Task-oriented Dialogue System for Automatic Disease Diagnosis via Hierarchical Reinforcement Learning

In this paper, we focus on automatic disease diagnosis with reinforcement learning (RL) methods in task-oriented dialogues setting. Different from conventional RL tasks, the action space for disease diagnosis (i.e., symptoms) is inevitably large, especially when the number of diseases increases. However, existing approaches to this problem employ a flat RL policy, which typically works well in simple tasks but has significant challenges in complex scenarios like disease diagnosis. Towards this end, we propose to integrate a hierarchical policy of two levels into the dialogue policy learning. The high level policy consists of a model named master that is responsible for triggering a model in low level, the low level policy consists of several symptom checkers and a disease classifier. Experimental results on both self-constructed real-world and synthetic datasets demonstrate that our hierarchical framework achieves higher accuracy in disease diagnosis compared with existing systems. Besides, the datasets (http://www.sdspeople.fudan.edu.cn/zywei/data/Fudan-Medical-Dialogue2.0) and codes (https://github.com/nnbay/MeicalChatbot-HRL) are all available now

Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B-/- mouse model of ASD. Male and female Shank3B-/- mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions

T cells establish and maintain CNS viral infection in HIV-infected humanized mice

The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell–only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/ CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state

Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo

Long-lasting, latently infected resting CD4+ T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy (ART). Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir1. Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect2–9. Here we show that activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of ART-suppressed bone-marrow–liver–thymus (BLT) humanized mice and rhesus macaques infected with HIV and SIV, respectively. Analysis of resting CD4+ T cells from tissues after AZD5582 treatment revealed increased SIV RNA expression in the lymph nodes of macaques and robust induction of HIV in almost all tissues analysed in humanized mice, including the lymph nodes, thymus, bone marrow, liver and lung. This promising approach to latency reversal—in combination with appropriate tools for systemic clearance of persistent HIV infection—greatly increases opportunities for HIV eradication

Numerical study on the smoke movement and control in main roadway for mine fires occurred in branch

Mine exogenous fire is the main disaster in coal mines. Owing to the complicated structure and the ventilation network, the smoke movement and control in branched roadway fires of coal mines is more complicated than that in traffic tunnel fires. In this study, the smoke backlayering length and critical velocity in a main roadway for fires that occurred in a branch were studied with varying fire locations. The results suggest that the smoke from the branch does not spread along the width centerline of the main roadway, but forms an early “snake-shaped” structure. The variation of dimensionless backlayering length with the dimensionless variable ln(Q˙*1/3/V*) is divided into two regions with different slopes by the line of L* = 1.6. Besides, branched roadway fires have a lower backlayering length and critical velocity compared to single-hole tunnel fires. These two parameters increase with decreasing the fire-node distance. Combined with dimensionless analysis and simulation results, calculation models considering fire location were proposed to estimate the smoke backlayering length and critical velocity. The credibility of prediction models is validated by comparing them with simulation results. The outcomes of the current study guide smoke control in similar-structured mine roadways and traffic tunnels

Olfactory Ensheathing Cells Alleviate Facial Pain in Rats with Trigeminal Neuralgia by Inhibiting the Expression of P2X7 Receptor

Trigeminal neuralgia (TN) is a common facial neuropathic pain that is mainly characterized by spontaneous or induced needling or electric shock pain in the innervation area of the trigeminal nerve. It is also referred to as “the cancer that never dies”. The olfactory ensheathing cell (OEC) is a special glial cell in the nervous system that has a strong supportive function in nerve regeneration. Cell transplantation therapy is a useful treatment modality that we believe can be applied in TN management. In this study, OECs were transplanted into the ligation site of the infraorbital nerve of rats. We found that after the OEC transplantation, mechanical pain threshold in the face of the rats was significantly increased. Western blotting, immunofluorescence assay, and reverse transcription-quantitative polymerase chain reaction were performed on the trigeminal ganglia (TG) of model rats. The results revealed a decrease in the expression of P2X7 receptor (P2X7R) in the trigeminal ganglia. Our findings show that OEC transplantation has a good therapeutic effect on TN in rats, and that can reduce the expression of P2X7R in trigeminal ganglia. Therefore, we think that OEC transplantation may be a suitable treatment for TN

Development of Plastid Genomic Resources for Discrimination and Classification of Epimedium wushanense (Berberidaceae)

Epimedium wushanense (Berberidaceae) is recorded as the source plant of Epimedii Wushanensis Folium in the Chinese Pharmacopoeia. However, controversies exist on the classification of E. wushanense and its closely related species, namely, E. pseudowushanense, E. chlorandrum, E. mikinorii, E. ilicifolium, and E. borealiguizhouense. These species are often confused with one another because of their highly similar morphological characteristics. This confusion leads to misuse in the medicinal market threatening efficiency and safety. Here, we studied the plastid genomes of these Epimedium species. Results show that the plastid genomes of E. wushanense and its relative species are typical circular tetramerous structure, with lengths of 156,855–158,251 bp. A total of 112 genes were identified from the Epimedium plastid genomes, including 78 protein-coding, 30 tRNA, and 4 rRNA genes. A loss of rpl32 gene in E. chlorandrum was found for the first time in this study. The phylogenetic trees constructed indicated that E. wushanense can be distinguished from its closely related species. E. wushanense shows a closer relationship to species in ser. Dolichocerae. In conclusion, the use of plastid genomes contributes useful genetic information for identifying medicinally important species E. wushanense and provides new evidence for understanding phylogenetic relationships within the Epimedium genus

Epidemiological, clinical and histological characteristics of HBV/HDV co-infection: a retrospective cross-sectional study in Guangdong, China.

The epidemiology of hepatitis D virus (HDV) in China is fairly unknown. The mechanisms whereby HDV leads to accelerated liver disease in hepatitis B virus (HBV)/HDV co-infected patients and the histological characteristics of chronic hepatitis D (CHD) patients need further investigation.The prevalence of HDV was retrospectively evaluated in all consecutive hospitalized patients with chronic HBV infection from May 2005 to October 2011. HBV/HDV co-infected patients and HBV mono-infected patients were compared clinically and histologically. Significant histological abnormality was defined as significant necroinflammation (grade ≥A2) and/or significant fibrosis (stage ≥ F2).6.5% of patients (426/6604) tested positive for IgM anti-HDV. HDV was more common in patients over 50 years old than those under 50 (11.7% vs. 5.1%, P5×ULN respectively.The prevalence of HDV is not low in patients with chronic HBV infection. HDV may contribute to progression to ESLD through late-phase HBV DNA reactivation