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Background: Observational data have suggested that patients with moderate to severe ischemia benefit from revascularization. However, this was not confirmed in a large, randomized trial. Objectives: Using a contemporary, multicenter registry, the authors evaluated differences in the association between quantitative ischemia, revascularization, and outcomes across important subgroups. Methods: Patients who underwent myocardial perfusion imaging in 12 centers were included in this retrospective analysis. The population was divided into original (2009-2014) and recent (2014-2021) registry sites. Early revascularization was defined as any revascularization within 90 days of myocardial perfusion imaging. A propensity score was developed to adjust for nonrandomization. Propensity score-adjusted survival analyses were used to evaluate the associations between quantitative ischemia, early revascularization, and death or myocardial infarction (MI) to identify at what severity of ischemia the HR for early revascularization crosses 1 (threshold for potential benefit). Results: Overall, 40,449 patients were included with a median follow-up of 3.5 (IQR: 2.4-4.6) years, during which death or MI occurred in 2,797 (6.9%). Early revascularization was associated with reduced death or MI in patients with >9.0% myocardial ischemia (95% upper CI: 11.2%, interaction P 10.0%) and male patients (>8.6%). Conclusions: Early revascularization was associated with reduced risk in patients with a higher burden of quantitative ischemia in more recent populations. These findings suggest that methods integrating more factors than just ischemia are needed to improve patient selection for revascularization.

Background: Emerging data in the general population and those with coronary artery disease demonstrate higher risk of adverse outcomes with high (>70 mg/dL) HDL-C levels. There are limited data on the risk of adverse outcomes in women with suspected ischemic heart disease. Objective: To investigate relationships between high (>70 mg/dL), average (50–70 mg/dL), and low (

Objective: Cervical squamous cell carcinoma (CESC) is a cancer with high mortality caused by human papillomavirus. The aim of this study was to uncover potential CESC biomarkers to help early diagnosis and treatment. Materials and methods: The mRNA transcriptome data and DNA methylation data were downloaded from database for the identification of differentially expressed mRNAs (DEmRNAs) and DNA methylation analysis. Functional analysis was used to reveal the molecular functions. Then, the association between differential methylation and DEmRNA was analyzed. Protein–protein interaction (PPI) network analysis was performed on the selected differentially methylated genes (DEGs). Subsequently, we analyzed the prognosis and constructed a prognostic risk model. We also performed diagnostic analyses of risk model genes. In addition, we verified the protein expression level of identified DEGs. Results: 1438 DEmRNAs, 1669 differentially methylated sites (DMSs), 46 differentially methylated CpG islands and 53 differential methylation genes (DMGs) were obtained. In PPI, the highest interaction scores were MX2 and IRF8, and their interaction score was 0.928. Interestingly, 5 DMGs were found to be associated with CESC prognosis. In addition, our results demonstrated that high risk score was associated with poor prognosis of CESC. Furthermore, it was found that ZIK1, ZNRF2, HHEX, VCAM1 could be diagnostic molecular markers for CESC. Conclusion: Analysis of methylated-differentially expressed genes may contribute to the identification of early diagnosis and therapeutic targets of CESC. In addition, a prognostic model based on 5 DMGs can be used to predict the prognosis of CESC.

Solid solution phases dominate the thermodynamic competition with intermetallic phases in high-entropy alloys (HEAs), known as the high-entropy effect. However, owing to inevitable local substitutions in multi-component intermetallics (MCIMs), imposed thermodynamic changes are often overlooked. This study investigated a partially disordered MCIM, C14 Laves phase, in a dual-phase CrHfNbTaTi refractory HEA. The chemical formula and site preferences were determined based on the observation of spatial atomic arrangement. Furthermore, a parameter kdis was proposed to describe the disorder degree of MCIMs. As kdis increased from 0 to 0.2 due to local substitutions, the formation enthalpy of the C14 Laves phase significantly increased, resulting in higher energy and lower stability. Therefore, when feasible composition regulation and site occupancy design are adopted to manipulate the kdis of the potential MCIM, the high-entropy solid solution is able to be superior to the MCIM even at intermediate temperatures. The study provides insights into the high-entropy effect by considering MCIM enthalpies, providing a valuable phase-regulation strategy for future design of HEAs.

Surveys are widely used to assess hospital management with the aim of understanding differences in management practices. However, survey measures with prior notice can make hospitals change their routine practices and are unable to reflect the actual hospital management level. The World Management Survey (WMS) methodology has been developed to ameliorate these issues. It uses a double-blinded method and open-ended question design. The Chinese Hospital Management Survey (CHMS) project is the first to adapt the WMS methodology in China, which it uses to measure hospital management level in 510 hospitals. This paper provides an instrument to better measure actual management practices, which makes it possible to compare the management level of hospitals in China and other countries.

Summary: Background: COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults. Methods: This combined open-label and randomised, phase 1 trial was done at the City of Hope Comprehensive Cancer Center (Duarte, CA, USA). We included participants aged 18–54 years with a negative SARS-CoV-2 antibody and PCR test, normal haematology and chemistry panels, a normal electrocardiogram and troponin concentration, negative pregnancy test if female, body-mass index of 30 kg/m2 or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1·0 × 107 plaque-forming units (PFU; low dose), 1·0 × 108 PFU (medium dose), and 2·5 × 108 PFU (high dose) of COH04S1 were administered by intramuscular injection on day 0 and 28 to sentinel participants using a queue-based statistical design to limit risk. In a randomised dose expansion cohort, additional participants were randomly assigned (3:3:1), using block size of seven, to receive two placebo vaccines (placebo group), one low-dose COH04S1 and one placebo vaccine (low-dose COH04S1 plus placebo group), or two low-dose COH04S1 vaccines (low-dose COH04S1 group). The primary outcome was safety and tolerability, with secondary objectives assessing vaccine-specific immunogenicity. The primary immunological outcome was a four times increase (seroconversion) from baseline in spike-specific or nucleocapsid-specific IgG titres within 28 days of the last injection, and seroconversion rates were compared with participants who received placebo using Fisher's exact test. Additional secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ClinicalTrials.gov, NCT046339466. Findings: Between Dec 13, 2020, and May 24, 2021, 56 participants initiated vaccination. On day 0 and 28, 17 participants received low-dose COH04S1, eight received medium-dose COH04S1, nine received high-dose COH04S1, five received placebo, 13 received low-dose COH04S1 followed by placebo, and four discontinued early. Grade 3 fever was observed in one participant who received low-dose COH04S1 and placebo, and grade 2 anxiety or fatigue was seen in one participant who received medium-dose COH04S1. No severe adverse events were reported. Seroconversion was observed in all 34 participants for spike protein and 32 (94%) for nucleocapsid protein (p

Pioneer species are crucial for the ecological restoration of degraded forests, but what drives variation in their demographic performance is still unclear. Here, we studied three populations of the dominant tree, Pinus massoniana, corresponding to three levels (low, medium, high) of ecological restoration of secondary subtropical forests. Vital rates (growth, survival, and reproduction) were censused during 2019–2020, and integral projection models (IPMs) were parameterized to evaluate the population growth rate (λ) of P. massoniana. The results showed that the survival probability of large-sized individuals, stem growth, and λ of P. massoniana increased as the ecological restoration progressed. In contrast, the survival rate of seedlings declined substantially. The reproduction probability of small individuals was more likely at low than medium/high restoration levels. Elasticity analysis showed that survival contributes most to λ and fecundity the least. λ was primarily determined by the high survival of seedlings/small trees and large trees in the low- and high-restoration level populations, respectively. Life table response experiments showed that increases in survival were mostly responsible for augmented λ during ecological restoration; hence, the high-restoration population had the highest λ due to a higher survival rate. This work shows P. massoniana is capable of undergoing life-history strategy shifts. Its high recruitment and survival of small individuals make it a suitable species for restoring forests, whereby large-sized individuals eventually maintain populations at low risk of mortality.

As a dominant and active component across ecological restoration processes, the population dynamics of pioneer tree species significantly affect species composition and community assemblage. To assess the effect of pioneer populations on species diversity, this study investigated species diversity and population characteristics in five secondary forests dominated by Pinus massoniana in southeastern China. For 40 years, all anthropogenic activities (e.g., logging, farming, etc.) have been banned on the hillsides of these five secondary forests to promote afforestation, for which these forests have thereafter been left to grow naturally. We found that: (1) the basal area (BA) of P. massoniana drove changes in species diversity across forest plots, explaining 31.6% of total variation. The species richness of the herb layer was negatively correlated to BA, while the diversity and evenness of the tree and shrub layers were both positively correlated to the BA. (2) As the size of individual P. massoniana specimens increased, the trend in species richness of the shrub layer and the diversity indexes of both the tree and shrub layer was first to increase and then to decrease once again, while the species richness of the tree layer stabilized after reaching a certain threshold. (3) Species diversity of the forest plots did not improve over time along with an increase in the density of the pioneer species. When the P. massoniana population density was low, the diversity indexes of both the tree and shrub layer increased with an increase in population density. Conversely, when the P. massoniana population density reached 2800 plants/ha, species diversity began to decline. However, when the P. massoniana population density increased to 3733 plants/ha, species diversity of the plant community exhibited an upward trend. Our results indicated that forest species diversity was extremely sensitive to P. massoniana population dynamics during the pioneer stage of ecological succession. Moreover, the pioneer population was the driving factor for both development and change in species diversity, and it did so through habitat adjustment of its ecological relationships.