A group decision making method with preference analysis to re-build the Global Entrepreneurship Index.

This study proposes a group decision making (GDM) method with preference analysis to re-build the Global Entrepreneurship Index (GEI). Specifically, a single decision maker is firstly identified using a specified individual judgement about the importance order of three sub-indices of the GEI. A preliminary group decision matrix is constructed in terms of taking all possible individual judgments into account. Then the analysis of the preferential differences and preferential priorities with respect to the preliminary group decision matrix is conducted to obtain a revised group decision matrix, in which preferential differences calculate the weighted differences as the degrees of differences among different alternatives for each decision maker, preferential priorities describe the favorite ranking of alternatives for each decision maker. Finally, we employ the Stochastic Multicriteria Acceptability Analysis for group decision-making (SMAA-2) to create the holistic acceptability indices for measuring the entrepreneurship performance. In addition, a satisfaction index is developed to indicate the merits of proposed GDM method. A case study using the GEI-2019 of 19 G20 countries is carried out to validate our GDM method.

A multifunctional hydrogel loaded with two nanoagents improves the pathological microenvironment associated with radiation combined with skin wounds.

Persistent oxidative stress and recurring waves of inflammation with excessive reactive oxygen species (ROS) and free radical accumulation could be generated by radiation. Exposure to radiation in combination with physical injuries such as wound trauma would produce a more harmful set of medical complications, which was known as radiation combined with skin wounds (RCSWs). However, little attention has been given to RCSW research despite the unsatisfactory therapeutic outcomes. In this study, a dual-nanoagent-loaded multifunctional hydrogel was fabricated to ameliorate the pathological microenvironment associated with RCSWs. The injectable, adhesive, and self-healing hydrogel was prepared by crosslinking carbohydrazide-modified gelatin (Gel-CDH) and oxidized hyaluronic acid (OHA) through the Schiff-base reaction under mild condition. Polydopamine nanoparticles (PDA-NPs) and mesenchymal stem cell-secreted small extracellular vesicles (MSC-sEV) were loaded to relieve radiation-produced tissue inflammation and oxidation impairment and enhance cell vitality and angiogenesis individually or jointly. The proposed PDA-NPs@MSC-sEV hydrogel enhanced cell vitality, as shown by cell proliferation, migration, colony formation, and cell cycle and apoptosis assays in vitro, and promoted reepithelization by attenuating microenvironment pathology in vivo. Notably, a gene set enrichment analysis of proteomic data revealed significant enrichment with adipogenic and hypoxic pathways, which play prominent roles in wound repair. Specifically, target genes were predicted based on differential transcription factor expression. The results suggested that MSC-sEV- and PDA-NP-loaded multifunctional hydrogels may be promising nanotherapies for RCSWs. STATEMENT OF SIGNIFICANCE: The small extracellular vesicle (sEV) has distinct advantages compared with MSCs, and polydopamine nanoparticles (PDA-NPs), known as the biological materials with good cell affinity and histocompatibility which have been reported to scavenge ROS free radicals. In this study, an adhesive, injectable, self-healing, antibacterial, ROS scavenging and amelioration of the radiation related microenvironment hydrogel encapsulating nanoscale particles of MSC-sEV and PDA-NPs (PDA-NPs@MSC-sEV hydrogel) was synthesized for promoting radiation combined with skin wounds (RCSWs). GSEA analysis profiled by proteomics data revealed significant enrichments in the regulations of adipogenic and hypoxic pathways with this multi-functional hydrogel. This is the first report of combining this two promising nanoscale agents for the special skin wounds associated with radiation.

Single-Cell and Spatial Transcriptomics Decodes Wharton's Jelly-Derived Mesenchymal Stem Cells Heterogeneity and a Subpopulation with Wound Repair Signatures.

The highly heterogeneous characteristics of Wharton's jelly mesenchymal stem cells (WJ-MSCs) may be responsible for the poor clinical outcomes and poor reproducibility of treatments based on WJ-MSCs. Exploration of WJ-MSC heterogeneity with multimodal single-cell technologies will aid in establishing accurate MSC subtyping and developing screening protocols for dominant functional subpopulations. Here, the characteristics of WJ-MSCs are systematically analyzed by single cell and spatial transcriptome sequencing. Single-cell transcriptomics analysis identifies four WJ-MSC subpopulations, namely proliferative_MSCs, niche-supporting_MSCs, metabolism-related_MSCs and biofunctional-type_MSCs. Furthermore, the transcriptome, cellular heterogeneity, and cell-state trajectories of these subpopulations are characterized. Intriguingly, the biofunctional-type MSCs (marked by S100A9, CD29, and CD142) selected in this study exhibit promising wound repair properties in vitro and in vivo. Finally, by integrating omics data, it has been found that the S100A9+ CD29+ CD142+ subpopulation is more enriched in the fetal segment of the umbilical cord, suggesting that this subpopulation deriving from the fetal segment may have potential for developing into an ideal therapeutic agent for wound healing. Overall, the presented study comprehensively maps the heterogeneity of WJ-MSCs and provides an essential resource for future development of WJ-MSC-based drugs.

Wharton's jelly mesenchymal stem cell-derived small extracellular vesicles as natural nanoparticles to attenuate cartilage injury via microRNA regulation.

The main strategy of tissue repair and regeneration focuses on the application of mesenchymal stem cells and cell-based nanoparticles, but there are still multiple challenges that may have negative impacts on human safety and therapeutic efficacy. Cell-free nanotechnology can effectively overcome these obstacles and limitations. Mesenchymal stem cell (MSC)-derived natural small extracellular vesicles (sEVs) represent ideal nanotherapeutics due to their low immunogenicity and lack of tumorigenicity. Here, sEVs harvested from Wharton's jelly mesenchymal stem cells (WJMSCs) were identified. In vitro results showed that WJMSC-sEVs efficiently entered chondrocytes in the osteoarthritis (OA) model, further promoted chondrocyte migration and proliferation and modulated immune reactivity. In vivo, WJMSC-sEVs notably promoted chondrogenesis, which was consistent with the effect of WJMSCs. RNA sequencing results revealed that sEV-microRNA-regulated biocircuits can significantly contribute to the treatment of OA, such as by promoting the activation of the calcium signaling pathway, ECM-receptor interaction pathway and NOTCH signaling pathway. In particular, let-7e-5p, which is found in WJMSC-sEVs, was shown to be a potential core molecule for promoting cartilage regeneration by regulating the levels of STAT3 and IGF1R. Our findings suggest that WJMSC-sEV-induced chondrogenesis is a promising innovative and feasible cell-free nanotherapy for OA treatment.

Using individual preferences and BWM with entropy measures to modify the Global Entrepreneurship Index.

The Global Entrepreneurship and Development Institute (GEDI) annually releases the Global Entrepreneurship Index (GEI) to measure the quality and dynamics of entrepreneurship ecosystems at a national and regional level. The published Global Entrepreneurship Index takes the arithmetic mean value of the individual level of entrepreneurial attitudes, abilities and aspirations. In this paper, we alternatively consider all individual preferences among these three sub-indices, the performance results of which are obtained by means of a sophisticated manner. The entropy values of these performance results are derived to reduce the information redundancy. The best-worst method (BWM) is employed to determine the common weights with respect to each individual preference. An empirical study using the data of GEI-2019 is performed to indicate the validness of our methodology.

Comparison of Curative Effect of Human Umbilical Cord-Derived Mesenchymal Stem Cells and Their Small Extracellular Vesicles in Treating Osteoarthritis.

INTRODUCTION: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and their small extracellular vesicles (hUC-MSC-sEVs) have shown attractive prospects applying in regenerative medicine. This study aimed to compare the therapeutic effects of two agents on osteoarthritis (OA) and investigate underlying mechanism using proteomics. METHODS: In vitro, the proliferation and migration abilities of chondrocytes treated with hUC-MSCs or hUC-MSC-sEVs were detected by Cell Counting Kit-8 assay and scratch wound assay. In vivo, hUC-MSCs (a single dose of 5 × 105) or hUC-MSC-sEVs (30 µg/time) were injected into the knee joints of anterior cruciate ligament transection-induced OA model. Hematoxylin and eosin, Safranin O/Fast Green staining were used to observe cartilage degeneration. The levels of cartilage matrix metabolic molecules (Collagen II, MMP13 and ADAMTS5) and macrophage polarization markers (CD14, IL-1ß, IL-10 and CD206) were assessed by immunohistochemistry. Finally, proteomics analysis was performed to characterize the proteinaceous contents of two agents. RESULTS: In vitro data showed that hUC-MSC-sEVs were taken up by chondrocytes. A total of 15 µg/mL of sEVs show the greatest proliferative and migratory capacities among all groups. In the animal study, hUC-MSCs and hUC-MSC-sEVs alleviated cartilage damage. This effect was mediated via maintaining cartilage homeostasis, as was confirmed by upregulation of the COL II and downregulation of the MMP13 and ADAMTS5. Moreover, the M1 macrophage markers (CD14) were significantly reduced, while the M2 macrophage markers (CD206 and IL-10) were increased in the hUC-MSCs and hUC-MSC-sEVs relative to the untreated group. Mechanistically, we found that many proteins connected to cartilage repair were more abundant in sEVs. Notably, compared to hUC-MSCs, the upregulated proteins in sEVs were mostly involved in the regulation of immune effector process, extracellular matrix organization, PI3K-AKT signaling pathways, and Rap1 signaling pathway. CONCLUSION: Our study indicated that hUC-MSC-sEVs protect cartilage from damage and many cartilage repair-related proteins are probably involved in the restoration process. These data suggest the promising potential of hUC-MSC-sEVs as a therapeutic agent for OA.

Longitudinal follow-up of patients with mild traumatic brain injury by magnetic resonance spectroscopic technique.

OBJECTIVE: To explore the changes in the concentrations of neural markers immediately or several months after mild traumatic brain injury (mTBI). METHODS: The metabolic markers of neurons in white matter tissues above the lateral ventricle were semi-quantitatively determined by employing 1H magnetic resonance spectroscopic technique (1-H-MRS) in 30 clinically diagnosed cases of mTBI. At the same time, the neurological functions of the subjects, including ability to pay attention, memory, working memory and operational capacity etc were also assessed. RESULTS: The patients were followed up for, on average, 13 days after mTBI and the results showed that Cre, PCre and Glx in the white matter tissues were significantly elevated in mTBI patients. 17 patients (57%) recovered from the injury during the follow-up (median was defined as the 40th post-trauma day). Comparison in terms of intelligence among groups revealed that the levels of neural markers of intelligence development was positively related with intelligence scores). CONCLUSIONS: Change in Glx concentrations is most sensitive during trauma or in ensuing repairing processes, and might be different from normal status in the following months and Glx level tends to be accompanied with change in Cre, another energy-related marker.

High-resolution MRI of cranial nerves in posterior fossa at 3.0 T.

OBJECTIVE: To evaluate the influence of high-resolution imaging obtainable with the higher field strength of 3.0 T on the visualization of the brain nerves in the posterior fossa. METHODS: In total, 20 nerves were investigated on MRI of 12 volunteers each and selected for comparison, respectively, with the FSE sequences with 5 mm and 2 mm section thicknesses and gradient recalled echo (GRE) sequences acquired with a 3.0-T scanner. The MR images were evaluated by three independent readers who rated image quality according to depiction of anatomic detail and contrast with use of a rating scale. RESULTS: In general, decrease of the slice thickness showed a significant increase in the detection of nerves as well as in the image quality characteristics. Comparing FSE and GRE imaging, the course of brain nerves and brainstem vessels was visualized best with use of the three-dimensional (3D) pulse sequence. CONCLUSIONS: The comparison revealed the clear advantage of a thin section. The increased resolution enabled immediate identification of all brainstem nerves. GRE sequence most distinctly and confidently depicted pertinent structures and enables 3D reconstruction to illustrate complex relations of the brainstem.

Characteristics of neurovascular compression in facial neuralgia patients by 3D high-resolution MRI and fusion technology.

OBJECTIVE: To evaluate the anatomical characteristics and patterns of neurovascular compression in patients suffering trigeminal neuralgia, using 3D high-resolution magnetic resonance imaging methods and fusion technologies. METHODS: The analysis of the anatomy of the facial nerve, brain stem and the vascular structures related to this nerve was made in 100 consecutive patients for TN. 3D high resolution MRI studies (3D SPGR, T1 enhanced 3D MP-RAGE and T2/T1 3D FIESTA) simultaneous visualization were used to assessed using the software 3D DOCTOR. RESULTS: In 93 patients (93%), there were one or several locals of neurovascular compression (NVC). The superior cerebellar artery was involved in 71 cases (76%), the other vessels including the antero-inferior cerebellar artery, the basilar artery, the vertebral artery, and some venous structures. The mean distance between NVC and nerve origin site in the brainstem was (3.76 ± 2.90) mm). In 39 patients (42%), the vascular compression was located proximally and in 42 (45%) the compression was located distally. Nerve dislocation or distortion by the vessel was observed in 30 cases (32%). CONCLUSIONS: This 3D high resolution MRI and image fusion technology could be useful for diagnostic and therapeutic decisions in TN.

Comparison between magnitude reconstruction and phase-sensitive mR imaging in the detection of myocardial infarction.

OBJECTIVE: To determine the deference between phase sensitive magnetic resonance (MR) imaging and magnitude reconstruction to detect infracted myocardium. METHODS: Twenty patients (16 men; 4 women; mean age, 56 years). experienced Q-wave myocardial infarction 2 weeks earlier were examined with a 3.0-T MR system 10 minutes after administration of 0.1 mmol/kg body weight gadobenate dimeglumine. To determine the optimal TI, a TI scout sequence was used. A segmented 2D IR true fast imaging with steady-state precession (trueFISP) sequence that produces both phase-sensitive and magnitude-reconstructed images were used at TI values of 200-600 msec (TI values were varied in 100-msec steps) and at optimal TI (mean value, 330 msec). Contrast-noise ratios (CNRs) of normal and infarcted myocardium and the area of infarcted myocardium were determined. Two-tailed unpaired sample Student t test was used to compare CNRs, and area of infarction. RESULTS: MMean CNR phase-sensitive and magnitude-reconstructed images at optimal TI (mean value, 330 msec) were 6.2, and 6.1, respectively. For a TI of 200 msec, CNR values were 5.5, and 4.2, respectively; for TI of 600 msec, CNR values were 5.8 and 4.3, respectively. Area of infarcted myocardium was underestimated on magnitude-reconstruction images (P = 0.002-0.03) for short TI values (ie., 200 msec) but not on phase sensitive reconstructed when compared with IR tureFISP images obtained at optimal TI. CONCLUSIONS: LPhase-sensitive image reconstruction results in reduced need for precise choice of TI and more consistent image quality.

Delay enhancement patterns in apical hypertrophic cardiomyopathy by phase-sensitive inversion recovery sequence.

OBJECTIVE: Late gadolinium enhancement (LGE) patterns of cardiovascular magnetic resonance (CMR) relying on PSIR (phase-sensitive inversion recovery sequence) techniques had been used to determine the characteristics of LGE in apical hypertrophic cardiomyopathy (ApHCM). METHODS: Forty patients pure ApHCM [age, (60.2±10.4) years, 31 men] were enrolled. LGE images were acquired using PSIR, and analyzed using a 17-segment model. Summing the LGE areas in all short axis slices yielded the total volume of late enhancement, which was subsequently presented as a proportion of total LV myocardium (% LGE). RESULTS: Mean maximal apical wall thickness was (17.9±2.3) mm, and mean left ventricular (LV) ejection fraction was (67.7±8.0)%. LGE was detected in 130 segments of 30 patients (75.0%), occupying (4.9±5.5)% of LV myocardium. LGE was mainly detected at the junction between left and right ventricles in 12 (30%) and at the apex in 28 (70%), although LGE-positive areas were widely distributed, and not limited to the apex. Focal LGE at the non-hypertrophic LV segments was found in some ApHCM patients, even without LGE of hypertrophied apical segments. CONCLUSIONS: LGE was frequently observed not only in the thickened apex of the heart but also in other LV segments, irrespective of the presence or absence of hypertrophy. The simple presence of LGE on CMR was not representative of adverse prognosis in this population.

Structural abnormalities of trigeminal root with neurovascular compression revealed by high resolution diffusion tensor imaging.

OBJECTIVE: To detect neurovascular compression-induced structural abnormalities of trigeminal nerves (TGN) by diffusion tensor imaging (DTI). METHODS: The affected ipsilateral TGN (iTGN) and unaffected contralateral TGN (cTGN) of 20 trifacial neuralgia (TN) patients as well as the bilateral TGN of 10 normal controls (nTGN) were examined by DTI and 3D high resolution MRI using a 3.0 T MRI scanner. The fractional anisotropy and apparent diffusion coefficient (ADC) were determined. RESULTS: Compared with the cTGN and nTGN, the iTGN had significantly lower fraction of anisotropy (FA), significantly higher ADC, and significantly smaller volume and cross-sectional area (P<0.05). CONCLUSIONS: The increase in ADC and decrease in FA has a close relationship with morphological changes of TGN, and the DTI could provide valuable diagnostic information on TGN structure for TN patients.

Characterization of neurovascular compression in facial neuralgia patients by 3D high-resolution MRI and image fusion technique.

OBJECTIVE: To describe the anatomical characteristics and patterns of neurovascular compression (NVC) in patients suffering trigeminal neuralgia (TN) by 3D high-resolution magnetic resonance imaging (MRI) method and image fusion technique. METHODS: The anatomic structure of trigeminal nerve, brain stem and blood vessel was observed in 100 consecutive TN patients by 3D high resolution MRI (3D SPGR, contrast-enhanced T1 3D MP-RAGE and T2/T1 3D FIESTA). The 3D image sources were fused and visualized using 3D DOCTOR software. RESULTS: One or several NVC sites, which usually appeared 0-9.8 mm away from brain stem, were found on the symptomatic side in 93% of the TN cases. Superior cerebellar artery was involved in 76% (71/93) of these cases. The other vessels including antero-inferior cerebellar artery, vertebral artery, basilar artery and veins also contributed to the occurrence of NVC. The NVC sites were found to be located in the proximal segment in 42% of these cases (39/93) and in the distal segment in 45% (42/93). Nerve dislocation or distortion was observed in 32% (30/93). CONCLUSIONS: Various 3D high resolution MRI methods combined with the image fusion technique could provide pathologic anatomic information for the diagnosis and treatment of TN.