Paired immunoglobulin-like type 2 receptor alpha (PILRA) plays a vital role in regulating broad immune responses. However, the roles of PILRA in cancer immunity remain unexplored yet. In the current ...study, we comprehensively analyzed the oncogenic and immunologic roles of PILRA at a pan-cancer level based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PILRA was significantly dysregulated and frequently mutated in pan-cancer. Its expression and mutation status significantly impacted patient prognosis in several cancers. Besides, PILRA expression was positively correlated with ESTIMATE scores and the abundances of tumor-infiltrating immune cells. Concurrently, PILRA expression was significantly associated with predictive biomarkers of cancer immunotherapy, and positively correlated with the prognostic outcomes of cancer patients receiving immunotherapy. Mechanistically, enrichment analysis implied that PILRA might be involved in the regulation of immune response and metabolic process. This study uncovered the immunological roles of PILRA in cancers and its potential as a novel biomarker and therapeutic target for cancer immunotherapy.
Abstract Purpose The goal of this study was to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on lipid profiles in patients with type 2 diabetes. Methods The MEDLINE, ...Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from inception through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional antidiabetic drugs with a duration ≥8 weeks. The weighted mean difference for changes in lipid profiles was estimated by using the random effects model, and a network meta-analysis was performed to supplement direct comparisons. Findings Thirty-five trials with 13 treatments were included in the analysis. GLP-1 RAs decreased HDL-C with a range of –0.06 mmol/L (95% CI, –0.11 to –0.01) to –0.13 mmol/L (95% CI, –0.17 to –0.10) compared with thiazolidinediones, whereas thiazolidinediones were associated with a significant increase in HDL-C compared with placebo (0.09 mmol/L 95% CI, 0.06 to 0.12). A significant reduction in LDL-C was detected for all GLP-1 RAs versus placebo (range, –0.08 to –0.16 mmol/L), insulin (range, –0.10 to –0.19 mmol/L), and thiazolidinediones (range, –0.16 to –0.24 mmol/L). Exenatide, liraglutide 1.8 mg once daily, and taspoglutide decreased total cholesterol with a range of –0.16 mmol/L (95% CI, –0.26 to –0.06) to –0.27 mmol/L (95% CI, –0.41 to –0.12) versus placebo and thiazolidinediones (range, –0.26 to –0.37 mmol/L). The decreased effect was more evident in exenatide long-acting release and liraglutide 1.8 mg once daily. A significant reduction in triglyceride levels was observed with liraglutide 1.8 mg once daily (–0.30 mmol/L 95% CI, –0.49 to –0.11) and taspoglutide 20 mg once weekly (–0.17 mmol/L 95% CI, –0.31 to –0.01) versus placebo. Implications GLP-1 RAs were associated with modest reductions in LDL-C, total cholesterol, and triglycerides but no significant improvement in HDL-C. Further evidence is needed to determine if improvements in lipid profiles might translate into reductions in cardiovascular outcomes.
Learning the Information Divergence Dikmen, Onur; Zhirong Yang; Oja, Erkki
IEEE transactions on pattern analysis and machine intelligence,
2015-July-1, 2015-Jul, 2015-7-1, 20150701, Letnik:
37, Številka:
7
Journal Article
Recenzirano
Information divergence that measures the difference between two nonnegative matrices or tensors has found its use in a variety of machine learning problems. Examples are Nonnegative Matrix/Tensor ...Factorization, Stochastic Neighbor Embedding, topic models, and Bayesian network optimization. The success of such a learning task depends heavily on a suitable divergence. A large variety of divergences have been suggested and analyzed, but very few results are available for an objective choice of the optimal divergence for a given task. Here we present a framework that facilitates automatic selection of the best divergence among a given family, based on standard maximum likelihood estimation. We first propose an approximated Tweedie distribution for the β-divergence family. Selecting the best β then becomes a machine learning problem solved by maximum likelihood. Next, we reformulate α-divergence in terms of β-divergence, which enables automatic selection of α by maximum likelihood with reuse of the learning principle for β-divergence. Furthermore, we show the connections between γ- and β-divergences as well as Renyi- and α-divergences, such that our automatic selection framework is extended to non-separable divergences. Experiments on both synthetic and real-world data demonstrate that our method can quite accurately select information divergence across different learning problems and various divergence families.
The mechanical properties of metastable β-titanium alloys are highly susceptible during the thermal mechanical processing (TMP). In this process, the recrystallization process plays an important role ...in determining the microstructure and texture evolution. The implementation of dynamic recrystallization (DRX), a process for achieving β-grain refinement, is considered of great significance for the improvement of the properties of metastable β-titanium alloys and their industrial production. Along these lines, in this work, an isothermal compression test of TB8 titanium alloy was carried out by using a Gleeble-3500 thermal simulator. As a result, the rheological stress behavior was analyzed, the thermal processing map was accurately established based on the stress-strain curve, and the optimal processing interval was determined. The DRX kinetic and the DRX grain size models were developed, on the basis of which a new DRX intrinsic model was established to improve the material parameters. Therefore, the actual situation in the working process could be better predicted. The microstructural evolution of TB8 titanium alloy during thermal deformation was comprehensively investigated using the electron backscatter diffraction (EBSD) technique. The obtained results demonstrate a close correlation between the diversity of DRX mechanisms in TB8 alloy and the distribution of dislocation density. Four microstructural textures during thermal deformation were identified, in which the cube texture of (001) and the R-Gorss Nd texture of (110) dominate. Due to the random orientation of the dynamically recrystallized grains, the strength of the R-Gorss Nd texture of (110) increases with the increase in the volume fraction of DRX. On the contrary, it was verified that the dynamic recrystallization behavior has a significant weakening impact on the cube texture of (001) .
Since the outbreak of COVID-19, olfactory dysfunction (OD) has become an important and persistent legacy problem that seriously affects the quality of life. The purpose of this paper is to ...quantitatively analyze and visualize the current research status and development trend of COVID-19 related OD by using VOSviewer software. Based on the Web of Science database, a total of 1,592 relevant documents were retrieved in January 2023, with publication time spanning from 2020 to 2023. The bibliometric analysis revealed that the most influential research results in the field of COVID-19 related OD were concentrated in journals of related disciplines such as otorhinolaryngology, medicine, general and internal, virology, neurosciences, etc. The knowledge base of the research is mainly formed in two fields: COVID-19 clinical research and OD specialized research. The research hotspots are mainly concentrated in six directions: COVID-19, long COVID, smell, anosmia, OD, and recovery. Based on the results of the bibliometric analysis, the temporal trends of COVID-19 related OD studies were visually revealed, and relevant suggestions for future research were proposed.
Summary
Kallistatin, an endogenous protein, protects against vascular injury by inhibiting oxidative stress and inflammation in hypertensive rats and enhancing the mobility and function of ...endothelial progenitor cells (EPCs). We aimed to determine the role and mechanism of kallistatin in vascular senescence and aging using cultured EPCs, streptozotocin (STZ)‐induced diabetic mice, and Caenorhabditis elegans (C. elegans). Human kallistatin significantly decreased TNF‐α‐induced cellular senescence in EPCs, as indicated by reduced senescence‐associated β‐galactosidase activity and plasminogen activator inhibitor‐1 expression, and elevated telomerase activity. Kallistatin blocked TNF‐α‐induced superoxide levels, NADPH oxidase activity, and microRNA‐21 (miR‐21) and p16INK4a synthesis. Kallistatin prevented TNF‐α‐mediated inhibition of SIRT1, eNOS, and catalase, and directly stimulated the expression of these antioxidant enzymes. Moreover, kallistatin inhibited miR‐34a synthesis, whereas miR‐34a overexpression abolished kallistatin‐induced antioxidant gene expression and antisenescence activity. Kallistatin via its active site inhibited miR‐34a, and stimulated SIRT1 and eNOS synthesis in EPCs, which was abolished by genistein, indicating an event mediated by tyrosine kinase. Moreover, kallistatin administration attenuated STZ‐induced aortic senescence, oxidative stress, and miR‐34a and miR‐21 synthesis, and increased SIRT1, eNOS, and catalase levels in diabetic mice. Furthermore, kallistatin treatment reduced superoxide formation and prolonged wild‐type C. elegans lifespan under oxidative or heat stress, although kallistatin's protective effect was abolished in miR‐34 or sir‐2.1 (SIRT1 homolog) mutant C. elegans. Kallistatin inhibited miR‐34, but stimulated sir‐2.1 and sod‐3 synthesis in C. elegans. These in vitro and in vivo studies provide significant insights into the role and mechanism of kallistatin in vascular senescence and aging by regulating miR‐34a‐SIRT1 pathway.
In Nonnegative Matrix Factorization (NMF), a nonnegative matrix is approximated by a product of lower-rank factorizing matrices. Most NMF methods assume that each factorizing matrix appears only once ...in the approximation, thus the approximation is linear in the factorizing matrices. We present a new class of approximative NMF methods, called Quadratic Nonnegative Matrix Factorization (QNMF), where some factorizing matrices occur twice in the approximation. We demonstrate QNMF solutions to four potential pattern recognition problems in graph partitioning, two-way clustering, estimating hidden Markov chains, and graph matching. We derive multiplicative algorithms that monotonically decrease the approximation error under a variety of measures. We also present extensions in which one of the factorizing matrices is constrained to be orthogonal or stochastic. Empirical studies show that for certain application scenarios, QNMF is more advantageous than other existing nonnegative matrix factorization methods.
► We present a new class of approximative nonnegative matrix factorization methods. ► The approximation in this class is quadratic to some factorizing matrices. ► We show how to derive convergent multiplicative algorithms for various divergences. ► Our method can accommodate the stochasticity or orthogonality constraint. ► The proposed method is more advantageous in four pattern recognition problems.
Fruits of persimmon plants are traditional healthy food in China, Korea and Japan. However, due to the shortage of morphological and DNA markers, the development of persimmon industry has been ...heavily inhibited.
Chloroplast genomes of Diospyros cathayensis, D. virginiana, D. rhombifolia and D. deyangensis were newly sequenced. Comparative analyses of ten chloroplast genomes including six previously published chloroplast genomes of Diospyros provided new insights into the genome sequence diversity and genomic resources of the genus. Eight hyper-variable regions, trnH-psbA, rps16-trnQ, rpoB-trnC, rps4-trnT-trnL, ndhF, ndhF-rpl32-trnL, ycf1a, and ycf1b, were discovered and can be used as chloroplast DNA markers at/above species levels. The complete chloroplast genome sequences provided the best resolution at inter-specific level in comparison with different chloroplast DNA sequence datasets.
Diospyros oleifera, D. deyangensis, D. virginiana, D. glaucifolia, D. lotus and D. jinzaoshi are important wild species closely related to the cultivated persimmon D. kaki. The hyper-variable regions can be used as DNA markers for global genetic diversity detection of Diospyros. Deeper study on these taxa would be helpful for elucidating the origin of D. kaki.
The relationship between non-alcoholic fatty liver degree as well as non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) remains poorly understood. We aimed to investigate ...the prospective association of non-alcoholic fatty liver degree as well as NAFLD with incident IBS in a large-scale population-based cohort.
Participants free of IBS, coeliac disease, inflammatory bowel disease, alcoholic liver disease, and any cancer at baseline from the UK Biobank were included. Non-alcoholic fatty liver degree was measured by a well-validated fatty liver index (FLI), with FLI ≥ 60 as an indicator of NAFLD. Primary outcome was incident IBS. Cox proportional hazard model was used to investigate the associated risk of incident IBS.
Among 396,838 participants (mean FLI was 48.29 ± 30.07), 153,203(38.6%) were with NAFLD diagnosis at baseline. During a median of 12.4-year follow-up, 7129 cases of incident IBS were identified. Compared with non-NAFLD, NAFLD patients showed a 13% higher risk of developing IBS (HR = 1.13, 95%CI: 1.05-1.17) after multivariable adjustment. Compared with the lowest, the highest FLI quartile was associated with a significantly increased risk of IBS (HR
= 1.21, 1.13-1.30, P
< 0.001). Specifically, the positive association between non-alcoholic fatty liver degree and IBS was also observed by per SD change of FLI (adjusted HR = 1.08, 1.05-1.10). Further sensitivity analysis and subgroup analysis indicated similar results, with the positive association particularly observed in females, but not in males.
High degree of non-alcoholic fatty liver as well as non-alcoholic fatty liver disease is associated with increased risk of incident IBS. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms.
To analyze the relationship of Adler grade by transvaginal color Doppler flow imaging (TV-CDFI) and the clinical pathological parameters of patients with cervical cancer, and to identify the value of ...Adler grade in the diagnosis and treatment of cervical cancer. A total of 162 patients with cervical cancer were included. With the increase of Adler severity, the clinical stage of cervical cancer increased accordingly. the cancer size differed significantly in patients with different Adler grade (p = 0.004); There were significant differences in the level of CA125, CA199 between the squamous cell carcinoma and adenocarcinoma (all p<0.05). the Adler grade was positively related with the clinical stage, pathological type and squamous cell carcinoma subtypes of cervical cancer (all p0.05). The area under ROC curve of the cervical squamous cell carcinoma predicted by Adler grade based on FIGO results and pathological results was 0.811and 0.762 respectively (all p<0.05). Adler grades are closely associated with the clinical pathology of cervical cancer, which may be a convenient and effective approach for the assisting assessment of cervical cancer.
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