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  • Anker Levin posted an update 4 months, 1 week ago

    The convergence of artificial intelligence (AI) and precision medicine promises to revolutionize health care. Precision medicine methods identify phenotypes of patients with less-common responses to treatment or unique healthcare needs. AI leverages sophisticated computation and inference to generate insights, enables the system to reason and learn, and empowers clinician decision making through augmented intelligence. Recent literature suggests that translational research exploring this convergence will help solve the most difficult challenges facing precision medicine, especially those in which nongenomic and genomic determinants, combined with information from patient symptoms, clinical history, and lifestyles, will facilitate personalized diagnosis and prognostication.

    There are important differences in the treatment and prognosis of adult intracranial low-grade ependymomas (grade II) versus anaplastic ependymomas (grade III). We evaluated the value of the apparent diffusion coefficient (ADC) for differentiating these two tumors and further investigated the relationship between ADC values and the Ki-67 proliferation index.

    Clinical and preoperative magnetic resonance imaging data of 35 cases of adult intracranial ependymomas were retrospectively analyzed, including 20 low-grade ependymomas and 15 anaplastic ependymomas. The minimum ADC (ADCmin), average ADC (ADCmean), and normalized ADC (nADC) were compared between the two groups. Receiver operating characteristic curves were drawn to evaluate the differentiating accuracy of ADC values. The Ki-67 proliferation index of the solid tumor components was also measured to explore its relationship with ADC values.

    The ADCmin (.89±.17 vs. .66±.09 × 10

    mm

    /second), ADCmean (.98±.21 vs. .72±.11 × 10

    mm

    /second), and nADeir treatment.Infections by flaviviruses, such as Dengue, West Nile, Yellow Fever and Zika viruses, represent a growing risk for global health. There are vaccines only for few flaviviruses while no effective treatments are available. Flaviviruses share epidemiological, structural, and ecologic features and often different viruses can co-infect the same host. Therefore, the identification of broad-spectrum inhibitors is highly desirable either for known flaviviruses or for viruses that likely will emerge in the future. Strategies targeting both virus and host factors have been pursued to identify broad-spectrum antiflaviviral agents. In this review, we describe the most promising and best characterized targets and their relative broad-spectrum inhibitors, identified by drug repurposing/libraries screenings and by focused medicinal chemistry campaigns. Finally, we discuss about future strategies to identify new broad-spectrum antiflavivirus agents.Conotrachelus dimidiatus (Coleoptera Curculionidae) interacts with immature guava fruits (Psidium guajava L.) for feed, sleep, mate and oviposit. Determination of the volatile organic compounds (VOCs) emitted by the insect and immature fruits can help improve understanding of plant-insect and intraspecific insect interactions between females and males of C. dimidiatus. Daytime fruit setting emissions of immature guava consist mainly of limonene, caryophyllene, and aromadendrene. In addition to the host’s volatiles, the aim of this study was to assess the VOCs released by the insect. Static headspace-solid phase microextraction (SHS-SPME), combined with gas chromatography/quadrupole time of flight mass spectrometry (GC/Q-ToF-MS), allowed the identification of the C10 terpenoids grandlure I, II, II, IV, grandisoic acid, papayanol and papayanal bioactive compounds released by female and male C. dimidiatus under laboratory conditions. These chemical compounds are candidates for the preparation of a lure formulation.Some marine plankton called dinoflagellates emit light in response to the movement of surrounding water, resulting in a phenomenon called milky seas or sea sparkle. The underlying concept, a shear-stress induced permeabilisation of biocatalytic reaction compartments, is transferred to polymer-based nanoreactors. Amphiphilic block copolymers that carry nucleobases in their hydrophobic block are self-assembled into polymersomes. The membrane of the vesicles can be transiently switched between an impermeable and a semipermeable state by shear forces occurring in flow or during turbulent mixing of polymersome dispersions. Nucleobase pairs in the hydrophobic leaflet separate when mechanical force is applied, exposing their hydrogen bonding motifs and therefore making the membrane less hydrophobic and more permeable for water soluble compounds. This polarity switch is used to release payload of the polymersomes on demand, and to activate biocatalytic reactions in the interior of the polymersomes.

    It has been proposed that different stages of bipolar disorder may be underpinned by distinct neurobiological substrates. RMC-7977 molecular weight However, structural neuroimaging studies in early stages of the illness are limited by small sample sizes yielding inconsistent findings. The purpose of this systematic review and meta-analysis, therefore, was to identify regional grey matter volume (GMV) changes that are consistently associated with first episode of mania (FEM).

    Following PRISMA guidelines, we conducted a systematic search of the literature to identify Voxel-Based Morphometry (VBM) studies in FEM patients compared with healthy individuals. We then conducted a voxel-wise meta-analysis using Seed-based d-Mapping technique. Finally, we performed univariate meta-regression analyses to explore the potential effects of moderator variables including age, gender, and percentage of lithium users on GMV alterations.

    We identified 15 VBM studies and included 12 studies in the meta-analysis. Four studies found no regional differences in GM volumes while other 11 studies reported volume changes in frontal and temporal regions as well as anterior cingulate cortex (ACC), cerebellum and basal ganglia. The meta-analysis revealed a single cluster of GMV reduction in bilateral pregenual ACC in patients with FEM compared to healthy individuals (P<.001). The Egger’s test showed no evidence of publication bias at peak voxel level (P=.447). Meta-regression analyses revealed no significant effects of moderators evaluated.

    Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM.

    Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM.Peroneal nerve palsy with resultant foot drop has significant impacts on gait and quality of life. Traditional management includes ankle-foot-orthosis, tendon transfer, and arthrodesis-each with certain disadvantages. While nerve transfers for peroneal nerve injury have been reported in adults, with variable results, they have not been described in the pediatric population. We report the use of partial tibial nerve transfer for foot drop from deep peroneal nerve palsy in three pediatric patients. The first sustained a partial common peroneal nerve laceration and underwent transfer of a single tibial nerve branch to deep peroneal nerve 7 months after injury. Robust extensor hallucis longus and extensor digitorum longus reinnervation was obtained without satisfactory tibialis anterior function. The next patient sustained a thigh laceration with partial sciatic nerve injury and underwent transfer of two tibial nerve branches directly to the tibialis anterior component of deep peroneal nerve 9 months after injury. The final patient sustained a blast injury to the posterior knee and similarly underwent a double fascicular transfer directly to tibialis anterior 4 months after injury. The latter two patients obtained sufficient strength (MRC 4-5) at 1 year to discontinue orthosis. In all patients, we used flexor hallucis longus and/or flexor digitorum longus branches as donors without postoperative loss of toe flexion. Overall, our experience suggests that early double fascicular transfer to an isolated tibialis anterior target, combined with decompression, could produce robust innervation. Further study and collaboration are needed to devise new ways to treat lower extremity nerve palsies.

    Recently, serum hepatitis B virus (HBV)-RNA has been reported to be detectable even when HBV particle production is inhibited by nucleot(s)ide analogues (NAs). However, the dynamics of the HBV-RNA sequence compared with those of HBV-DNA during the emergence of antiviral resistance are yet to be elucidated.

    First, we quantified serum HBV-RNA in 181 infected patients, and its relationships with clinical characteristics as well as HBV markers were investigated. Next, we undertook simultaneous deep sequencing of HBV-RNA/HBV-DNA and their dynamics among four patients receiving NA therapy who were experiencing viral breakthrough.

    Serum HBV-RNA was detected in 25% (31/123) of cases among patients with HBV without NAs, and the detection rate was significantly high in hepatitis B e antigen-positive cases with high viral activity. In patients with chronic hepatitis, hepatitis B core-related antigen was significantly correlated with serum HBV-RNA irrespective of NA use. In the analysis of the four patients experiencing viral breakthrough, no NA resistance mutation was detected in the serum HBV-RNA immediately before the breakthrough. However, NA-resistant sequences appeared at the rates of 0%, 3%, 14%, and 100%, and the NA-resistant HBV-RNA sequence rate was correlated with the peak HBV-DNA titer multiplied by the HBV-DNA detection duration during the breakthrough (R

     = 0.978) observed before redisappearance of HBV-DNA following the addition of new NA.

    Serum HBV-RNA could reflect the transcriptional activity of covalently closed circular DNA and hepatitis B core-related antigen. The dynamics of HBV-RNA could help understanding of the turnover process of HBV covalently closed circular DNA in the liver.

    Serum HBV-RNA could reflect the transcriptional activity of covalently closed circular DNA and hepatitis B core-related antigen. The dynamics of HBV-RNA could help understanding of the turnover process of HBV covalently closed circular DNA in the liver.

    Deformable image registration (DIR) in low-contrast tissues is often suboptimal because of low visibility of landmarks, low driving-force to deform, and low penalty for misalignment. We aim to overcome the shortcomings for improved reconstruction of time-resolved four-dimensional magnetic resonance imaging (TR-4DMRI).

    Super-resolution TR-4DMRI reconstruction utilizes DIR to combine high-resolution (highR2x2x2mm

    ) breath-hold (BH) and low-resolution (lowR5x5x5mm

    ) free-breathing (FB) 3D cine (2Hz) images to achieve clinically acceptable spatiotemporal resolution. A 2-step hybrid DIR approach was developed to segment low-dynamic-range (LDR) regions low-intensity lungs and high-intensity “bodyshell” (=body-lungs) for DIR refinement after conventional DIR. The intensity in LDR regions was renormalized to the full dynamic range (FDR) to enhance local tissue contrast. A T1-mapped 4D XCAT digital phantom was created, and seven volunteers and five lung cancer patients were scanned with two BH and one 3D cine series per subject to compare the 1-step conventional and 2-step hybrid DIR using (a) the ground truth in the phantom, (b) highR-BH references, which were used to simulate 3D cine images by down-sampling and Rayleigh-noise-adding, and (c) cross-verification between two TR-4DMRI images reconstructed from two BHs.

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