bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin
Authors: Bertin Gwladys , Briand Valérie , Bonaventure Diana , Carrieu Ambre , Massougbodji Achille , Cot Michel , Deloron Philippe 
Published: July 2011

Abstract

Background
The prevention of malaria faces with the repeated emergence of Plasmodium falciparum resistance to drugs, often involving point mutations of the target gene. In the pregnant woman, currently the WHO recommendation is the administration of an intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine. Sulphadoxine-pyrimethamine (SP) resistance has increased for several years in Africa, stressing the need for alternative molecules. In this context, the first randomized clinical trial comparing the efficacy of SP and mefloquine for IPTp has been conducted recently in Benin. Using samples from this trial, the current study evaluated and quantified the prevalence of mutations on the pfdhfr and pfdhps genes as well as the copy number of the pfmdr1 gene in parasites from P. falciparum-infected pregnant women before first and second IPTp administration, and at delivery.

Methods
PCR-restriction fragment length polymorphism of polymorphic codons of the pfdhfr gene (51, 59, 108, and 164) was performed. The identification of mutations in three codons of the pfdhps gene (436, 437 and 540) was achieved by PCR and sequencing. Copy number quantification for pfmdr1 gene was performed using real-time PCR.

Results
Results show a high prevalence rate of mutant parasites in women taking IPTp with sulphadoxine-pyrimethamine or mefloquine. The prevalence of triple and quadruple mutants was high before first drug regimen administration (79/93, 85%), and remained similar until delivery. Infection with mutant parasites was not correlated with low birth weight nor placental infection. In all samples, the copy number of pfmdr1 gene was equal to one.

Conclusions
The clinical trial comparing SP and mefloquine efficacy during IPTp showed SP remained efficacious in preventing low birth weight. The present study shows a high prevalence of triple and quadruple mutations implicated in SP resistance. Although the pfdhfr/pfdhps triple and quadruple mutations were frequent, there was no evidence of correlation between these genotypes and the lack of efficacy of SP in the context of IPTp. Nevertheless, it is now obvious that SP will soon be compromised in whole Africa. Molecular markers have been recommended to monitor SP efficacy for IPTp, but given the current prevalence of mutant parasites their usefulness is questionable.
Follow-up study on lead exposure in children living in a smelter community in northern Mexico
Authors: Rubio-Andrade Marisela , Valdés-Pérezgasga Francisco , Alonso J , Rosado Jorge L , Cebrián Mariano E , García-Vargas Gonzalo G 
Published: July 2011

Abstract

Background
To study the changes of children lead exposure in the city of Torreon during the last five years, after environmental and public health interventions, using the timeline of lead in blood concentration as the biomarker of exposure and its relation to lead in soil concentrations.

Methods
This follow-up study started in 2001 and consisted of 232 children living in nine neighborhoods in Torreon. Children were tested at 0, 6, 12 and 60 months. Lead in blood concentrations, Hemoglobin, Zinc-Protoporphyrin, anthropometric measures and socioeconomic status questionnaire was supplied to the parents.

Results
Median and range of lead in blood concentrations obtained at 0, 6, 12, 60 months were: 10.12 μg/dl (1.9 - 43.8), 8.75 μg/dl (1.85 - 41.45), 8.4 μg/dl (1.7 - 35.8) and 4.4 μg/dl (1.3 - 30.3), respectively. The decrease of lead in blood levels was significantly related to ages 0, 6, 12 and 60 months of the follow-up study. The timeline of B-Pb was associated with the timeline of lead in soil concentrations.

Conclusions
B-Pb levels have significantly decreased in the group of children studied. This could be explained by a) environmental interventions by authorities and the smelter companies, b) normal changes in hygienic habits as children age and c) lead redistribution from blood to hard tissues.
Development of a PCR Assay to detect Papillomavirus Infection in the Snow Leopard
Authors: Mitsouras Katherine , Faulhaber Erica A , Hui Gordon , Joslin Janis O , Eng Curtis , Barr Margaret C , Irizarry Kristopher JL 
Published: July 2011

Abstract

Background
Papillomaviruses (PVs) are a group of small, non-encapsulated, species-specific DNA viruses that have been detected in a variety of mammalian and avian species including humans, canines and felines. PVs cause lesions in the skin and mucous membranes of the host and after persistent infection, a subset of PVs can cause tumors such as cervical malignancies and head and neck squamous cell carcinoma in humans. PVs from several species have been isolated and their genomes have been sequenced, thereby increasing our understanding of the mechanism of viral oncogenesis and allowing for the development of molecular assays for the detection of PV infection. In humans, molecular testing for PV DNA is used to identify patients with persistent infections at risk for developing cervical cancer. In felids, PVs have been isolated and sequenced from oral papillomatous lesions of several wild species including bobcats, Asian lions and snow leopards. Since a number of wild felids are endangered, PV associated disease is a concern and there is a need for molecular tools that can be used to further study papillomavirus in these species.

Results
We used the sequence of the snow leopard papillomavirus UuPV1 to develop a PCR strategy to amplify viral DNA from samples obtained from captive animals. We designed primer pairs that flank the E6 and E7 viral oncogenes and amplify two DNA fragments encompassing these genes. We detected viral DNA for E6 and E7 in genomic DNA isolated from saliva, but not in paired blood samples from snow leopards. We verified the identity of these PCR products by restriction digest and DNA sequencing. The sequences of the PCR products were 100% identical to the published UuPV1 genome sequence.

Conclusions
We developed a PCR assay to detect papillomavirus in snow leopards and amplified viral DNA encompassing the E6 and E7 oncogenes specifically in the saliva of animals. This assay could be utilized for the molecular investigation of papillomavirus in snow leopards using saliva, thereby allowing the detection of the virus in the anatomical site where oral papillomatous lesions develop during later stages of infection and disease development.
Histological subtype is the most important determinant of survival in metastatic papillary thyroid cancer
Authors: Chrisoulidou Alexandra , Boudina Maria , Tzemailas Athanasios , Doumala Eleni , Iliadou Pashalia K , Patakiouta Frideriki , Pazaitou-Panayiotou Kalliopi 
Published: July 2011

Abstract

Background
Papillary thyroid cancer (PTC) comprises the commonest type of thyroid cancer and carries the highest rate of survival. However, when metastatic disease occurs, survival is significantly affected.

Methods
We aimed to identify prognostic histopathological and clinical factors that modify survival in metastatic PTC. All cases of metastatic PTC treated at our department in the last 20 years were reviewed and analyzed.

Results
Histological subtype was the most important determinant of survival, as classic PTC demonstrated clearly improved survival compared to follicular subtype of PTC and other less frequently seen histological subtypes. The instant risk of death for the other histological subtypes was 4.56 times higher than the risk for the classic papillary type. Overall, a 10-year survival of 76.6% in our patients was seen.

Conclusions
Patients with aggressive variants of PTC are more at risk for the development of metastatic disease. In these patients, established treatment modalities (surgery, radioiodine therapy) should be offered promptly, as well as close follow-up.
Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study
Authors: Mekontso Dessap Armand , Ouanes Islem , Rana Nerlep , Borghi Beatrice , Bazin Christophe , Katsahian Sandrine , Hulin Anne , Brun-Buisson Christian 
Published: July 2011

Abstract
Introduction
Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.

Methods
We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.

Results
Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 [6–14] vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.

Conclusions
Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
Dextromethorphan As a Phenotyping Test to Predict Endoxifen Exposure in Patients on Tamoxifen Treatment
Authors: de Graan Anne-Joy M. , Teunissen Sebastiaan F. , de Vos Filip Y.F.L. , Loos Walter J. , van Schaik Ron H.N. , de Jongh Felix E. , de Vos Aad I. , van Alphen Robbert J. , van der Holt Bronno , Verweij Jaap , Seynaeve Caroline , Beijnen Jos H. , Mathijssen Ron H.J. 
Published: July 2011

Purpose Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics. Methods In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated. Results A strong and highly significant correlation (r = −0.72; P < .001) was found between the exposures of dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration–time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = −0.70; P < .001). In a single patient using the potent CYP2D6 inhibitor paroxetine, the low endoxifen concentration was accurately predicted by dextromethorphan exposure. Conclusion Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies.
Randomized Phase II Study of Erlotinib Plus Tivantinib Versus Erlotinib Plus Placebo in Previously Treated Non–Small-Cell Lung Cancer
Authors: Sequist Lecia V. , von Pawel Joachim , Garmey Edward G. , Akerley Wallace L. , Brugger Wolfram , Ferrari Dora , Chen Yinpu , Costa Daniel B. , Gerber David E. , Orlov Sergey , Ramlau Rodryg , Arthur Susan , Gorbachevsky Igor , Schwartz Brian , Schiller Joan H. 
Published: July 2011

Purpose c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non–small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor. Methods Previously treated patients with EGFR TKI–naive advanced NSCLC were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). The primary end point was progression-free survival (PFS). At the time of progression, cross-over from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required. Results One hundred sixty-seven patients were randomly assigned to ET (n = 84) and to EP (n = 83). Median PFS was 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 (95% CI, 0.05 to 0.70; interaction P = .006). Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. There were no significant differences in adverse events between study arms. Conclusion The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with NSCLC is planned.
Clinical and Biologic Features Predictive of Survival After Relapse of Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project
Authors: London Wendy B. , Castel Victoria , Monclair Tom , Ambros Peter F. , Pearson Andrew D.J. , Cohn Susan L. , Berthold Frank , Nakagawara Akira , Ladenstein Ruth L. , Iehara Tomoko , Matthay Katherine K. 
Published: July 2011

Purpose Survival after neuroblastoma relapse is poor. Understanding the relationship between clinical and biologic features and outcome after relapse may help in selection of optimal therapy. Our aim was to determine which factors were significantly predictive of postrelapse overall survival (OS) in patients with recurrent neuroblastoma—particularly whether time from diagnosis to first relapse (TTFR) was a significant predictor of OS. Patients and Methods Patients with first relapse/progression were identified in the International Neuroblastoma Risk Group (INRG) database. Time from study enrollment until first event and OS time starting from first event were calculated. Cox regression models were used to calculate the hazard ratio of increased death risk and perform survival tree regression. TTFR was tested in a multivariable Cox model with other factors. Results In the INRG database (N = 8,800), 2,266 patients experienced first progression/relapse. Median time to relapse was 13.2 months (range, 1 day to 11.4 years). Five-year OS from time of first event was 20% (SE, ± 1%). TTFR was statistically significantly associated with OS time in a nonlinear relationship; patients with TTFR of 36 months or longer had the lowest risk of death, followed by patients who relapsed in the period of 0 to less than 6 months or 18 to 36 months. Patients who relapsed between 6 and 18 months after diagnosis had the highest risk of death. TTFR, age, International Neuroblastoma Staging System stage, and MYCN copy number status were independently predictive of postrelapse OS in multivariable analysis. Conclusion Age, stage, MYCN status, and TTFR are significant prognostic factors for postrelapse survival and may help in the design of clinical trials evaluating novel agents.
Four-Year Follow-Up of Trastuzumab Plus Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Joint Analysis of Data From NCCTG N9831 and NSABP B-31
Authors: Perez Edith A. , Romond Edward H. , Suman Vera J. , Jeong Jong-Hyeon , Davidson Nancy E. , Geyer Charles E. , Martino Silvana , Mamounas Eleftherios P. , Kaufman Peter A. , Wolmark Norman 
Published: July 2011

Purpose Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited. Patients and Methods Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis. Results At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm (P < .001). Similarly, there continues to be a statistically significant 39% reduction in death rate in favor of the trastuzumab-containing arm (P < .001). Conclusion These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date. The clinical benefits continue to outweigh the risks of adverse effects.
From the Beginnings: Debates on the History of Science in Brazil
Authors: Kropf Simone Petraglia , Hochman Gilberto 
Published: July 2011

Abstract
This article analyzes the ways in which the book Beginnings of Brazilian Science: Oswaldo Cruz, Medical Research and Policy, 1890 – 1920, published by Nancy Leys Stepan in 1976, has been received in the debates on science and the history of science in Brazil. Our purpose is to show how the discussions prompted by Stepan’s book have been directly linked to the emergence of a new historiography of science in that country since the early 1980s, as a professionalized and institutionalized scholarly field. This process has been associated, in turn, with a broader policy debate in Brazil and Spanish America on the particular features of science, and of the history of science, in the so-called developing countries. We also seek to show the extent to which some of the questions posed in The Beginnings of Brazilian Science are still richly relevant to academic and political consideration of the complexity and specificity of the historical and social process of institutionalization of science. Rather than attempt an exhaustive analysis of the readings of Stepan’s work, we will focus on the main areas of historiographic debate, based on the more representative works and authors, especially in the 1980s and 1990s.
A Complex Fabric: Intersecting Histories of Race, Gender, and Science in Latin America
Authors: Rodriguez Julia 
Published: July 2011

Abstract
This essay describes historians’ recent and growing awareness of the significance of science in modern Latin America. It focuses first on the work and influence of the historian Nancy Leys Stepan, who in the past 30 years pioneered the joining of methods in the history of science — in particular, the tendency to see science in its specific social context — with some of the most central concerns of Latin Americanists. For example, a key contribution of Stepan’s work is her analysis of scientific representations of human difference that shaped the creation and legitimating of racist and sexist ideas across Latin American societies. Moreover, her work was part of an early wave that brought the application of feminist and critical race theory to the field, with valuable outcomes. Her work has been a springboard for continuing investigations of the interplay between scientific ideas and practices and larger social forces. After an overview of Stepan’s approach and findings, the essay discusses two major trends in the literature that emerge from and build on Stepan’s work: the incorporation of sexuality along with race, gender, and class in studies of science and medicine in Latin American history; and further developments in the history of transatlantic science in the modern period.
“The Hour of Eugenics” in Veracruz, Mexico: Radical Politics, Public Health, and Latin America’s Only Sterilization Law
Authors: Stern Alexandra Minna 
Published: July 2011

Abstract
In 1932, the Mexican state of Veracruz passed Latin America’s only eugenic sterilization law. Building on the foundational scholarship of Nancy Leys Stepan, this article critically examines Veracruz’s eugenics movement, exploring how it intersected with public health, antivice campaigns, and radical agrarian and labor politics. I pay particular attention to Governor Adalberto Tejeda, who, during his second term in office (1928 – 1932) incorporated a zealous version of Latin eugenics into state laws and policies. This article suggests that Veracruz’s experiment with eugenics, especially the state’s sterilization statute, was intimately connected to concerns about prostitution, sexual health, and working-class vigor. This article highlights an unexplored dimension of society and medicine in Latin America and raises questions about the orientation and limits of preventive eugenics in Mexico, and about the homologies among eugenics movements in the Americas and across the globe in the twentieth century.