bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome–positive chronic myeloid leukemia patients with resistance or intolerance to imatinib
Authors: Cortes Jorge E. , Kantarjian Hagop M. , Brümmendorf Tim H. , Kim Dong-Wook , Turkina Anna G. , Shen Zhi-Xiang , Pasquini Ricardo , Khoury H. Jean , Arkin Steven , Volkert Angela , Besson Nadine , Abbas Richat , Wang Junyuan , Leip Eric , Gambacorti-Passerini Carlo 
Published: August 2011

Abstract
Bosutinib, a dual Src/Abl kinase inhibitor, has shown potent activity against chronic myeloid leukemia (CML). In this phase 1/2 study we evaluated bosutinib in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. Part 1 was a dose-escalation study to determine the recommended starting dose for part 2; part 2 evaluated the efficacy and safety of bosutinib 500 mg once-daily dosing. The study enrolled 288 patients with imatinib-resistant (n = 200) or imatinibintolerant (n = 88) CML and no other previous kinase inhibitor exposure. At 24 weeks, 31% of patients achieved major cytogenetic response (primary end point). After a median follow-up of 24.2 months, 86% of patients achieved complete hematologic remission, 53% had a major cytogenetic response (41% had a complete cytogenetic response), and 64% of those achieving complete cytogenetic response had a major molecular response. At 2 years, progression-free survival was 79%; overall survival at 2 years was 92%. Responses were seen across Bcr-Abl mutants, except T315I. Bosutinib exhibited an acceptable safety profile; the most common treatment-emergent adverse event was mild/moderate, typically self-limiting diarrhea. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (9%), rash (9%), and vomiting (3%). These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. This trial was registered at http://www.clinicaltrials.gov as NCT00261846.
Roles of planar cell polarity pathways in the development of neutral tube defects
Authors: Wu Gang , Huang Xupei , Hua Yimin , Mu Dezhi 
Published: August 2011

Abstract
Neural tube defects (NTDs) are the second most common birth defect in humans. Despite many advances in the understanding of NTDs and the identification of many genes related to NTDs, the fundamental etiology for the majority of cases of NTDs remains unclear. Planar cell polarity (PCP) signaling pathway, which is important for polarized cell movement (such as cell migration) and organ morphogenesis through the activation of cytoskeletal pathways, has been shown to play multiple roles during neural tube closure. The disrupted function of PCP pathway is connected with some NTDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of NTDs.
The contribution of water contact behavior to the high Schistosoma mansoni Infection rates observed in the Senegal River Basin
Authors: Sow Seydou , de Vlas Sake J , Stelma Foekje , Vereecken Kim , Gryseels Bruno , Polman Katja 
Published: August 2011

Abstract

Background
Schistosomiasis is one of the major parasitic diseases in the world in terms of people infected and those at risk. Infection occurs through contact with water contaminated with larval forms of the parasite, which are released by freshwater snails and then penetrate the skin of people. Schistosomiasis infection and human water contact are thus essentially linked, and more knowledge about their relationship will help us to develop appropriate control measures. So far, only few studies have related water contact patterns to infection levels.

Methods
We have conducted detailed direct water contact observations in a village in Northern Senegal during the first years of a massive Schistosoma mansoni outbreak to determine the role of human water contact in the extent of the epidemic.
We quantified water contact activities in terms of frequency and duration, and described how these vary with age and sex. Moreover, we assessed the relationship between water contact- and infection intensity patterns to further elucidate the contribution of exposure to the transmission of schistosomiasis.

Results
This resulted in over 120,000 recorded water contacts for 1651 subjects over 175 observation days. Bathing was the main activity, followed by household activities. Frequency and duration of water contact depended on age and sex rather than season. Water contacts peaked in adolescents, women spent almost twice as much time in the water as men, and water contacts were more intense in the afternoon than in the morning, with sex-specific intensity peaks. The average number of water contacts per person per day in this population was 0.42; the average time spent in the water per person per day was 4.3 minutes.

Conclusions
The observed patterns of water contact behavior are not unusual and have been described before in various other settings in sub-Saharan Africa. Moreover, water contact levels were not exceptionally high and thus cannot explain the extremely high S. mansoni infection intensities as observed in Northern Senegal. Comparison with fecal egg counts in the respective age and sex groups further revealed that water contact levels did not unambiguously correspond with infection levels, indicating that factors other than exposure also play a role in determining intensity of infection.
Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer
Authors: Singh Preetinder P , Joshi Swapna , Russell Pamela J , Nair Sham , Khatri Aparajita 
Published: August 2011

Abstract

Background
Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells.

Methods
The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses.

Results
Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins.

Conclusion
Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.
Clinical management of gastric cancer: results of a multicentre survey
Authors: Zhang Xiaolong , Li Nanjing , Wei Wen , Yao Wenxiu , Xie Ke , Hu Jiankun , Shen Lida , Ji Weizheng , Lu You , Wen Feng , Jiang Yu , Xu Feng , Feng Hong , Bi Feng , Li Qiu ,   The Western Cooperative Gastrointestinal Oncology Group of China
Published: August 2011

Abstract

Background
The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatment of patients with gastric cancer. The aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the recommended guidelines.

Methods
A questionnaire asking the treatment options for gastric cancer cases was sent to 394 Chinese oncology specialists, including surgical oncologists, medical oncologists, and radiation oncologists working in hospitals joined in The Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire involved a series of clinical scenarios regarding the interpretation of surgery, neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer.

Results
Analysis of 358 respondents (91%) showed variations between each specialization and from the recommended guidelines in the management approaches to specific clinical scenarios. The majority of specialists admitted that less than 50% of patients received multidisciplinary evaluation before treatment. The participants gave different responses to questions involving adjuvant, neoadjuvant, and advanced settings, compared to the recommended guidelines.

Conclusions
These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines.
Dimensionality and scale properties of the Edinburgh Depression Scale (EDS) in patients with type 2 diabetes mellitus: the DiaDDzoB study
Authors: de Cock Evi SA , Emons Wilco HM , Nefs Giesje , Pop Victor JM , Pouwer François 
Published: August 2011

Abstract

Background
Depression is a common complication in type 2 diabetes (DM2), affecting 10-30% of patients. Since depression is underrecognized and undertreated, it is important that reliable and validated depression screening tools are available for use in patients with DM2. The Edinburgh Depression Scale (EDS) is a widely used method for screening depression. However, there is still debate about the dimensionality of the test. Furthermore, the EDS was originally developed to screen for depression in postpartum women. Empirical evidence that the EDS has comparable measurement properties in both males and females suffering from diabetes is lacking however.

Methods
In a large sample (N = 1,656) of diabetes patients, we examined: (1) dimensionality; (2) gender-related item bias; and (3) the screening properties of the EDS using factor analysis and item response theory.

Results
We found evidence that the ten EDS items constitute a scale that is essentially one dimensional and has adequate measurement properties. Three items showed differential item functioning (DIF), two of them showed substantial DIF. However, at the scale level, DIF had no practical impact. Anhedonia (the inability to be able to laugh or enjoy) and sleeping problems were the most informative indicators for being able to differentiate between the diagnostic groups of mild and severe depression.

Conclusions
The EDS constitutes a sound scale for measuring an attribute of general depression. Persons can be reliably measured using the sum score. Screening rules for mild and severe depression are applicable to both males and females.
Effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind clinical trial
Authors: Wang Yuanyuan , Hall Stephen , Hanna Fahad , Wluka Anita E , Grant Gail , Marks Paul , Feletar Marie , Cicuttini Flavia M 
Published: August 2011

AbstractBackgroundAlthough viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA.MethodsIn this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods.ResultsFifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05).ConclusionsSix monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA.Trial RegistrationThe study was registered with ClinicalTrials.gov (NCT00393393).
Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola
Authors: Gama Bianca E , Pereira-Carvalho Guilhermina AL , Lutucuta Kosi Florbela JI , Almeida de Oliveira Natália K , Fortes Filomeno , Rosenthal Philip J , do Rosário Virgílio E , Daniel-Ribeiro Cláudio Tadeu , Fátima Ferreira-da-Cruz Maria de 
Published: August 2011

Abstract

Background

Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola.

Methods

Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes.

Results
The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples).

Conclusion
This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola.
Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico
Authors: Del Razo Luz M , García-Vargas Gonzalo G , Valenzuela Olga L , Castellanos Erika Hernández , Sánchez-Peña Luz C , Currier Jenna M , Drobná Zuzana , Loomis Dana , Stýblo Miroslav 
Published: August 2011

Abstract

Background
Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico.

Methods
We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity.

Results
The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance.

Conclusions
Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII.
Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke
Authors: Yuen Chun-Man , Sun Cheuk-Kwan , Lin Yu-Chun , Chang Li-Teh , Kao Ying-Hsien , Yen Chia-Hung , Chen Yung-Lung , Tsai Tzu-Hsien , Chua Sarah , Shao Pei-Lin , Leu Steve , Yip Hon-Kan 
Published: August 2011

Abstract

Background
This study tested the superiority of combined cyclosporine A (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS).

Methods
Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after occlusion of distal left internal carotid artery.

Results
BIA on day 21 after acute IS was higher in group 2 than in other groups and lowest in group 5 (all p < 0.01). The sensorimotor functional test showed higher frequency of left turning in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were higher in group 2 than in other groups and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The expressions of inflammatory and oxidized protein were higher in group 2 than in other groups and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and other groups (all p < 0.05). The number of aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01).

Conclusion
combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS.
Synthesis and characterization of aligned ZnO/BeO core/shell nanocable arrays on glass substrate
Authors: Zhou Minjie , Yi Zao , Li Kai , Zhang Jicheng , Wu Weidong 
Published: August 2011

Abstract
By sequential hydrothermal growth of ZnO nanowire arrays and thermal evaporation of Be, large-scale vertically aligned ZnO/BeO core/shell nanocable arrays on glass substrate have been successfully synthesized without further heat treatment. Detailed characterizations on the sample morphologies, compositions, and microstructures were systematically carried out, which results disclose the growth behaviors of the ZnO/BeO nanocable. Furthermore, incorporation of BeO shell onto ZnO core resulted in distinct improvement of optical properties of ZnO nanowire, i.e., significant enhancement of near band edge (NBE) emission as well as effective suppression of defects emission in ZnO. In particular, the NBE emission of nanocable sample shows a noticeable blue-shift compared with that of pristine ZnO nanowire, which characteristics most likely originate from Be alloying into ZnO. Consequently, the integration of ZnO and BeO into nanoscale heterostructure could bring up new opportunities in developing ZnO-based device for application in deep ultraviolet region.

PACS

61.46.K; 78.67.Uh; 81.07.Gf.
Ensemble Encoding of Nociceptive Stimulus Intensity in the Rat Medial and Lateral Pain Systems
Authors: Zhang Yang , Wang Ning , Wang Jin-Yan , Chang Jing-Yu , Woodward Donald J , Luo Fei 
Published: August 2011

Background: The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding. Results: Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs). MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable. Conclusion: This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain.