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Background The triglyceride-glucose (TyG) index is a new alternative measure for insulin resistance. This meta-analysis was conducted to assess the associations of the TyG index with the risks of cardiovascular diseases and mortality in the general population. Methods The PubMed, Cochrane Library and Embase databases were searched for randomized controlled trials or observational cohort studies reporting associations of the TyG index with cardiovascular diseases and mortality from inception to April 16, 2022. Effect sizes were pooled using random-effects models. Robust error meta-regression methods were applied to fit nonlinear dose–response associations. Evidence quality levels and recommendations were assessed using the Grading of Recommendations Assessment, Development and Evaluation system (GRADE). Results Twelve cohort studies (6 prospective and 6 retrospective cohorts) involving 6,354,990 participants were included in this meta-analysis. Compared with the lowest TyG index category, the highest TyG index was related to a higher incidence of coronary artery disease (CAD) (3 studies; hazard ratio [HR] = 2.01; 95% confidence interval [CI] 1.68–2.40; I 2  = 0%), myocardial infarction (MI) (2 studies; HR = 1.36; 95% CI 1.18–1.56; I 2  = 35%), and composite cardiovascular disease (CVD) (5 studies; HR = 1.46; 95% CI 1.23–1.74; I 2  = 82%). However, there was no association between the TyG index and mortality (cardiovascular mortality [3 studies; HR = 1.10; 95% CI 0.82–1.47; I 2  = 76%] or all-cause mortality [4 studies; HR = 1.08; 95% CI 0.92–1.27; I 2  = 87%]). In the dose–response analysis, there was a linear association of the TyG index with the risk of CAD (P nonlinear  = 0.3807) or CVD (P nonlinear  = 0.0612). GRADE assessment indicated very low certainty for CVD, MI, cardiovascular mortality and all-cause mortality, and moderate certainty for CAD. Conclusions Based on our current evidence, a higher TyG index may be associated with an increased incidence of CAD (moderate certainty), MI (very low certainty) and CVD (very low certainty) in the general population. There is a potential linear association of the TyG index with CAD and the composite CVD incidence. Further prospective studies (especially in non-Asians) are needed to confirm our findings.

Coverage rate, a critical variable for gridded forest area, has been neglected by previous studies in estimating the annual gross primary production (GPP) of global forest ecosystems. In this study, we investigated to what extent the coverage rate could impact forest GPP estimates from 1982 to 2011. Here we show that the traditional calculation without considering the coverage rate globally overestimated the forest gross carbon dioxide uptake by approximately 8.7%, with a value of 5.12 ± 0.23 Pg C yr −1 , which is equivalent to 48% of the annual emissions from anthropogenic activities in 2012. Actually, the global annual GPP of forest ecosystems is approximately 53.71 ± 4.83 Pg C yr −1 for the past 30 years by taking the coverage rate into account. Accordingly, we argue that forest annual GPP calculated by previous studies has been overestimated due to the exaggerated forest area and therefore, coverage rate may be a required factor to further quantify the global carbon cycle.

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

Background The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. Methods We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. Results Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92–2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91–5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64–14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79–1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40–1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. Conclusions Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19.

Background The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). Methods We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. Results Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55–2.17, I 2  = 68%) and CAC (OR: 1.66; 95% CI 1.51–1.82, I 2  = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35–1.69, I 2  = 82%) and CAC (OR: 1.73, 95% CI 1.36–2.20, I 2  = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21–2.27, I 2  = 0, in category analysis, OR = 1.47, 95% CI 1.29–1.68, I 2  = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (P nonlinearity  < 0.001). Conclusion An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality. Graphical Abstract

Objective The triglyceride–glucose (TyG) index has been shown to be a new alternative measure for insulin resistance. However, no study has attempted to investigate the association of the TyG index with incident atrial fibrillation (AF) in the general population without known cardiovascular diseases. Methods Individuals without known cardiovascular diseases (heart failure, coronary heart disease, or stroke) from the Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and incident AF was examined using Cox regression. Results Of 11,851 participants, the mean age was 54.0 years; 6586 (55.6%) were female. During a median follow-up of 24.26 years, 1925 incidents of AF cases (0.78/per 100 person-years) occurred. An increased AF incidence with a graded TyG index was found by Kaplan‒Meier curves ( P  < 0.001). In multivariable-adjusted analysis, both < 8.80 (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval [CI] 1.02, 1.29) and > 9.20 levels (aHR 1.18, 95% CI 1.03, 1.37) of the TyG index were associated with an increased risk of AF compared with the middle TyG index category (8.80–9.20). The exposure-effect analysis confirmed the U-shaped association between the TyG index and AF incidence ( P  = 0.041). Further sex-specific analysis showed that a U-shaped association between the TyG index and incident AF still existed in females but not in males. Conclusions A U-shaped association between the TyG index and AF incidence is observed in Americans without known cardiovascular diseases. Female sex may be a modifier in the association between the TyG index and AF incidence. Graphical Abstract

Background The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. Methods The Nation Health and Nutrition Examination Survey (NHANES) (2009–2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. Results This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation ( r  = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02–1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1–3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). Conclusions Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.

BackgroundPatients with atrial fibrillation (AF) and frailty are a considerable group in clinical practice. However, existing studies provide insufficient evidence of anticoagulation strategies for these patients. Therefore, we conducted a meta-analysis to determine the effectiveness and safety outcomes of direct oral anticoagulants (DOACs) for these patients.MethodsRandomized controlled trials or observational studies reporting the data about the DOACs and warfarin therapy among frail AF patients were included. The search was performed in the PubMed and Embase databases up to March 2022. Frailty was defined using the most widely used claims-based frailty index or the cumulative deficit model-based frailty index.ResultsA total of 4 studies involving 835,520 patients were included. Compared with warfarin, DOACs therapy reduced the risks of stroke or systemic embolism (HR = 0.79, 95%CI: 0.69–0.90), ischemic stroke (HR = 0.79, 95%CI: 0.71–0.87), hemorrhagic stroke (HR = 0.52, 95%CI: 0.35–0.76), and all-cause death (HR = 0.90, 95%CI: 0.84–0.96). In safety outcomes, DOACs was significantly associated with reduced risks of major bleeding (HR = 0.79, 95%CI: 0.64–0.97) and intracranial hemorrhage (HR = 0.58, 95%CI: 0.52–0.65) compared to warfarin, but there were no statistically differences in gastrointestinal bleeding (HR = 0.97, 95%CI: 0.73–1.29).ConclusionsDOACs exerted superior effectiveness and safety outcome than warfarin in AF patients with frailty.

On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.

Individual-based models (IBMs) of complex systems emerged in the 1960s and early 1970s, across diverse disciplines from astronomy to zoology. Ecological IBMs arose with seemingly independent origins out of the tradition of understanding the ecosystems dynamics of ecosystems from a 'bottom-up' accounting of the interactions of the parts. Individual trees are principal among the parts of forests. Because these models are computationally demanding, they have prospered as the power of digital computers has increased exponentially over the decades following the 1970s. This review will focus on a class of forest IBMs called gap models. Gap models simulate the changes in forests by simulating the birth, growth and death of each individual tree on a small plot of land. The summation of these plots comprise a forest (or set of sample plots on a forested landscape or region). Other, more aggregated forest IBMs have been used in global applications including cohort-based models, ecosystem demography models, etc. Gap models have been used to provide the parameters for these bulk models. Currently, gap models have grown from local-scale to continental-scale and even global-scale applications to assess the potential consequences of climate change on natural forests. Modifications to the models have enabled simulation of disturbances including fire, insect outbreak and harvest. Our objective in this review is to provide the reader with an overview of the history, motivation and applications, including theoretical applications, of these models. In a time of concern over global changes, gap models are essential tools to understand forest responses to climate change, modified disturbance regimes and other change agents. Development of forest surveys to provide the starting points for simulations and better estimates of the behavior of the diversity of tree species in response to the environment are continuing needs for improvement for these and other IBMs.