Ranking of triangular intuitionistic fuzzy numbers (TIFNs) is an important problem, which is solved by the value and ambiguity based ranking method developed in this paper. Firstly, the concept of TIFNs is introduced. Arithmetic operations and cut sets over TIFNs are investigated. Then, the values and ambiguities of the membership degree and the non-membership degree for TIFNs are defined as well as the value-index and ambiguity-index. Finally, a value and ambiguity based ranking method is developed and applied to solve multiattribute decision making problems in which the ratings of alternatives on attributes are expressed using TIFNs. A numerical example is examined to demonstrate the implementation process and applicability of the method proposed in this paper. Furthermore, comparison analysis of the proposed method is conducted to show its advantages over other similar methods.
Cavernous malformations (CMs) affecting the central nervous system occur in approximately 0.16% to 0.4% of the general population. The majority (85%) of the CMs are in a sporadic form, but the genetic background of sporadic CMs remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in 2 genes: MAP3K3 and PIK3CA by whole-exome sequencing (WES). The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P < 0.001), MRI appearance (P = 0.004) and haemorrhage events (P = 0.006). PIK3CA mutation was a significant predictor of overt haemorrhage events (P = 0.003, OR = 11.252, 95% CI = 2.275-55.648). Enrichment of endothelial cell (EC) population was associated with a higher fractional abundance of the somatic mutations. Overexpression of the MAP3K3 mutation perturbed angiogenesis of EC models in vitro and zebrafish embryos in vivo. Distinct transcriptional signatures between different genetic subgroups of sporadic CMs were identified by single-cell RNA-sequencing (scRNA-seq) and verified by pathological staining. Significant apoptosis in MAP3K3 mutation carriers and overexpression of GDF15 and SERPINA5 in PIK3CA mutation carriers contributed to their phenotype. We identified activating MAP3K3 and PIK3CA somatic mutations in the majority (90.1%) of sporadic CMs and PIK3CA mutations could confer a higher risk for overt haemorrhage. Our data provide insights into genomic landscapes, propose a mechanistic explanation and underscore the possibility of a molecular classification for sporadic CMs.
PurposeIn recent years, metabolic syndrome has risen in prevalence and brought a heavy disease burden to modern society. As the representative aspect of metabolic syndrome, obesity has been shown to be related to an increased risk of stroke. Given that visceral adipose tissue (VAT) forms the fundamental basis of central obesity, we sought to explore a causal relationship between VAT and stroke by using mendelian randomization (MR) methods.MethodsBased on two large genome-wide association studies (GWAS) including 325,153 and 35,762 cases of VAT and stroke, respectively, we conducted a MR study which has the inherent advantage of reducing the noise of confounding and reverse causation.ResultsVAT had a significant causal association with ischemic stroke (OR, per 1kg increase in VAT mass, 1.30; 95% CI, 1.18 ~ 1.45; P = 5.87E-07) as opposed to intracranial hemorrhage (ICH) (OR, 1.15; 95% CI, 0.70 ~ 1.88, P = 5.81E-01) as evaluated with inverse-variance weighting (IVW). Regarding subtypes of ischemic stroke, there was a significant causal effect for cardioembolic stroke (OR, 1.34; 95% CI, 1.13 ~ 1.58, P = 8.07E-04), and potential causal effect for small-vessel stroke (OR, 1.32; 95% CI, 1.06 ~ 1.65, P = 1.39E-02) and large-artery atherosclerotic stroke (OR, 1.33; 95% CI, 1.03 ~ 1.70, P = 2.59E-02).ConclusionsThis study provides potential evidence for a causal role of VAT in ischemic stroke and could suggest novel genetical therapeutic strategies for distinct subtypes of ischemic stroke.
BACKGROUND:The natural history of spinal cord cavernous malformations (SCCMs) remains relatively unclear. OBJECTIVE: To investigate the natural history for hemorrhagic risks and neurological outcomes, as well as relevant predicting factors, of SCCMs. METHODS: All patients between 2002 and 2019 with diagnosis of SCCMs were identified retrospectively. An observational study of patients with conservative management was performed to reveal the natural history of SCCMs. RESULTS: We identified 305 patients in the full cohort, including 126 patients who were conservatively treated for at least 6 months (median observational period, 24.0 months). Fortyfive hemorrhage events occurred during 527 person-years of follow-up, yielding an annual hemorrhage rate of 8.5% per person-year. The 1-, 2-, and 5-year cumulative risks of hemorrhage were 13.9%, 26.1%, and 35.1%, respectively. Prior hemorrhage (hazard ratio [HR] = 12.948, P = .012) and pediatric patients (HR = 2.841, P = .031) were independent predictors of hemorrhage in the long-term follow-up. Familial form (adjusted odds ratio [OR] = 30.695, P = .010) and subsequent hemorrhage events (adjusted OR = 16.333, P = .000) were independent risk factors for worsening of neurological function, and baseline neurological status (adjusted OR = 78.984, P = .000) and presence of subsequent hemorrhage (adjusted OR = 9.611, P = .001) were significantly associated with neurological outcomes. CONCLUSION: The natural history of SCCMs varies. Baseline characteristics, such as pediatric patients, familial form, and baseline neurological status, as well as prior and subsequent hemorrhagic events, significantly affect the natural history of the SCCMs, which prompts a differentiated treatment strategy.
Background: Although pericallosal artery aneurysms (PAAs) are relatively uncommon, accounting for only 1–9% of all intracranial aneurysms (IAs), they exhibit a considerably high propensity to rupture. Nevertheless, our current knowledge of the risk factors for PAA rupture is still very limited. To fill this gap, we investigated rupture risk factors for PAAs based on morphological computer-assisted semiautomated measurement (CASAM) and hemodynamic analysis.Methods: Patients with PAAs were selected from the IA database in our institute and their baseline data were collected. Morphological parameters were measured in all enrolled patients by applying CASAM. Computational fluid dynamics simulation (CFD) was performed to evaluate the hemodynamic difference between ruptured and unruptured PAAs.Results: From June 2017 to June 2020, among 2141 patients with IAs in our institute, 47 had PAAs (2.2%). Thirty-one patients (mean age 57.65 ± 9.97 years) with 32 PAAs (20 unruptured and 12 ruptured) were included in the final analysis. Comparing with unruptured PAAs, ruptured PAAs had significantly higher aspect ratio (AR), mean normalized wall shear stress (NWSS), and mean oscillatory shear index (OSI) values than the unruptured PAAs (all P < 0.05) in univariate analyses. Multivariable analysis showed that a high mean OSI was an independent risk factor for PAA rupture (OR = 6.45, 95% CI 1.37–30.32, P = 0.018).Conclusion: This preliminary study indicates that there are morphological and hemodynamic differences between ruptured and unruptured PAAs. In particular, a high mean OSI is an independent risk factor for PAA rupture. Further research with a larger sample size is warranted in the future.
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