bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenomic Prediction of Anthracycline-Induced Cardiotoxicity in Children
Authors: Visscher Henk , Ross Colin J.D. , Rassekh S. Rod , Barhdadi Amina , Dubé Marie-Pierre , Al-Saloos Hesham , Sandor George S. , Caron Huib N. , van Dalen Elvira C. , Kremer Leontien C. , van der Pal Helena J. , Brown Andrew M.K. , Rogers Paul C. , Phillips Michael S. , Rieder Michael J. , Carleton Bruce C. , Hayden Michael R. ,   Canadian Pharmacogenomics Network for Drug Safety Consortium
Published: September 2011

Purpose Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity and mortality. Our aim was to identify genetic variants associated with ACT in patients treated for childhood cancer. Patients and Methods We carried out a study of 2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug biotransformation genes in a discovery cohort of 156 anthracycline-treated children from British Columbia, with replication in a second cohort of 188 children from across Canada and further replication of the top SNP in a third cohort of 96 patients from Amsterdam, the Netherlands. Results We identified a highly significant association of a synonymous coding variant rs7853758 (L461L) within the SLC28A3 gene with ACT (odds ratio, 0.35; P = 1.8 × 10−5 for all cohorts combined). Additional associations (P < .01) with risk and protective variants in other genes including SLC28A1 and several adenosine triphosphate–binding cassette transporters (ABCB1, ABCB4, and ABCC1) were present. We further explored combining multiple variants into a single-prediction model together with clinical risk factors and classification of patients into three risk groups. In the high-risk group, 75% of patients were accurately predicted to develop ACT, with 36% developing this within the first year alone, whereas in the low-risk group, 96% of patients were accurately predicted not to develop ACT. Conclusion We have identified multiple genetic variants in SLC28A3 and other genes associated with ACT. Combined with clinical risk factors, genetic risk profiling might be used to identify high-risk patients who can then be provided with safer treatment options.
Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epidermal Growth Factor Receptor, in Patients With Advanced Solid Tumors
Authors: Paz-Ares Luis G. , Gomez-Roca Carlos , Delord Jean-Pierre , Cervantes Andres , Markman Ben , Corral Jesus , Soria Jean-Charles , Bergé Yann , Roda Desamparados , Russell-Yarde Fiona , Hollingsworth Simon , Baselga José , Umana Pablo , Manenti Luigi , Tabernero Josep 
Published: September 2011

Purpose We conducted a phase I dose-escalation study to characterize the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), a humanized and glycoengineered immunoglobulin G1 anti–epidermal growth factor receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity. Patients and Methods Seventy-five patients with advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus-three trial design. Results No maximum-tolerated dose was reached for any dosing schedule. Common adverse events (AEs) included rash (80% of patients), infusion-related reactions (77%), and hypomagnesemia (56%). Grades 3 and 4 AEs were rash (grade 3, 25%), infusion-related reaction (grade 3, 7%; grade 4, 1%), paronychia (grade 3, 3%), and hypomagnesemia (grade 3, 1%; grade 4, 1%). RG7160 exposure increased greater than proportionally over the 50- to 400-mg dose range (with greater than proportional decline in clearance) and approximately dose proportionally above 400 mg (where clearance plateaued). A marked reduction in circulating natural killer cells and increased infiltration of immune effector cells into skin rash were seen. Clinical efficacy included one complete response and two partial responses in patients with colorectal cancer (including one with KRAS mutation) and disease stabilization in 27 patients. Conclusion RG7160 had an acceptable safety profile with manageable AEs and demonstrated promising efficacy in this heavily pretreated patient cohort. On the basis of modeling of available PK parameters, the RG7160 dose selected for part two of this study is 1,400 mg on days 1 and 8 followed by 1,400 mg every 2 weeks.
American Society of Clinical Oncology Endorsement of the Cancer Care Ontario Practice Guideline on Adjuvant Ovarian Ablation in the Treatment of Premenopausal Women With Early-Stage Invasive Breast Cancer
Authors: Griggs Jennifer J. , Somerfield Mark R. , Anderson Holly , Henry N. Lynn , Hudis Clifford A. , Khatcheressian James L. , Partridge Ann H. , Prestrud Ann Alexis , Davidson Nancy E. 
Published: September 2011

Purpose The American Society of Clinical Oncology (ASCO) has policies and procedures for endorsing practice guidelines that have been developed by other professional organizations. Methods The Cancer Care Ontario (CCO) Guideline on Adjuvant Ovarian Ablation (OA) in the Treatment of Premenopausal Women With Early-Stage Invasive Breast Cancer was reviewed for developmental rigor by methodologists. An ad hoc review panel of experts reviewed the content. Results The ASCO ad hoc OA guideline review panel concurred that the recommendations are clear, thorough, based on the most relevant scientific evidence in this content area, and present options that will be acceptable to patients. According to the CCO guideline: one, OA should not be routinely added to systemic therapy with chemotherapy, tamoxifen, or the combination of tamoxifen and chemotherapy; two, OA alone is not recommended as an alternative to any other form of systemic therapy, except in the specific case of patients who are candidates for other forms of systemic therapy but who, for some reason, will not receive any other systemic therapy (eg, patients who cannot tolerate other forms of systemic therapy or patients who choose no other form of systemic therapy); and three, when chemical suppression using luteinizing hormone–releasing hormone agonists is the chosen method of OA, in the opinion of the Breast Cancer Disease Site Group, monthly injection is the recommended mode of administration. The mode of administration in nearly all of the available trials has been monthly administration. Conclusion The ASCO review panel agrees with the recommendations as stated in the CCO guideline, with the qualification that ongoing research studies may alter the recommendations of the panel.
Pulmonary compliance and lung volume varies with ecomorphology in anuran amphibians: implications for ventilatory-assisted lymph flux
Authors: Hedrick Michael S. , Hillman Stanley S. , Drewes Robert C. , Withers Philip C. 
Published: September 2011

SUMMARY
Vertical movement of lymph from ventral regions to the dorsally located lymph hearts in anurans is accomplished by specialized skeletal muscles working in concert with lung ventilation. We hypothesize that more terrestrial species with greater lymph mobilization capacities and higher lymph flux rates will have larger lung volumes and higher pulmonary compliance than more semi-aquatic or aquatic species. We measured in situ mean and maximal compliance (Δvolume/Δpressure), distensibility (%Δvolume/Δpressure) and lung volume over a range of physiological pressures (1.0 to 4.0 cmH2O) for nine species of anurans representing three families (Bufonide, Ranidae and Pipidae) that span a range of body masses and habitats from terrestrial to aquatic. We further examined the relationship between these pulmonary variables and lymph flux for a semi-terrestrial bufonid (Rhinella marina), a semi-aquatic ranid (Lithobates catesbeianus) and an aquatic pipid (Xenopus laevis). Allometric scaling of pulmonary compliance and lung volume with body mass showed significant differences at the family level, with scaling exponents ranging from ∼0.75 in Bufonidae to ∼1.3 in Pipidae. Consistent with our hypothesis, the terrestrial Bufonidae species had significantly greater pulmonary compliance and greater lung volumes compared with semi-aquatic Ranidae and aquatic Pipidae species. Pulmonary distensibility ranged from ∼20 to 35% cmH2O–1 for the three families but did not correlate with ecomorphology. For the three species for which lymph flux data are available, R. marina had a significantly higher (P&lt;0.001) maximal compliance (84.9±2.7 ml cmH2O–1 kg–1) and lung volume (242.1±5.5 ml kg–1) compared with L. catesbeianus (54.5±0.12 ml cmH2O–1 kg–1 and 139.3±0.5 ml kg–1) and X. laevis (30.8±0.7 ml cmH2O–1 kg–1 and 61.3±2.5 ml kg–1). Lymph flux rates were also highest for R. marina, lowest for X. laevis and intermediate in L. catesbeianus. Thus, there is a strong correlation between pulmonary compliance, lung volume and lymph flux rates, which suggests that lymph mobilization capacity may explain some of the variation in pulmonary compliance and lung volume in anurans.
Social control of unreliable signals of strength in male but not female crayfish,Cherax destructor
Authors: Walter Gregory M. , van Uitregt Vincent O. , Wilson Robbie S. 
Published: September 2011

SUMMARYThe maintenance of unreliable signals within animal populations remains a highly controversial subject in studies of animal communication. Crustaceans are an ideal group for studying unreliable signals of strength because their chela muscles are cryptically concealed beneath an exoskeleton, making it difficult for competitors to visually assess an opponent's strength. In this study, we examined the importance of social avenues for mediating the possible advantages gained by unreliable signals of strength in crustaceans. To do this, we investigated the factors that determine social dominance and the relative importance of signalling and fighting during aggressive encounters in male and female freshwater crayfish, Cherax destructor. Like other species of crayfish, we expected substantial variation in weapon force for a given weapon size, making the assessment of actual fighting ability of an opponent difficult from signalling alone. In addition, we expected fighting would be used to ensure that individuals that are weak for their signal (i.e. chela) size would not achieve higher than expected dominance. For both male and female C. destructor, we found large variation in the actual force of their chela for any given weapon size, indicating that it is difficult for competitors to accurately assess an opponent's force on signal size alone. For males, these unreliable signals of strength were controlled socially through increased levels of fighting and a decreased reliance on signalling, thus directly limiting the benefits accrued to individuals employing high-quality signals (large chelae) with only low resource holding potential. However, in contrast to our predictions, we found that females primarily relied on signalling to settle disputes, resulting in unreliable signals of strength being routinely used to establish dominance. The reliance by females on unreliable signals to determine dominance highlights our poor current understanding of the prevalence and distribution of dishonesty in animal communication.
Forelimb kinematics and motor patterns of swimming loggerhead sea turtles (Caretta caretta): are motor patterns conserved in the evolution of new locomotor strategies?
Authors: Rivera Angela R. V. , Wyneken Jeanette , Blob Richard W. 
Published: September 2011

SUMMARYNovel functions in animals may evolve through changes in morphology, muscle activity or a combination of both. The idea that new functions or behavior can arise solely through changes in structure, without concurrent changes in the patterns of muscle activity that control movement of those structures, has been formalized as the neuromotor conservation hypothesis. In vertebrate locomotor systems, evidence for neuromotor conservation is found across evolutionary transitions in the behavior of terrestrial species, and in evolutionary transitions from terrestrial species to flying species. However, evolutionary transitions in the locomotion of aquatic species have received little comparable study to determine whether changes in morphology and muscle function were coordinated through the evolution of new locomotor behavior. To evaluate the potential for neuromotor conservation in an ancient aquatic system, we quantified forelimb kinematics and muscle activity during swimming in the loggerhead sea turtle, Caretta caretta. Loggerhead forelimbs are hypertrophied into wing-like flippers that produce thrust via dorsoventral forelimb flapping. We compared kinematic and motor patterns from loggerheads with previous data from the red-eared slider, Trachemys scripta, a generalized freshwater species exhibiting unspecialized forelimb morphology and anteroposterior rowing motions during swimming. For some forelimb muscles, comparisons between C. caretta and T. scripta support neuromotor conservation; for example, the coracobrachialis and the latissimus dorsi show similar activation patterns. However, other muscles (deltoideus, pectoralis and triceps) do not show neuromotor conservation; for example, the deltoideus changes dramatically from a limb protractor/elevator in sliders to a joint stabilizer in loggerheads. Thus, during the evolution of flapping in sea turtles, drastic restructuring of the forelimb was accompanied by both conservation and evolutionary novelty in limb motor patterns.
Long-term olfactory memories are stabilised via protein synthesis in Camponotus fellah ants
Authors: Guerrieri Fernando J. , d'Ettorre Patrizia , Devaud Jean-Marc , Giurfa Martin 
Published: September 2011

SUMMARY
Ants exhibit impressive olfactory learning abilities. Operant protocols in which ants freely choose between rewarded and non-rewarded odours have been used to characterise associative olfactory learning and memory. Yet, this approach precludes the use of invasive methods allowing the dissection of molecular bases of learning and memory. An open question is whether the memories formed upon olfactory learning that are retrievable several days after training are indeed based on de novo protein synthesis. Here, we addressed this question in the ant Camponotus fellah using a conditioning protocol in which individually harnessed ants learn an association between odour and reward. When the antennae of an ant are stimulated with sucrose solution, the insect extends its maxilla–labium to absorb the solution (maxilla–labium extension response). We differentially conditioned ants to discriminate between two long-chain hydrocarbons, one paired with sucrose and the other with quinine solution. Differential conditioning leads to the formation of a long-term memory retrievable at least 72 h after training. Long-term memory consolidation was impaired by the ingestion of cycloheximide, a protein synthesis blocker, prior to conditioning. Cycloheximide did not impair acquisition of either short-term memory (10 min) or early and late mid-term memories (1 or 12 h). These results show that, upon olfactory learning, ants form different memories with variable molecular bases. While short- and mid-term memories do not require protein synthesis, long-term memories are stabilised via protein synthesis. Our behavioural protocol opens interesting research avenues to explore the cellular and molecular bases of olfactory learning and memory in ants.
Deciphering a methylome: what can we read into patterns of DNA methylation?
Authors: Flores Kevin B. , Amdam Gro V. 
Published: September 2011

Summary
The methylation of cytosines within cytosine–guanine (CG) dinucleotides is an epigenetic mark that can modify gene transcription. With the advent of high-throughput sequencing, it is possible to map methylomes, i.e. detect methylated CGs on a genome-wide scale. The methylomes sequenced to date reveal a divergence in prevalence and targeting of CG methylation between taxa, despite the conservation of the DNA methyltransferase enzymes that cause DNA methylation. Therefore, interspecific methylation usage is predicted to diverge. In various taxa, this tenet gains support from patterns of CG depletion that can be traced in DNA before methylomes are explicitly mapped. Depletion of CGs in methylated genomic regions is expected because methylated cytosines are subject to increased mutability caused by nucleotide deamination. However, the basis of diverging interspecific methylation usage is less clear. We use insights from the methylome of honeybees (Apis mellifera) to emphasize the possible importance of organismal life histories in explaining methylation usage and the accuracy of methylation prediction based on CG depletion. Interestingly, methylated genes in honeybees are more conserved across taxa than non-methylated genes despite the divergence in utilization of methylation and the increased mutability caused by deamination.
Comparison of Intravenous Immunoglobulin Formulations: Product Formulary, and Cost Considerations
Authors: Mark Scott M. 
Published: September 2011

Purpose A review of the different formulations of intravenous immunoglobulin (IVIG) replacement therapy for primary immunodeficiency and other severe diseases, focusing on the comparative efficacy, safety, and tolerability of these formulations. This review discusses the manufacturing processes, physicochemical properties, and other attributes of IVIG therapy that affect its clinical utility. Summary IVIG therapy is a preferred treatment for patients with certain types of primary immunodeficiency, neuroimmunologic, and autoimmune hematologic disorders, as well as for immunomodulation in bone marrow and some solid organ transplants. The IVIG products available in the United States include lyophilized, 5% liquid, and 10% ready-to-use liquid formulations. Differences among these formulations in their manufacturing processes, excipients, pH, and physicochemical properties may be reflected as differences in clinical efficacy, safety, and tolerability. For example, compared with lyophilized and 5% liquid IVIG formulations, 10% ready-to-use IVIG liquid formulations may be associated with better tolerability because of lower IgA concentrations, optimal pH, use of glycine or proline stabilizers, low sodium content, and less osmolality. Liquid formulations (both 5% and 10%) may provide greater convenience than lyophilized formulations for both patients and health care providers, because they do not require further dilution before administration and have shorter infusion times. Conclusion Before selecting an IVIG product for a hospital formulary, pharmacists should be knowledgeable about the product's concentration to ensure delivery of the proper dosage, the staff training needed for proper administration, the potential benefits and problems of brand substitution, the safety and efficacy of each formulation, the hospital's policies on off-label use of IVIG, and the impact of reimbursement.
Cost Savings Associated with a Dedicated Drug Information Service in an Academic Medical Center
Authors: Brown Jamie N. 
Published: September 2011

Objectives Document interventions made by a drug information center affiliated with a single academic medical center and calculate the cost avoidance associated with the identified interventions. Methods All drug information requests received by the drug information center from January 1, 2008 through December 31, 2008 were reviewed. Responses were put into an economic model for cost avoidance, and avoidance of research time was calculated for each profession. Results The drug information center documented 270 drug information requests during the study period. Pharmacists were the heaviest users of the drug information center, and the most common classification of drug information questions asked were therapeutic evaluations. There were 186 drug information responses that met the economic model definition for a patient-specific intervention, totaling an estimated cost avoidance of $130,200. In regard to research time savings, the drug information center invested a total of 554.4 research hours into question responses, associated with a total workload savings of $27,283 in research time avoided. Conclusion A beneficial effect of having a dedicated drug information center was demonstrated at an academic tertiary care teaching medical center. Cost avoidance calculations for all interventions and research time avoided totaled $157,483 for the 1-year study period.
Heavy Drinking and Use of Sedative or Anxiolytic Drugs Among Aging Men: An II-Year Follow-Up of the FinDrink Study
Authors: Ilomäki Jenni , Bell J Simon , Kauhanen Jussi , Enlund Hannes 
Published: September 2011

Background: Most studies on heavy drinking and sedative/anxiolytic drug use have been cross-sectional, and evidence for a possible temporal association is lacking. Objective: To prospectively investigate whether heavy drinking predicts initiation, continuation, or discontinuation of sedative/anxiolytic drugs at 4 arid 11 years and, conversely, whether sedative/anxiolytic drug use predicts heavy drinking. Method: This was a longitudinal population-based study conducted in Kuopio, Finland, An age-stratified random sample of 1516 men aged 42, 48, 54, and 60 years received a structured clinical examination at baseline (August 1986-December 1989). Follow-up clinical examinations were conducted at 4 (n − 1038) and 11 (n = 854) years. Multinomial logistic regression was used to compute odds ratios and 95% confidence intervals for the association between sedative/anxiolytic drug use and initiation, continuation, and discontinuation of heavy drinking (≥14 drinks/wk). The reverse association between heavy drinking and sedative/anxiolytic drug use was also investigated. Regression models were adjusted for age, working status, smoking, and depressive symptoms. Results: At baseline 12.9% (134/1038) of participants were heavy drinkers and 4.0% (41/1030) used sedative/anxiolytic drugs. In multivariate analyses, baseline heavy drinking predicted initiation of sedative/anxiolytic drug use at 4 years (OR 2.96; 95% CI 1.23 to 7.15). Conversely, baseline sedative/anxiolytic drug use predicted continuation of heavy drinking at 11 years in unadjusted analysis (OR 3.30; 95% CI 1.19 to 8.44). However, the association was not statistically significant in adjusted analyses (OR 2.69; 95% CI 0.86 to 8.44). Conclusions: The main finding of this study was the association between heavy drinking and subsequent initiation of sedative/anxiolytic drugs that was not fully explained by baseline depressive symptoms. This may inform strategies to optimize the use of sedative/anxiolytic drugs, and assist in the early identification of patients at risk of heavy drinking. Clinicians should consider a patent's alcohol consumption prior to prescribing or dispensing sedative/anxiolytic drugs. Clinicians should also monitor patients prescribed sedative/anxiolytic drugs for subsequent heavy drinking.
Der Gebrauch der typographischen Zeichen und der Interpunktionszeichen im Französischen, Deutschen und Rumänischen
Authors: Sinner Carsten 
Published: September 2011

AbstractPunctuation marks have special importance in bringing out the meaning of a text. Nonetheless, they are not normally taken into consideration in text production in foreign languages and therefore constitute a strong source of interference. This article analyses the use of a series of punctuation marks (hyphen, quotation marks, etc.) in French, German and Romanian, highlighting the differences and trying to give explanations for the abuse of several signs in texts in the different languages written by non-native and native authors. Evidence is given that the use of the punctuation marks in a foreign language following the norms of the mother tongue may produce misunderstandings on behalf of native readers. Furthermore, it can be shown that the prescriptive and descriptive grammars of the implied languages do not represent current tendencies of use.