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Our study is aimed to access the efficacy and safety outcomes for coronavirus disease 2019 (COVID-19) patients treated with Paxlovid. According to inclusion and exclusion criteria, databases were used to retrieve articles from 1 January 2020 to 1 January 2023. Article screening, quality evaluation and data extraction were completed and cross-checked. The meta-analysis and trial sequential analysis (TSA) were conducted using RevMan, StataMP, and TSA software. A total of 42 original articles were included. Overall meta-analysis results showed that for death, hospitalisation, death or hospitalisation, emergency department (ED) visit, intensive care unit (ICU) admission, and extra oxygen requirement outcomes, every odds ratio (OR) was <1 and p < 0.05. For rebound outcome, the OR was >1 and p > 0.05. For adverse events (AEs) outcome, the OR was >1 and p < 0.05. In conclusion, Paxlovid effectively reduced the risks of death, hospitalisation, death or hospitalisation, ED visit, ICU admission, and extra oxygen requirement. There was no significant statistical difference considering rebound, but people should pay attention to possible AEs. However, for rebound and AEs outcomes, observations in certain subgroups suggested conclusions contrary to the overall meta-analysis. Trial sequential analysis indicated these two outcomes have a risk of false negative or false positive conclusions, so additional original studies are needed for further validation.
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COVID-19 , Humanos , Ritonavir/efeitos adversos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Antivirais/efeitos adversosRESUMO
PURPOSE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD). METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed. RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings. CONCLUSION: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.
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Quimiocina CCL2 , Predisposição Genética para Doença , Degeneração Macular , Polimorfismo de Nucleotídeo Único , Humanos , Degeneração Macular/genética , Quimiocina CCL2/genéticaRESUMO
The performance analysis of polarization M-ary differential chaos shift keying (P-MDCSK) has been expressed using a tight upper bound with the Q-function. However, evaluating the Q-function directly is not a closed expression and there has been less work on closed expression for the upper bound. In order to solve the problem, this paper presents approximate closed-form expressions on the error probability of P-MDCSK. This expression is derived by employing a polynomial approximation of the Q-function. These closed-form expressions are verified through simulations conducted under both additive white Gaussian noise (AWGN) and multipath Rayleigh fading channels. The simulation results reveal that there exists only a negligible gap between the simulations and the derived closed-form expressions. For example, it is observed that the theoretical approximate closed-form expressions exhibit a marginal deviation of approximately 0.4 dB from the simulations when the bit error rate (BER) reaches 10-4. Although the proposed method can only give approximate closed-form expressions of the upper bound, it provides an effective method for other communication schemes where the exact BER closed-form formula cannot be obtained.
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In this article, a graph-theoretic method (taking advantage of constraints among sets associated with the corresponding parity-check matrices) is applied for the construction of a double low-density parity-check (D-LDPC) code (also known as LDPC code pair) in a joint source-channel coding (JSCC) system. Specifically, we pre-set the girth of the parity-check matrix for the LDPC code pair when jointly designing the two LDPC codes, which are constructed by following the set constraints. The constructed parity-check matrices for channel codes comprise an identity submatrix and an additional submatrix, whose column weights can be pre-set to be any positive integer numbers. Simulation results illustrate that the constructed D-LDPC codes exhibit significant performance improvement and enhanced flexible frame length (i.e., adaptability under various channel conditions) compared with the benchmark code pair.
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As an accelerated evolutionary tool, genome shuffling is largely dependent on the high fusion frequency of different parental protoplasts. However, it was unclear how many types of parental protoplasts would afford the highest fusion frequency. Here, we applied the Monte Carlo method to simulate the simplified processes of protoplast fusion, to achieve maximal useful fusions in genome shuffling. The basic principle of this simulation is that valid fusions would take place when the minimum distance between two different types of parent protoplasts is smaller than that between two of the same types. Accordingly, simulations indicated that the highest fusion frequency would be achieved from eight to 12 different parental protoplasts. Based on the simulation results, eight parental protoplasts of the fungal endophyte Phomopsis sp. A123 were subjected to genome shuffling for yield improvement of deacetylmycoepoxydiene (DAM), an antitumor natural product with a novel chemical structure. After only two rounds of genome shuffling, four high-yield DAM-producing strains, namely G2-119, G2-448, G2-866, and G2-919, were obtained with the aid of activity screening and HPLC analysis. The results showed that the DAM yield in these four strains were 243-, 241-, 225-, and 275-fold, respectively, higher than that of the starting strain A123. This is the first time Monte Carlo simulation is introduced into the field of cell fusion and is also the first report on the optimization of genome shuffling focusing on the number of parental types in protoplast fusions.
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Antineoplásicos/metabolismo , Ascomicetos/genética , Ascomicetos/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Embaralhamento de DNA/métodos , Endófitos/genética , Genoma Fúngico/genética , Pironas/metabolismo , Rhizophoraceae/microbiologia , Produtos Biológicos/metabolismo , Fusão Celular , Método de Monte CarloRESUMO
BACKGROUND: Lenvatinib plus PD-1 inhibitors and interventional (LPI) therapy have demonstrated promising treatment effects in unresectable hepatocellular carcinoma (HCC). However, biomarkers for predicting the response to LPI therapy remain to be further explored. We aimed to develop a radiomics model to noninvasively predict the efficacy of LPI therapy. METHODS: Clinical data of patients with HCC receiving LPI therapy were collected in our institution. The clinical model was built with clinical information. Nine machine learning classifiers were tested and the multilayer perceptron classifier with optimal performance was used as the radiomics model. The clinical-radiomics model was constructed by integrating clinical and radiomics scores through logistic regression analysis. RESULTS: 151 patients were enrolled in this study (2:1 randomization, 101 and 50 in the training and validation cohorts), of which three achieved complete response, 69 showed partial response, 46 showed stable disease, and 33 showed progressive disease. The objective response rate, disease control rate, and conversion resection rates were 47.7, 78.1 and 23.2%. 14 features were selected from the initially extracted 1223 for radiomics model construction. The area under the curves of the radiomics model (0.900 for training and 0.893 for validation) were comparable to that of the clinical-radiomics model (0.912 for training and 0.892 for validation), and both were superior to the clinical model (0.669 for training and 0.585 for validation). Meanwhile, the radiomics model can categorize participants into high-risk and low-risk groups for progression-free survival (PFS) and overall survival (OS) in the training (HR 1.913, 95% CI 1.121 to 3.265, p=0.016 for PFS; HR 4.252, 95% CI 2.051 to 8.816, p=0.001 for OS) and validation sets (HR 2.347, 95% CI 1.095 to 5.031, p=0.012 for PFS; HR 2.592, 95% CI 1.050 to 6.394, p=0.019 for OS). CONCLUSION: The promising machine learning radiomics model was developed and validated to predict the efficacy of LPI therapy for patients with HCC and perform risk stratification, with comparable performance to clinical-radiomics model.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizado de Máquina , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Quinolinas/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tomografia Computadorizada por Raios X/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , RadiômicaRESUMO
Objective: To explore the effectiveness and advantages of using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair compared with traditional arthroscopic suture shuttle. Methods: The clinical data of 41 patients with Bankart lesion, who met the selection criteria and were admitted between August 2019 and October 2021, was retrospectively analyzed. Under arthroscopy, the inferior capsulolabral complex was stitched with Fastpass Scorpion suture passer in 27 patients (FS group) and with arthroscopic suture shuttle in 14 patients (ASS group). There was no significant difference between the two groups ( P>0.05) in gender, age, injured side, frequency of shoulder dislocation, time from first dislocation to operation, and preoperative Rowe score of shoulder. Taking successful suture and pull-tightening as the criteria for completion of repair, the number of patients that were repaired at 5â¶00 to 6â¶00 (<6:00) and 6â¶00 to 7â¶00 positions of the glenoid in the two groups was compared. The operation time, and the difference of Rowe shoulder score betwee pre- and post-operation, the occurrence of shoulder joint dislocation, the results of apprehension test, and the constituent ratio of recovery to the pre-injury movement level between the two groups at 1 year after operation. Results: Both groups completed the repair at 5â¶00 to 6â¶00 (<6â¶00), and the constituent ratio of patients completed at 6â¶00 to 7â¶00 was significantly greater in the FS group than in the ASS group ( P<0.05). The operation time was significantly shorter in the FS group than in the ASS group ( P<0.05). All incisions in the two groups healed by first intention. All patients were followed up 12-36 months (mean, 19.1 months). No anchor displacement or neurovascular injury occurred during follow-up. Rowe score of shoulder in the two groups significantly improved at 1 year after operation than preoperative scores ( P<0.05), and there was no significant difference in the difference of Rowe shoulder score between pre- and post-operation between the two groups ( P>0.05). At 1 year after operation, no re-dislocation occurred, and there was no significant difference in the apprehension test and the constituent ratio of recovery to the pre-injury movement level between the two groups ( P>0.05). Conclusion: Compared with the arthroscopic suture shuttle, using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair is more convenient, saves operation time, and has good effectiveness.
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Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Artroscopia/métodos , Instabilidade Articular/cirurgia , Amplitude de Movimento Articular , Recidiva , Estudos Retrospectivos , Escorpiões , Luxação do Ombro/cirurgia , Articulação do Ombro/cirurgia , Âncoras de Sutura , Suturas , Resultado do TratamentoRESUMO
BACKGROUND: Biofilm-immobilized continuous fermentation has the potential to enhance cellular environmental tolerance, maintain cell activity and improve production efficiency. RESULTS: In this study, different biofilm-forming genes (FLO5, FLO8 and FLO10) were integrated into the genome of S. cerevisiae for overexpression, while FLO5 and FLO10 gave the best results. The biofilm formation of the engineered strains 1308-FLO5 and 1308-FLO10 was improved by 31.3% and 58.7% compared to that of the WT strain, respectively. The counts of cells adhering onto the biofilm carrier were increased. Compared to free-cell fermentation, the average ethanol production of 1308, 1308-FLO5 and 1308-FLO10 was increased by 17.4%, 20.8% and 19.1% in the biofilm-immobilized continuous fermentation, respectively. Due to good adhering ability, the fermentation broth turbidity of 1308-FLO5 and 1308-FLO10 was decreased by 22.3% and 59.1% in the biofilm-immobilized fermentation, respectively. Subsequently, for biofilm-immobilized fermentation coupled with membrane separation, the engineered strain significantly reduced the pollution of cells onto the membrane and the membrane separation flux was increased by 36.3%. CONCLUSIONS: In conclusion, enhanced biofilm-forming capability of S. cerevisiae could offer multiple benefits in ethanol fermentation.
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BACKGROUND: Several case-control studies have been conducted on the relationship between rs3775290 C/T and rs3853839 C/G single nucleotide polymorphisms of the Toll-like receptor (TLR) gene and hand, foot, and mouth disease (HFMD) susceptibility and severity. This meta-analysis aimed to offer a systemic review of HFMD susceptibility and severity among the Chinese Han population associated with the C/T (rs3775290) polymorphism of the TLR3 gene or C/G (rs3853839) polymorphism of the TLR7 gene. METHODS: A computer search was conducted using PubMed, Web of Science, Embase, CNKI, CBM, VIP, and WanFang databases. The time ranges were from database establishment to 30/7/2021. Articles selected according to the inclusion and exclusion criteria underwent data extraction and methodological quality evaluation. RevMan 5.4 and Stata 16.0 were adopted for meta-analysis, and the incorporated odds ratio (OR) values and 95% confidence intervals (CIs) were calculated. Sensitivity and publication bias assessments were performed. RESULTS: 8 articles with 9 studies were selected. Among them, there were 858 cases and 577 controls in TLR3 rs3775290 studies as well as 2151 cases and 1554 controls in TLR7 rs3853839 studies. Regarding rs3775290 of TLR3, susceptibilities of the severe type of T-possessing individuals were larger than those of C-possessing individuals [OR = 1.34, 95%CI (1.10, 1.64), P = .004]. The susceptibility of individuals with the severe TT genotype was 1.61 times that of individuals with the CC genotype [95%CI (1.07, 2.43), P=0.02], while susceptibility to HFMD was not influenced by the genotype. In terms of the rs3853839 of the TLR7 gene, C allele carriers have a higher risk of developing HFMD than G allele carriers. The susceptibility to HFMD in CC+CG individuals was 1.24 times than that in GG individuals [95%CI (1.07, 1.43), P = .004]. However, no relationship was found between this polymorphism and severity of the severe type. No significant publication bias was observed in this study. CONCLUSIONS: rs3775290 (C/T) of TLR3 is associated with susceptibility to the severe type, whereas rs3853839 (C/G) of TLR7 is associated with susceptibility to HFMD. However, owing to the limited quantity and quality of the research, the aforementioned conclusions are yet to be justified by more high-quality research.
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Infecções por Enterovirus , Doença de Mão, Pé e Boca , Receptor 3 Toll-Like , Receptor 7 Toll-Like , Estudos de Casos e Controles , China , Enterovirus Humano A , Infecções por Enterovirus/genética , Predisposição Genética para Doença , Genótipo , Doença de Mão, Pé e Boca/genética , Humanos , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Receptor 7 Toll-Like/genéticaRESUMO
Objective: Systematic review of the association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene 1858 and 1123 sites single nucleotide polymorphism (SNP) with the susceptibility of primary immune thrombocytopenia (ITP). Method: Database searched includes PubMed, Embase, Web of Science, CNKI, CBM, VIP and WanFang Data. The retrieval period is from the establishment of the database to 30 June 2021. After screening articles according to inclusion and exclusion criteria, the data were extracted and methodological quality of the included studies was evaluated. Meta-analysis was performed using RevMan 5.4 and Stata 16.0 software. The combined OR value and its 95%CI were calculated. Sensitivity analysis and publication bias assessment were performed. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software. Results: A total of 10 studies with 10 articles were included, with a total of 932 cases and 2,112 controls. The results of meta-analysis showed that for SNP1858, the susceptibility of TT genotype to ITP was 5.01 times higher than CC genotype [95%CI (1.81, 13.86), p = 0.002]. For SNP1123, G allele carriers were more susceptible to ITP than C allele carriers [OR = 1.23, 95%CI (1.05, 1.45), p = 0.01], and GG genotype carriers were 1.51 times more susceptible to ITP than CC genotype carriers [95%CI (1.11, 2.06), p = 0.009]. Although the results are statistically significant, the results of sensitivity analysis showed certain limitations of stability, and the TSA analysis still indicated the possibility of false positive. No significant publication bias was observed. Conclusion: PTPN22 gene SNP1858 (rs2476601) and SNP1123 (rs2488457) polymorphisms are associated with susceptibility to primary immune thrombocytopenia. Due to the limitation of the number and quality of the included studies, the above conclusions need to be verified by more high-quality studies.
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Based on X-ray diffraction, thin section and scanning electron microscopy observation, helium porosity and permeability tests and high-pressure mercury intrusion experiments, the pore and throat distributions of tight sandstone reservoirs were revealed on a nm-µm scale, and their control on gas productivity in the Shenfu area, northeastern Ordos Basin, China was discussed. The results show that lithic sandstones are the main rock types. As the burial depth increases, the quartz content increases, while the feldspar content decreases. There is approximately 5-25% of interstitial material varying between the different layers, and this interstitial material is mainly composed of mud, kaolinite and Fe-calcite. These tight sandstone reservoirs generally have porosities <10% and permeabilities <1 mD. Except for the Shiqianfeng Formation, the dissolution pores in other Upper Paleozoic strata all account for more than 80% of pores. The main pore types are mainly intragranular dissolution pores, intergranular dissolution pores and cement dissolution pores. Generally, the pore radius is approximately 500 nm, while the pore throats are much smaller are variable in size. Wells with high amounts of sandstones but low gas production rate are generally characterized by dominant intercrystalline pores, few macropores, and low effective porosity. The lithology and reservoir characteristics, which are controlled by primary deposition and secondary diagenesis, are speculated to be main factors controlling the gas contents.