bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of self‐controlled designs in pharmacoepidemiology
Authors: Hallas J. , Pottegård A. 
Published: March 2014

AbstractSelf‐controlled observational study designs, such as the case–crossover design and the self‐controlled case series, are reviewed, and their respective rationale, strengths and limitations are compared. Although no single design is generally superior to the others, they share the trait of being robust towards confounders that are stable over time. The self‐controlled designs can be particularly useful when using secondary healthcare data for pharmacoepidemiological research and might be useful in screening for adverse drug effects. The main limitations of self‐controlled designs are that they are amenable only to transient effects; some may be inefficient with long‐term exposure; and they may be sensitive towards trends in exposure.
The acute promyelocytic leukaemia success story: curing leukaemia through targeted therapies
Authors: Rice K. L. , de Thé H. 
Published: March 2014

AbstractThe recent finding that almost all patients with acute promyelocytic leukaemia (APL) may be cured using a combination of retinoic acid (RA) and arsenic trioxide (As2O3) (N Engl J Med, 369, 2013 and 111) highlights the progress made in our understanding of APL pathogenesis and therapeutic approaches over the past 25 years. The study of APL has revealed many important lessons related to transcriptional control, nuclear organization, epigenetics and the role of proteolysis in biological control. Even more important has been the clinical demonstration that molecularly targeted therapy can eradicate disease.
The Capitalization of Insurance Premiums in House Prices
Authors: Nyce Charles , Dumm Randy E. , Sirmans G. Stacy , Smersh Greg 
Published: March 2014

AbstractThis study uses Miami‐Dade County, Florida home sales, and Citizens Property Insurance Corporation data for the period 2004 through 2009 to measure the capitalization effect of increases in premiums on house prices. Using hedonic pricing models, spatial autocorrelation models, and difference‐in‐differences models, we find that new information was conveyed to homeowners in the higher risk areas by the 2004/2005 storms and that consumers appear to use the insurance premium as a “risk signal.” We also find some support for the hypothesis that the risk of potential hurricane losses is communicated to potential homebuyers through windzone maps.
Molecular Characterization of Phytoplasmas Related to Apple Proliferation and Aster Yellows Groups Associated with Pear Decline Disease in Iran
Authors: Hashemi‐Tameh Mahdis , Bahar Masoud , Zirak Leila 
Published: March 2014

AbstractPear trees showing pear decline disease symptoms were observed in pear orchards in the centre and north of Iran. Detection of phytoplasmas using universal primer pair P1A/P7A followed by primer pair R16F2n/R16R2 in nested PCR confirmed association of phytoplasmas with diseased pear trees. However, PCR using group‐specific primer pairs R16(X)F1/R16(X)R1 and rp(I)F1A/rp(I)R1A showed that Iranian pear phytoplasmas are related to apple proliferation and aster yellows groups. Moreover, PCR results using primer pair ESFYf/ESFYr specific to 16SrX‐B subgroup indicated that ‘Ca. Phytoplasma prunorum’ is associated with pear decline disease in the north of Iran. RFLP analyses using HaeIII, HhaI, HinfI, HpaII and RsaI restriction enzymes confirmed the PCR results. Partial 16S rRNA, imp, rp and secY genes sequence analyses approved that ‘Ca. Phytoplasma pyri’ and ‘Ca. Phytoplasma asteris’ cause pear decline disease in the centre of Iran, whereas ‘Ca. Phytoplasma prunorum’ causes disease in the north of Iran. This is the first report of the association of ‘Ca. Phytoplasma asteris’ and ‘Ca. Phytoplasma prunorum’ with pear decline disease worldwide.
Accuracy and Reliability of Severity Estimates Using Linear or Logarithmic Disease Diagram Sets in True Colour or Black and White: a Study Case for Rice Brown Spot
Authors: Schwanck André Aguiar , Del Ponte Emerson Medeiros 
Published: March 2014

AbstractFour disease diagram sets to aid in assessments of rice brown spot severity were developed and evaluated with regard to accuracy and reliability of the estimates. These sets had severity increments in a linear (LIN) or logarithmic (LOG) fashion with the diagrams depicted in true colour (COL) or black and white (BW). Ten inexperienced raters evaluated one of the sets, totalling forty raters. On each group of raters, the assessment was made first unaided and then aided with the respective diagram set. The minimum and the maximum severities of the diagram sets were 0.5 and 36%, respectively, and the five intermediate severity values were 6, 12, 18, 24 and 32% for the LIN diagram sets, and 1.8, 3.3, 6, 11 and 20% for the LOG sets. Overall agreement, measured by the Lin's concordance correlation coefficient (ρc), increased considerably when using the aid (unaided mean ρc = 0.53, aided mean ρc = 0.87) due to a strong reduction in the systematic bias, measured by the bias correction factor Cb (unaided mean Cb = 0.60, aided mean Cb = 0.95). All diagrams led to similar accuracy and precision, but a consistent overestimation was still observed when using the LIN sets, and variability for the absolute errors was higher for the LOG sets, compared with the LIN sets. Estimates using the diagram sets were more reliable based on the intraclass correlation (mean ρ = 0.79–0.86) compared with unaided estimates (mean ρ = 0.51–0.67). Raters exhibited preference for specific values, such as the ‘knots’ (10, 20, 30%, etc.), and the severity values represented in the diagrams, especially when using the LIN sets. The diagram sets similarly helped to improve accuracy and reliability of estimates of rice brown spot epidemics.
Melatonin reduces endothelin‐1 expression and secretion in colon cancer cells through the inactivation of FoxO‐1 and NF‐κβ
Authors: León Josefa , Casado Jorge , Jiménez Ruiz Sergio M. , Zurita María Sol , González‐Puga Cristina , Rejón Juan D. , Gila Ana , Muñoz de Rueda Paloma , Pavón Esther J. , Reiter Russel J. , Ruiz‐Extremera Angela , Salmerón Javier 
Published: March 2014

AbstractMelatonin is an indoleamine that is synthesised from tryptophan under the control of the enzymes arylalkylamine N‐acetyltransferase (AA‐NAT) and acetylserotonin methyltransferase (ASMT). Melatonin inhibits colon cancer growth in both in vivo and in vitro models; however, a precise mechanism responsible for inhibiting tumour growth has not been clearly described. Endothelin‐1 (ET‐1) is a peptide that acts as a survival factor in colon cancer, inducing cell proliferation, protecting carcinoma cells from apoptosis and promoting angiogenesis. The data presented show that melatonin inhibits edn‐1 mRNA expression (the first step in ET‐1 synthesis), ECE‐1 protein expression and the release of ET‐1 from colorectal cancer cells in vitro. ET‐1 levels in cultured media present a similar inhibition pattern to that of edn‐1 mRNA expression despite the inhibition of ECE‐1 protein after melatonin treatment, which suggests that an endopeptidase other than ECE‐1 could be mainly responsible for ET‐1 synthesis. The inhibition of edn‐1 expression is due to an inactivation of FoxO1 and NF‐κβ transcription factors. FoxO1 inactivation is associated with an increased Src phosphorylation, due to elevated cAMP content and PKA activity, whereas NF‐κβ inactivation is associated with the blockade of Akt and ERK phosphorylation due to the inhibition of PKC activity after melatonin treatment. Melatonin also inhibits edn‐1 promoter activity regulated by FoxO1 and NF‐κβ. Finally, a significant correlation was observed between AA‐NAT and edn‐1 expression downregulation in human colorectal cancer tissues. In conclusion, melatonin may be useful in treating colon carcinoma in which the activation of ET‐1 plays a role in tumour growth and progression.
A review of metal‐catalyzed molecular damage: protection by melatonin
Authors: Romero Alejandro , Ramos Eva , de Los Ríos Cristóbal , Egea Javier , del Pino Javier , Reiter Russel J. 
Published: March 2014

AbstractMetal exposure is associated with several toxic effects; herein, we review the toxicity mechanisms of cadmium, mercury, arsenic, lead, aluminum, chromium, iron, copper, nickel, cobalt, vanadium, and molybdenum as these processes relate to free radical generation. Free radicals can be generated in cells due to a wide variety of exogenous and endogenous processes, causing modifications in DNA bases, enhancing lipid peroxidation, and altering calcium and sulfhydryl homeostasis. Melatonin, an ubiquitous and pleiotropic molecule, exerts efficient protection against oxidative stress and ameliorates oxidative/nitrosative damage by a variety of mechanisms. Also, melatonin has a chelating property which may contribute in reducing metal‐induced toxicity as we postulate here. The aim of this review was to highlight the protective role of melatonin in counteracting metal‐induced free radical generation. Understanding the physicochemical insights of melatonin related to the free radical scavenging activity and the stimulation of antioxidative enzymes is of critical importance for the development of novel therapeutic strategies against the toxic action of these metals.
Pharmacokinetics of gallium maltolate in Lawsonia intracellularis‐infected and uninfected rabbits
Authors: Sampieri F. , Alcorn J. , Allen A. L. , Clark C. R. , Vannucci F. A. , Pusterla N. , Mapes S. , Ball K. R. , Dowling P. M. , Thompson J. , Bernstein L. R. , Gebhart C. J. , Hamilton D. L. 
Published: March 2014

Oral gallium maltolate (GaM) pharmacokinetics (PK) and intestinal tissue (IT) concentrations of elemental gallium ([Ga]) and iron ([Fe]) were investigated in a rabbit model of equine proliferative enteropathy (EPE). New Zealand white does (uninfected controls and EPE‐infected, n = 6/group) were given a single oral GaM dose (50 mg/kg). Serial blood samples were collected from 0 to 216 h post‐treatment (PT) and IT samples after euthanasia. Serology, qPCR, and immunohistochemistry confirmed, or excluded, EPE. Blood and IT [Ga] and [Fe] were determined using inductively coupled plasma–mass spectrometry. PK parameters were estimated through noncompartmental approaches. For all statistical comparisons on [Ga] and [Fe] α = 5%. The Ga log‐linear terminal phase rate constant was lower in EPE rabbits vs. uninfected controls [0.0116 ± 0.004 (SD) vs. 0.0171 ± 0.0028 per hour; P = 0.03]; but half‐life (59.4 ± 24.0 vs. 39.4 ± 10.8 h; P = 0.12); Cmax (0.50 ± 0.21 vs. 0.59 ± 0.42 μg/mL; P = 0.45); tmax (1.75 ± 0.41 vs. 0.9 ± 0.37 h; P = 0.20); and oral clearance (6.743 ± 1.887 vs. 7.208 ± 2.565 L/h; P = 0.74) were not. IT's [Ga] and [Fe] were higher (P < 0.0001) in controls. In conclusion, although infection reduces IT [Ga] and [Fe], a 48 h GaM dosing interval is appropriate for multidose studies in EPE rabbits.
n‐3 polyunsaturated fatty acids worsen inflammation and fibrosis in experimental nonalcoholic steatohepatitis
Authors: Provenzano Angela , Milani Stefano , Vizzutti Francesco , Delogu Wanda , Navari Nadia , Novo Erica , Maggiora Marina , Maurino Valter , Laffi Giacomo , Parola Maurizio , Marra Fabio 
Published: March 2014

AbstractBackground & Aimsn‐3 polyunsaturated fatty acids (PUFA) ameliorate fatty liver in experimental models, but their effects on inflammation and fibrosis during steatohepatitis are either controversial or lacking. We compared the effects of supplementation with olive oil (OO) alone or OO and n‐3 PUFA on the development and progression of experimental steatohepatitis.MethodsBalb/C mice (≥5 mice/group) were fed a methionine‐ and choline‐deficient (MCD) diet or a control diet for 4 or 8 weeks. At the same time, mice were supplemented with n‐3 PUFA (eicosapentaenoic and docosahexahenoic acid, 25 mg together with 75 mg OO), or OO alone (100 mg), two times a week by intragastric gavage.ResultsAfter 8 weeks, mice on MCD/n‐3 had higher ALT levels compared to MCD/OO and more severe scores of inflammation, including a significant increase in the number of lipogranulomas (26.4 ± 8.4 vs. 5.1 ± 5 per field, P < 0.001). Intrahepatic expression of TNF‐α and CCL2 was higher in MCD/n‐3 mice at both time points. In addition, increased expression of the profibrogenic genes TIMP‐1 and TGF‐β, and more severe histological scores of fibrosis were evident in MCD/n‐3 mice. After 8 week of MCD diet, portal pressure was higher in mice receiving n‐3 than in those on OO alone (5.1 ± 1.4 vs. 7.0 ± 0.9 mmHg, P < 0.05). Analysis of hepatic fatty acid profile showed that supplementation resulted in effective incorporation of n‐3 PUFA.ConclusionsIn a murine model of steatohepatitis, supplementation with n‐3 PUFA and OO is associated with more severe necro‐inflammation and fibrosis than in mice treated with OO only.
The origins of crown group birds: molecules and fossils
Authors: Mayr Gerald 
Published: March 2014

AbstractKnowledge of the evolutionary history of crown group birds (Neornithes) has significantly improved through emerging congruence among phylogenetic hypotheses and the description of numerous newPalaeogene stem group representatives. However, controversies still persist about the precise interrelationships of many extant and fossil taxa and about the timing of the diversification of the neornithine crown group. Using the example ofPhaethontiformes (tropicbirds) andPsittaciformes (parrots), it is shown how new sequence‐based phylogenies may shed light on the relationships of fossils with an unexpected character mosaic, and how such fossils can improve our understanding of character evolution in morphologically disparate avian taxa. The earliest occurrences of neornithine birds are plotted on a current phylogeny. As noted by previous authors, an extensive diversification of neornithine birds before the latestCretaceous is not supported by the fossil record, and the existence of essentially modern‐type representatives ofTelluraves (the clade including most arboreal birds) in theCretaceous, such as suggested from molecular calibrations, is highly unlikely.
Implications of the mesophyll conductance to CO2 for photosynthesis and water‐use efficiency during long‐term water stress and recovery in two contrasting Eucalyptus species
Authors: CANO F. JAVIER , LÓPEZ ROSANA , WARREN CHARLES R. 
Published: March 2014

AbstractWater stress (WS) slows growth and photosynthesis (An), but most knowledge comes from short‐time studies that do not account for longer term acclimation processes that are especially relevant in tree species. Using two Eucalyptus species that contrast in drought tolerance, we induced moderate and severe water deficits by withholding water until stomatal conductance (gsw) decreased to two pre‐defined values for 24 d, WS was maintained at the target gsw for 29 d and then plants were re‐watered. Additionally, we developed new equations to simulate the effect on mesophyll conductance (gm) of accounting for the resistance to refixation of CO2. The diffusive limitations to CO2, dominated by the stomata, were the most important constraints to An. Full recovery of An was reached after re‐watering, characterized by quick recovery of gm and even higher biochemical capacity, in contrast to the slower recovery of gsw. The acclimation to long‐term WS led to decreased mesophyll and biochemical limitations, in contrast to studies in which stress was imposed more rapidly. Finally, we provide evidence that higher gm under WS contributes to higher intrinsic water‐use efficiency (iWUE) and reduces the leaf oxidative stress, highlighting the importance of gm as a target for breeding/genetic engineering.
Notch signaling in the pigmented epithelium of the anterior eye segment promotes ciliary body development at the expense of iris formation
Authors: Sarode Bhushan , Nowell Craig S. , Ihm JongEun , Kostic Corinne , Arsenijevic Yvan , Moulin Alexandre P. , Schorderet Daniel F. , Beermann Friedrich , Radtke Freddy 
Published: March 2014

SummaryThe ciliary body and iris are pigmented epithelial structures in the anterior eye segment that function to maintain correct intra‐ocular pressure and regulate exposure of the internal eye structures to light, respectively. The cellular and molecular factors that mediate the development of the ciliary body and iris from the ocular pigmented epithelium remain to be fully elucidated. Here, we have investigated the role of Notch signaling during the development of the anterior pigmented epithelium by using genetic loss‐ and gain‐of‐function approaches. Loss of canonical Notch signaling results in normal iris development but absence of the ciliary body. This causes progressive hypotony and over time leads to phthisis bulbi, a condition characterized by shrinkage of the eye and loss of structure/function. Conversely, Notch gain‐of‐function results in aniridia and profound ciliary body hyperplasia, which causes ocular hypertension and glaucoma‐like disease. Collectively, these data indicate that Notch signaling promotes ciliary body development at the expense of iris formation and reveals novel animal models of human ocular pathologies.
Metabotropic glutamate receptor 1 mediates melanocyte transformation via transactivation of insulin‐like growth factor 1 receptor
Authors: Teh Jessica L. F. , Shah Raj , Shin Seung‐Shick , Wen Yu , Mehnert Janice M. , Goydos James , Chen Suzie 
Published: March 2014

SummaryOur laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1‐mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet‐R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both mGluR1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable mGluR1‐melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between mGluR1 and tyrosine kinase, insulin‐like growth factor 1 receptor (IGF‐1R).
Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma
Authors: Jeck William R. , Parker Joel , Carson Craig C. , Shields Janiel M. , Sambade Maria J. , Peters Eldon C. , Burd Christin E. , Thomas Nancy E. , Chiang Derek Y. , Liu Wenjin , Eberhard David A. , Ollila David , Grilley‐Olson Juneko , Moschos Stergios , Neil Hayes D. , Sharpless Norman E. 
Published: March 2014

SummarySomatic sequencing of cancers has produced new insight into tumorigenesis, tumor heterogeneity, and disease progression, but the vast majority of genetic events identified are of indeterminate clinical significance. Here, we describe a NextGen sequencing approach to fully analyzing 248 genes, including all those of known clinical significance in melanoma. This strategy features solution capture of DNA followed by multiplexed, high‐throughput sequencing and was evaluated in 31 melanoma cell lines and 18 tumor tissues from patients with metastatic melanoma. Mutations in melanoma cell lines correlated with their sensitivity to corresponding small molecule inhibitors, confirming, for example, lapatinib sensitivity in ERBB4 mutant lines and identifying a novel activating mutation of BRAF. The latter event would not have been identified by clinical sequencing and was associated with responsiveness to a BRAF kinase inhibitor. This approach identified focal copy number changes of PTEN not found by standard methods, such as comparative genomic hybridization (CGH). Actionable mutations were found in 89% of the tumor tissues analyzed, 56% of which would not be identified by standard‐of‐care approaches. This work shows that targeted sequencing is an attractive approach for clinical use in melanoma.
Topical Photodynamic Therapy Using Different Porphyrin Precursors Leads to Differences in Vascular Photosensitization and Vascular Damage in Normal Mouse Skin
Authors: Middelburg Tom A. , de Vijlder Hannah C. , de Bruijn Henriette S. , van der Ploeg‐van den Heuvel Angélique , Neumann H. A. Martino , de Haas Ellen R. M. , Robinson Dominic J. 
Published: March 2014

AbstractDifferent distributions of hexyl aminolevulinate (HAL), aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) in the superficial vasculature are not well studied but they are hypothesized to play an important role in topical photodynamic therapy (PDT). The colocalization of fluorescent CD31 and protoporphyrin IX (PpIX) was calculated using confocal microscopy of mouse skin sections to investigate the vascular distribution after topical application. Vascular damage leads to disruption of the normal endothelial adherens junction complex, of which CD144 is an integral component. Therefore, normal CD31 combined with loss of normal fluorescent CD144 staining was visually scored to assess vascular damage. Both the vascular PpIX concentration and the vascular damage were highest for HAL, then ALA and then MAL. Vascular damage in MAL was not different from normal contralateral control skin. This pattern is consistent with literature data on vasoconstriction after PDT, and with the hypothesis that the vasculature plays a role in light fractionation that increases efficacy for HAL and ALA‐PDT but not for MAL. These findings indicate that endothelial cells of superficial blood vessels synthesize biologically relevant PpIX concentrations, leading to vascular damage. Such vascular effects are expected to influence the oxygenation of tissue after PDT which can be important for treatment efficacy.
Measuring health literacy – the Swedish Functional Health Literacy scale
Authors: Wångdahl Josefin M. , Mårtensson Lena I. 
Published: March 2014

BackgroundThe benefits of health promotion efforts vary due to a complexity of reasons. One possible reason for an absence of effects is the level of functional health literacy among the individuals that participate in the interventions. Thus, valid and reliable instruments that capture these kinds of skills are needed. The aim of this study was to develop a Swedish Functional Health Literacy scale to use in health promotion and health prevention by translating the Japanese Functional Health Literacy scale into Swedish and testing some aspects of its validity and test–retest reliability.MethodsThe research project comprised six phases including translation and back translation, validity tests of the two first versions of the instrument based on interviews with professionals and representatives for the target group of the instrument, and a test–retest of the first version among target groups.ResultsThe items in the first two versions were experienced as unclear, which led to improvements of the next version. The final version of the translated instrument (the Swedish Functional Literacy scale) showed evidence of content validity, and the test–retest confirmed that the instrument had stability over time with a percentage agreement for the items ranging from 63% to 92% (M = 77.2%).ConclusionThe items in the Swedish version of the scale are equivalent to the original Japanese scale in terms of language and contents and cover the major aspects of functional health literacy as it is defined in the literature. The translated instrument shows stability over time, that is, reliability, at least for a part of the Swedish population. More validity tests of the Swedish Functional Health Literacy scale based on a broader population are needed.