Effectiveness and safety of co-administration of moxifloxacin with netilmicin in drug-resistant tuberculosis patients, and its impact on inflammatory factors and immune function

Purpose: To study the effectiveness and safety of co-administration of moxifloxacin with netilmicin in drug-resistant tuberculosis (TB) patients, and its impact on levels of inflammatory factors and immune function. Methods: We enrolled 100 patients with drug-resistant TB admitted to People’s Hospital of Rizhao between May 2017 and October 2019. The patients were randomly allocated to control group and study group, with 50 patients per group. The control group received moxifloxacin at a dose of 0.2 g t.i.d. for 6 months and the study group received netilmicin at a dose of 0.1 g t.i.d. plus. The response, incidence of adverse reactions, expression levels of inflammatory factors, immune function, and sputum-negative status after 2, 4 and 6 months of TB treatment were compared. Results: The study group showed markedly higher response than the control group (p < 0.05). Moreover, there were lower incidence of adverse effects in the study group than in the control group (p < 0.05). The expression levels of inflammatory factors were significantly lower in the study group, while the concentrations of CD3+, CD4+, and CD8+ were markedly higher (p < 0.05). After 2, 4 and 6 months of TB treatment, cases of sputum-negative conversion were significantly higher in the study group than in the control group (p < 0.05). Conclusion: Co-administration of moxifloxacin with netilmicin produces much higher effectiveness and safety than moxifloxacin monotherapy, decreases inflammatory factor levels and improves immune function in patients with drug-resistant TB

TripleRE: Knowledge Graph Embeddings via Tripled Relation Vectors

Translation-based knowledge graph embedding has been one of the most important branches for knowledge representation learning since TransE came out. Although many translation-based approaches have achieved some progress in recent years, the performance was still unsatisfactory. This paper proposes a novel knowledge graph embedding method named TripleRE with two versions. The first version of TripleRE creatively divide the relationship vector into three parts. The second version takes advantage of the concept of residual and achieves better performance. In addition, attempts on using NodePiece to encode entities achieved promising results in reducing the parametric size, and solved the problems of scalability. Experiments show that our approach achieved state-of-the-art performance on the large-scale knowledge graph dataset, and competitive performance on other datasets

NCOA3 Loss Disrupts Molecular Signature of Chondrocytes and Promotes Posttraumatic Osteoarthritis Progression

Background/Aims: Osteoarthritis (OA) is the most common joint disease. Recently, a novel variant near the nuclear receptor coactivator 3 (NCOA3) has been identified in association with greater risk of developing OA. However, how NCOA3 is regulated in chondrocytes and involved in OA pathogenesis remain elusive. Methods: The expression and DNA methylation of NCOA3 in knee OA cartilage and in vitro dedifferentiated chondrocytes with or without rs6094710 SNP were analyzed by qRT-PCR, immunoblotting, methylation-specific PCR and bisulfite sequencing. NCOA3 was depleted by siRNA or shRNA or inhibited by a chemical inhibitor to assess its role in chondrocyte dedifferentiation or OA pathogenesis in posttraumatic OA animal model established by cruciate ligament transection surgery. Results: We found that compared with normal counterparts, samples with rs6094710 SNP failed to upregulate NCOA3. Further evidence associated this phenotype with DNMT1-mediated hypermethylation in gene promoter region. Moreover, we showed that NCOA3 maintained the molecular signature of chondrocytes dedifferentiating in vitro or exposed to IL-1β, nevertheless, NCOA3 appeared dispensable for preventing OA initiation, since NCOA3 loss did not trigger OA in young mice. Instead, NCOA3 loss promoted posttraumatic OA progression, and in parallel, enhanced NF-κB activation. Finally, the promoted posttraumatic OA progression was significantly retarded when administrated with NF-κB pathway inhibitor, suggesting that NCOA3 lose promotes posttraumatic OA at least partially by enhancing NF-κB activation. Conclusion: Thus, our findings indicate a critical role of NCOA3 in chondrocytes, and imply that manipulating NCOA3 might present a potential therapeutic approach to interfere OA progression

DeteX: A highly accurate software for detecting SNV and InDel in single and paired NGS data in cancer research

Background: Genetic testing is becoming more and more accepted in the auxiliary diagnosis and treatment of tumors. Due to the different performance of the existing bioinformatics software and the different analysis results, the needs of clinical diagnosis and treatment cannot be met. To this end, we combined Bayesian classification model (BC) and fisher exact test (FET), and develop an efficient software DeteX to detect SNV and InDel mutations. It can detect the somatic mutations in tumor-normal paired samples as well as mutations in a single sample.Methods: Combination of Bayesian classification model (BC) and fisher exact test (FET).Results: We detected SNVs and InDels in 11 TCGA glioma samples, 28 clinically targeted capture samples and 2 NCCL-EQA standard samples with DeteX, VarDict, Mutect, VarScan and GatkSNV. The results show that, among the three groups of samples, DeteX has higher sensitivity and precision whether it detects SNVs or InDels than other callers and the F1 value of DeteX is the highest. Especially in the detection of substitution and complex mutations, only DeteX can accurately detect these two kinds of mutations. In terms of single-sample mutation detection, DeteX is much more sensitive than the HaplotypeCaller program in Gatk. In addition, although DeteX has higher mutation detection capabilities, its running time is only .609 of VarDict, which is .704 and .343 longer than VarScan and MuTect, respectively.Conclusion: In this study, we developed DeteX to detect SNV and InDel mutations in single and paired samples. DeteX has high sensitivity and precision especially in the detection of substitution and complex mutations. In summary, DeteX from NGS data is a good SNV and InDel caller

ModelScope-Agent: Building Your Customizable Agent System with Open-source Large Language Models

Large language models (LLMs) have recently demonstrated remarkable capabilities to comprehend human intentions, engage in reasoning, and design planning-like behavior. To further unleash the power of LLMs to accomplish complex tasks, there is a growing trend to build agent framework that equips LLMs, such as ChatGPT, with tool-use abilities to connect with massive external APIs. In this work, we introduce ModelScope-Agent, a general and customizable agent framework for real-world applications, based on open-source LLMs as controllers. It provides a user-friendly system library, with customizable engine design to support model training on multiple open-source LLMs, while also enabling seamless integration with both model APIs and common APIs in a unified way. To equip the LLMs with tool-use abilities, a comprehensive framework has been proposed spanning over tool-use data collection, tool retrieval, tool registration, memory control, customized model training, and evaluation for practical real-world applications. Finally, we showcase ModelScopeGPT, a real-world intelligent assistant of ModelScope Community based on the ModelScope-Agent framework, which is able to connect open-source LLMs with more than 1000 public AI models and localized community knowledge in ModelScope. The ModelScope-Agent library\footnote{https://github.com/modelscope/modelscope-agent} and online demo\footnote{https://modelscope.cn/studios/damo/ModelScopeGPT/summary} are now publicly available

A desinstitucionalização e as alternativas habitacionais ao dispor de indivíduos com perturbações mentais: Um novo modelo habitacional – A habitação apoiada

Desde o início do processo de desinstitucionalização desinstitucionalização que este se tem vindo a deparar com dificuldades. Passando pelos poucos recursos ao dispor dos serviços de saúde mental, à tendência para trabalhar com os elementos que apresentam maiores probabilidades de sucesso, à não articulação entre os serviços hospitalares e os centros comunitários de saúde mental, até à falta de investimentos em alternativas habitacionais de carácter permanente. Estas têm sido algumas das situações a que os consumidores de serviços de saúde mental se têm sujeitado. Actualmente, assistimos à emergência de um paradigma que assenta na crença de que se deverá prestar apoio a estes consumidores numa casa tipicamente normal, com uma vivência na comunidade, em que o apoio é disponibilizado consoante as necessidades de cada indivíduo sem que exista uma limitação temporal à sua prestação. Torna-se assim necessário criar novos papéis para os técnicos, no sentido de que estes ajudem os consumidores a escolher, a obter, e a manter uma habitação. É pois urgente o desenvolvimento de um conjunto diversificado de alternativas habitacionais que se baseiem nos recursos e capacidades das comunidades locais, no sentido de garantir que o processo de desinstitucionalização se conclua com sucesso. Palavras-chave: desinstitucionalização, habitação apoiada, satisfação dos consumidores, doença mental.ABSTRACT: Since its beginning the deinstitutiondeinstitutionalization process has faced some difficulties, such as the mental health services lack of resources, the trend to work with the individual who presents higher probability of success, the lack of articulation between hospital services and community mental health centers, and the lack of investments on accommodations for long periods of time. These are some of the situations that consumers of mental health services have endured. Nowadays we witness the emerging of a paradigm which lies on the idea that these consumers need to be supported at a ordinary house, living in community, where the support is provided according to each person’s needs, and without a time limit. This paradigm also creates a need for the professionals to find new roles so that they will be able to help the consumers to choose, get, and keep a home. To ensure the success of deinstitutionalization it is vital that the establishment of different alternatives of accommodation be based on communities’ resources and capabilities.info:eu-repo/semantics/publishedVersio