890 research outputs found

    Diagnosis Code Assignment Using Sparsity-Based Disease Correlation Embedding

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    © 1989-2012 IEEE. With the latest developments in database technologies, it becomes easier to store the medical records of hospital patients from their first day of admission than was previously possible. In Intensive Care Units (ICU), modern medical information systems can record patient events in relational databases every second. Knowledge mining from these huge volumes of medical data is beneficial to both caregivers and patients. Given a set of electronic patient records, a system that effectively assigns the disease labels can facilitate medical database management and also benefit other researchers, e.g., pathologists. In this paper, we have proposed a framework to achieve that goal. Medical chart and note data of a patient are used to extract distinctive features. To encode patient features, we apply a Bag-of-Words encoding method for both chart and note data. We also propose a model that takes into account both global information and local correlations between diseases. Correlated diseases are characterized by a graph structure that is embedded in our sparsity-based framework. Our algorithm captures the disease relevance when labeling disease codes rather than making individual decision with respect to a specific disease. At the same time, the global optimal values are guaranteed by our proposed convex objective function. Extensive experiments have been conducted on a real-world large-scale ICU database. The evaluation results demonstrate that our method improves multi-label classification results by successfully incorporating disease correlations

    Vpr14-88-Apobec3G Fusion Protein Is Efficiently Incorporated into Vif-Positive HIV-1 Particles and Inhibits Viral Infection

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    APOBEC3G (A3G), a deoxycytidine deaminase, is a potent host antiviral factor that can restrict HIV-1 infection. During Vif-negative HIV-1 replication, A3G is incorporated into HIV-1 particles, induces mutations in reverse transcribed viral DNA and inhibits reverse transcription. However, HIV-1 Vif counteracts A3G's activities by inducing its degradation and by blocking its incorporation into HIV-1 particles. Thus, it is interesting to elucidate a mechanism that would allow A3G to escape the effects of Vif in order to rescue its potent antiviral activity and to provide a possible novel therapeutic strategy for treating HIV-1 infection.In this study, we generated an R88-A3G fusion protein by fusing A3G to a virion-targeting polypeptide (R14-88) derived from HIV-1 Vpr protein and compared its antiviral effects relative to those of HA-tagged native A3G (HA-A3G). Our study showed that transient expression of the R88-A3G fusion protein in both Vif(-) and Vif(+) HIV-1 producing cells drastically inhibited viral infection in HeLa-CD4-CCR5-cells, CD4(+) C8166 T cells and human primary PBMCs. Moreover, we established CD4(+) C8166 T cell lines that stably express either R88-A3G or HA-A3G by transduction with VSV-G-pseudotyped lentiviral vector that harbor expression cassettes for R88-A3G or HA-A3G, respectively, and tested their susceptibility to Vif(+) HIV-1 infection. Our results clearly reveal that expression of R88-A3G in transduced CD4(+) C8166 cells significantly blocked Vif(+) HIV-1 infection. In an attempt to understand the mechanism underlying the antiviral activity of R88-A3G, we demonstrated that R88-A3G was efficiently incorporated into viral particles in the presence of Vif. Moreover, PCR analysis revealed that R88-A3G significantly inhibited viral cDNA synthesis during the early stage of Vif(+) virus infection.Our results clearly indicate that R88 delivers A3G into Vif(+) HIV-1 particles and inhibits infectivity and spread of the virions among CD4(+) T cells. This study provides evidence for an effective strategy to modify a host protein with innate anti-HIV-1 activity and rescue its potent anti-HIV potential in the presence of Vif. Further characterization and optimization of this system may lead to the development of an effective therapeutic approach against HIV-1 infection

    Re-evaluating early breast neoplasia

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    Historically, histomorphological and epidemiological data suggested that atypical ductal hyperplasia and ductal carcinoma in situ are the earliest recognizable neoplastic stages of breast cancer progression. Over the past several years, detailed high-throughput molecular genetic, gene expression and epigenetic analyses have enhanced our understanding of these early neoplastic lesions and have re-shaped our view of human breast cancer progression to include multiple distinct pathways of evolution

    Long-standing Small-scale Reconnection Processes at Saturn Revealed by Cassini

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    The internal mass source from the icy moon Enceladus in Saturn’s rapidly rotating magnetosphere drives electromagnetic dynamics in multiple spatial and temporal scales. The distribution and circulation of the internal plasma and associated energy are thus crucial in understanding Saturn’s magnetospheric environment. Magnetic reconnection is one of the key processes in driving plasma and energy transport in the magnetosphere, and also a fundamental plasma process in energizing charged particles. Recent works suggested that reconnection driven by Saturn’s rapid rotation might appear as a chain of microscale structures, named drizzle-like reconnection. The drizzle-like reconnection could exist not only in the nightside magnetodisk, but also in the dayside magnetodisk. Here, using in situ measurements from the Cassini spacecraft, we report multiple reconnection sites that were successively detected during a time interval longer than one rotation period. The time separation between two adjacently detected reconnection sites can be much less than one rotation period, implying that the reconnection processes are likely small-scale, or frequently repetitive. The spatial distribution of the identified long-standing multiple small reconnection site sequences shows no significant preference on local times. We propose that the small reconnection sites discussed in this Letter are rotationally driven and rotate with the magnetosphere. Since the reconnection process on Saturn can be long-durational, the rotational regime can cause these smallscale reconnection sites to spread to all local times, resulting in global release of energy and mass from the magnetosphere

    The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

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    The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with Ssubstitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening

    Unexpected elevated alanine aminotransferase, asparte aminotransferase levels and hepatitis E virus infection among persons who work with pigs in accra, ghana

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    <p>Abstract</p> <p>Background</p> <p>Several studies have suggested that elevated serum alanine aminotransferase (ALT) and asparte aminotransferase (AST) may be markers of hepatitis E virus (HEV) infection. Thus, individuals with elevated ALT and AST may have ongoing subclinical infection of HEV. We estimated the prevalence of anti-HEV antibodies and serum ALT and AST levels among persons who work with pigs in Accra, Ghana.</p> <p>Results</p> <p>Three hundred and fifty- persons who work with pigs provided blood samples for unlinked anonymous testing for the presence of antibodies to HEV, ALT and AST levels. The median age of participants was 32.85 ± 11.38 years (range 15-70 years). HEV seroprevelance was 34.84%. Anti-HEV IgG was detected in 19.26% while anti-HEV IgM was detected in 15.58% of the persons who tested positive. On multivariate analysis, the independent determinants of HEV infection were, being employed on the farm for less than six months [odds ratio (OR) 8.96; 95% confidence interval (95% CI) 5.43-14.80], having piped water in the household and/or on the farm (OR 13.33; 95% CI 5.23-33.93) and consumption of alcohol (OR 4.91: 95% CI 2.65-9.10). Levels >3× the expected maximum were found for both ALT and AST among individuals who tested positive for anti-HEV IgG (ALT, 210.17 ± 11.64 U/L; AST, 127.18 ± 11.12 U/L) and anti-HEV IgM (ALT, 200.97 ± 10.76 U/L; AST, 120.00 ± 15.96 U/L).</p> <p>Conclusion</p> <p>Consistent with similar studies worldwide, the results of our studies revealed a high prevalence of HEV infection, ALT and AST values in pig handlers.</p

    Flow characteristic of highly underexpanded jets from various nozzle geometries

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    Flow characteristics of highly underexpanded jets at the same nozzle pressure ratio of 5.60 but issuing from four different nozzles, i.e., the circular, elliptic, square, and rectangular nozzles, are studied using large eddy simulations. The results show that the square jet penetrates fastest, although the turbulence transition is similar for different jets. The penetration rates of different jets show the similar linear dependency on the square root of time, but the penetration constant Gamma for the noncircular jets deviates more than 5% from the theoretical value of 3.0. The circular and square jets both correspond to a three-dimensional helical instability mode, while the elliptic and rectangular jets haveatwo-dimensional flapping instability in their minor axis planes. All the jets undergo a Mach reflection forming the Mach disk, but the Mach disk in the elliptic and rectangular jets is not easily visible. The intercepting shocks in the square jet originate at the four corners of the nozzle exit at first, while the formation of the intercepting shocks is only observed in the major axis planes for the elliptic and rectangular jets. In addition, great differences are observed on the mixing characteristics between different jets. In particular, the elliptic jet penetrates slowest, has the shortest length of jet potential core, and takes the largest mixing area. (C) 2017 Elsevier Ltd. All rights reserved.</p
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