bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study and meta-analysis of meta-analysis studies for the correlation of genomic markers with early cancer detection
Authors: Lanara Zoi , Giannopoulou Efstathia , Fullen Marta , Kostantinopoulos Evangelos , Nebel Jean-Christophe , Kalofonos Haralabos P , Patrinos George P , Pavlidis Cristiana 
Published: June 2013

Abstract
A large number of common disorders, including cancer, have complex genetic traits, with multiple genetic and environmental components contributing to susceptibility. A literature search revealed that even among several meta-analyses, there were ambiguous results and conclusions. In the current study, we conducted a thorough meta-analysis gathering the published meta-analysis studies previously reported to correlate any random effect or predictive value of genome variations in certain genes for various types of cancer. The overall analysis was initially aimed to result in associations (1) among genes which when mutated lead to different types of cancer (e.g. common metabolic pathways) and (2) between groups of genes and types of cancer. We have meta-analysed 150 meta-analysis articles which included 4,474 studies, 2,452,510 cases and 3,091,626 controls (5,544,136 individuals in total) including various racial groups and other population groups (native Americans, Latinos, Aborigines, etc.). Our results were not only consistent with previously published literature but also depicted novel correlations of genes with new cancer types. Our analysis revealed a total of 17 gene-disease pairs that are affected and generated gene/disease clusters, many of which proved to be independent of the criteria used, which suggests that these clusters are biologically meaningful.
Bupropion, methylphenidate, and 3,4-methylenedioxypyrovalerone antagonize methamphetamine-induced efflux of dopamine according to their potencies as dopamine uptake inhibitors: implications for the treatment of methamphetamine dependence
Authors: Simmler Linda D , Wandeler Rebecca , Liechti Matthias E 
Published: June 2013

Abstract

Background
Methamphetamine-abuse is a worldwide health problem for which no effective therapy is available. Inhibition of methamphetamine-induced transporter-mediated dopamine (DA) release could be a useful approach to treat methamphetamine-addiction. We assessed the potencies of bupropion, methylphenidate, and 3,4-methylenedioxypyrovalerone (MDPV) to block DA uptake or to inhibit methamphetamine-induced DA release in HEK-293 cells expressing the human DA transporter.

Findings
Bupropion, methylphenidate, and MDPV inhibited methamphetamine-induced DA release with relative potencies corresponding to their potencies to block DA uptake (potency ranks: MDPV > methylphenidate > bupropion).

Conclusions
Bupropion and methylphenidate antagonize the effects of methamphetamine in vitro and may be potential candidates for the treatment of stimulant addiction. However, drugs that very potently antagonize the effect of methamphetamine are likely to also exhibit considerable abuse liability (MDPV > methylphenidate > bupropion).
Aldose reductase from Schistosoma japonicum: crystallization and structure-based inhibitor screening for discovering antischistosomal lead compounds
Authors: Liu Jian , Dyer David H , Cheng Jingdong , Wang Jipeng , Wang Shuqi , Yang Zhong , Wang Xiaoning , Hu Wei 
Published: June 2013

Abstract

Background
Schistosomiasis is a neglected tropical disease with high morbidity and mortality in the world. Currently, the treatment of this disease depends almost exclusively on praziquantel (PZQ); however, the emergence of drug resistance to PZQ in schistosomes makes the development of novel drugs an urgent task. Aldose reductase (AR), an important component that may be involved in the schistosome antioxidant defense system, is predicted as a potential drug target.

Methods
The tertiary structure of Schistosoma japonicum AR (Sj AR) was obtained through X-ray diffraction method and then its potential inhibitors were identified from the Maybridge HitFinder library by virtual screening based on this structural model. The effects of these identified compounds on cultured adult worms were evaluated by observing mobility, morphological changes and mortality. To verify that Sj AR was indeed the target of these identified compounds, their effects on recombinant Sj AR (rSj AR) enzymatic activity were assessed. The cytotoxicity analysis was performed with three types of human cell lines using a Cell Counting Kit-8.

Results
We firstly resolved the Sj AR structure and identified 10 potential inhibitors based on this structural model. Further in vitro experiments showed that one of the compounds, renamed as AR9, exhibited significant inhibition in the activity of cultured worms as well as inhibition of enzymatic activity of rSj AR protein. Cytotoxicity analysis revealed that AR9 had relatively low toxicity towards host cells.

Conclusions
The work presented here bridges the gap between virtual screening and experimental validation, providing an effective and economical strategy for the development of new anti-parasitic drugs. Additionally, this study also found that AR9 may become a new potential lead compound for developing novel antischistosomal drugs against parasite AR.
Impact of neuroradiologist second opinion on staging and management of head and neck cancer
Authors: Lysack John T , Hoy Monica , Hudon Mark E , Nakoneshny Steven C , Chandarana Shamir P , Matthews T Wayne , Dort Joseph C 
Published: June 2013

Objective Patients with head and neck cancer frequently present to academic tertiary referral centers with imaging studies that have been performed and interpreted elsewhere. At our institution, these outside head and neck imaging studies undergo formal second opinion reporting by a fellowship-trained academic neuroradiologist with expertise in head and neck imaging. The purpose of this study was to determine the impact of this practice on cancer staging and patient management. Methods Our institutional review board approved the retrospective review of randomized original and second opinion reports for 94 consecutive cases of biopsy proven or clinically suspected head and neck cancer in calendar year 2010. Discrepancy rates for staging and recommended patient management were calculated and, for the 32% (30/94) of cases that subsequently went to surgery, the accuracies of the reports were determined relative to the pathologic staging gold standard. Results Following neuroradiologist second opinion review, the cancer stage changed in 56% (53/94) of cases and the recommended management changed in 38% (36/94) of patients with head and neck cancer. When compared to the pathologic staging gold standard, the second opinion was correct 93% (28/30) of the time. Conclusion In a majority of patients with head and neck cancer, neuroradiologist second opinion review of their outside imaging studies resulted in an accurate change in their cancer stage and this frequently led to a change in their management plan.
Mass spectrometry for the detection of potential psychiatric biomarkers
Authors: Ngounou Wetie Armand G , Sokolowska Izabela , Wormwood Kelly , Beglinger Katherine , Michel Tanja Maria , Thome Johannes , Darie Costel C , Woods Alisa G 
Published: June 2013

Abstract
The search for molecules that can act as potential biomarkers is increasing in the scientific community, including in the field of psychiatry. The field of proteomics is evolving and its indispensability for identifying biomarkers is clear. Among proteomic tools, mass spectrometry is the core technique for qualitative and quantitative identification of protein markers. While significant progress has been made in the understanding of biomarkers for neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis and Parkinson’s disease, psychiatric disorders have not been as extensively investigated. Recent and successful applications of mass spectrometry-based proteomics in fields such as cardiovascular disease, cancer, infectious diseases and neurodegenerative disorders suggest a similar path for psychiatric disorders. In this brief review, we describe mass spectrometry and its use in psychiatric biomarker research and highlight some of the possible challenges of undertaking this type of work. Further, specific examples of candidate biomarkers are highlighted. A short comparison of proteomic with genomic methods for biomarker discovery research is presented. In summary, mass spectrometry-based techniques may greatly facilitate ongoing efforts to understand molecular mechanisms of psychiatric disorders.
Source country characteristics and immigrants’ optimal migration duration decision
Authors: Kırdar Murat G 
Published: June 2013

Abstract

Abstract
This paper examines how immigrants’ optimal migration duration in the host country responds to the purchasing power parity (ppp) and relative wages between the host and source countries. A theoretical model of joint migration duration and saving decisions reveals that the optimal migration duration decreases in ppp unless the elasticity of intertemporal substitution of consumption is well above typical estimated values for this parameter. In fact, empirical results from immigrants in Germany reveal that optimal migration duration decreases in ppp. The empirical findings also imply that—holding individual immigrant characteristics constant— immigrants from poorer source countries have shorter predicted migration duration than immigrants from wealthier source countries. In addition, this paper shows that longitudinal data on intentions can be informative by examining how observed event realizations lead to revisions to intentions.

JEL classification codes
F22, J61
3,5-T2 Is an Alternative Ligand for the Thyroid Hormone Receptor β1
Authors: Mendoza A. , Navarrete-Ramírez P. , Hernández-Puga G. , Villalobos P. , Holzer G. , Renaud J.P. , Laudet V. , Orozco A. 
Published: June 2013

Abstract
Several liganded nuclear receptors have alternative ligands acting in a tissue-specific fashion and playing important biological roles. We present evidence that 3,5-diiodothyronine (T2), a naturally occurring iodothyronine that results from T3 outer-ring deiodination, is an alternative ligand for thyroid hormone receptor β1 (TRβ1). In tilapia, 2 TRβ isoforms differing by 9 amino acids in the ligand-binding domain were cloned. Binding and transactivation studies showed that T2 activates the human and the long tilapia TRβ1 isoform, but not the short one. A chimeric human TRβ1 (hTRβ1) that contained the 9–amino-acid insert showed no response to T2, suggesting that the conformation of the hTRβ1 naturally allows T2 binding and that other regions of the receptor are implicated in TR activation by T2. Indeed, further analysis showed that the N terminus is essential for T2-mediated transactivation but not for that by T3 in the long and hTRβ1, suggesting a functional interaction between the N-terminal domain and the insertion in the ligand-binding domain. To establish the functional relevance of T2-mediated TRβ1 binding and activation, mRNA expression and its regulation by T2 and T3 was evaluated for both isoforms. Our data show that long TRβ1expression is 106-fold higher than that of the short isoform, and T3 and T2 differentially regulate the expression of these 2 TRβ1 isoforms in vivo. Taken together, our results prompted a reevaluation of the role and mechanism of action of thyroid hormone metabolites previously believed to be inactive. More generally, we propose that classical liganded receptors are only partially locked to very specific ligands and that alternative ligands may play a role in the tissue-specific action of receptors.
Effects of intraspecific variation in reproductive traits, pectoral fin use and burst swimming on metabolic rates and swimming performance: a study on the Trinidadian guppy (Poecilia reticulataPeters)
Authors: Svendsen Jon C. , Banet Amanda I. , Christensen Rune H. B. , Steffensen John F. , Aarestrup Kim 
Published: June 2013

SummaryThere is considerable intraspecific variation in metabolic rates and locomotor performance in aquatic ectothermic vertebrates, however, the mechanistic basis remains poorly understood. Using pregnant Trinidadian guppies (Poecilia reticulata Peters), a live-bearing teleost, we examined effects of reproductive traits, pectoral fin use, and burst-assisted swimming on the swimming metabolic rate, standard metabolic rate (MO2std) and prolonged swimming performance (Ucrit). Reproductive traits (RT) included reproductive allocation and pregnancy stage; the former defined as the mass of the reproductive tissues divided by the total body mass. Results showed that the metabolic rate increased curvilinearly with swimming speed. The slope of the relationship was used as an index of swimming cost. There was no evidence that RT correlated with the swimming cost, MO2std, or Ucrit. In contrast, data revealed strong effects of pectoral fin use on swimming cost and Ucrit. P. reticulata employed body-caudal fin (BCF) swimming at all tested swimming speeds, however, fish with a high simultaneous use of the pectoral fins exhibited increased swimming cost and decreased Ucrit. These data indicated that combining BCF swimming and pectoral fin movement over a wide speed range, presumably to support swimming stability and control, is an inefficient swimming behaviour. Finally, transition to burst-assisted swimming was associated with an increase in aerobic metabolic rate. Our study highlights other factors than swimming speed affecting swimming cost and suggests that intraspecific diversity in biomechanical performance, such as pectoral fin use, is an important source of variation in both locomotor cost and maximal performance.
Wind induces variations in spider web geometry and sticky spiral droplet volume
Authors: Wu Chao-Chia , Blamires Sean J. , Wu Chung-Lin , Tso I-Min 
Published: June 2013

SummaryTrap building by animals is rare because it comes at substantial costs. Using materials with properties that vary across environments maintains trap functionality. The sticky spiral silks of spider orb webs are used to catch flying prey. Web geometry, accompanied by compensatory changes in silk properties, may change across environments to sustain web functionality. We exposed the spider Cyclosa mulmeinensis to wind to test if wind-induced changes in web geometry are accompanied by changes in aggregate silk droplet morphology, axial thread width or spiral stickiness. We compared: (i) web catching area, (ii) length of total silks, (iii) mesh height, (iv) number of radii, (v) aggregate droplet morphology and (vi) spiral thread stickiness, between webs made by spiders exposed to wind with those not exposed to wind. We interpreted co-variation in droplet morphology or spiral stickiness with web capture area, mesh height or spiral length as the silk properties functionally compensating for changes in web geometry to reduce wind drag. Wind-exposed C. mulmeinensis built webs with smaller capture areas, shorter capture spiral lengths, and more widely spaced capture spirals, resulting in the expenditure of less silk. Individuals that were exposed to wind also deposited larger droplets of sticky silk but the stickiness of the spiral threads remained unchanged. The larger droplets may be a product of greater investment in water, or low molecular weight compounds facilitating atmospheric water uptake. Either way droplet dehydration in wind is likely to be minimized.
Selective Addition of P(O)–H Bonds to Alkynes Catalyzed by Transition Metals Immobilized on Polystyrene-bound Triphenylphosphine
Authors: Chen Tieqiao , Zhou Yongbo , Guo Cancheng , Han Li-Biao 
Published: June 2013

Abstract
Addition of P(O)–H bonds to alkynes catalyzed by transition metals (Rh, Pd, and Ni) immobilized on polystyrene-bound triphenylphosphine proceeded efficiently to afford high yields of the addition products with high regioselectivity. The immobilized catalysts were easily recovered from the reaction mixture via simple centrifugal separation and could be reused several times without severe deactivation.
Exploring the Feasibility of Solar Photo-Voltaic Power Plants in Brunei Darussalam
Authors: Mathew Sathyajith , Lim Chee Ming , Philip Geetha Susan 
Published: June 2013

Aiming for a sustainable and secure energy future, policies are being formulated in Brunei Darussalam for supplementing the national energy base with renewable resources and technologies. Some preliminary studies in this direction indicated that solar energy could be a potential energy option for the country. Technical feasibility and economic viability of such grid integrated solar PV power plants, under the Bruneian environment, are investigated in this study. The prevailing energy scenario is analyzed and future trends in electricity consumption are predicted based on the time series energy use data. The forecast indicates that the annual electricity consumption may reach up to 4.32 Billion kWh by the year 2020. The possibility of exploiting the available solar energy resource for meeting this growing electricity demand is investigated. Five year's solar radiation data from Maura district were collected and analyzed under the study. The solar energy resource is characterized in terms of monthly averaged total daily global, beam and diffused radiations and hourly variations in solar intensity. Availability of solar energy in the region is also statistically modeled using Beta distribution. Performance of a solar photovoltaic power plant under these levels of insolation was simulated using the RETScreen model. With a total panel area of 10,619 m2such a plant is expected to show a capacity factor of 18.1 per-cent and generate 1899.2 MWh electricity annually. This clearly indicates the technical feasibility of grid integrated solar power plants in Brunei Darussalam. Under the economic analysis, the unit cost of electricity generation was estimated to be BND 0.30/kWh. A detailed cost benefit analysis, over the life cycle of such power projects, is also presented.
Apparent Argatroban Resistance in a Patient with Elevated Factor VIII Levels
Authors: Kennedy Dina M , Alaniz Cesar 
Published: June 2013

OBJECTIVE To report a case in which there was a lack of activated partial thromboplastin time (aPTT) correlation with plasma argatroban concentrations in a patient with elevated factor VIII levels who was diagnosed with heparin-induced thrombocytopenia (HIT). CASE SUMMARY A 59-year-old female with a history significant for basal cell carcinoma was transferred from an outside hospital and underwent resection of a third ventricle mass. The postoperative hospital course was complicated by subdural hematoma, HIT, and pulmonary embolism. Upon initiation of argatroban, we faced difficulty in maintaining therapeutic aPTT values despite administration of significantly higher than usual doses of argatroban (up to 7 μg/kg/min). A coagulation abnormality was suspected and an argatroban concentration was obtained; results showed an elevated level of 2.2 μg/mL (therapeutic range 0.4–1.2), with a corresponding aPTT of 53.1 seconds. A coagulopathy workup revealed an excess of factor VIII activity. Thereafter, argatroban concentrations were used for dose adjustments and the infusion was titrated to a final rate of 2.75 μg/kg/min. DISCUSSION The lack of correlation of aPPT values with argatroban administration has not been described in the literature and, to our knowledge, similar cases have not been reported. We were unable to achieve an increase in aPTT, despite aggressive argatroban dosing in a patient with increased factor VIII activity. A definitive mechanism for this is not entirely known; however, it is thought to be secondary to contributing underlying causes such as excessive clotting factors, circulating inflammatory proteins, or other aspects. CONCLUSIONS With the initiation of argatroban therapy, particular attention should be given to ensure that aPTTs correlate with dosing to prevent life-threatening bleeding complications. Excessive argatroban dosing requirements should prompt further investigation into potential confounders such as elevated factor VIII levels.
Impact of Severe Hypothyroidism on Cyclophosphamide Disposition and Routes of Metabolism and Transport in a Patient with Treatment-Resistant Lupus Nephritis
Authors: Jang So Yoon , Dooley Mary Anne , Joy Melanie S 
Published: June 2013

OBJECTIVE To report what we believe to be the first case of severe hypothyroidism with reduced drug metabolism and transport activity. CASE SUMMARY A 32-year-old African American woman with a history of treatmentresistant lupus nephritis and concurrent hypothyroidism was participating in a clinical study to evaluate cyclophosphamide pharmacokinetics in patients with glomerulonephritis due to lupus nephritis and small-vessel vasculitis. Thyroid-stimulating hormone levels ranged from 60 to 300 μIU/mL, despite high doses of thyroid replacement hormone (levothyroxine 400 μg twice weekly). The pharmacokinetics of the probe drug cocktail (flurbiprofen/fexofenadine) were altered, with formation clearance of flurbiprofen (CYP2C9 function) lower in our patient versus the average value in our study cohort, suggesting a reduction in activity. The area under the concentration-time curve from 0 to 24 hours for fexofenadine (transporter function) was 2-fold higher in our patient compared to that of other study patients. Pharmacokinetic data showed markedly decreased cyclophosphamide clearance and exposure to 4-hydroxycyclophosphamide, as well as a reduced metabolic ratio of 4-hydroxycyclophosphamide to cyclophosphamide. DISCUSSION Previous cases of altered pharmacokinetics and toxicity of medications in patients with mild to moderate thyroid dysfunction have been published. Our case evaluated the impact of a severe form of hypothyroidism on cyclophosphamide pharmacokinetics and probe drug metabolism and transport. If changes were not demonstrated at the extreme spectrum of hypothyroidism, there would be little concern for changes in patients with less severe disease. Profound hypothyroidism likely contributed to the patient's poor response to cyclophosphamide treatment through its influence on CYP isoenzymes responsible for the activation to 4-hydroxycyclophosphamide and possibly through reduced transport function. CONCLUSIONS Clinicians should monitor for significant hypothyroidism in patients who are prescribed drugs (eg, cyclophosphamide) that require metabolic conversion to form active therapeutic moieties.