bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholic acid for hepatic steatosis in patients with lipodystrophy: a randomized, controlled trial
Authors: Ahmad Zahid , Subramanyam Lalitha , Szczepaniak Lidia , Simha Vinaya , Adams-Huet Beverley , Garg Abhimanyu 
Published: February 2013

ObjectiveHepatic steatosis is a common complication in patients with lipodystrophies and can lead to cirrhosis. There is no proven effective therapy for hepatic steatosis, but cholic acid (CA), a farnesoid X receptor agonist, has previously been shown to reduce hepatic triglyceride (TG) content in mice and serum TG in humans. Our objective was to assess clinical efficacy and tolerability of CA therapy in patients with lipodystrophy and hepatic steatosis.DesignA randomized, double-blind, placebo-controlled, crossover study.MethodsEighteen patients with genetic or autoimmune lipodystrophies and elevated hepatic TG content participated in the study. The intervention was CA (15 mg/kg per day) compared with placebo for a period of 6 months each. Hepatic TG content, the primary outcome variable, was measured with1H magnetic resonance spectroscopy at baseline and at 3 and 6 months during each study period. Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and TG were secondary end points of the study.ResultsCompared with placebo, CA did not reduce (median (interquartile range) hepatic TG content (14.8% (9.4–19.0%) vs 15.9% (10.5–26.5%) respectively;P=0.42) or serum TG ((340 mg/dl (233–433 mg/dl) vs 390 mg/dl (233–595 mg/dl) respectively;P=0.45)). CA therapy also did not change AST, ALT, or GGT levels. Two patients developed diarrhea and excessive flatus while taking CA and these symptoms resolved after reducing the dose of CA.ConclusionCA was well tolerated but did not reduce hepatic TG content in patients with lipodystrophy.
An Experimental Investigation of the Interactions among Intentions, Reciprocity, and Control
Authors: Christ Margaret H. 
Published: February 2013

ABSTRACT
Prior academic research finds that formal controls can cause employees to engage in dysfunctional behaviors (e.g., decreased effort, fraud, or theft). This study investigates one specific aspect of formal control that contributes to employees' negative reactions—employees' beliefs about management's intentions signaled by the control. I use two interactive experiments to examine the effects on employee effort and firm profit of: (1) employees' beliefs regarding management's intentions when implementing control (i.e., perceived intentionality), and (2) employees' preferences for reciprocity. Consistent with prior literature, I find that formal control can cause employees to exert low effort, resulting in reduced firm profit. However, I find that the adverse consequences only occur when management clearly imposes the control and, therefore, employees interpret it as a signal of distrust. Further, employees respond negatively to controls that are unambiguously imposed by managers, even when managers have entrusted them with a large amount of resources. Thus, when employees are faced with simultaneous, conflicting signals regarding managers' trust, the distrust signaled by the control crowds out employees' positive reciprocity. Alternatively, when managers' intentions for imposing control are ambiguous or clearly do not signal distrust (i.e., it is exogenously imposed), the control does not cause such negative effects. I find that all of the observed effects persist over time. In supplemental analysis, I also find that managers accurately predict that employees' response to formal control is influenced by their beliefs regarding management's intentions, and entrust fewer resources to employees when they have imposed the control than when it is imposed exogenously. The results of this study suggest that organizations should carefully consider employees' beliefs about management's intentions when implementing formal controls, because these beliefs influence employee behavior.
Electrical response of ammonium-rich water ice
Authors: Stillman David E. , Macgregor Joseph A. , Grimm Robert E. 
Published: February 2013

AbstractThe electrical properties of water ice impact the study of diverse frozen environments, in particular the radar sounding of ice masses. The high-frequency response of meteoric polar ice depends partly on the bulk concentration of ammonium (NH4+), but the nature of this response has been unclear. Here we use broadband dielectric spectroscopy to investigate the electrical response of laboratory-frozen solutions. By analyzing the relaxation frequency of these samples and its temperature dependence, we show that the mobility of Bjerrum D-defects formed in the ice lattice by ammonium is 1.4 ±0.8 x 10–9m2 V–1 s–1 at -20°C, or about an order of magnitude smaller than that of Bjerrum L-defects formed by chloride. However, co-substitution of both ions increases the ice-lattice solubility of chloride by a factor of ∼7, causing an enhanced conductivity response due to greater concentrations of Bjerrum L-defects. Thus, despite its low mobility, ammonium can also affect the high-frequency electrical response of polar ice, but its covariance with chloride must be considered.
Automated Volumes-of-Interest Identification for Classical and Atypical Parkinsonian Syndrome Differentiation Using T2’ MR Imaging
Authors: Schmidt-Richberg A. , Treszl A. , Hilgetag C. , Fiehler J. , Münchau A. , Handels H. , Boelmans K. , Forkert N. D. 
Published: February 2013

Summary
Objectives: In clinical routine, patients with classical Parkinsonian syndromes (CPS) need to be differentiated from those with atypical Parkinsonian syndromes (APS), particularly with respect to prognosis and treatment decision. To date, this diagnosis is mainly based on clinical criteria, leading to failure rates up to 25%, motivating the development of image-based decision support systems. Magnetic resonance imaging (MRI) and in particular T2´ image sequences have been suggested as a potential marker for differential diagnosis. The aim of this study was to investigate whether automatically identified T2´ volumes-of-interest (VOIs) can be used for an automatic differentiation of CPS and APS patients.
Material and Methods: 74 MRI datasets were available for this hypothesis generating trial, including image sequences from 24 healthy subjects, 33 CPS and 17 APS patients. First, a problem-specific reference atlas was generated using the healthy control datasets. Next, patients’ datasets were registered to the atlas. Voxel-wise t-tests, reflecting significance levels of T2´ value differences between CPS and APS patients, were then applied for calculation of a p-map. Finally, the calculated p-map was thresholded and a connected component analysis was performed for final VOI detection. In parallel, manually defined VOIs were determined in grey and white matter for comparison.
Results: Three VOIs in parts of the basal ganglia and the left occipital lobe were automatically identified by the presented method. There was a trend for higher area under the curve on multivariable receiver operating characteristic curves for automatically determined VOIs over manually defined VOIs (0.939 vs. 0.818, p = 0.0572).
Conclusion: The diagnostic role of automatically defined VOIs in differentiation of CPS and APS patients based on T2´ image sequences should be further investigated.
Winged fruits and associated leaves of Shorea (Dipterocarpaceae) from the Late Eocene of South China and their phytogeographic and paleoclimatic implications
Authors: Feng Xinxin , Tang Biao , Kodrul Tatiana M. , Jin Jianhua 
Published: February 2013

• Premise of the study: Dipterocarps are the representative component of tropical rain forests in Southeast Asia and hold important economic and ecological significance, but their origin and migration are controversial. Information on dipterocarpaceous fossils, particularly the more convincing reproductive structures, not only can improve the phylogenetic and phytogeographic studies of this family, but also provide important information for reconstructing paleoclimate.• Methods: Morphologically preserved winged fruits and associated leaves were collected from the Late Eocene Huangniuling Formation, Maoming Basin, South China. We determined their taxonomic positions based on comparative morphology with similar extant and fossil specimens and discuss their phytogeographic and paleoclimatic implications by consulting the distribution and habitat of fossil and modern populations.• Key results: The Late Eocene winged fruits are attributed to Shorea Roxburgh ex Gaertner (Dipterocarpaceae) as Shorea maomingensis sp. nov. The associated leaves are recognized as Shorea sp. based on leaf architecture, and they are likely to be conspecific with the winged fruits.• Conclusions: The discovery of dipterocarps indicates that they had arrived in tropical and humid South China by the Late Eocene. Dipterocarps including Shorea exhibit a wide range of physiological tolerance to climate; palynological analysis suggests an increase in aridity and seasonality in the Maoming Basin from the Late Eocene. Dipterocarps became adapted to this seasonal climate from the Late Eocene to Early Miocene, expanded northward in the climatic optimum of the Middle Miocene, and declined and gradually disappeared from the southeastern part of the continent from the Late Miocene.
Inbreeding depression and partitioning of genetic load in the invasive biennial Alliaria petiolata (Brassicaceae)
Authors: Mullarkey Alicia A. , Byers Diane L. , Anderson Roger C. 
Published: February 2013

• Premise of the study: Invasive species are nonnative species that enter novel environments, establish sustained populations, and can negatively impact native species. Here we assess a potential weakness of invasive species (genetic load) and show how species might overcome genetic barriers. Colonization of novel habitats by invasive species typically involves few individuals, exposing populations to founder effects. We empirically tested a central Illinois population of an invasive biennial plant, Alliaria petiolata, for evidence of a founder effect by assessing the pattern of genetic load.• Methods: To estimate genetic load, we assayed offspring from three cross types (self‐pollinated, outcrossed within‐ and between‐populations) in a greenhouse. Vegetative and reproductive traits were measured on first‐year plants grown with or without intraspecific competition.• Key results: We found substantial genetic load in this population of A. petiolata, which can mostly be attributed to genetic drift (founder effect) and not inbreeding depression. Between‐population heterosis was expressed more than inbreeding depression under intraspecific competition.• Conclusions: Inbreeding may be adaptive for A. petiolata in its introduced range by providing reproductive assurance, with limited inbreeding load. Nevertheless, most of the genetic load in this population of A. petiolata is due to fixation of deleterious alleles. Drift load is expected, given that this population is near the edge of its continuous geographic range in highly fragmented habitats, and gene flow between isolated populations is likely highly limited. Preventing additional introduction and movement of propagules between isolated local populations should reduce heterosis and A. petiolata competitiveness.
Refractive Error Assessment: Influence of Different Optical Elements and Current Limits of Biometric Techniques
Authors: Ribeiro Filomena , Castanheira-Dinis Antonio , Dias Joao Mendanha 
Published: February 2013

PURPOSE:
To identify and quantify sources of error on refractive assessment using exact ray tracing.

METHODS:
The Liou-Brennan eye model was used as a starting point and its parameters were varied individually within a physiological range. The contribution of each parameter to refractive error was assessed using linear regression curve fits and Gaussian error propagation analysis. A MonteCarlo analysis quantified the limits of refractive assessment given by current biometric measurements.

RESULTS:
Vitreous and aqueous refractive indices are the elements that influence refractive error the most, with a 1% change of each parameter contributing to a refractive error variation of +1.60 and −1.30 diopters (D), respectively. In the phakic eye, axial length measurements taken by ultrasound (vitreous chamber depth, lens thickness, and anterior chamber depth [ACD]) were the most sensitive to biometric errors, with a contribution to the refractive error of 62.7%, 14.2%, and 10.7%, respectively. In the pseudophakic eye, vitreous chamber depth showed the highest contribution at 53.7%, followed by postoperative ACD at 35.7%. When optic measurements were considered, postoperative ACD was the most important contributor, followed by anterior corneal surface and its asphericity. A MonteCarlo simulation showed that current limits of refractive assessment are 0.26 and 0.28 D for the phakic and pseudophakic eye, respectively.

CONCLUSIONS:
The most relevant optical elements either do not have available measurement instruments or the existing instruments still need to improve their accuracy. Ray tracing can be used as an optical assessment technique, and may be the correct path for future personalized refractive assessment.
Implantation of Three-Piece Silicone Toric Additive IOLs in Challenging Clinical Cases With High Astigmatism
Authors: Thomas Bettina C. , Auffarth Gerd U. , Reiter Josef , Holzer Mike P. , Rabsilber Tanja M. 
Published: February 2013

PURPOSE:
To analyze the refractive outcomes and safety of three-piece silicone toric sulcus-fixated add-on intraocular lenses (IOLs) (HumanOptics/Dr.Schmidt Intraocularlinsen, Erlangen, Germany) in complex clinical cases with high astigmatism such as in cases with previous penetrating keratoplasty.

METHODS:
Interventional case series of 21 eyes of 20 patients enrolled at two German centers. Functional results including power vector analysis, accuracy of IOL power calculation, rotational stability, and postoperative complications were evaluated from 2 months to 6 years postoperatively.

RESULTS:
The preoperative subjective cylinder exceeded or was equal to −6.00 diopters (D) in 81% of eyes (range: −2.00 to −17.00 D). The median follow-up period was 7.6 months (range: 57 days to 6 years). The efficacy analysis focused on the 2 to 6 months follow-up visit. Postoperatively, there was a median reduction of astigmatism by 70.59% (subjective cylinder range: 0.00 to −5.00 D), improvement of uncorrected distance visual acuity, and unchanged median corrected distance visual acuity. The attempted spherical equivalent was achieved within ± 0.50 D in 45% and within ± 1.00 D in 65% of cases. Five eyes received secondary surgical alignment of axis. Other complications related to the surgical procedure were mainly transient shortly after implantation, such as intraocular pressure elevation (2 of 21 eyes) or corneal edema (2 of 21 eyes). Persisting changes were seen only in rare cases and included pigment dispersion (1 of 21 eyes) or corneal edema requiring a second keratoplasty within 9 months after surgery (2 of 21 eyes).

CONCLUSIONS:
Toric add-on IOLs may be useful in reducing high astigmatism and anisometropia and increasing spectacle independence even in complex clinical conditions with high refractive errors.
Fast Dendritic Cells Stimulated with Alternative Maturation Mixtures Induce Polyfunctional and Long-Lasting Activation of Innate and Adaptive Effector Cells with Tumor-Killing Capabilities
Authors: Massa Chiara , Seliger Barbara 
Published: February 2013

Abstract
The clinical usage of dendritic cells (DC) for tumor immunotherapy still requires improvements. In this study, three alternative maturation mixtures were compared with the cytokine-based gold standard, and the overall interaction of the resulting DC with effector cells from the innate as well as the adaptive immunity was evaluated in healthy donors. Stimulation with the TLR-4 ligand monophosphoryl lipid A together with IFN-γ (alt-2 DC) resulted in DC with the highest levels of costimulatory molecule expression and IL-12p70/IL-10 ratio. Whereas all alternative DC were able to induce NK and γδ T cells to acquire cytotoxic properties and secrete type 1 and proinflammatory cytokines, after both short (20-h)- and long (5–8 d)-time coculture, secretion of IFN-γ by the innate populations was induced in response to alt-2 and alt-1 DC (TNF-α, IFN-α, IFN-γ, IL-1β, poly IC), but not to alt-3 DC (TNF-α, IFN-γ, IL-1β, CL097). Regarding CD8+ T cell–mediated Ag-specific immune responses, a heterogeneous pattern of responses was obtained among the healthy donors, suggesting rather a competition than a synergy among the different effector cells. Our data promote further evaluation of alt-2 fast DC for translatability into clinical immunotherapy trials, while also fostering the need to identify biomarkers for immune cell responsiveness and tumor susceptibility to be able to select for each patient the best possible DC-based therapy.
Impaired TLR5 Functionality Is Associated with Survival in Melioidosis
Authors: West T. Eoin , Chantratita Narisara , Chierakul Wirongrong , Limmathurotsakul Direk , Wuthiekanun Vanaporn , Myers Nicolle D. , Emond Mary J. , Wurfel Mark M. , Hawn Thomas R. , Peacock Sharon J. , Skerrett Shawn J. 
Published: February 2013

Abstract
Melioidosis is infection caused by the flagellated saprophyte Burkholderia pseudomallei. TLR5 is a pathogen recognition receptor activated by bacterial flagellin. We studied a genetic variant that encodes a defective TLR5 protein, TLR51174C&gt;T, to elucidate the role of TLR5 in melioidosis. We measured NF-κB activation induced by B. pseudomallei in human embryonic kidney–293 cells transfected with TLR5 and found that B. pseudomallei induced TLR51174C- but not TLR51174T-dependent activation of NF-κB. We tested the association of TLR51174C&gt;T with outcome in 600 Thai subjects with melioidosis. In a dominant model, TLR51174C&gt;T was associated with protection against in-hospital death (adjusted odds ratio: 0.20; 95% confidence interval: 0.08–0.50; p = 0.001) and organ failure (adjusted odds ratio: 0.37; 95% confidence interval: 0.19–0.71; p = 0.003). We analyzed blood cytokine production induced by flagellin or heat-killed B. pseudomallei by TLR51174C&gt;T genotype in healthy subjects. Flagellin induced lower monocyte-normalized levels of IL-6, IL-8, TNF-α, IL-10, MCP-1, IL-1ra, G-CSF, and IL-1β in carriers of TLR51174T compared with carriers of TLR51174C. B. pseudomallei induced lower monocyte-normalized levels of IL-10 in carriers of TLR51174T. We conclude that the hypofunctional genetic variant TLR51174C&gt;T is associated with reduced organ failure and improved survival in melioidosis. This conclusion suggests a deleterious immunoregulatory effect of TLR5 that may be mediated by IL-10 and identifies this receptor as a potential therapeutic target in melioidosis.
Macrophage Scavenger Receptor A Promotes Tumor Progression in Murine Models of Ovarian and Pancreatic Cancer
Authors: Neyen Claudine , Plüddemann Annette , Mukhopadhyay Subhankar , Maniati Eleni , Bossard Maud , Gordon Siamon , Hagemann Thorsten 
Published: February 2013

Abstract
Alternatively activated macrophages express the pattern recognition receptor scavenger receptor A (SR-A). We demonstrated previously that coculture of macrophages with tumor cells upregulates macrophage SR-A expression. We show in this study that macrophage SR-A deficiency inhibits tumor cell migration in a coculture assay. We further demonstrate that coculture of tumor-associated macrophages and tumor cells induces secretion of factors that are recognized by SR-A on tumor-associated macrophages. We tentatively identified several potential ligands for the SR-A receptor in tumor cell–macrophage cocultures by mass spectrometry. Competing with the coculture-induced ligand in our invasion assay recapitulates SR-A deficiency and leads to similar inhibition of tumor cell invasion. In line with our in vitro findings, tumor progression and metastasis are inhibited in SR-A−/− mice in two in vivo models of ovarian and pancreatic cancer. Finally, treatment of tumor-bearing mice with 4F, a small peptide SR-A ligand able to compete with physiological SR-A ligands in vitro, recapitulates the inhibition of tumor progression and metastasis observed in SR-A−/− mice. Our observations suggest that SR-A may be a potential drug target in the prevention of metastatic cancer progression.
Cell-Seeded Extracellular Matrices for Bladder Reconstruction: An ex vivo Comparative Study of their Biomechanical Properties
Authors: Davis Niall F. , Mooney Rory , Piterina Anna V. , Callanan Anthony , Flood Hugh D. , McGloughlin Tim M. 
Published: February 2013

Purpose Autogenous ileal tissue remains the gold-standard biomaterial for bladder replacement purposes; however, cell-seeded extracellular matrix (ECM) scaffolds have shown promise. Although the biological advantages of cell-seeded ECMs in urological settings are well documented, there is a paucity of data available on their biomechanical properties. In this study, the biomechanical properties of cell-seeded ECMs are compared with autogenous ileal tissue. Methods Human urothelial cells (UCs) and smooth muscle cells (SMCs) were obtained by bladder biopsy and cultured onto porcine urinary bladder matrix (UBM) scaffolds under dynamic and static growth conditions for 14 days. The biomechanical properties of cell-seeded UBM (n = 12), and porcine ileum (n = 12) were determined with uni-axial tensile testing protocols and compared with stress-strain curves. In addition, their biomechanical properties were compared with porcine bladder tissue (n = 12) and unseeded UBM (n = 12). Results There were significant differences in the biomechanical properties of each biomaterial assessed. Strain to failure occurred at 92 ± 24% for dynamically cultured cell-seeded UBM compared to 42.2 ± 5.20% for ileal tissue (p<0.01). Values for linear stiffness at 30% strain were significantly lower in dynamically cultured cell-seeded UBM compared to ileal tissue (0.36 ± 0.14 MPa versus 0.67 ± 0.32 MPa respectively, p<0.01). Bladder tissue remained the most distensible biomaterial throughout, with linear stiffness measuring 0.066 ± 0.034 MPa at 30% strain. Conclusions Dynamically cultured cell-seeded ECMs are biomechanically superior to ileal tissue for bladder replacement purposes. Additional comparative in vivo studies will be necessary before their role as a reliable alternative is clearly established.