Overrepresentation of Injection Drug Use Route of Infection Among Human Immunodeficiency Virus Long-term Nonprogressors: A Nationwide, Retrospective Cohort Study in China, 1989-2016.

BackgroundWhy some persons living with human immunodeficiency virus (HIV) (PLWH) progress quickly and others remain "healthy" for a decade or more without treatment remains a fundamental question of HIV pathology. We aimed to assess the epidemiological characteristics of HIV long-term nonprogressors (LTNPs) based on a cohort of PLWH in China observed between 1989 and 2016.MethodsWe conducted a nationwide, retrospective cohort study among Chinese PLWH with HIV diagnosed before 1 January 2008. Records were extracted from China's national HIV/AIDS database on 30 June 2016. LTNPs were defined as those with AIDS-free, antiretroviral therapy-naive survival, with CD4 cell counts consistently ≥500/μL for ≥8 years after diagnosis. Prevalence was calculated, characteristics were described, and determinants were assessed by means of logistic regression. Potential sources of bias were also investigated.ResultsOur cohort included 89 201 participants, of whom 1749 (2.0%) were categorized as LTNPs. The injection drug use (IDU) route of infection was reported by 70.7% of LTNPs, compared with only 37.1% of non-LTNPs. The odds of LTNP status were greater among those infected via IDU (adjusted odds ratio [95% confidence interval], 2.28 [1.94-2.68]) and with HIV diagnosed in settings with large populations of persons who inject drugs (1.75 [1.51-2.02] for detention centers, 1.61 [1.39-1.87] for Yunnan, 1.94 [1.62-2.31] for Guangdong, and 2.90 [2.09-4.02] for Xinjiang).ConclusionsOverrepresentation of the IDU route of infection among LTNPs is a surprising finding worthy of further study, and this newly defined cohort may be particularly well suited to exploration of the molecular biological mechanisms underlying HIV long-term nonprogression

On single and double soft behaviors in NLSM

In this paper, we study the single and double soft behaviors of tree level off-shell currents and on-shell amplitudes in nonlinear sigma model(NLSM). We first propose and prove the leading soft behavior of the tree level currents with a single soft particle. In the on-shell limit, this single soft emission becomes the Adler's zero. Then we establish the leading and sub-leading soft behaviors of tree level currents with two adjacent soft particles. With a careful analysis of the on-shell limit, we obtain the double soft behaviors of on-shell amplitudes where the two soft particles are adjacent to each other. By applying Kleiss-Kuijf (KK) relation, we further obtain the leading and sub-leading behaviors of amplitudes with two nonadjacent soft particles.Comment: 41 pages, 6 tables, 9 figures, minor revised, more content about nonadjacent double soft limit, update the reference

Synthesis and antibacterial activity against ralstonia solanacearum for novel hydrazone derivatives containing a pyridine moiety

<p>Abstract</p> <p>Background</p> <p><it>Ralstonia solanacearum</it>, one of the most important bacterial diseases on plants, is a devastating, soil-borne plant pathogen with a global distribution and an unusually wide host range. In order to discover new bioactive molecules and pesticides acting on tobacco bacterial wilt, we sought to combine the active structure of hydrazone and pyridine together to design and synthesize a series of novel hydrazone derivatives containing a pyridine moiety.</p> <p>Results</p> <p>A series of hydrazone derivatives containing a pyridine moiety were synthesized. Their structures were characterized by ¹H-NMR, ¹³C-NMR, IR, and elemental analysis. The preliminary biological activity tests showed that compound 3e and 3g exhibited more than 80% activity against <it>Ralstonia solanacearum </it>at 500 mg/L, especially compound 3g displayed relatively good activity to reach 57.0% at 200 mg/L.</p> <p>Conclusion</p> <p>A practical synthetic route to hydrazone derivatives containing a pyridine moiety by the reaction of intermediates 2 with different aldehydes in ethanol at room temperature using 2-chloronicotinic acid and 2-amino-5-chloro-3-methylbenzoic acid as start materials is presented. This study suggests that the hydrazone derivatives containing a substituted pyridine ring could inhibit the growth of <it>Ralstonia solanacearum</it>.</p

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients

Impaired Resting-State Functional Integrations within Default Mode Network of Generalized Tonic-Clonic Seizures Epilepsy

Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Computer simulation of leadership, consensus decision making and collective behaviour in humans

The aim of this study is to evaluate the reliability of a crowd simulation model developed by the authors by reproducing Dyer et al.’s experiments(published in Philosophical Transactions in 2009) on human leadership and consensus decision-­making in a computer-­based environment. The theoretical crowd model of the simulation environment is presented, and its results are compared and analysed against Dyer et al.’s original experiments. It is concluded that the results are 11 largely consistent with the experiments, which demonstrates the reliability of the crowd model. Furthermore, the simulation data also reveals several additional new findings, namely: 1) the phenomena of sacrificing accuracy to reach a quicker consensus decision found in ants colonies was also discovered in the simulation; 2) the ability of reaching consensus in groups has a direct impact on the time and accuracy of arriving at the target position; 3) the positions of the informed individuals or leaders in the crowd could have significant impact on the overall crowd movement; 4) the simulation also confirmed Dyer et al.’s anecdotal evidence of the proportion of the leadership in large crowds and its effect on crowd movement. The potential applications of these findings are highlighted in the final discussion of this paper

Exploring the usability of a connected autonomous vehicle human machine interface designed for older adults

Users of Level 4–5 connected autonomous vehicles (CAVs) should not need to intervene with the dynamic driving task or monitor the driving environment, as the system will handle all driving functions. CAV human-machine interface (HMI) dashboards for such CAVs should therefore offer features to support user situation awareness (SA) and provide additional functionality that would not be practical within non-autonomous vehicles. Though, the exact features and functions, as well as their usability, might differ depending on factors such as user needs and context of use. The current paper presents findings from a simulator trial conducted to test the usability of a prototype CAV HMI designed for older adults and/or individuals with sensory and/or physical impairments: populations that will benefit enormously from the mobility afforded by CAVs. The HMI was developed to suit needs and requirements of this demographic based upon an extensive review of HMI and HCI principles focused on accessibility, usability and functionality [1, 2], as well as studies with target users. Thirty-one 50-88-year-olds (M 67.52, three 50–59) participated in the study. They experienced four seven-minute simulated journeys, involving inner and outer urban settings with mixed speed-limits and were encouraged to explore the HMI during journeys and interact with features, including a real-time map display, vehicle status, emergency stop, and arrival time. Measures were taken pre-, during- and post- journeys. Key was the System Usability Scale [3] and measures of SA, task load, and trust in computers and automation. As predicted, SA decreased with journey experience and although cognitive load did not, there were consistent negative correlations. System usability was also related to trust in technology but not trust in automation or attitudes towards computers. Overall, the findings are important for those designing, developing and testing CAV HMIs for older adults and individuals with sensory and/or physical impairments