Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential impact of local and regional aortic stiffness on left ventricular remodeling: a cardiovascular magnetic resonance study

Background: Left ventricular (LV) remodeling and aortic stiffness have independent predictive value for all causes and cardiovascular mortality. Because elastic properties of the arterial wall vary along the aortic pathway, we hypothesized that local and regional aortic stiffness could differently impact on LV remodeling. Methods and results: Regional aortic stiffness was determined from carotid–femoral pulse wave velocity (cfPWV) measured by aplanation tonometry. Aortic arch pulse wave velocity was measured by phase contrast cardiovascular magnetic resonance (CMR). Local stiffness was calculated in the ascending aorta pulse wave velocity (aaPWV) and descending aorta pulse wave velocity using central pulse pressure measurement, cine CMR acquisition, and surface change estimation. CMR LV remodeling was expressed as LV mass to end-diastolic volume ratio. We evaluated 146 study participants (41 ± 15 years) free of overt cardiovascular disease. In stepwise multivariate regression analysis, cfPWV and aaPWV were significantly and independently correlated to mass to end-diastolic volume ratio (partial R2 = 0.07 and R2 = 0.10, respectively, all P < 0.005) after adjustment for age, sex, BMI, brachial mean blood pressure, and central pulse pressure. Descending aorta pulse wave velocity was correlated with mass to end-diastolic volume ratio to a lower extent (R2 = 0.04, P = 0.0115) and aortic arch pulse wave velocity was not independently associated with mass to end-diastolic volume ratio. CfPWV and aaPWV were both independently associated with mass to end-diastolic volume ratio, explaining 5 and 8% of mass to end-diastolic volume ratio variance, respectively. Conclusion: In study participants free of overt cardiovascular disease, stiffness of the ascending aorta representing the local proximal aortic function face to the LV and of the downstream aortic pathway assessed by cfPWV reflecting more advanced alterations of material properties involving the entire aorta, are independent determinants of LV remodeling after adjustment to age, BMI, mean blood pressure, and sex.
Ex vivo diffusion tensor MRI of human hearts: Relative effects of specimen decomposition

Recently, diffusion tensor MRI has been utilized as a tool to reconstruct, with high resolution, the three‐dimensional myofiber orientation of hearts ex vivo. However, because of limited availability of human hearts, it is common to recover specimens postmortem, after some degree of decomposition has occurred. In this study, we describe the ability to reconstruct local fiber orientation within a unique set of human hearts using diffusion tensor MRI; relative effects of specimen decomposition were also assessed. The mean diffusivity, fractional anisotropy, and principal eigenvalues (E1, E2, and E3) were measured in hearts with varying postmortem intervals from 0 to 27 days (n = 17), and local fiber orientations were reconstructed. Mean diffusivities and principal eigenvalues nonlinearly increased as a function of postmortem interval, while fractional anisotropies nonlinearly decreased. There were good correlations between postmortem intervals and changes in diffusion properties after linear transformation of the data (R2 > 0.7). Thus, we determined that there were regional discontinuities in the reconstruction of local fiber orientation in hearts where postmortem intervals were greater than 3 days. Therefore, any delay in tissue fixation after death (if not properly preserved using organ transplantation techniques) will compromise measurement of fiber orientation and delineation of diseased pathology, e.g., based, in part, on fractional anisotropy. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.
Preoperative assessment for and outcomes of mandibular conservation surgery

The role of marginal mandibulectomy and other conservative resective procedures for patients with early cortical mandibular invasion from squamous carcinoma of the oral cavity remains poorly defined. The purpose of this retrospective study was to evaluate the efficacy of preoperative assessment for bone invasion and the outcomes of different mandibular resective procedures that preserve mandibular continuity.
Wideband characterization of the mobile radio signal in a vegetated environment

This article presents the dispersion parameters of a mobile radio channel obtained from the measurements carried out using time domain wideband sounding, in a mixed vegetated environment with buildings, with a STDCC (Swept-Time Delay Cross Correlation) sounder. In addition, some comparisons are made with parameters obtained from other publications, in similar environments, and conclusions and suggestions are given.
Controls for Managing Risks Across Different Stages of ERP Projects

Enterprise Resource Planning (ERP) implementations can be highly risky, posing numerous challenges to companies that implement them. Prior research has mainly focussed on identifying and assessing risks in ERP projects. Still little is known on mitigating risks by means of managerial control. Thus, this ongoing research aims to address these gaps by exploring how organisations exercise control in regards to identified risks during different stages of an ERP project. By using a case study approach this study particularly seeks to answer if and why control choices for risks change across different project stages. The preliminary results indicate that there is support for both, the need to collate the learnt experiences of ERP participants for these risks and their relative controls to be evaluated at all stages of the ERP project as the importance of risks and controls differ for each phase of the implementation project.
The need for more efficient trial designs

The development lifecycle of most clinical products eventually includes the requirement of clinical trials. The objective of the clinical trials usually is the demonstration of the safety and efficacy of the product. The standard methods for sample size determination of these trials have the potential to be extremely inefficient. Adaptive techniques, in certain circumstances, have the potential to result in much more efficient designs. This would then result in the reduction of unnecessary additional exposure of study subjects to experimental products, and help minimize the costs and time to arrive at a statistically appropriate answer to the primary study questions. Copyright © 2006 John Wiley & Sons, Ltd.
Nonsphericity Index and Size Ratio Identify Morphologic Differences between Growing and Stable Aneurysms in a Longitudinal Study of 93 Cases

BACKGROUND AND PURPOSE: Recent studies have strongly associated intracranial aneurysm growth with increased risk of rupture. Identifying aneurysms that are likely to grow would be beneficial to plan more effective monitoring and intervention strategies. Our hypothesis is that for unruptured intracranial aneurysms of similar size, morphologic characteristics differ between aneurysms that continue to grow and those that do not. MATERIALS AND METHODS: From aneurysms in our medical center with follow-up imaging dates in 2015, ninety-three intracranial aneurysms (23 growing, 70 stable) were selected. All CTA images for the aneurysm diagnosis and follow-up were collected, a total of 348 3D imaging studies. Aneurysm 3D geometry for each imaging study was reconstructed, and morphologic characteristics, including volume, surface area, nonsphericity index, aspect ratio, and size ratio were calculated. RESULTS: Morphologic characteristics were found to differ between growing and stable groups. For aneurysms of <3 mm, nonsphericity index (P < .001); 3–5 mm, nonsphericity index (P < .001); 5–7 mm, size ratio (P = .003); >7 mm, volume (P < .001); surface area (P < .001); and nonsphericity index (P = .002) were significant. Within the anterior communicating artery, the nonsphericity index (P = .008) and, within the posterior communicating artery, size ratio (P = .004) were significant. The nonsphericity index receiver operating characteristic area under the curve was 0.721 for discriminating growing and stable cases on the basis of initial images. CONCLUSIONS: Among aneurysms with similar sizes, morphologic characteristics appear to differ between those that are growing and those that are stable. The nonsphericity index, in particular, was found to be higher among growing aneurysms. The size ratio was found to be the second most significant parameter associated with growth.
Pyoverdin is essential for virulence of Pseudomonas aeruginosa

The role of pyoverdin, the main siderophore in iron-gathering capacity produced by Pseudomonas aeruginosa, in bacterial growth in vivo is controversial, although iron is important for virulence. To determine the ability of pyoverdin to compete for iron with the human iron-binding protein transferrin, wild-type P. aeruginosa ATCC 15692 (PAO1 strain) and PAO pyoverdin-deficient mutants were grown at 37 degrees C in bicarbonate-containing succinate medium to which apotransferrin had been added. Growth of the pyoverdin-deficient mutants was fully inhibited compared with that of the wild type but was restored when pyoverdin was added to the medium. Moreover, when growth took place at a temperature at which no pyoverdin production occurred (43 degrees C), the wild-type PAO1 strain behaved the same as the pyoverdin-deficient mutants, with growth inhibited by apotransferrin in the presence of bicarbonate and restored by pyoverdin supplementation. Growth inhibition was never observed in bicarbonate-free succinate medium, whatever the strain and the temperature for growth. In vivo, in contrast to results obtained with the wild-type strain, pyoverdin-deficient mutants demonstrated no virulence when injected at 10(2) CFU into burned mice. However, virulence was restored when purified pyoverdin originating from the wild-type strain was supplemented during the infection. These results strongly suggest that pyoverdin competes directly with transferrin for iron and that it is an essential element for in vivo iron gathering and virulence expression in P. aeruginosa. Rapid removal of iron from [59Fe]ferritransferrin by pyoverdin in vitro supports this view.
Modelling the radionuclide contamination of the Black Sea in the result of Chernobyl accident using circulation model and data assimilation

Assimilation of observations is a powerful tool to improve the predictive capabilities of models for radionuclide transport and fate. We describe results of numerical experiments on assimilation of the data on radionuclide contamination of the Black Sea in the result of Chernobyl accident using the three-dimensional model of circulation and radionuclide transport THREETOX. Data assimilation can be formulated as a procedure that contains two steps: update and forecast. On the update step THREETOX is run from the time of release or deposition to the time of the forecast using the updated input from all the measured data available at this period to be assimilated. On the forecast step THREETOX is run from the forecast time to the end of the modeling period using the results of the update step to produce the forecast of radionuclide transport. The data assimilation method called "method of iterations to optimal solution" (IOS) was used at the update step. The approach has been applied to the assimilation of the observational data of 137 Cs concentration measured in the "Typhoon" surveys for the period June 1986 to September 1990. From the results of numerical experiments we conclude that usage of a data assimilation procedure can essentially improve predictive capability of the models for radionuclide transport. The computational time for the data assimilation method chosen is small in comparison with the general time of calculations. Results from the study will provide a better understanding of the processes of radionuclide transport in the seas. This novel approach was implemented in the EU DSS RODOS for the real-time simulation of radioactivity transport in the marine environment.
Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer

Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)–polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T2-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers.
PFK 1 Glycosylation Is a Key Regulator of Cancer Cell Growth and Central Metabolic Pathways

Cancer cells need to meet the metabolic demands of rapid cell growth within a continually changing microenvironment. Genetic mechanisms for reprogramming cellular metabolism toward proliferative, pro-survival pathways are well-reported. However, post-translational mechanisms, which would enable more rapid, reversible adaptations of cellular metabolism in response to protein signaling or environmental sensing systems, are less well understood. Here we demonstrate that the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) is a key metabolic regulator of glucose metabolism. O-GlcNAc is dynamically induced at Ser529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibits PFK1 activity and redirects the flux of glucose from glycolysis through the pentose phosphate pathway (PPP), thereby conferring a selective growth advantage to cancer cells. Blocking glycosylation of PFK1 at Ser529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal an unexpected mechanism for the regulation of metabolic enzymes and pathways, and pinpoint a new therapeutic approach for combating cancer. Rapid physiological response is critical for the growth of tumors, which must satisfy the metabolic demands of increased cell proliferation in the face of a dynamically changing microenvironment. It is now well established that cancer cells undergo significant reprogramming of their cellular metabolism to facilitate the efficient generation of ATP, nucleotide and lipid precursors for macromolecular synthesis, and NADPH to maintain redox homeostasis (1-5). Mutations in tumor suppressors and oncogenic pathways are known to contribute to these altered metabolic phenotypes (1, 6-8), but such changes constitute a slower, more permanent response compared to the rapid, reversible responses needed to adapt to tumor microenvironments in vivo. Integration of metabolic flux with rapid-response mechanisms, such as phosphorylation or other post-translational mechanisms, would provide cancer cells with the ability to regulate cellular physiology ‡To whom correspondence should be addressed. lhw@caltech.edu. Supporting Online Material www.sciencemag. org/cgi/content/full/ NIH Public Access Author Manuscript Science. Author manuscript; available in PMC 2013 January 03. Published in final edited form as: Science. 2012 August 24; 337(6097): 975–980. doi:10.1126/science.1222278.
Virologic Failure in First-Line Human Immunodeficiency Virus Therapy with a CCR5 Entry Inhibitor, Aplaviroc, plus a Fixed-Dose Combination of Lamivudine-Zidovudine: Nucleoside Reverse Transcriptase Inhibitor Resistance Regardless of Envelope Tropism

ABSTRACT The CCR102881 (ASCENT) study evaluated the antiviral activity of the novel CCR5 entry inhibitor aplaviroc plus a fixed-dose combination of lamivudine-zidovudine (Combivir) in drug-naïve human immunodeficiency virus type 1-infected subjects with only CCR5-tropic virus detected in plasma. Although the trial was stopped prematurely due to idiosyncratic hepatotoxicity, eight subjects met protocol-defined virologic failure criteria. Clonal analyses of the viral envelope tropism, aplaviroc susceptibility, and env sequencing were performed on plasma at baseline and at the time of virologic failure. Molecular evolutionary analyses were also performed. The majority of the subjects with virologic failure (six of eight) acquired the lamivudine resistance-associated mutation M184V, and none had evidence of reduced susceptibility to aplaviroc at the time of virologic failure, even at the clonal level. Six subjects with virologic failure maintained CCR5 tropism, while two exhibited a change in population tropism readout to dual/mixed-tropic with R5X4-tropic clones detected prior to therapy. Two evolutionary patterns were observed: five subjects had no evidence of population turnover, while three subjects had multiple lines of evidence for env population turnover. The acquisition of the M184V mutation is the primary characteristic of virologic failure in first-line therapy with aplaviroc plus lamivudine-zidovudine, regardless of the envelope tropism.
Role of intestinal mucus on the uptake of latex beads by Peyer's patches and on their transport to mesenteric lymph nodes in rats.

BACKGROUND The effects of N-acetylcysteine (NAC) as a mucolytic agent on the uptake of fluorescent polystyrene microparticles by Peyer's patches, on intestinal permeability, and on subsequent transport to mesenteric lymph nodes (MLNs) were investigated to establish the role of mucus gel layer in this process. METHODS Twenty rats were divided into two groups: control (n = 10) and NAC (n = 10). Fluorescent polystyrene latex beads of 3.2+/-0.2 microm in diameter were used as a probe for measuring the previously mentioned parameters. The solution of latex beads (0.1 mL) was injected into a 2-cm length of ileal loop containing Peyer's patches, with 0.1 mL of saline (control group) or with 0.1 mL of NAC solution (NAC group) within 10 cm proximal from the ileocaecal valve. Intestinal loops, portal blood, and neighboring MLNs were taken within 1 hour of injection. Intestinal sections were stained by periodic acid-Schiff reagent. Peyer's patches and MLNs were analyzed for the count of particles by image analysis using a confocal laser scanning microscope. RESULTS Morphologically, periodic acid-Schiff positive uniform mucus gel was present in front of Peyer's patches of the control group, and mucus gel layer was disrupted and noncontinuous in the NAC group. The number of particles within Peyer's patches and MLNs in the NAC group was significantly higher than that in the control group (p<.001). Intestinal permeability of latex beads in the NAC group was significantly higher than that in the control group (p<.001). CONCLUSIONS These data suggest that the mucus gel layer located in front of Peyer's patches is one of the important factors for the uptake of noxious macromolecules, and this in turn plays a major role on small intestinal permeability and subsequent translocation to MLNs.
Uses and misuses of definitions of genetic polymorphism. A perspective from population pharmacogenetics.

Definitions of genetic polymorphism currently employed in the pharmacological literature have been incorrectly used (Kalow, 1984) and uncritically imported from population genetics [e.g., Weinshilboum (1984), Evans (1977)], apparently without regard to the problems their application might present in pharmacogenetics or, more specifically, in pharmacogenetic studies of populations. Since a strong background in population genetics is not widespread amongst population pharmacogeneticists and especially amongst pharmacologists, there is a growing danger that these definitions will be misinterpreted or incorrectly used, as research on potentially polymorphic biotransformation routes increases. The term polymorphism was first defined by E. B. Ford who stated that
A comparison of comorbidity measurements to predict healthcare expenditures.

OBJECTIVE To compare the performance of the Elixhauser, Charlson, and RxRisk-V comorbidity indices and several simple count measurements, including counts of prescriptions, physician visits, hospital claims, unique prescription classes, and diagnosis clusters. STUDY DESIGN Each measurement was calculated using claims data during a 1-year period before the initial filling of an antihypertensive medication among 20 378 members of a managed care organization. The primary outcome variable was the log-transformed sum of prescription, physician, and hospital expenditures in the year following the prescription encounter. METHODS In addition to descriptive statistics and Spearman rank correlations between measurements, the predictive performance was determined using linear regression models and corresponding adjusted R(2) statistics. RESULTS The Charlson index and the Elixhauser index performed similarly (adjusted R(2) = 0.1172 and 0.1148, respectively), while the prescription claims-based RxRisk-V (adjusted R(2) = 0.1573) outperformed both. An age- and gender-adjusted regression model that included a count of diagnosis clusters was the best individual predictor of payments (adjusted R(2) = 0.1814). This outperformed age- and gender-adjusted models of the number of unique prescriptions filled (adjusted R(2) = 0.1669), number of prescriptions filled (R(2) = 0.1573), number of physician visits (adjusted R(2) = 0.1546), logtransformed prior healthcare payments (adjusted R(2) = 0.1359), and number of hospital claims (adjusted R(2) = 0.1115). CONCLUSION Simple count measurements appear to be better predictors of future expenditures than the comorbidity indices, with a count of diagnosis clusters being the single best predictor of future expenditures among the measurements examined.
Exploiting a Large Strongly Comparable Corpus

This article describes a large comparable corpus for Basque and Spanish and the methods employed to build a parallel resource from the original data. The EITB corpus, a strongly comparable corpus in the news domain, is to be shared with the research community, as an aid for the development and testing of methods in comparable corpora exploitation, and as basis for the improvement of data-driven machine translation systems for this language pair. Competing approaches were explored for the alignment of comparable segments in the corpus, resulting in the design of a simple method which outperformed a state-of-the-art method on the corpus test sets. The method we present is highly portable, computationally efficient, and significantly reduces deployment work, a welcome result for the exploitation of comparable corpora.