bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic tumour volume delineation in respiratory‐gated PET images
Authors: Gubbi Jayavardhana , Kanakatte Aparna , Tomas Kron , Binns David , Srinivasan Bala , Mani Nallasamy , Palaniswami Marimuthu 
Published: March 2011

AbstractIntroduction: Positron emission tomography (PET) is a state‐of‐the‐art functional imaging technique used in the accurate detection of cancer. The main problem with the tumours present in the lungs is that they are non‐stationary during each respiratory cycle. Tumours in the lungs can get displaced up to 2.5 cm during respiration. Accurate detection of the tumour enables avoiding the addition of extra margin around the tumour that is usually used during radiotherapy treatment planning.Methods: This paper presents a novel method to detect and track tumour in respiratory‐gated PET images. The approach followed to achieve this task is to automatically delineate the tumour from the first frame using support vector machines. The resulting volume and position information from the first frame is used in tracking its motion in the subsequent frames with the help of level set (LS) deformable model.Results: An excellent accuracy of 97% is obtained using wavelets and support vector machines. The volume calculated as a result of the machine learning (ML) stage is used as a constraint for deformable models and the tumour is tracked in the remaining seven phases of the respiratory cycle. As a result, the complete information about tumour movement during each respiratory cycle is available in relatively short time.Conclusions: The combination of the LS and ML approach accurately delineated the tumour volume from all frames, thereby providing a scope of using PET images towards planning an accurate and effective radiotherapy treatment for lung cancer.
A benefit analysis of screening for invasive species – base‐rate uncertainty and the value of information
Authors: Sahlin Ullrika , Rydén Tobias , Nyberg Cecilia D. , Smith Henrik G. 
Published: March 2011

Summary1.. Implementation of the full spectra of screening tools to prevent the introduction of invasive species results in a need to evaluate the cost‐efficiency of gathering the information needed to screen for these species.2.. We show how the Bayesian value of information approach can be used to derive the benefit of a screening model based on species traits, which in combination with the base rate of invasiveness, i.e. the proportion of invasive species among those introduced and established, predicts species‐specific invasiveness.3.. A pre‐posterior Bayesian analysis demonstrated that the benefit of the screening model of invasiveness depends on both the accuracy in predictions and the uncertainty in the base rate of invasiveness. However, even though increasing model accuracy always generates higher model benefit, acknowledging or neglecting the uncertainty in the base rate of invasiveness does not. This means that uncertainty in the base rate is important to consider in the cost‐benefit analysis of the screening model.4.. As an example, we derived the benefit of basing decisions on a screening model trained for a data set on species traits of invasive and non‐invasive marine macroalgae introduced into Europe. The benefit ranged from 0·6% to 19% of the loss of introducing an invasive species, where the actual value can be estimated if we know the monetary values of impacts from introducing invasive and not introducing non‐invasive species.5.. Cost‐benefit analyses of screening models for invasive species is one means to reach efficient management of the risks of non‐indigenous species. Value of information is a useful tool for benefit analysis of predictive models with respect to decision‐making, which goes beyond the investigations of model accuracy. Here, we use value of information analysis to evaluate which sources of uncertainty that is most worth while to reduce and how to set the cost of gathering further species‐specific information which will improve the accuracy of a screening.
4-Aminoquinolines Active against Chloroquine-Resistant Plasmodium falciparum: Basis of Antiparasite Activity and Quantitative Structure-Activity Relationship Analyses
Authors: Hocart Simon J. , Liu Huayin , Deng Haiyan , De Dibyendu , Krogstad Frances M. , Krogstad Donald J. 
Published: March 2011

ABSTRACT

Chloroquine (CQ) is a safe and economical 4-aminoquinoline (AQ) antimalarial. However, its value has been severely compromised by the increasing prevalence of CQ resistance. This study examined 108 AQs, including 68 newly synthesized compounds. Of these 108 AQs, 32 (30%) were active only against CQ-susceptible
Plasmodium falciparum
strains and 59 (55%) were active against both CQ-susceptible and CQ-resistant
P. falciparum
strains (50% inhibitory concentrations [IC
50
s], ≤25 nM). All AQs active against both CQ-susceptible and CQ-resistant
P. falciparum
strains shared four structural features: (i) an AQ ring without alkyl substitution, (ii) a halogen at position 7 (Cl, Br, or I but not F), (iii) a protonatable nitrogen at position 1, and (iv) a second protonatable nitrogen at the end of the side chain distal from the point of attachment to the AQ ring via the nitrogen at position 4. For activity against CQ-resistant parasites, side chain lengths of ≤3 or ≥10 carbons were necessary but not sufficient; they were identified as essential factors by visual comparison of 2-dimensional (2-D) structures in relation to the antiparasite activities of the AQs and were confirmed by computer-based 3-D comparisons and differential contour plots of activity against
P. falciparum
. The advantage of the method reported here (refinement of quantitative structure-activity relationship [QSAR] descriptors by random assignment of compounds to multiple training and test sets) is that it retains QSAR descriptors according to their abilities to predict the activities of unknown test compounds rather than according to how well they fit the activities of the compounds in the training sets.
Pharmacokinetic Interactions of Maraviroc with Darunavir-Ritonavir, Etravirine, and Etravirine-Darunavir-Ritonavir in Healthy Volunteers: Results of Two Drug Interaction Trials
Authors: Kakuda Thomas N. , Abel Samantha , Davis John , Hamlin Julia , Schöller-Gyüre Monika , Mack Rebecca , Ndongo Noella , Petit Wendy , Ridgway Caroline , Sekar Vanitha , Tweedy Sarah , Hoetelmans Richard M. W. 
Published: March 2011

ABSTRACTThe effects of darunavir-ritonavir at 600 and 100 mg twice daily (b.i.d.) alone, 200 mg of etravirine b.i.d. alone, or 600 and 100 mg of darunavir-ritonavir b.i.d. with 200 mg etravirine b.i.d. at steady state on the steady-state pharmacokinetics of maraviroc, and vice versa, in healthy volunteers were investigated in two phase I, randomized, two-period crossover studies. Safety and tolerability were also assessed. Coadministration of 150 mg maraviroc b.i.d. with darunavir-ritonavir increased the area under the plasma concentration-time curve from 0 to 12 h (AUC12) for maraviroc 4.05-fold relative to 150 mg of maraviroc b.i.d. alone. Coadministration of 300 mg maraviroc b.i.d. with etravirine decreased the maraviroc AUC12by 53% relative to 300 mg maraviroc b.i.d. alone. Coadministration of 150 mg maraviroc b.i.d. with etravirine-darunavir-ritonavir increased the maraviroc AUC123.10-fold relative to 150 mg maraviroc b.i.d. alone. Maraviroc did not significantly affect the pharmacokinetics of etravirine, darunavir, or ritonavir. Short-term coadministration of maraviroc with darunavir-ritonavir, etravirine, or both was generally well tolerated, with no safety issues reported in either trial. Maraviroc can be coadministered with darunavir-ritonavir, etravirine, or etravirine-darunavir-ritonavir. Maraviroc should be dosed at 600 mg b.i.d. with etravirine in the absence of a potent inhibitor of cytochrome P450 3A (CYP3A) (i.e., a boosted protease inhibitor) or at 150 mg b.i.d. when coadministered with darunavir-ritonavir with or without etravirine.
Novel Mutations in a Patient Isolate of Streptococcus agalactiae with Reduced Penicillin Susceptibility Emerging after Long-Term Oral Suppressive Therapy
Authors: Longtin Jean , Vermeiren Christie , Shahinas Dea , Tamber Gurdip Singh , McGeer Allison , Low Donald E. , Katz Kevin , Pillai Dylan R. 
Published: March 2011

ABSTRACT
Penicillin nonsusceptibility has been demonstrated in group B streptococci (GBS), but there is limited information regarding mechanisms of resistance. We report a case of GBS with reduced susceptibility to penicillin emerging after long-term suppressive oral penicillin therapy for a prosthetic joint infection. Molecular characterization of the isolate before and after long-term penicillin therapy revealed 5 mutations in the ligand-binding regions of PBP1a, -2a, and -2x not previously reported in GBS.
Preclinical Characterization of Naturally Occurring Polyketide Cyclophilin Inhibitors from the Sanglifehrin Family
Authors: Gregory Matthew A. , Bobardt Michael , Obeid Susan , Chatterji Udayan , Coates Nigel J. , Foster Teresa , Gallay Philippe , Leyssen Pieter , Moss Steven J. , Neyts Johan , Nur-e-Alam Mohammad , Paeshuyse Jan , Piraee Mahmood , Suthar Dipen , Warneck Tony , Zhang Ming-Qiang , Wilkinson Barrie 
Published: March 2011

ABSTRACT

Cyclophilin inhibitors currently in clinical trials for hepatitis C virus (HCV) are all analogues of cyclosporine (CsA). Sanglifehrins are a group of naturally occurring cyclophilin binding polyketides that are structurally distinct from the cyclosporines and are produced by a microorganism amenable to biosynthetic engineering for lead optimization and large-scale production by fermentation. Preclinical characterization of the potential utility of this class of compounds for the treatment of HCV revealed that the natural sanglifehrins A to D are all more potent than CsA at disrupting formation of the NS5A-CypA, -CypB, and -CypD complexes and at inhibition of CypA, CypB, and CypD isomerase activity. In particular, sanglifehrin B (SfB) was 30- to 50-fold more potent at inhibiting the isomerase activity of all Cyps tested than CsA and was also shown to be a more potent inhibitor of the 1b subgenomic replicon (50% effective concentrations [EC
50
s] of 0.070 μM and 0.16 μM in Huh 5-2 and Huh 9-13 cells, respectively). Physicochemical and mouse pharmacokinetic analyses revealed low oral bioavailability (
F
< 4%) and low solubility (<25 μM), although the half-lives (
t
1/2
) of SfA and SfB in mouse blood after intravenous (i.v.) dosing were long (
t
1/2
> 5 h). These data demonstrate that naturally occurring sanglifehrins are suitable lead compounds for the development of novel analogues that are less immunosuppressive and that have improved metabolism and pharmacokinetic properties.
PER-7, an Extended-Spectrum β-Lactamase with Increased Activity toward Broad-Spectrum Cephalosporins in Acinetobacter baumannii
Authors: Bonnin Rémy A. , Potron Anaïs , Poirel Laurent , Lecuyer Hervé , Neri Rita , Nordmann Patrice 
Published: March 2011

ABSTRACT

Acinetobacter baumannii
isolate AP2 was recovered from a bronchial lavage sample of a patient hospitalized in Paris, France.
A. baumannii
AP2 was resistant to all β-lactams, including carbapenems, and expressed the extended-spectrum β-lactamase (ESBL) PER-7, which differs from PER-1 by 4 amino acid substitutions. Compared to PER-1, PER-7 possessed higher-level hydrolytic activities against cephalosporins and aztreonam. The
bla
PER-7
gene was chromosomally located and associated with a mosaic class 1 integron structure. Additionally, isolate AP2 expressed the carbapenem-hydrolyzing oxacillinase OXA-23 and the 16S RNA methylase ArmA, conferring high-level resistance to aminoglycosides.
Randomised, Controlled Study of Preoperative Eletroacupuncture for Postoperative Pain Control after Cardiac Surgery
Authors: Coura Luiz Eduardo Faria , Manoel Cláudia Hideco Uratsuka , Poffo Robinson , Bedin Antonio , Westphal Glauco Adrieno 
Published: March 2011

Background This study aims to evaluate the effects of preoperative electroacupuncture (EA) on the need for opioids in the postoperative stage of conventional cardiac surgery. Methods A prospective, randomised and controlled study was conducted at Unimed Hospital Centre in Joinville, SC, Brazil. The day before the surgery, 32 patients undergoing cardiac surgery were randomised into two groups: patients from the treatment group received preoperative EA at bilateral points (LI4–LI11, LR3–ST36, PC6–TE5) for 30 min with alternating frequencies of 3 and 15 Hz. Patients from the control group received sham transcutaneous electrical nerve stimulation (TENS). Use of fentanyl during the postoperative period was measured. Results 10 patients were excluded because of hemodynamic and ventilatory instability leaving 13 (10 male) in the treatment group and 9 (4 male) in the control group. The average total doses of fentanyl given were 13.1±2.2 and 16.3±1.6 μg/kg in the treatment and control groups respectively (p<0.002). The doses of patient controlled analgesia were 4.1±2.0 and 6.9±1.7 μg/kg in the treatment and control groups respectively (p<0.003). The number of boluses issued also differed (treatment 13.9±7.0 vs control 24.8±7.0, p<0.002). Pain intensity scores differed between the groups (treatment 2.5±1.1 vs control 4.0±2.0, p<0.04). One patient from the control group experienced drowsiness that justified a change in fentanyl infusion, as decided by the anaesthetist. Conclusion Preoperative electro-acupuncture in conventional cardiac surgery may reduce the postoperative consumption of fentanyl.
Disease, diagnosis or syndrome?
Authors: Pearce J M S 
Published: March 2011

The advance of medical semantics is, in general, towards causation. As knowledge increases, the common consequence is the re-definition of disease. This starts with symptoms then a disorder of structure or function, abnormalities of images, genetics or biochemistry, the ultimate aim being a specific aetiological mechanism which replaces broader descriptions. But medical terminology of diseases, diagnoses and syndromes is inherently imprecise. Careless nomenclature causes confused dialogue and communication. Symptoms of uncertain cause are commonly lumped together and given a new ‘diagnostic’ label which also may confuse and produce false concepts that stultify further thought and research. Such medicalisation of non-specific aggregations of symptoms should be avoided. The defining characteristics of diseases and diagnoses should be validated and agreed. The pragmatic diagnoses of ‘symptom of unknown cause’ or ‘non-disease’ are preferable to falsely labelling patients with obscure or non-existent diseases.“I tried to unveil the stillness of existence through a counteracting murmur of words, and, above all, I confused things with their names: that is belief.”Jean-Paul Sartre (The Words, 1964).
Serum Omega-3 and Omega-6 Fatty Acids and Cutaneous p53 Expression in an Australian Population
Authors: van der Pols Jolieke C. , Xu Chunxia , Boyle Glen M. , Hughes Maria C. , Carr Samuel J. , Parsons Peter G. , Green Adèle C. 
Published: March 2011

Abstract
Background: There is some evidence from experimental studies that long-chain n-3 and n-6 fatty acids may be able to modify early skin carcinogenesis, but whether this applies in the general population is not known.
Methods: We investigated associations between serum polyunsaturated fatty acid concentrations and p53 expression in normal skin, as a biomarker of early UV-induced carcinogenesis, in an unselected sample of Australian adults. Participants in the Nambour Skin Cancer Prevention Trial provided a dorsal hand punch biopsy which was used for immunohistochemical assessment of p53 immunoreactivity. Cross-sectional associations with serum fatty acid concentrations were analyzed in 139 participants, adjusting for confounding variables including skin phenotype, past sun exposure, and smoking status.
Results: There was an inverse association, showing a dose–response relationship, between total n-3 fatty acid serum concentrations and p53 immunoreactivity in the whole epidermis and the basal layer. This was particularly due to eicosapentanoic acid and docosahexanoic acid concentrations. There was no evidence for increased p53 immunoreactivity in participants with relatively high serum n-6 fatty acid concentrations. The ratio of n-3 to n-6 fatty acid concentrations was not associated with p53 immunoreactivity.
Conclusion: These results add to growing evidence that long-chain fatty acids may be able to modify early skin carcinogenesis.
Impact: The prospect that increased intake of n-3 fatty acids could help prevent skin cancer is attractive. Cancer Epidemiol Biomarkers Prev; 20(3); 530–6. ©2011 AACR.
Body Size, Physical Activity, and Risk of Triple-Negative and Estrogen Receptor–Positive Breast Cancer
Authors: Phipps Amanda I. , Chlebowski Rowan T. , Prentice Ross , McTiernan Anne , Stefanick Marcia L. , Wactawski-Wende Jean , Kuller Lewis H. , Adams-Campbell Lucile L. , Lane Dorothy , Vitolins Mara , Kabat Geoffrey C. , Rohan Thomas E. , Li Christopher I. 
Published: March 2011

Abstract
Background: Triple-negative breast cancer, characterized by a lack of hormone receptor and HER2 expression, is associated with a particularly poor prognosis. Focusing on potentially modifiable breast cancer risk factors, we examined the relationship between body size, physical activity, and triple-negative disease risk.
Methods: Using data from 155,723 women enrolled in the Women's Health Initiative (median follow-up, 7.9 years), we assessed associations between baseline body mass index (BMI), BMI in earlier adulthood, waist and hip circumference, waist–hip ratio, recreational physical activity, and risk of triple-negative (n = 307) and estrogen receptor–positive (ER+, n = 2,610) breast cancers.
Results: Women in the highest versus lowest BMI quartile had 1.35-fold (95% CI, 0.92–1.99) and 1.39-fold (95% CI, 1.22–1.58) increased risks of triple-negative and ER+ breast cancers, respectively. Waist and hip circumferences were positively associated with risk of ER+ breast cancer (Ptrend = 0.01 for both measures) but were not associated with triple-negative breast cancer. Compared with women who reported no recreational physical activity, women in the highest activity tertile had similarly lower risks of triple-negative and ER+ breast cancers (HR = 0.77; 95% CI, 0.51–1.13; and HR = 0.85; 95% CI, 0.74–0.98, respectively).
Conclusions: Despite biological and clinical differences, triple-negative and ER+ breast cancers are similarly associated with BMI and recreational physical activity in postmenopausal women. The biological mechanisms underlying these similarities are uncertain and these modest associations require further investigation.
Impact: If confirmed, these results suggest potential ways postmenopausal women might modify their risk of both ER+ and triple-negative breast cancers. Cancer Epidemiol Biomarkers Prev; 20(3); 454–63. ©2011 AACR.
Fumonisin B1 as a Urinary Biomarker of Exposure in a Maize Intervention Study Among South African Subsistence Farmers
Authors: van der Westhuizen Liana , Shephard Gordon S. , Burger Hester M. , Rheeder John P. , Gelderblom Wentzel C.A. , Wild Christopher P. , Gong Yun Yun 
Published: March 2011

Abstract
Background: The consumption of maize highly contaminated with carcinogenic fumonisins has been linked to high oesophageal cancer rates. The aim of this study was to validate a urinary fumonisin B1 (UFB1) biomarker as a measure of fumonisin exposure and to investigate the reduction in exposure following a simple and culturally acceptable intervention.
Methods: At baseline home-grown maize, maize-based porridge, and first-void urine samples were collected from female participants (n = 22), following their traditional food practices in Centane, South Africa. During intervention the participants were trained to recognize and remove visibly infected kernels, and to wash the remaining kernels. Participants consumed the porridge prepared from the sorted and washed maize on each day of the two-day intervention. Porridge, maize, and urine samples were collected for FB1 analyses.
Results: The geometric mean (95% confidence interval) for FB1 exposure based on porridge (dry weight) consumption at baseline and following intervention was 4.84 (2.87–8.14) and 1.87 (1.40–2.51) μg FB1/kg body weight/day, respectively, (62% reduction, P &lt; 0.05). UFB1C, UFB1 normalized for creatinine, was reduced from 470 (295–750) at baseline to 279 (202–386) pg/mg creatinine following intervention (41% reduction, P = 0.06). The UFB1C biomarker was positively correlated with FB1 intake at the individual level (r = 0.4972, P &lt; 0.01). Urinary excretion of FB1 was estimated to be 0.075% (0.054%–0.104%) of the FB1 intake.
Conclusion: UFB1 reflects individual FB1 exposure and thus represents a valuable biomarker for future fumonisin risk assessment.
Impact: The simple intervention method, hand sorting and washing, could positively impact on food safety and health in communities exposed to fumonisins. Cancer Epidemiol Biomarkers Prev; 20(3); 483–9. ©2011 AACR.
Radon and Lung Cancer in the American Cancer Society Cohort
Authors: Turner Michelle C. , Krewski Daniel , Chen Yue , Pope C. Arden , Gapstur Susan , Thun Michael J. 
Published: March 2011

Abstract
Background: Case–control studies conducted in North America, Europe, and Asia provided evidence of increased lung cancer risk due to radon in homes. Here, the association between residential radon and lung cancer mortality was examined in a large-scale cohort study.
Methods: Nearly 1.2 million Cancer Prevention Study-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment [mean (SD) = 53.5 Bq/m3 (38.0)]. Cox proportional hazards regression models were used to obtain adjusted HR and 95% CI for lung cancer mortality associated with radon. Potential effect modification by cigarette smoking, ambient sulfate concentrations, and other risk factors was assessed on both the additive and multiplicative scales.
Results: Through 1988, 3,493 lung cancer deaths were observed among 811,961 participants included in the analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (P = 0.02). A 15% (95% CI, 1–31) increase in the risk of lung cancer mortality was observed per 100 Bq/m3 increase in radon. Participants with mean radon concentrations above the EPA guideline value (148 Bq/m3) experienced a 34% (95% CI, 7–68) increase in risk for lung cancer mortality relative to those below the guideline value.
Conclusions: This large prospective study showed positive associations between ecological indicators of residential radon and lung cancer.
Impact: These results further support efforts to reduce radon concentrations in homes to the lowest possible level. Cancer Epidemiol Biomarkers Prev; 20(3); 438–48. ©2011 AACR.