Quantification of HTLV-I proviral load in experimentally infected rabbits

BACKGROUND: Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection. RESULTS: A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1. CONCLUSION: Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals

Demystifying Structural Disparity in Graph Neural Networks: Can One Size Fit All?

Recent studies on Graph Neural Networks(GNNs) provide both empirical and theoretical evidence supporting their effectiveness in capturing structural patterns on both homophilic and certain heterophilic graphs. Notably, most real-world homophilic and heterophilic graphs are comprised of a mixture of nodes in both homophilic and heterophilic structural patterns, exhibiting a structural disparity. However, the analysis of GNN performance with respect to nodes exhibiting different structural patterns, e.g., homophilic nodes in heterophilic graphs, remains rather limited. In the present study, we provide evidence that Graph Neural Networks(GNNs) on node classification typically perform admirably on homophilic nodes within homophilic graphs and heterophilic nodes within heterophilic graphs while struggling on the opposite node set, exhibiting a performance disparity. We theoretically and empirically identify effects of GNNs on testing nodes exhibiting distinct structural patterns. We then propose a rigorous, non-i.i.d PAC-Bayesian generalization bound for GNNs, revealing reasons for the performance disparity, namely the aggregated feature distance and homophily ratio difference between training and testing nodes. Furthermore, we demonstrate the practical implications of our new findings via (1) elucidating the effectiveness of deeper GNNs; and (2) revealing an over-looked distribution shift factor on graph out-of-distribution problem and proposing a new scenario accordingly.Comment: 54 pages, 24 figure

miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase

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Immunologic Changes during Pandemic (H1N1) 2009, China

We analyzed changes in immunologic values over time for 28 hospitalized patients with pandemic (H1N1) 2009. Levels of interleukin-6, interferon-γ, and interleukin-10 increased 1 day after illness onset and then decreased to baseline levels. Levels of virus-specific antibody were undetectable 1 day after illness onset and peaked 36 days later

Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization for refractory non-small-cell lung cancer and its impact on quality of life: A multicenter prospective study

ObjectiveThis study aimed to prospectively observe the efficacy and safety of CalliSpheres drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) for refractory non-small-cell lung cancer (NSCLC).MethodsThe interventional therapy plan was as follows: 300–500 μm CalliSpheres drug-loaded microspheres were loaded with epirubicin, and then slow embolization of tumor supplying artery was performed after microcatheter superselection. Chest enhanced computed tomography and related hematological examination were reviewed after 2 months of DEB-BACE, and the tumor response after the first interventional therapy was evaluated using modified response evaluation criteria in solid tumors. The overall survival (OS) of patients was determined, and the quality of life and the incidence rate of adverse reactions were observed.ResultsFrom January 2019 to January 2021, 43 patients with refractory NSCLC were enrolled. The patients were followed up until June 2022. All 43 patients underwent DEB-BACE 1.79 ± 0.69 times on average. The 3-, 6-, 12-, and 24-month survival rates were 100%, 86.0%, 41.9%, and 11.8%, respectively. The median OS was 11.5 months. After the first interventional treatment, cough and wheezing significantly improved in 31 patients, hemoptysis was effectively controlled in 12 patients, and superior vena cava compression disappeared in 2 patients after 2 times of treatment. The general health status of the patients after treatment significantly improved compared with that before treatment, including the improvement in physical and emotional functions. Fatigue, nausea and vomiting, dyspnea, and insomnia improved significantly after treatment. No serious adverse events, such as spinal cord injury and cerebral embolism, were observed during the perioperative period. The main adverse reaction after DEB-BACE was chest pain (13/43, grade 1) followed by fever (10/43, grade 1–2), which was significantly relieved within 3–5 days after symptomatic treatment. Other adverse reactions included irritating cough, nausea and vomiting, and bone marrow suppression, and the incidence was less than 20%.ConclusionsDEB-BACE was effective and safe in treating refractory NSCLC, which could significantly improve patients’ quality of life and was worthy of clinical promotion and application

Thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis (TRACE trial): protocol of a multicentre, randomised, double-blind, placebo-controlled, parallel-group trial

Introduction Infected pancreatic necrosis (IPN) and its related septic complications are the major causes of death in patients with acute necrotising pancreatitis (ANP). Therefore, the prevention of IPN is of great clinical value, and immunomodulatory therapy with thymosin alpha 1 may be beneficial. This study was designed to test the hypothesis that the administration of thymosin alpha 1 during the acute phase of ANP will result in a reduced incidence of IPN. Methods and analysis This is a randomised, multicentre, double-blind, placebo-controlled study. 520 eligible patients with ANP will be randomised in a 1:1 ratio to receive either the thymosin alpha 1 or the placebo using the same mode of administration. The primary endpoint is the incidence of IPN during the index admission. Most of the secondary endpoints will be registered within the index admission including in-hospital mortality, the incidence of new-onset organ failure and new-onset persistent organ failure (respiration, cardiovascular and renal), receipt of new organ support therapy, requirement for drainage or necrosectomy, bleeding requiring intervention, human leucocyte antigens-DR(HLA-DR) on day 0, day 7, day 14, and so on and adverse events. Considering the possibility of readmission, an additional follow-up will be arranged 90 days after enrolment, and IPN and death at day 90 will also be served as secondary outcomes. Ethics and dissemination This study was approved by the ethics committee of Jinling Hospital, Nanjing University (Number 2015NZKY-004-02). The thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis(TRACE) trial was designed to test the effect of a new therapy focusing on the immune system in preventing secondary infection following ANP. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration number ClinicalTrials.gov Registry (NCT02473406)

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte