Temporomandibular Joint Disorders in Patients with Rheumatoid Arthritis

BackgroundTemporomandibular joint disorders (TMD) are not uncommon in patients with rheumatoid arthritis (RA). However, the extent of involvement and its clinical relevance have not been well characterized. This study evaluated the correlation between the severity of RA-related TMD and RA, as well as determined the potential predictors for early identification and management of TMD in RA patients.MethodsWe sequentially recruited 56 adult RA patients from our Arthritis Clinic. TMD and RA were surveyed, clinically by questionnaires and physical examinations, and radiologically by tomography in TMD and conventional radiography in RA. The patients were stratified into no, mild and severe TMD groups according to the physical and tomographic examinations. The correlation of the severity of TMD and RA were evaluated. The relative importance of relevant predictors of severe TMD was analyzed by a logistic regression model.ResultsPhysical and radiologic temporomandibular joint abnormalities were found to be highly prevalent (85.7% and 74.5%) in these patients, and the occurrence increased to as much as 92.9% when the 2 data sets were combined. More than half of the patients had severe TMD presenting with debilitating symptoms or with a significant degree of bony destruction. The severity of TMD was variably correlated with RA severity. The score of hand-joint space narrowing was found to be the most influential predictor of severe TMD by logistic regression analysis.ConclusionThere was a high prevalence of TMD in RA patients. The severity of TMD variably correlated with RA severity. Clinically, a high score of hand-joint space narrowing may serve as an early indicator of RA patients at risk of severe TMD. This may facilitate early management and prevent the functional impairment of the temporomandibular joint

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy

Attractive or Faithful? Popularity-Reinforced Learning for Inspired Headline Generation

With the rapid proliferation of online media sources and published news, headlines have become increasingly important for attracting readers to news articles, since users may be overwhelmed with the massive information. In this paper, we generate inspired headlines that preserve the nature of news articles and catch the eye of the reader simultaneously. The task of inspired headline generation can be viewed as a specific form of Headline Generation (HG) task, with the emphasis on creating an attractive headline from a given news article. To generate inspired headlines, we propose a novel framework called POpularity-Reinforced Learning for inspired Headline Generation (PORL-HG). PORL-HG exploits the extractive-abstractive architecture with 1) Popular Topic Attention (PTA) for guiding the extractor to select the attractive sentence from the article and 2) a popularity predictor for guiding the abstractor to rewrite the attractive sentence. Moreover, since the sentence selection of the extractor is not differentiable, techniques of reinforcement learning (RL) are utilized to bridge the gap with rewards obtained from a popularity score predictor. Through quantitative and qualitative experiments, we show that the proposed PORL-HG significantly outperforms the state-of-the-art headline generation models in terms of attractiveness evaluated by both human (71.03%) and the predictor (at least 27.60%), while the faithfulness of PORL-HG is also comparable to the state-of-the-art generation model.Comment: AAAI 202

NCNet: Deep Learning Network Models for Predicting Function of Non-coding DNA

The human genome consists of 98.5% non-coding DNA sequences, and most of them have no known function. However, a majority of disease-associated variants lie in these regions. Therefore, it is critical to predict the function of non-coding DNA. Hence, we propose the NCNet, which integrates deep residual learning and sequence-to-sequence learning networks, to predict the transcription factor (TF) binding sites, which can then be used to predict non-coding functions. In NCNet, deep residual learning networks are used to enhance the identification rate of regulatory patterns of motifs, so that the sequence-to-sequence learning network may make the most out of the sequential dependency between the patterns. With the identity shortcut technique and deep architectures of the networks, NCNet achieves significant improvement compared to the original hybrid model in identifying regulatory markers

Crystal Structure of the Receptor-Binding Domain from Newly Emerged Middle East Respiratory Syndrome Coronavirus

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans

Stage-Specific Expression of TNFα Regulates Bad/Bid-Mediated Apoptosis and RIP1/ROS-Mediated Secondary Necrosis in Birnavirus-Infected Fish Cells

Infectious pancreatic necrosis virus (IPNV) can induce Bad-mediated apoptosis followed by secondary necrosis in fish cells, but it is not known how these two types of cell death are regulated by IPNV. We found that IPNV infection can regulate Bad/Bid-mediated apoptotic and Rip1/ROS-mediated necrotic death pathways via the up-regulation of TNFα in zebrafish ZF4 cells. Using a DNA microarray and quantitative RT-PCR analyses, two major subsets of differentially expressed genes were characterized, including the innate immune response gene TNFα and the pro-apoptotic genes Bad and Bid. In the early replication stage (0–6 h post-infection, or p.i.), we observed that the pro-inflammatory cytokine TNFα underwent a rapid six-fold induction. Then, during the early-middle replication stages (6–12 h p.i.), TNFα level was eight-fold induction and the pro-apoptotic Bcl-2 family members Bad and Bid were up-regulated. Furthermore, specific inhibitors of TNFα expression (AG-126 or TNFα-specific siRNA) were used to block apoptotic and necrotic death signaling during the early or early-middle stages of IPNV infection. Inhibition of TNFα expression dramatically reduced the Bad/Bid-mediated apoptotic and Rip1/ROS-mediated necrotic cell death pathways and rescued host cell viability. Moreover, we used Rip1-specific inhibitors (Nec-1 and Rip1-specific siRNA) to block Rip1 expression. The Rip1/ROS-mediated secondary necrotic pathway appeared to be reduced in IPNV-infected fish cells during the middle-late stage of infection (12–18 h p.i.). Taken together, our results indicate that IPNV triggers two death pathways via up-stream induction of the pro-inflammatory cytokine TNFα, and these results may provide new insights into the pathogenesis of RNA viruses