Why is the risk of industrial non-routine activities high and how can it be evaluated? An integrated approach.

Non-routine activities such as startup, shutdown, maintenance, and operation commissioning require increased human interaction with the corresponding process. Owing to operator or procedural violations, the risk of accidents can be high during non-routine activities, even though they are performed less frequently. To identify and evaluate the hazards of non-routine processes, an integrated method combining job hazard analysis (JHA), hazard and operability analysis (HAZOP), and deviation degrees is proposed. JHA is applied to break down an operational process into steps, which are further defined as nodes in HAZOP for hazard scenario analysis. The concept of deviation degree is defined by integrating the operational and control function deviations to quantify the deviation analysis. Finally, the heating-furnace startup process in an oil and gas gathering and transmission station was selected to illustrate the proposed integrated method. The results show that this method constitutes a systematical and intuitive approach to identify hazard scenarios and evaluate risks, as well as to establish preventive measures for non-routine processes.

Superconductivity of cubic MB6 (M = Na, K, Rb, Cs).

Previous studies have shown that NaB6, KB6, and RbB6 adopting Pm3̄m are superconductors with a relatively high Tc under ambient conditions. In this paper, we conducted systematic structural and related properties research on CsB6 through a genetic evolution algorithm and total energy calculations based on density functional theory between 0 and 20 GPa. Our results reveal a cubic Pm3̄m CsB6, which is dynamically stable under the pressures we studied. We systematically calculated the formation enthalpies, electronic properties, and superconducting properties of Pm3̄m MB6 (M = Na, K, Rb, Cs). They all exhibit metallic features, and boron has high contributions to band structures, density of states, and electron-phonon coupling (EPC). The calculated results about the Helmholtz free energy difference of Pm3̄m CsB6 at 0, 10, and 20 GPa indicate that it is stable upon chemical decomposition (decomposition to simple substances Cs and B) from 0 to 400 K. The phonon density of states indicates that boron atoms occupy the high frequency area. The EPC results show that Pm3̄m CsB6 is a superconductor with Tc = 11.7 K at 0 GPa, close to NaB6 (13.1 K), KB6 (11.7 K), and RbB6 (11.3 K) at 0 GPa in our work, which indicates that boron atoms play an essential role in superconductivity: vibrations of B6 regular octagons lead to the high Tc of Pm3̄m MB6. Our work about Pm3̄m hexaborides provides a supplementary study on the borides of the group IA elements (without Fr and Li) and has an important guiding significance for the experimental synthesis of CsB6.

Stable nanoscale sea-island structure of biobased polyamide 56/poly (butylene adipate-co-terephthalate) blends compatibilized by interfacial hyperbranched structure: Toward biobased polymer blends with ultrahigh toughness.

Developing biobased materials is a considerably effective approach to save fossil resources and reduce emissions. Biobased polyamide 56 (PA56) is an excellent engineering material, but it has low toughness. Herein, to enhance the toughness of PA56, an ultra-tough biodegradable material, i.e., poly (butylene adipate-co-terephthalate) (PBAT) was introduced into PA56. Moreover, a self-synthesized epoxy-terminated hyperbranched polyester (EHBP) was used to improve the compatibility of the blended materials. The results of differential scanning calorimetry and Fourier-transform infrared spectroscopy indicated that the epoxide group of EHBP could react with PA56 and PBAT to form a block-like polymer structure and limit the crystallization behavior of the blends. The scanning electron microscopy results show that the addition of EHBP considerably reduced the dispersed-phase size in the blends, forming a nanoscale island structure. Moreover, the hydrogen bonds formed between EHBP and PA56/PBAT enhanced the intermolecular interaction between the two materials. Thus, PA56 blends with ultrahigh toughness were successfully prepared. The prepared PA56/PBAT/EHBP blend exhibited a notch impact strength of 20.71 kJ/m2 and a breaking elongation of 38.3 %, which represent increases of 427.3 % and 252.8 %, respectively, compared with those of pure PA56. Thus, the proposed method is suitable for toughening PA56 and broadening its applications.

A Surface Matrix of Au NPs Decorated Graphdiyne for Multifunctional Laser Desorption/Ionization Mass Spectrometry.

The development of the valid strategy to enhance laser desorption/ionization efficiency gives rise to widespread concern in surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) technology. Herein, a hybrid of Au NP-decorated graphdiyne (Au/GDY) was fabricated and employed as the SALDI-MS matrix for the first time, and a mechanism based on photothermal and photochemical energy conversions was proposed to understand LDI processes. Given theoretical simulations and microstructure characterizations, it was revealed that the formation of a coupled thermal field and internal electric field endow the as-prepared Au/GDY matrix with superior desorption and ionization efficiency, respectively. Moreover, laser-induced matrix ablation introduced strain and defect level into the Au/GDY hybrid, suppressing the recombination of charge carriers and thereby facilitating analyte ionization. The optimized Au/GDY matrix allowed for reliable detection of trace sulfacetamide and visualization of exogenous/endogenous components in biological tissues. This work offers an integrated solution to promote LDI efficiency based on collaborative photothermal conversion and internal electric field, and may inspire the design of novel semiconductor-based surface matrices.

SlMYB7, an AtMYB4-Like R2R3-MYB Transcription Factor, Inhibits Anthocyanin Accumulation in Solanum lycopersicum Fruits.

Tomato is a horticultural crop with an incomplete flavonoid metabolic pathway that does not typically accumulate anthocyanins in the fruit. In recent years, intensive studies of the loci Anthocyanin fruit (Aft) and atroviolacium (atv) have clarified the functions of positive regulators (R2R3-MYBs) and a negative regulator (CPC-MYB) in anthocyanin biosynthesis in the fruits. However, little is known about the R2R3-MYB repressors. Here, we used transient overexpression analysis to show that SlMYB7, a subgroup 4 AtMYB4-like R2R3-MYB, inhibited anthocyanin accumulation and reduced expression of anthocyanin synthase genes in the 'black pearl' tomato fruits, which usually accumulate high concentrations of anthocyanins. These findings revealed that SlMYB7 served as a repressor of anthocyanin production. Furthermore, SlMYB7 actively repressed SlANS expression by binding its promoter and passively inhibited anthocyanin synthesis by interacting with the basic helix-loop-helix (bHLH) proteins SlJAF13 and SlAN1, which are involved in the formation of MBW complexes. Thus, SlMYB7 and the MBW complex may coregulate the anthocyanin content of 'black pearl' tomato fruits via a negative feedback loop. These findings provide a theoretical basis for the future enhancement of tomato anthocyanin contents through genetic manipulation of the biosynthetic regulatory network.

Hybrid neuromorphic hardware with sparing 2D synapse and CMOS neuron for character recognition.

Neuromorphic computing enables efficient processing of data-intensive tasks, but requires numerous artificial synapses and neurons for certain functions, which leads to bulky systems and energy challenges. Achieving functionality with fewer synapses and neurons will facilitate integration density and computility. Two-dimensional (2D) materials exhibit potential for artificial synapses, including diverse biomimetic plasticity and efficient computing. Considering the complexity of neuron circuits and the maturity of complementary metal-oxide-semiconductor (CMOS), hybrid integration is attractive. Here, we demonstrate a hybrid neuromorphic hardware with 2D MoS2 synaptic arrays and CMOS neural circuitry integrated on board. With the joint benefit of hybrid integration, frequency coding and feature extraction, a total cost of twelve MoS2 synapses, three CMOS neurons, combined with digital/analogue converter enables alphabetic and numeric recognition. MoS2 synapses exhibit progressively tunable weight plasticity, CMOS neurons integrate and fire frequency-encoded spikes to display the target characters. The synapse- and neuron-saving hybrid hardware exhibits a competitive accuracy of 98.8% and single recognition energy consumption of 11.4 µW. This work provides a viable solution for building neuromorphic hardware with high compactness and computility.

Chemically and biologically driven carbon transformation flow in MSW leachate treated by a high-solids anaerobic membrane bioreactor system.

Carbon transformation is important for an anaerobic process but is often overlooked when using an anaerobic membrane bioreactor (AnMBR). Material flow in an AnMBR treating calcium-rich MSW leachate was thus quantitatively investigated to illustrate how chemical and biological factors affect carbon transformation. The results show that a remarkable amount of carbon in the leachate was degraded, with 50.1% of it should be converted into CH4 and 37.7% of it into CO2. However, a much smaller value of 40.6% and 14.2% were experimentally obtained. Chemical analysis indicated that the precipitation of calcium carbonate captured 1.23 g/day of carbon. At the same time, about 23.2 g/L HCO3- and 16.6 mg/L CH4 (both as carbon) were dissolved in the liquid. Those features facilitated the high CH4 (74%) content in biogas. A carbon transformation model was therefore established and showed carbon flow into the gas, liquid, and solid phases, respectively. Carbon existed in biogas, permeate, and discharged sludge was also obtained.

Mitochondria in cancer stem cells: Achilles heel or hard armor.

Previous studies have shown that mitochondria play core roles in not only cancer stem cell (CSC) metabolism but also the regulation of CSC stemness maintenance and differentiation, which are key regulators of cancer progression and therapeutic resistance. Therefore, an in-depth study of the regulatory mechanism of mitochondria in CSCs is expected to provide a new target for cancer therapy. This article mainly introduces the roles played by mitochondria and related mechanisms in CSC stemness maintenance, metabolic transformation, and chemoresistance. The discussion mainly focuses on the following aspects: mitochondrial morphological structure, subcellular localization, mitochondrial DNA, mitochondrial metabolism, and mitophagy. The manuscript also describes the recent clinical research progress on mitochondria-targeted drugs and discusses the basic principles of their targeted strategies. Indeed, an understanding of the application of mitochondria in the regulation of CSCs will promote the development of novel CSC-targeted strategies, thereby significantly improving the long-term survival rate of patients with cancer.

Global burden and trends of the Entamoeba infection-associated diseases from 1990 to 2019: An observational trend study.

BACKGROUND: Entamoeba infection-associated diseases (EIADs) in humans are a worldwide public health problem, but there is a lack of a global picture of EIADs, which is vital to prevention and control. METHODS: We applied 2019 Global Burden of Disease (GBD) data collected from multiple sources at global, national and regional levels. The disability-adjusted life years (DALYs) with corresponding 95% uncertainty intervals (95% UIs) were extracted as the main measure of the burden of EIADs. The Joinpoint regression model was used to estimate the trends of age-standardised DALY rates by age, sex, geographical region, and sociodemographic index (SDI). Besides, a generalized linear model was conducted to analyze the influence of sociodemographic factors on the DALY rate of EIADs. RESULTS: In 2019, there were 2,539,799 (95% UI 850,865-6,186,972) DALY cases attributable to Entamoeba infection, and the global age-standardised DALY rate of EIADs was 36.77/100,000 (95% UI: 12.03-90.49). Although over the past 30 years, the age-standardised DALY rate of EIADs presented significantly declining trends [average annual percent change (AAPC) = -3.79%, 95% CI: -4.05% - -3.53%], it has remained a heavy burden among the age group of <5 years (257.43/100,000, 95% UI: 67.73-676.78) and the low SDI regions (100.47/100,000, 95% UI: 32.27-249.09). The age-standardized DALY rate in high-income North America and Australia had an increasing trend (AAPC = 0.38%, 95% CI: 0.47% - 0.28% and 0.38%, 95% CI: 0.46% - 0.29%, respectively). Furthermore, the DALY rates in high SDI regions showed statistically significant increasing trends among the age groups of 14-49, 50-69 years and 70+ years, with AAPCs of 1.01% (95% CI: 0.87% - 1.15%), 1.58% (95% CI: 1.43% - 1.73%), and 2.93% (95% CI: 2.58% - 3.29%), respectively. CONCLUSIONS: Over the past 30 years, the burden of EIADs has declined significantly. However, it has still caused a high burden in the low SDI regions and the age group of <5 years. At the same time, in adults and the elderly of the high SDI regions, the increasing trends of Entamoeba infection-associated burden should also be given more attention.

Neuromorphic Photonic Memory Devices Using Ultrafast, Non-Volatile Phase-Change Materials.

The search for ultrafast photonic memory devices is inspired by the ever-increasing number of cloud-computing, supercomputing, and artificial-intelligence applications, together with the unique advantages of signal processing in the optical domain such as high speed, large bandwidth, and low energy consumption. By embracing silicon photonics with chalcogenide phase-change materials (PCMs), non-volatile integrated photonic memory is developed with promising potential in photonic integrated circuits and nanophotonic applications. While conventional PCMs suffer from slow crystallization speed, scandium-doped antimony telluride (SST) has been recently developed for ultrafast phase-change random-access memory applications. An ultrafast non-volatile photonic memory based on an SST thin film with a 2 ns write/erase speed is demonstrated, which is the fastest write/erase speed ever reported in integrated phase-change photonic devices. SST-based photonic memories exhibit multilevel capabilities and good stability at room temperature. By mapping the memory level to the biological synapse weight, an artificial neural network based on photonic memory devices is successfully established for image classification. Additionally, a reflective nanodisplay application using SST with optoelectronic modulation capabilities is demonstrated. Both the optical and electrical changes in SST during the phase transition and the fast-switching speed demonstrate their potential for use in photonic computing, neuromorphic computing, nanophotonics, and optoelectronic applications.

Bioinspired Self-Growing Hydrogels by Harnessing Interfacial Polymerization.

The production of natural materials is achieved through a bottom-up approach, in which materials spontaneously grow and adapt to the external environment. Synthetic materials are specifically designed and fabricated as engineered materials; however, they are far away from these natural self-growing attributes. Thus, design and fabrication of synthetic material systems to replicate the self-growing characteristics of those natural prototypes (i.e., hairs and nails) remains challenging. Inspired by the self-growing behaviors of keratin proteins, here the fabrication of synthetic hydrogels (i.e., polyacrylamide (PAAm)) from the free radical polymerization at the interface between AAm precursor solution and liquid metals (i.e., eutectic gallium-indium (EGaIn)) is reported. The newly formed hydrogel materials at the EGaIn/AAm precursor interface gradually push the whole hydrogel upward, enabling the self-growing of these synthetic hydrogel materials. This work not only endows the fabrication of synthetic materials with unprecedented self-growing characters, but also broadens the potential applications of self-growing materials in actuation and soft robotics.

Effects of gibberellins on important agronomic traits of horticultural plants.

Horticultural plants such as vegetables, fruits, and ornamental plants are crucial to human life and socioeconomic development. Gibberellins (GAs), a class of diterpenoid compounds, control numerous developmental processes of plants. The roles of GAs in regulating growth and development of horticultural plants, and in regulating significant progress have been clarified. These findings have significant implications for promoting the quality and quantity of the products of horticultural plants. Here we review recent progress in determining the roles of GAs (including biosynthesis and signaling) in regulating plant stature, axillary meristem outgrowth, compound leaf development, flowering time, and parthenocarpy. These findings will provide a solid foundation for further improving the quality and quantity of horticultural plants products.

Chronic unpredictable mild stress-induced mouse ovarian insufficiency by interrupting lipid homeostasis in the ovary.

Ovarian insufficiency results from a number of disorders, and a certain causal relationship between psychological stress and ovarian insufficiency has been reported, but the underlying mechanism remains unclear. In our study, C57BL/6J female mice were subjected to chronic unpredictable mild stress (CUMS), and depression-like mice were selected and identified according to the behavioral tests. The defective ovarian follicle development, low 17 ß-estradiol (E2), and anti-Mullerian hormone (AMH) levels, which were consistent with the clinical characteristics of ovarian insufficiency, indicated that depression-like mice may be used to assess the effects of psychological stress on female reproductive function. To investigate a possible mechanism, lipid homeostasis of the ovary was detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, and the decreased abundance of cholesteryl ester (CE 24:4) was supported to be associated with the downregulated E2. Moreover, granulosa cells did undergo more apoptosis in response to psychological stress, which was caused by downregulated Bcl2 and Bcl2/Bax in granulosa cells. Additionally, the disorder of cell death and growth-related pathways in depression-like mouse ovaries was confirmed by RNA-seq analysis. Taken together, this study will provide a better understanding of the female reproductive problem under psychological stress.

Au NPs decorated holey g-C3N4 as a dual-mode sensing platform of SERS and SALDI-MS for selective discrimination of L-cysteine.

Development of reliable sensing strategy combining surface-enhanced Raman scattering (SERS) and surface-assisted laser desorption/ionization-mass spectrometry (SALDI-MS) is of significant interest to distinguish cysteine enantiomers in body fluid for understanding their physiological roles and toxicity hazards. In this work, a SERS/SALDI-MS dual-mode sensing platform of gold nanoparticles (Au NPs) decorated holey carbon nitride (hg-C3N4) was fabricated for sensitive detecting cysteine. The designed Au@hg-C3N4 matrix featured a uniform distribution of Au NPs with the help of anchoring effect of hg-C3N4 holey structure, which was conducive to produce highly repeatable signals. Moreover, the combination of Au NPs and holey g-C3N4 endowed this matrix with superior enrichment capacity, enhanced charge transfer and strong UV absorption. These merits allowed the matrix to acquire high sensitivity and enhanced reproducibility for l-cysteine by means of SERS/SALDI-MS. Likewise, reliable detection of l-cysteine and efficient recognition of d-cysteine in human serum jointly revealed its prospect for detecting cysteine enantiomers in body fluids. This work offers a reliable SERS/SALDI-MS strategy for determining L/D-cysteine enantiomers, and the designed Au@hg-C3N4 matrix becomes a potential application candidate for selective detection of bio-enantiomers.

An innovative strategy to enhance the ensiling quality and methane production of excessively wilted wheat straw: Using acetic acid or hetero-fermentative lactic acid bacterial community as additives.

Ensiling is an effective storage strategy for agricultural biomass, especially for energy crops (mainly energy grasses and maize). However, the ensiling of excessively wilted crop straw is limited due to material characteristics, such as a high lignocellulosic content and low water-soluble carbohydrate and moisture contents. In this study, acetic acid or hetero-fermentative lactic acid bacterial community (hetero-fermentative LAB) were employed as silage additives to improve the ensiling process of excessively wilted wheat straw (EWS). The results showed that the additives inhibited the growth of Enterobacteriaceae and Clostridium_sensu_stricto_12, whose abundances decreased from 55.8% to 0.03-0.2%, respectively. The growth of Lactobacillus was accelerated, and the abundances increased from 1.3% to 80.1-98.4% during the ensiling process. Lactic acid fermentation was the dominant metabolic pathway in the no additive treatment. The additives increased acetic acid fermentation and preserved the hemicellulose and cellulose contents, increasing the methane yield by 17.7-23.9%. This study shows that ensiling with acetic acid or hetero-fermentative LAB is an effective preservation and storage strategy for efficient methane production from EWS.

Mitigating membrane fouling in a high solid food waste thermophilic anaerobic membrane bioreactor by incorporating fixed bed bio-carriers.

Hybrid anaerobic membrane bioreactor (Hy-AnMBR) was developed by incorporating polyurethane sponge carriers to mitigate membrane fouling. The results showed that the membrane fouling was well controlled in Hy-AnMBR from the aspects of sludge property and membrane filtration performance. The solid concentration, including TS and MLSS in the Hy-AnMBR was reduced after introducing the fixed bed carrier, which was 13% and 20% lower than the control AnMBR (Con-AnMBR), and this resulted in improved filtration performance. The scanning electron microscope (SEM) photograph showed that membrane pores could still be observed on the Hy-AnMBR surface, indicating that the cake layer fouling of the Hy-AnMBR was less than the Con-AnMBR. The increase of the EPS and SMP promoted the acceleration of the membrane fouling rate. Analysis through confocal laser scanning microscopy (CLSM) and membrane cleaning revealed that adding sponge carriers mitigated 3.3%-9% pore-blocking, and the total membrane resistance in the Hy-AnMBR was reduced by 52% compared to the Con-AnMBR. Chemical cleaning was essential for pollutant removal, and membrane permeability recovery was more than 97%.

Result and technique consideration of radiofrequency catheter ablation of tachycardia in patients with dextrocardia.

BACKGROUND: Patients with tachycardia, in the context of pre-existing dextrocardia, could benefit from catheter ablation. However, anatomical complexities hinder effective conduct of this procedure. We aimed to retrospectively summarize the clinical characteristics and the safety and efficiency, and recommended the technique considerations. METHODS: Twenty-one cases from 19 patients with tachycardia and dextrocardia, who underwent catheter ablation between 2009 and 2021, were enrolled. All patients underwent echocardiography and computed tomography (CT) to confirm the anatomical malformations. Transseptal puncture was guided by fluoroscopy or intracardiac echocardiography when left atrial access was necessary and the ablation process was guided by three-dimensional (3D) mapping. RESULTS: Six cases exhibited situs solitus while nine cases exhibited situs inversus. Fourteen cases had atrial fibrillation, seven had atrial flutter, and two had atrioventricular reentrant tachycardia (AVRT); two cases had combined atrial fibrillation and atrial flutter. Acute success was achieved in 18 cases (85.7%, 18/21). The 3D mapping system was not employed in the three cases which failed. During long-term follow-up (20.71 ± 21.86 months), eight cases (72.7%, 8/11) of atrial fibrillation with dextrocardia successfully attained sinus rhythm. None of AVRT cases had recurrence. Half of the atrial flutter cases with dextrocardia, especially those with a history of surgical correction for cardiac malformations, underwent recurrence. One case had cardiac tamponade. CONCLUSIONS: Catheter ablation for tachycardia patients with dextrocardia is safe, efficient, and feasible. It is imperative to integrate echocardiography, cardiac computer tomography, and 3D mapping, and apply 3D reconstruction to facilitate the success of catheter ablation.

The ultrastructure of spermatogenic cells and morphological evaluation of testicular development in the silver pomfret (Pampus argenteus).

The silver pomfret (Pampus argenteus) is a widely distributed and economically important marine fish in the Indo-Pacific. In this study, we acquired the second generation of wild P. argenteus by artificial breeding and further studied the testicular development and ultrastructure of spermatogenesis. The results of gonadosomatic index (GSI) showed the spawning period of this marine fish was from April to June. Besides, through morphological analysis, we found that P. argenteus had an anastomosing tubular testis surrounded by a layer of tunica albuginea, in which spermatogenesis occurred in cysts where the synchronous germ cells were completely surrounded by the cytoplasmic projection of Sertoli cells. Meanwhile, based on submicroscopic characteristics, the germ cells are classified into nine different types. During the ontogenesis of testis, both the early stage of spermatogenesis and sperm were observed in P. argenteus. At sperm maturation stage, different types of spermatozoa and activation of sperms occurred non-synchronously in the tubules. Cytoplasmic bridges also were observed among synchronous germ cells within the cysts, suggesting an interrelated and differentiated relationship among these germ cells.

The prevalence and clinical features of pulmonary embolism in patients with AE-COPD: A meta-analysis and systematic review.

BACKGROUND: The prevalence of pulmonary embolism (PE) in the acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is highly controversial. We conducted a systematic review and meta-analysis to summarize the epidemiology and characteristics of PE with AE-COPD for current studies. METHODS: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies published prior to October 21, 2020. Pooled proportions with 95% confidence intervals (95% CIs) were calculated using a random effects model. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals were used as effect measures for dichotomous and continuous variables, respectively. RESULTS: A total of 17 studies involving 3170 patients were included. The prevalence of PE and deep vein thrombosis (DVT) in AE-COPD patients was 17.2% (95% CI: 13.4%-21.3%) and 7.1% (95% CI: 3.7%-11.4%%), respectively. Dyspnea (OR = 6.77, 95% CI: 1.97-23.22), pleuritic chest pain (OR = 3.25, 95% CI: 2.06-5.12), lower limb asymmetry or edema (OR = 2.46, 95% CI:1.51-4.00), higher heart rates (MD = 20.51, 95% CI: 4.95-36.08), longer hospital stays (MD = 3.66, 95% CI: 3.01-4.31) were associated with the PE in the AE-COPD patients. Levels of D-dimer (MD = 1.51, 95% CI: 0.80-2.23), WBC counts (MD = 1.42, 95% CI: 0.14-2.70) were significantly higher and levels of PaO2 was lower (MD = -17.20, 95% CI: -33.94- -0.45, P<0.05) in the AE-COPD with PE group. The AE-COPD with PE group had increased risk of fatal outcome than the AE-COPD group (OR = 2.23, 95% CI: 1.43-3.50). CONCLUSIONS: The prevalence of PE during AE-COPD varies considerably among the studies. AE-COPD patients with PE experienced an increased risk of death, especially among the ICU patients. Understanding the potential risk factors for PE may help clinicians identify AE-COPD patients at increased risk of PE. PROSPERO REGISTRATION NUMBER: CRD42021226568.