAP-1 proteins heterodimerize via their LZ domains to bind TGACGTCA or TGACTCA, whereas C/EBPs dimerize to bind ATTGCGCAAT. We demonstrate that intact C/EBPα also heterodimerizes with c-Jun or c-Fos to bind a hybrid DNA element, TGACGCAA, or more weakly to TGATGCAA. A 2:1 ratio of c-Jun:C/EBPα or c-Fos:C/EBPα was sufficient for preferential binding. Semiquantitative Western blot analysis indicates that the summation of c-Jun, JunB, and c-Fos levels in differentiating myeloid cells is similar to or exceeds the entirety of C/EBPα and C/EBPβ, indicating the feasibility of heterodimer formation. Induction of AP-1 proteins during monocytic differentiation favored formation of C/EBP:AP-1 heterodimers, with C/EBPα homodimers more evident during granulopoiesis. Approximately 350 human and 300 murine genes contain the TGACGCAA motif between –2 kb and +1 kb of their transcription start sites. We focused on the murine Fosb promoter, which contains a C/EBP:AP-1 cis element at –56 and –253, with the hFOSB gene containing an identical site at –253 and a 1-bp mismatch at –56. C/EBPα:AP-1 heterodimers bound either site preferentially in a gel-shift assay, C/EBPα:c-Fos ER fusion proteins induced endogenous Fosb mRNA but not in the presence of CHX, C/EBP and AP-1 proteins bound the endogenous Fosb promoter, mutation of the –56 cis element reduced reporter activity fivefold, and endogenous FosB protein was expressed preferentially during monopoiesis versus granulopoiesis. Increased expression of Jun/Fos proteins elevates C/EBP:AP-1 heterodimer formation to potentially activate novel sets of genes during monopoiesis and potentially during other biologic processes.
Mutational analysis of the necdin gene in patients with congenital isolated hypogonadotropic hypogonadism
Authors: Beneduzzi Daiane , Iyer Anita K , Trarbach Ericka Barbosa , Silveira-Neto Acacio P , Silveira Letícia G , Tusset Cintia , Yip Kathleen , Mendonça Berenice B , Mellon Pamela L , Latronico Ana Claudia 
Published: May 2011

ContextNecdin activates GNRH gene expression and is fundamental for the development, migration, and axonal extension of murine GNRH neurons. In humans, necdin plays a potential role in the hypogonadotropic hypogonadism phenotype in patients with Prader–Willi syndrome.AimTo investigate necdin gene (NDN) variants in patients with isolated hypogonadotropic hypogonadism (IHH).Patients and methodsWe studied 160 Brazilian patients with IHH, which includes 92 with Kallmann syndrome and 68 with normosmic IHH. Genomic DNA was extracted and the single NDN exon was amplified and sequenced. To measure GNRH transcriptional activity, luciferase reporter plasmids containing GNRH regulatory regions were transiently transfected into GT1-7 cells in the presence and absence of overexpressed wild-type or mutant necdin.ResultsA heterozygous variant of necdin, p.V318A, was identified in a 23-year-old male with Kallmann syndrome. The p.V318A was also present in affected aunt and his father and was absent in 100 Brazilian control subjects. Previous FGFR1 gene analysis revealed a missense mutation (p.P366L) in this family. Functional studies revealed a minor difference in the activation of GNRH transcription by mutant protein compared with wild type in that a significant impairment of the necdin protein activity threshold was observed.ConclusionA rare variant of necdin (p.V318A) was described in a family with Kallmann syndrome associated with a FGFR1 mutation. Familial segregation and in vitro analysis suggested that this non-synonymous variant did not have a direct causative role in the hypogonadism phenotype. NDN mutations are not a frequent cause of congenital IHH.
Plant Genetics, Sustainable Agriculture and Global Food Security
Authors: Ronald Pamela 
Published: May 2011

Abstract
The United States and the world face serious societal challenges in the areas of food, environment, energy, and health. Historically, advances in plant genetics have provided new knowledge and technologies needed to address these challenges. Plant genetics remains a key component of global food security, peace, and prosperity for the foreseeable future. Millions of lives depend upon the extent to which crop genetic improvement can keep pace with the growing global population, changing climate, and shrinking environmental resources. While there is still much to be learned about the biology of plant–environment interactions, the fundamental technologies of plant genetic improvement, including crop genetic engineering, are in place, and are expected to play crucial roles in meeting the chronic demands of global food security. However, genetically improved seed is only part of the solution. Such seed must be integrated into ecologically based farming systems and evaluated in light of their environmental, economic, and social impacts—the three pillars of sustainable agriculture. In this review, I describe some lessons learned, over the last decade, of how genetically engineered crops have been integrated into agricultural practices around the world and discuss their current and future contribution to sustainable agricultural systems.
Comparison of two tourniquets and determination of amikacin sulfate concentrations after metacarpophalangeal joint lavage performed simultaneously with intravenous regional limb perfusion in horses
Authors: Alkabes Stephane B. , Adams Stephen B. , Moore George E. , Alkabes Kira C. 
Published: May 2011

Abstract
Objective—To determine whether joint lavage performed simultaneously with IV regional limb perfusion (IVRLP) reduces the effectiveness of IVRLP and to compare 2 types of tourniquets used for this procedure in horses.
Animals—11 adult horses.
Procedures—2 groups of 6 horses were tested by use of a pneumatic or an Esmarch tourniquet (1 horse was tested twice [once in each group]). Standing IVRLP with amikacin (500 mg) was performed for 30 minutes. Simultaneously, the metacarpophalangeal joint was lavaged with 2 L of lactated Ringer's solution and the egress fluids were collected. Samples of the distal interphalangeal joint synovial fluid and blood from the digital and jugular veins were collected at set time intervals. Amikacin concentrations in all fluids were determined via fluorescence polarization immunoassay.
Results—Less amikacin was measured in the systemic circulation with the Esmarch tourniquet than with the pneumatic tourniquet. Amikacin concentrations in the synovial fluid from the distal interphalangeal joints of the Esmarch tourniquet group ranged from 45.1 to 1,968 μg/mL and in the pneumatic tourniquet group ranged from 1.7 to 92.3 μg/mL after 30 minutes of IVRLP. Total loss of amikacin in the egress fluids from the joint lavage ranged from < 1.36 to 7.72 mg for the Esmarch tourniquet group and from < 1.20 to 1.75 mg for the pneumatic tourniquet group.
Conclusions and Clinical Relevance—On standing horses, IVRLP performed simultaneously with joint lavage resulted in negligible loss of amikacin in the egress lavage fluids. The Esmarch tourniquet was more effective in preventing loss of amikacin from the distal portion of the limb, easier to use, and less expensive than the pneumatic tourniquet.
Associations among behavioral and acute physiologic responses to lipopolysaccharide-induced clinical mastitis in lactating dairy cows
Authors: Zimov Jennifer L. , Botheras Naomi A. , Weiss William P. , Hogan Joseph S. 
Published: May 2011

Abstract
Objective—To examine behavioral and physiologic effects of lipopolysaccharide (LPS)-induced mastitis in lactating dairy cows.
Animals—20 Holstein cows.
Procedures—Cows were assigned to 5 blocks (4 cows/block) on the basis of parity and number of days in lactation. Intramammary infusion and IV treatments were assigned in a 2 × 2 factorial arrangement. Cows within each block were assigned to receive intramammary infusion with 25 μg of LPS or sterile PBS solution 3 hours after milking, and treatment with flunixin meglumine or sterile PBS solution was administered IV 4 hours after intramammary infusion. Video monitoring was continuously performed during the study.
Results—LPS-infused cows spent less time during the first 12 hours after infusion lying, eating, and chewing cud, compared with results for PBS solution-infused cows. Behavioral responses were correlated with physiologic responses for the first 12 hours after intramammary infusion. Flunixin meglumine administration after intramammary infusion mitigated some behavioral and clinical systemic responses.
Conclusions and Clinical Relevance—Intramammary infusion of LPS caused changes in both behavioral and physiologic variables in lactating dairy cows. Time spent lying, eating, and chewing cud were negatively correlated with physiologic responses in cows. Evaluation of behavior patterns may provide an ancillary measure, along with evaluation of physiologic variables, for monitoring well-being, clinical responses, and recovery from acute clinical mastitis.
Effects of industrial polystyrene foam insulation pads on the center of pressure and load distribution in the forefeet of clinically normal horses
Authors: Schleining Jennifer A. , McClure Scott R. , Derrick Timothy R. , Wang Chong 
Published: May 2011

Abstract
Objective—To evaluate the ability of industrial polystyrene foam insulation pads to redistribute loads placed on clinically normal weight-bearing structures of the foot and shift the location of the center of pressure palmarly in horses.
Animals—25 nonlame mature horses.
Procedures—Both forefeet from each horse were evaluated. Center of pressure data and solar load distribution patterns were recorded during a 5-second trial by use of a commercial pressure measurement system prior to placement of foam sole support and at 0, 6, 12, 24, and 48 hours after placement. Total contact surface area, contact pressure, peak contact pressure, and center of pressure positions were compared by use of a linear mixed model with repeated measurements.
Results—Total contact surface area was increased significantly at all time points, whereas contact pressure and peak contact pressure were significantly decreased at all time points following application of foam sole supports. Immediately following application of sole support, the position of the center of pressure was significantly moved cranially. However, by 48 hours, the center of pressure was significantly positioned more palmarly than prior to application of the foam supports.
Conclusions and Clinical Relevance—Results indicated that the use of foam sole supports may be an effective, economical, and immediate treatment for acute laminitis.