bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine
Authors: Ouattara Amed , Mu Jianbing , Takala-Harrison Shannon , Saye Renion , Sagara Issaka , Dicko Alassane , Niangaly Amadou , Duan Junhui , Ellis Ruth D , Miller Louis H , Su Xin-zhuan , Plowe Christopher V , Doumbo Ogobara K 
Published: June 2010

Abstract

Background
Extensive genetic diversity in vaccine antigens may contribute to the lack of efficacy of blood stage malaria vaccines. Apical membrane antigen-1 (AMA1) is a leading blood stage malaria vaccine candidate with extreme diversity, potentially limiting its efficacy against infection and disease caused by Plasmodium falciparum parasites with diverse forms of AMA1.

Methods
Three hundred Malian children participated in a Phase 2 clinical trial of a bivalent malaria vaccine that found no protective efficacy. The vaccine consists of recombinant AMA1 based on the 3D7 and FVO strains of P. falciparum adjuvanted with aluminum hydroxide (AMA1-C1). The gene encoding AMA1 was sequenced from P. falciparum infections experienced before and after immunization with the study vaccine or a control vaccine. Sequences of ama1 from infections in the malaria vaccine and control groups were compared with regard to similarity to the vaccine antigens using several measures of genetic diversity. Time to infection with parasites carrying AMA1 haplotypes similar to the vaccine strains with respect to immunologically important polymorphisms and the risk of infection with vaccine strain haplotypes were compared.

Results
Based on 62 polymorphic AMA1 residues, 186 unique ama1 haplotypes were identified among 315 ama1 sequences that were included in the analysis. Eight infections had ama1 sequences identical to 3D7 while none were identical to FVO. Several measures of genetic diversity showed that ama1 sequences in the malaria vaccine and control groups were comparable both at baseline and during follow up period. Pre- and post-immunization ama1 sequences in both groups all had a similar degree of genetic distance from FVO and 3D7 ama1. No differences were found in the time of first clinical episode or risk of infection with an AMA1 haplotype similar to 3D7 or FVO with respect to a limited set of immunologically important polymorphisms found in the cluster 1 loop of domain I of AMA1.

Conclusion
This Phase 2 trial of a bivalent AMA1 malaria vaccine found no evidence of vaccine selection or strain-specific efficacy, suggesting that the extreme genetic diversity of AMA1 did not account for failure of the vaccine to provide protection.
When cholesterol is not cholesterol: a note on the enzymatic determination of its concentration in model systems containing vegetable extracts
Authors: Jové Mariona , Serrano José CE , Bellmunt Maria Josep , Cassanyé Anna , Anglès Neus , Reguant Jordi , Morelló José R , Pamplona Reinald , Portero-Otín Manuel 
Published: June 2010

Abstract

Background
Experimental evidences demonstrate that vegetable derived extracts inhibit cholesterol absorption in the gastrointestinal tract. To further explore the mechanisms behind, we modeled duodenal contents with several vegetable extracts.

Results
By employing a widely used cholesterol quantification method based on a cholesterol oxidase-peroxidase coupled reaction we analyzed the effects on cholesterol partition. Evidenced interferences were analyzed by studying specific and unspecific inhibitors of cholesterol oxidase-peroxidase coupled reaction. Cholesterol was also quantified by LC/MS. We found a significant interference of diverse (cocoa and tea-derived) extracts over this method. The interference was strongly dependent on model matrix: while as in phosphate buffered saline, the development of unspecific fluorescence was inhibitable by catalase (but not by heat denaturation), suggesting vegetable extract derived H2O2 production, in bile-containing model systems, this interference also comprised cholesterol-oxidase inhibition. Several strategies, such as cholesterol standard addition and use of suitable blanks containing vegetable extracts were tested. When those failed, the use of a mass-spectrometry based chromatographic assay allowed quantification of cholesterol in models of duodenal contents in the presence of vegetable extracts.

Conclusions
We propose that the use of cholesterol-oxidase and/or peroxidase based systems for cholesterol analyses in foodstuffs should be accurately monitored, as important interferences in all the components of the enzymatic chain were evident. The use of adequate controls, standard addition and finally, chromatographic analyses solve these issues.
The clinical behavior of mixed ductal/lobular carcinoma of the breast: a clinicopathologic analysis
Authors: Suryadevara Aparna , Paruchuri Lakshmi P , Banisaeed Nassim , Dunnington Gary , Rao Krishna A 
Published: June 2010

Abstract

Background
To date, the clinical presentation and prognosis of mixed ductal/lobular mammary carcinomas has not been well studied, and little is known about the outcome of this entity. Thus, best management practices remain undetermined due to a dearth of knowledge on this topic.

Methods
In this paper, we present a clinicopathologic analysis of patients at our institution with this entity and compare them to age-matched controls with purely invasive ductal carcinoma (IDC) and historical data from patients with purely lobular carcinoma and also stain-available tumor specimens for E-cadherin. We have obtained 100 cases of ductal and 50 cases of mixed ductal/lobular breast carcinoma.

Results
Clinically, the behavior of mixed ductal/lobular tumors seemed to demonstrate some important differences from their ductal counterparts, particularly a lower rate of metastatic spread but with a much higher rate of second primary breast cancers.

Conclusions
Our data suggests that mixed ductal/lobular carcinomas are a distinct clinicopathologic entity incorporating some features of both lobular and ductal carcinomas and representing a pleomorphic variant of IDC.
Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish
Authors: Kim Hyejeong Rosemary , Richardson Joanna , van Eeden Freek , Ingham Philip W 
Published: June 2010

Abstract

Background
In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh) signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish.

Results
Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation.

Conclusion
Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.
Astaxanthin uptake in domestic dogs and cats
Authors: Park Jean Soon , Kim Hong Wook , Mathison Bridget D , Hayek Michael G , Massimino Stefan , Reinhart Gregory A , Chew Boon P 
Published: June 2010

AbstractBackgroundResearch on the uptake and transport of astaxanthin is lacking in most species. We studied the uptake of astaxanthin by plasma, lipoproteins and leukocytes in domestic dogs and cats.MethodsMature female Beagle dogs (18 to 19 mo old; 11 to 14 kg BW) were dosed orally with 0, 0.1, 0.5, 2.5, 10 or 40 mg astaxanthin and blood taken at 0, 3, 6, 9, 12, 18 and 24 h post-administration (n = 8/treatment). Similarly, mature domestic short hair cats (12 mo old; 3 to 3.5 kg body weight) were fed a single dose of 0, 0.02, 0.08, 0.4, 2, 5, or 10 mg astaxanthin and blood taken (n = 8/treatment) at the same interval.ResultsBoth dogs and cats showed similar biokinetic profiles. Maximal astaxanthin concentration in plasma was approximately 0.14 μmol/L in both species, and was observed at 6 h post-dosing. The plasma astaxanthin elimination half-life was 9 to 18 h. Astaxanthin was still detectable by 24 h in both species. In a subsequent study, dogs and cats were fed similar doses of astaxanthin daily for 15 to 16 d and astaxanthin uptake by plasma, lipoproteins, and leukocytes studied. In both species, plasma astaxanthin concentrations generally continued to increase through d 15 or 16 of supplementation. The astaxanthin was mainly associated with high density lipoprotein (HDL). In blood leukocytes, approximately half of the total astaxanthin was found in the mitochondria, with significant amounts also associated with the microsomes and nuclei.ConclusionDogs and cats absorb astaxanthin from the diet. In the blood, the astaxanthin is mainly associated with HDL, and is taken up by blood leukocytes, where it is distributed to all subcellular organelles. Certain aspects of the biokinetic uptake of astaxanthin in dogs and cats are similar to that in humans.
Ethnoveterinary treatments by dromedary camel herders in the Suleiman Mountainous Region in Pakistan: an observation and questionnaire study
Authors: Raziq Abdul , de Verdier Kerstin , Younas Muhammad 
Published: June 2010

Abstract
Background
The Suleiman mountainous region is an important cradle of animal domestication and the habitat of many indigenous livestock breeds. The dromedary camel is a highly appreciated and valued animal and represents an important genetic resource. Camel herders, living in remote areas, have developed their own ways to treat diseases in camels, based on a long time of experience.

Methods
Information about the diseases and the ethnoveterinary practices performed was collected from a total of 90 herders and healers by interviews and participant observations.

Results
The respondents classified the diseased in major and minor fractions. Clinical signs were given in detail. Mange followed by trypanosomosis and orf were considered the most prevalent diseases, and also caused the greatest economic losses. Orf was regarded the most complex disease. The season was considered to have great influence on the occurrence of the diseases. A variety of different treatments were described, such as medicinal plants, cauterization, odorant/fly repellents, pesticides, larvicides, cold drink, yogurt and supportive therapy (hot food, hot drink).

Conclusions
There is paramount need to document and validate the indigenous knowledge about animal agriculture in general and ethnoveterinary practices in particular. This knowledge is rapidly disappearing and represents a cultural heritage as well as a valuable resource for attaining food security and sovereignty.
Screening for several potential pathogens in feral pigeons (Columba livia) in Madrid
Authors: Vázquez Belén , Esperón Fernando , Neves Elena , López Juan , Ballesteros Carlos , Muñoz María Jesús 
Published: June 2010

Abstract

Background
Pathogens with the zoonotic potential to infect humans, such as Campylobacter jejuni, Campylobacter coli and Chlamydophila psittaci, can be found in feral pigeons (Columba livia). Given the high density of these birds in the public parks and gardens of most cities, they may pose a direct threat to public health.

Methods
A total of 118 pigeons were captured in three samplings carried out in 2006-2007 in public parks and gardens in Madrid, Spain. Standard haematological and morphological analyses were carried out on the pigeons. PCR was used to screen for the presence of Campylobacter jejuni, C. coli and Chlamydophila psittaci. Positive samples were confirmed by DNA sequencing.

Results
The analyses demonstrated a high prevalence of Chlamydophila psittaci (52.6%) and Campylobacter jejuni (69.1%) among the birds captured. In contrast, Campylobacter coli was rarely detected (1.1%).

Conclusions
Pigeons in Madrid can carry Chlamydophila psittaci and Campylobacter jejuni. They may be asymptomatic or subclinical carriers of both pathogens.
Role of sand lizards in the ecology of Lyme and other tick-borne diseases in the Netherlands
Authors: Tijsse-Klasen Ellen , Fonville Manoj , Reimerink Johan HJ , Spitzen - van der Sluijs Annemarieke , Sprong Hein 
Published: June 2010

Abstract

Background
Lizards are considered zooprophylactic for almost all Borrelia burgdorferi species, and act as dilution hosts in parts of North America. Whether European lizards significantly reduce the ability of B. burgdorferi to maintain itself in enzootic cycles, and consequently decrease the infection rate of Ixodes ricinus ticks for B. burgdorferi and other tick-borne pathogens in Western Europe is not clear.

Results
Ticks were collected from sand lizards, their habitat (heath) and from the adjacent forest. DNA of tick-borne pathogens was detected by PCR followed by reverse line blotting. Tick densities were measured at all four locations by blanket dragging. Nymphs and adult ticks collected from lizards had a significantly lower (1.4%) prevalence of B. burgdorferi sensu lato, compared to questing ticks in heath (24%) or forest (19%). The prevalence of Rickettsia helvetica was significantly higher in ticks from lizards (19%) than those from woodland (10%) whereas neither was significantly different from the prevalence in ticks from heather (15%). The prevalence of Anaplasma and Ehrlichia spp in heather (12%) and forest (14%) were comparable, but significantly lower in ticks from sand lizards (5.4%). The prevalence of Babesia spp in ticks varied between 0 and 5.3%. Tick load of lizards ranged from 1 - 16. Tick densities were ~ 5-fold lower in the heather areas than in woodlands at all four sites.

Conclusions
Despite their apparent low reservoir competence, the presence of sand lizards had insignificant impact on the B. burgdorferi s.l. infection rate of questing ticks. In contrast, sand lizards might act as reservoir hosts for R. helvetica. Remarkably, the public health risk from tick-borne diseases is approximately five times lower in heather than in woodland, due to the low tick densities in heather.
Exotic Rickettsiae in Ixodes ricinus: fact or artifact?
Authors: Tijsse-Klasen Ellen , Fonville Manoj , van Overbeek Leo , Reimerink Johan HJ , Sprong Hein 
Published: June 2010

Abstract
Several pathogenic Rickettsia species can be transmitted via Ixodes ricinus ticks to humans and animals. Surveys of I. ricinus for the presence of Rickettsiae using part of its 16S rRNA gene yield a plethora of new and different Rickettsia sequences. Interpreting these data is sometimes difficult and presenting these findings as new or potentially pathogenic Rickettsiae should be done with caution: a recent report suggested presence of a known human pathogen, R. australis, in questing I. ricinus ticks in Europe. A refined analysis of these results revealed that R. helvetica was most likely to be misinterpreted as R. australis. Evidence in the literature is accumulating that rickettsial DNA sequences found in tick lysates can also be derived from other sources than viable, pathogenic Rickettsiae. For example, from endosymbionts, environmental contamination or even horizontal gene transfer.
Prognostic Impact of Gene Expression–Based Classification for Neuroblastoma
Authors: Oberthuer André , Hero Barbara , Berthold Frank , Juraeva Dilafruz , Faldum Andreas , Kahlert Yvonne , Asgharzadeh Shahab , Seeger Robert , Scaruffi Paola , Tonini Gian Paolo , Janoueix-Lerosey Isabelle , Delattre Olivier , Schleiermacher Gudrun , Vandesompele Jo , Vermeulen Joëlle , Speleman Frank , Noguera Rosa , Piqueras Marta , Bénard Jean , Valent Alexander , Avigad Smadar , Yaniv Isaac , Weber Axel , Christiansen Holger , Grundy Richard G. , Schardt Katharina , Schwab Manfred , Eils Roland , Warnat Patrick , Kaderali Lars , Simon Thorsten , DeCarolis Boris , Theissen Jessica , Westermann Frank , Brors Benedikt , Fischer Matthias 
Published: June 2010

Purpose To evaluate the impact of a predefined gene expression–based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients. Patients and Methods Gene expression profiles of 440 internationally collected neuroblastoma specimens were investigated by microarray analysis, 125 of which were examined prospectively. Patients were classified as either favorable or unfavorable by a 144-gene prediction analysis for microarrays (PAM) classifier established previously on a separate set of 77 patients. PAM classification results were compared with those of current prognostic markers and risk estimation strategies. Results The PAM classifier reliably distinguished patients with contrasting clinical courses (favorable [n = 249] and unfavorable [n = 191]; 5-year event free survival [EFS] 0.84 ± 0.03 v 0.38 ± 0.04; 5-year overall survival [OS] 0.98 ± 0.01 v 0.56 ± 0.05, respectively; both P < .001). Moreover, patients with divergent outcome were robustly discriminated in both German and international cohorts and in prospectively analyzed samples (P ≤ .001 for both EFS and OS for each). In subgroups with clinical low-, intermediate-, and high-risk of death from disease, the PAM predictor significantly separated patients with divergent outcome (low-risk 5-year OS: 1.0 v 0.75 ± 0.10, P < .001; intermediate-risk: 1.0 v 0.82 ± 0.08, P = .042; and high-risk: 0.81 ± 0.08 v 0.43 ± 0.05, P = .001). In multivariate Cox regression models based on both EFS and OS, PAM was a significant independent prognostic marker (EFS: hazard ratio [HR], 3.375; 95% CI, 2.075 to 5.492; P < .001; OS: HR, 11.119, 95% CI, 2.487 to 49.701; P < .001). The highest potential clinical impact of the classifier was observed in patients currently considered as non–high-risk (n = 289; 5-year EFS: 0.87 ± 0.02 v 0.44 ± 0.07; 5-year OS: 1.0 v 0.80 ± 0.06; both P < .001). Conclusion Gene expression–based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.
IDH1andIDH2Mutations Are Frequent Genetic Alterations in Acute Myeloid Leukemia and Confer Adverse Prognosis in Cytogenetically Normal Acute Myeloid Leukemia WithNPM1Mutation WithoutFLT3Internal Tandem Duplication
Authors: Paschka Peter , Schlenk Richard F. , Gaidzik Verena I. , Habdank Marianne , Krönke Jan , Bullinger Lars , Späth Daniela , Kayser Sabine , Zucknick Manuela , Götze Katharina , Horst Heinz-A. , Germing Ulrich , Döhner Hartmut , Döhner Konstanze 
Published: June 2010

PurposeTo analyze the frequency and prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations in acute myeloid leukemia (AML).Patients and MethodsWe studied 805 adults (age range, 16 to 60 years) with AML enrolled on German-Austrian AML Study Group (AMLSG) treatment trials AML HD98A and APL HD95 for mutations in exon 4 of IDH1 and IDH2. Patients were also studied for NPM1, FLT3, MLL, and CEBPA mutations. The median follow-up for survival was 6.3 years.ResultsIDH mutations were found in 129 patients (16.0%) —IDH1 in 61 patients (7.6%), and IDH2 in 70 patients (8.7%). Two patients had both IDH1 and IDH2 mutations. All but one IDH1 mutation caused substitutions of residue R132; IDH2 mutations caused changes of R140 (n = 48) or R172 (n = 22). IDH mutations were associated with older age (P < .001; effect conferred by IDH2 only); lower WBC (P = .04); higher platelets (P < .001); cytogenetically normal (CN) –AML (P< .001); and NPM1 mutations, in particular with the genotype of mutated NPM1 without FLT3 internal tandem duplication (ITD; P < .001). In patients with CN-AML with the latter genotype, IDH mutations adversely impacted relapse-free survival (RFS; P = .02) and overall survival (P = .03), whereas outcome was not affected in patients with CN-AML who lacked this genotype. In CN-AML, multivariable analyses revealed a significant interaction between IDH mutation and the genotype of mutated NPM1 without FLT3-ITD (ie, the adverse impact of IDH mutation [RFS]; P = .046 was restricted to this patient subset).ConclusionIDH1 and IDH2 mutations are recurring genetic changes in AML. They constitute a poor prognostic factor in CN-AML with mutated NPM1 without FLT3-ITD, which allows refined risk stratification of this AML subset.
Absolute and Relative Risk of Cardiovascular Disease in Men With Prostate Cancer: Results From the Population-Based PCBaSe Sweden
Authors: Van Hemelrijck Mieke , Garmo Hans , Holmberg Lars , Ingelsson Erik , Bratt Ola , Bill-Axelson Anna , Lambe Mats , Stattin Pär , Adolfsson Jan 
Published: June 2010

Purpose Cardiovascular disease (CVD) is a potential adverse effect of endocrine treatment (ET) for prostate cancer (PC). We investigated absolute and relative CVD risk in 76,600 patients with PC undergoing ET, curative treatment, or surveillance. Methods PCBaSe Sweden is based on the National Prostate Cancer Register, which covers more than 96% of PC cases. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of ischemic heart disease (IHD), acute myocardial infarction (MI), arrhythmia, heart failure, and stroke were calculated to compare observed and expected (using total Swedish population) numbers of CVD, taking into account age, calendar time, and previous CVD. Results Between 1997 and 2007, 30,642 patients with PC received primary ET, 26,432 curative treatment, and 19,527 surveillance. SIRs for CVD were elevated in all men with the highest for those undergoing ET, independent of circulatory disease history (SIR MI for men without circulatory disease history: 1.40 [95% CI, 1.31 to 1.49], 1.15 [95% CI, 1.01 to 1.31], and 1.20 [95% CI, 1.11 to 1.30] for men undergoing ET, curative treatment, and surveillance, respectively). Absolute risk differences (ARD) showed that two (arrhythmia) to eight (IHD) extra cases of CVD would occur per 1,000 person-years. SMRs showed similar patterns, with ARD of zero (arrhythmia) to three (IHD) per 1,000 person-years. Conclusion Increased relative risks of nonfatal and fatal CVD were found among all men with PC, especially those treated with ET. Because ET is currently the only effective treatment for metastatic disease and the ARDs were rather small, our findings indicate that CVD risk should be considered when prescribing ET but should not constitute a contraindication when the expected gain is tangible.
The Birth of the Subspecialty of Medical Oncology and Examples of Its Early Scientific Foundations
Authors: Band Pierre R. 
Published: June 2010

“Passion is not accepting defeat.” —Emil Frei III In the early 1950s, an experimental and clinical program characterized by unique cross-fertilization was developed. The clinical importance of experimental animal models in drug screening and in establishing key chemotherapy concepts and the role of the pioneers of medical oncology in the design of the various phases of drug trials, using childhood acute leukemia and breast cancer as models, are discussed. Over a short time and with only a few drugs, principles of chemotherapy were laid out, which led to cures in such diseases as childhood acute leukemia and Hodgkin's disease and to improved disease-free survival in breast cancer. It is these and other achievements that paved the way to medical oncology. At the instigation of the American Society of Clinical Oncology (ASCO), the American Board of Internal Medicine made inquiries about a subspecialty in oncology. ASCO and B. J. Kennedy, MD, played key roles in the events leading to the official recognition of medical oncology as a new subspecialty of internal medicine in 1972.