bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skin Changes after Manual Or Electrical Acupuncture
Authors: Miao Edwin Yong 
Published: May 2011

Pigmentation of the skin after electroacupuncture (EA) or acupuncture in patients is not well recognised. Reporting and studying skin changes after acupuncture or EA would increase awareness among health services providers. This case series includes four cases of short-lived or long-term skin pigmentation after EA or acupuncture. Skin pigmentation or dark spots appeared in these four cases: after 12 treatments in Case 4, during the 14 treatments in Case 3, after one treatment course (16 treatments) in Case 1 and during the sixth month in a long-term treatment of duration 2 years (one or two treatments per week) in Case 2. These skin changes faded gradually after cessation of a course of acupuncture or EA. Skin pigmentation was hardly seen in one case after 14 days, and in another case after 42 days. Pigmentation of the skin could still be seen in one case after 42 days and could still be seen in another case after 2 years, however, in both cases, pigmentation has reduced in size and colour intensity by more than 50%. It is likely that pigmentation of the skin is a specific consequence of needling and may be closely linked to acupuncture dosage regardless of whether stimulation is given manually or by EA.
Centromere protein F and survivin are associated with high risk and a poor prognosis in colorectal gastrointestinal stromal tumours
Authors: Chen Wen-Bin , Cheng Xiao-Bin , Ding Wei , Wang Yang-Jing , Chen Dong , Wang Jin-Hai , Fei Ru-Shan 
Published: May 2011

AimsColorectal gastrointestinal stromal tumours (GISTs) are considered to be tumours with a relatively poor prognosis. Few reports have been performed to investigate the mechanisms behind their malignant behaviour and to identify new therapeutic strategies for their treatment. The authors conducted this study to explore potential targets for the treatment of colorectal GISTs (CRGISTs).MethodsIn the current study, the authors focused on centromere protein F and survivin, two markers that are known to affect the malignant behaviour of other tumours. Expression of centromere protein F and survivin was detected through the immunohistochemical staining of paraffin-embedded tumour tissues and then scored. The relationship between the expression of the two markers and their clinical parameters was analysed. Associated Survival analysis was available based on follow-up information.ResultsThe authors demonstrated for the first time that centromere protein F and survivin expression were significantly associated with high risk and a poor prognosis (p<0.05) in CRGISTs. The authors also found that centromere protein F expression was more prevalent in males (p=0.002).ConclusionsThe results suggest that centromere protein F and survivin are malignant behaviour markers for CRGISTs. The expression of centromere protein F or survivin points to a poor clinical outcome. Interfering with centromere protein F and/or survivin expression might be a potentially therapeutic strategy for treating malignant CRGISTs.
Does hypoxia reduce habitat quality for Lake Erie walleye (Sander vitreus)? A bioenergetics perspective
Authors: Brandt Stephen B. , Costantini Marco , Kolesar Sarah , Ludsin Stuart A. , Mason Doran M. , Rae Christopher M. , Zhang Hongyan 
Published: May 2011

In Lake Erie, the duration and extent of hypoxia (dissolved oxygen (DO) ≤ 2 mg·L–1) has increased in recent years, yet little is known on the corresponding impact on its fish, particularly the highly valued walleye ( Sander vitreus ) fishery. Here, we quantified the impact of hypoxia on walleye habitat quality, using a spatially explicit growth rate potential (GRP) modeling approach, which integrates the spatial arrangement of biological (prey availability) and environmental (DO, temperature, irradiance) measures. Data were collected along two types of transects: 60 km north–south transects (each sampled once during day and night) and 5 km east–west transects (sampled every 4 h for 24 h) during August (pre-hypoxia), September (peak-hypoxia), and October (post-hypoxia) 2005. Overall, the average monthly amount of high quality habitat (GRP > 0 g·g–1·day–1) for walleye declined slightly with hypoxia (<2.0%); however, hypoxia appeared to enhance habitat quality by concentrating prey in favorable temperature, DO, and light conditions. In September, percentages of walleye growth rates were at the upper end of the range, much more so than during August or October. Although an understanding of walleye distributions, foraging, and growth in relation to hypoxia is needed, our results do not suggest that hypoxia is negatively influencing walleye through reduced habitat quality.
Mysis diluvianapopulation and cohort dynamics in Lake Ontario before and after the establishment ofDreissena spp.,Cercopagis pengoi, andBythotrephes longimanus
Authors: Johannsson Ora E. , Bowen Kelly L. , Holeck Kristen T. , Walsh Maureen G. 
Published: May 2011

We investigated population responses of Mysis to ecosystem changes induced by invasion of dreissenids and predatory cladocerans, Cercopagis and Bythotrephes . Lake productivity declined as dreissenids invaded the offshore region. Whole-lake mysid biomass was compared before (early 1990s) and after (2002–2007) the invasion period; it declined 40%–45%. Abundance of young mysids and presence of a summer cohort increased with summer, epilmnetic, nighttime zooplankton biomass (i.e., food biomass index). Cercopagis + Bythotrephes biomass was negatively correlated with this index, implicating them in the mysid decline. Eggs per gravid female increased with autumn, total-water-column zooplankton biomass, reflecting the greater use of hypolimnetic waters by adults. Reproductive success was below replacement during the period 2002–2005. First-year mysid growth rate was maintained while population abundance declined, suggesting selection for individuals that feed effectively at low food concentrations. Mortality rates in the first and second years were dependent on cohort density, indicating that competition for food limited abundance in the first 2 years. Fish predation indices (smelt and alewife combined) were correlated positively with mortality rates and negatively with abundance in the third year. Thus, mysids cannot support as many fish in invaded compared with non-invaded lakes. They may also not be a stable food resource; unusual cohort losses occurred in some years.
The promises and pitfalls of including decadal-scale climate forcing of recruitment in groundfish stock assessment
Authors: Haltuch Melissa A. , Punt André E. 
Published: May 2011

Concurrent declines in demersal fish stock abundances and shifts in long-term average environmental conditions have been well documented in the Pacific. Management advice ignoring environmental forcing of recruitment may cause stocks to be over- or under-harvested, so it is important to consider including environmental forcing on recruitment in stock assessment models. Simulation testing is used to determine the statistical power of stock assessments to identify long-term, decadal-scale environmental forcing of recruitment and the ability to estimate management reference points when the duration of the fisheries time series is equal to or less than the period of the environmental cycle. Commonly used assessment methods generally lead to lower total type I (incorrectly rejecting the null hypothesis of no environmental impact) and type II (failing to detect an environmental impact when such a relationship exists) error rates. The promise of integrating environmental data with decadal-scale variability directly into stock assessments via the stock–recruitment relationship is outweighed by the pitfall of high type I error rates that are due to fishing-induced stock declines that coincide with directional environmental change. However, the impact of type I errors can be minimized by choosing an appropriate combination of assessment method and reference point estimators.
Seasonal forecasting of tuna habitat for dynamic spatial management
Authors: Hobday Alistair J. , Hartog Jason R. , Spillman Claire M. , Alves Oscar 
Published: May 2011

Capture of the target, bycatch, and protected species in fisheries is often regulated through spatial measures that partition fishing effort, including areal closures. In eastern Australian waters, southern bluefin tuna (SBT, Thunnus maccoyii ) are a quota-limited species in a multispecies longline fishery; minimizing capture by nonquota holders is an important management concern. A habitat preference model (conditioned with electronic tag data) coupled with ocean reanalysis data has been used since 2003 to generate real-time predicted maps of SBT distribution (nowcasts). These maps are used by fishery managers to restrict fisher access to areas with high predicted SBT distribution. Here we use the coupled ocean–atmosphere model, POAMA (predictive ocean atmosphere model for Australia), and a habitat model to forecast SBT distribution at lead times of up to 4 months. These forecasts are comparable with nowcasts derived from the operational system, and show skill in predicting SBT habitat boundaries out to lead-times of 3–4 months. For this fishery, seasonal forecasts can provide managers and fishers with valuable insights into future habitat distributions for the upcoming months, to better inform operational decisions.
COMPUTATIONAL MODELING AND SIMULATION OF NANOMOLECULAR SWITCH FOR ALZHEIMER'S DISEASE (A GENE SILENCING TECHNIQUE)
Authors: RADHAGAYATHRI K. U. , NAMBOORI P. K. KRISHNAN , MOHANDAS V. P. , SUBEESH T. , GOPAKUMAR DEEPA , RAMACHANDRAN K. I. 
Published: May 2011

The design of artificial gene regulatory networks has paved way for the construction of therapeutic gene circuits that would find application in next generation gene therapy approaches. The main challenge in such designs is in selecting the appropriate genetic components to make up the circuit in order to produce the anticipated or desired behavior. To eliminate this complexity, computational simulation tools are used to guide circuit design. This involves selection and genetic modification of components, until the required system behavior is achieved. In this work, we have designed a model for a synthetic nanogene network. The gene expression involved in diseases caused by mutation, like cancer, Alzheimer's disease (AD), etc., can be effectively controlled by "Nanogene silencing genetic switch". Here, we have considered the case of Alzheimer's disease. Genes that are responsible for genetic AD are APP, PSEN1, and PSEN2. Antimutagenic study of phytochemicals has been carried out with the common AD causing APP gene mutation. By our computational analysis, phytochemicals like curcumin, eugenol, and limonene have been identified as "molecular switch" devices to prevent mutation of AD gene. All these chemicals are found to be strongly interacted with the AD gene without making changes to the remaining part of the sequence. Among the analyzed chemicals, curcumin is found to be most interacting with AD gene protecting it from mutation. Hence, inclusion of curcumin-containing food items in our menu would prevent Alzheimer's disease to a large extent. This technique is a type of gene therapy leading to silencing of the mutated part of the gene and preventing mutation.
VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer
Authors: You Weon-Kyoo , Sennino Barbara , Williamson Casey W. , Falcón Beverly , Hashizume Hiroya , Yao Li-Chin , Aftab Dana T. , McDonald Donald M. 
Published: May 2011

Abstract
Angiogenesis inhibitors that block VEGF receptor (VEGFR) signaling slow the growth of many types of tumors, but eventually the disease progresses. Multiple strategies are being explored to improve efficacy by concurrent inhibition of other functionally relevant receptor tyrosine kinases (RTK). XL880 (foretinib, GSK1363089) and XL184 (cabozantinib) are small-molecule inhibitors that potently block multiple RTKs, including VEGFR and the receptor of hepatocyte growth factor c-Met, which can drive tumor invasion and metastasis. This study compared the cellular effects of XL880 and XL184 with those of an RTK inhibitor (XL999) that blocks VEGFR but not c-Met. Treatment of RIP-Tag2 mice with XL999 resulted in 43% reduction in vascularity of spontaneous pancreatic islet tumors over 7 days, but treatment with XL880 or XL184 eliminated approximately 80% of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal. Importantly, XL880 and XL184 also decreased invasiveness of primary tumors and reduced metastasis. Overall, these findings indicate that inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade and leads to rapid, robust, and progressive regression of tumor vasculature, increased intratumoral hypoxia and apoptosis, and reduced tumor invasiveness and metastasis. Cancer Res; 71(14); 4758–68. ©2011 AACR.
Insights into ALK-Driven Cancers Revealed through Development of Novel ALK Tyrosine Kinase Inhibitors
Authors: Lovly Christine M. , Heuckmann Johannes M. , de Stanchina Elisa , Chen Heidi , Thomas Roman K. , Liang Chris , Pao William 
Published: May 2011

Abstract
Aberrant forms of the anaplastic lymphoma kinase (ALK) have been implicated in the pathogenesis of multiple human cancers, where ALK represents a rational therapeutic target in these settings. In this study, we report the identification and biological characterization of X-376 and X-396, two potent and highly specific ALK small molecule tyrosine kinase inhibitors (TKIs). In Ambit kinome screens, cell growth inhibition studies, and surrogate kinase assays, X-376 and X-396 were more potent inhibitors of ALK but less potent inhibitors of MET compared to PF-02341066 (PF-1066), an ALK/MET dual TKI currently in clinical trials. Both X-376 and X-396 displayed potent antitumor activity in vivo with favorable pharmacokinetic and toxicity profiles. Similar levels of drug sensitivity were displayed by the three most common ALK fusion proteins in lung cancer (EML4-ALK variants E13;A20, E20;A20, and E6b;A20) as well as a KIF5B–ALK fusion protein. Moreover, X-396 could potently inhibit ALK kinases engineered with two point mutations associated with acquired resistance to PF-1066, L1196M, and C1156Y, when engineered into an E13;A20 fusion variant. Finally, X-396 displayed synergistic growth inhibitory activity when combined with the mTOR inhibitor rapamycin. Our findings offer preclinical proof-of-concept for use of these novel agents to improve therapeutic outcomes of patients with mutant ALK-driven malignancies. Cancer Res; 71(14); 4920–31. ©2011 AACR.
High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion
Authors: Muinelo-Romay Laura , Colas Eva , Barbazan Jorge , Alonso-Alconada Lorena , Alonso-Nocelo Marta , Bouso Marta , Curiel Teresa , Cueva Juan , Anido Urbano , Forteza Jeronimo , Gil-Moreno Antonio , Reventos Jaume , Lopez-Lopez Rafael , Abal Miguel 
Published: May 2011

Abstract
Endometrial cancer is among the three most common cancers in females in industrialized countries. In the majority of cases, the tumor is confined to the uterus at the time of diagnosis and presents a good prognosis. However, after primary surgery, 15% to 20% of these tumors recur and have limited response to systemic therapy. We carried out gene expression profiling of high-risk recurrence endometrial cancers to identify new therapeutic approaches targeting the molecular pathways involved in the acquisition of an aggressive tumor phenotype. A microarray gene-expression analysis on a total of 51 human endometrial carcinomas revealed 77 genes specifically altered in high-risk recurrence tumors (P &lt; 0.001). The bioinformatics analysis of gene–gene interactions and molecular relationships among these genes pointed to a prominent role for TGF-β1 signaling in the acquisition of an aggressive phenotype. We further showed that TGF-β1 has a principal role at the initiation of endometrial carcinoma invasion through the promotion of the epithelial to mesenchymal transition that leads to the acquisition of an invasive phenotype in HEC-1A and RL95-2 cells. Impairment of this initial step with SB-431542, a specific TGF-β1 inhibitor, precluded further persistent endometrial carcinoma invasion. In conclusion, we showed that the characterization of the molecular changes associated with the acquisition of an aggressive phenotype represents a realistic strategy for the rational identification and characterization of new potential therapeutic targets in an effort to improve the clinical management and the outcome of high-risk endometrial cancer patients. Mol Cancer Ther; 10(8); 1357–66. ©2011 AACR.
Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events
Authors: Freynhofer Matthias K. , Brozovic Ivan , Bruno Veronika , Farhan Serdar , Vogel Birgit , Jakl Gabriele , Willheim Martin , Hübl Wolfgang , Wojta Johann , Huber Kurt 
Published: May 2011

SummaryReduced antiplatelet effect of clopidogrel assessed with multiple electrode aggregometry (MEA) and vasodilator stimulated phosphoprotein-phosphorylation (VASP-P) assay has been proven to predict major adverse cardiovascular events (MACE) after coronary stenting. So far no consecutive registry has evaluated the usefulness of different adenosine diphosphate-based platelet function tests to predict outcome in unselected patients. Hence, our objective was to determine the feasibility of MEA and VASP-P for clinical routine and whether low-response to clopidogrel as determined by MEA and/or the VASP-P assays predicts MACE in a “real-life” population undergoing coronary stenting. Threehundred consecutive patients were included in this prospective registry. Blood was sampled 6–24 hours after stenting to measure MEA and VASP-P. The use of glycoprotein-IIb/IIIa-blockers limited MEA to 196 measurements. Concerning the VASP-P assay, 300 measurements were achieved. Receiver Operating Characteristics (ROC)-curves of sensitivity and specificity estimates for MACE were plotted for VASP-P assay. The area under the ROC-curve was 0.683 (p=0.014) for the platelet reactivity index (PRI) calculated from median fluorescence intensities (FI) with an optimal cut-off at 60.2% PRI. Patients above 60.2% had a significantly increased risk for MACE at six months follow-up (p=0.007). Estimating the cut-offs for the PRI from mean FI (52%) or from geometric mean FI (56.6%) led to clinically relevant differences. VASP-P assay is feasible for clinical routine to measure clopidogrel effects and to predict post-procedural MACE in unselected patients. With regard to differing cut-offs, exact standardisation of the VASP-P assay is mandatory. The use of GP-IIb/IIIa-blockers prevents MEA testing and limits its usability in unselected patients.
Clinical, genetic and confounding factors determine the dynamics of the in vitro response/non response to clopidogrel
Authors: Gremmel Thomas , Panzer Simon 
Published: May 2011

SummaryPlatelet inhibition by clopidogrel varies from one individual to the next. Further, in vitro high on-treatment residual adenosine-diphosphate inducible platelet reactivity (HRPR) is associated with an increased risk for major adverse cardiovascular events after percutaneous coronary intervention (PCI) with stent implantation. Recent studies identified numerous influencing factors for the antiplatelet effect of clopidogrel. Besides genetic predispositions, diverse clinical conditions as well as pharmacological interactions were shown to significantly impair clopidogrel-mediated platelet inhibition. Consequently, these influencing factors may affect clinical outcome after PCI and it is therefore desirable to identify cofounders of HRPR by platelet reactivity testing. It is apparent, that not all assays are sensitive to the same variables, and only cofounders of HRPR that are repeatedly identified by more than one test system may be clinically meaningful. However, treatment adjustment based on platelet function testing has not been associated with improved patients’ outcome. This summary shall provide an overview over current knowledge on influencing factors for clopidogrel-mediated platelet inhibition and aid guidance for critical interpretation of in vitro obtained data on HRPR.
Identification of the first Alu-mediated large deletion involving the F5 gene in a compound heterozygous patient with severe factor V deficiency
Authors: Guella Ilaria , Paraboschi Elvezia Maria , van Schalkwyk Willem A. , Asselta Rosanna , Duga Stefano 
Published: May 2011

SummaryFactor V (FV) deficiency is a rare autosomal recessive haemorrhagic disorder associated with moderate to severe bleeding symptoms. Conventional mutational screening leads to a complete molecular genetic diagnosis only in about 80–90% of cases. Large gene rearrangements, which could explain at least part of the “missing alleles” have not been reported so far in FV-deficient patients. In this work, we investigated a family with hereditary FV deficiency, in which the proband is compound heterozygous for a 205-Kb deletion, involving the first seven exons of F5, and the entire selectin P, L, and E genes, and for a novel splicing mutation (IVS12+5G>A). The deletion breakpoints, determined by using a combination of semi-quantitative real-time PCR and long PCR assays, occurred within AluY repeat sequences, suggesting an Alu-mediated unequal homologous recombination as the mechanism responsible for the deletion. The in vitro characterisation of the IVS12+5G>A mutation demonstrated that this mutation causes the skipping of exon 12 and the activation of a cryptic splice site. Low levels of residual wild-type splicing were also detectable, in agreement with the notion that the complete absence of FV may be not compatible with life.
Prognostic importance of anaemia in patients with acute pulmonary embolism
Authors: Donzé Jacques , Labarère José , Méan Marie , Jiménez David , Aujesky Drahomir 
Published: May 2011

SummaryAlthough associated with adverse outcomes in other cardiopulmonary diseases, limited evidence exists on the prognostic value of anaemia in patients with acute pulmonary embolism (PE). We sought to examine the associations between anaemia and mortality and length of hospital stay in patients with PE. We evaluated 14,276 patients with a primary diagnosis of PE from 186 hospitals in Pennsylvania, USA. We used random-intercept logistic regression to assess the association between anaemia at the time of presentation and 30-day mortality and discretetime logistic hazard models to assess the association between anaemia and time to hospital discharge, adjusting for patient (age, gender, race, insurance type, clinical and laboratory variables) and hospital (region, size, teaching status) factors. Anaemia was present in 38.7% of patients at admission. Patients with anaemia had a higher 30-day mortality (13.7% vs. 6.3%; p <0.001) and a longer length of stay (geometric mean, 6.9 vs. 6.6 days; p <0.001) compared to patients without anaemia. In multivariable analyses, anaemia remained associated with an increased odds of death (OR 1.82, 95% CI: 1.60–2.06) and a decreased odds of discharge (OR 0.85, 95% CI: 0.82–0.89). Anaemia is very common in patients presenting with PE and is independently associated with an increased short-term mortality and length of stay.