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Abstract Macrolide antibiotics, pivotal in clinical therapeutics, are confronting resistance challenges mediated by enzymes like macrolide esterases, which are classified into Ere-type and the less studied Est-type. In this study, we provide the biochemical confirmation of EstX, an Est-type macrolide esterase that initially identified as unknown protein in the 1980s. EstX is capable of hydrolyzing four 16-membered ring macrolides, encompassing both veterinary (tylosin, tidipirosin, and tilmicosin) and human-use (leucomycin A5) antibiotics. It uses typical catalytic triad (Asp233-His261-Ser102) from alpha/beta hydrolase superfamily for ester bond hydrolysis. Further genomic context analysis suggests that the dissemination of estX is likely facilitated by mobile genetic elements such as integrons and transposons. The global distribution study indicates that bacteria harboring the estX gene, predominantly pathogenic species like Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae, are prevalent in 74 countries across 6 continents. Additionally, the emergence timeline of the estX gene suggests its proliferation may be linked to the overuse of macrolide antibiotics. The widespread prevalence and dissemination of Est-type macrolide esterase highlight an urgent need for enhanced monitoring and in-depth research, underlining its significance as an escalating public health issue.

A circular shaft is often used to access a working well for deep underground space utilization. As the depth of underground space increases, the excavation depth of the shaft increases. In this study, the deformation characteristics of a circular shaft with a depth of 56.3 m were presented and analysed. The main monitoring contents included: (1) wall deflection; (2) vertical wall movement; (3) horizontal soil movement; (4) vertical surface movement; and (5) basal heave. Horizontally, the maximum wall deflection was only 7.7 mm. Compared with the wall deflection data collected for another 29 circular excavations, the ratio of maximum wall deflection to excavation depth of this shaft was smaller due to a smaller ratio of diameter to excavation depth. The wall deflection underwent two stages of deformation: the first stage was mainly circumferential compression caused by the mutual extrusion of joints between walls, and the second stage was typical vertical deflection deformation. The horizontal soil movement outside the shaft was greater than the wall deflection and the deep soil caused great horizontal movement because of dewatering at confined water layers. Vertically, a basal heave of 203.8 mm occurred in the pit centre near the bottom. Meanwhile, the shaft was uplifted over time and showed 3 stages of vertical movement. The surface outside the shaft exhibited settlement and uplift deformation at different locations due to different effects. The basal heave caused by excavation was the dominant factor, driving the vertical movement of the shaft as well as the surrounding surface. The correlation between the wall deflection and the surface settlement outside the shaft was weak.

Abstract Background During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. Methods REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. Results The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p

Abstract Motion blur can easily affect the quality of QR code image, making it difficult to recognize QR codes on moving objects. This paper proposes an algorithm for the recognition of motion-blurred QR codes based on generative adversarial network and attention mechanism. Firstly, a multi-scale feature extraction framework for motion defuzzification is designed using deep convolutional neural networks, and enhanced multi-scale residual blocks and multi-scale feature extraction modules are utilized to capture rich local and global features. Secondly, the efficient channel attention module is added to strengthen the weights of effective features and suppress invalid features by modeling the correlations between channels. In addition, training stability is achieved through the use of the WGAN-div loss function, leading to the generation of higher quality samples. Finally, the proposed algorithm is evaluated through qualitative and quantitative comparisons with several recent methods on both the GOPRO public dataset and a self-constructed QR code dataset, respectively. The experimental results demonstrate that, compared to the other methods, the proposed algorithm has shown significant improvements in both processing time and recognition accuracy when dealing with the task of severe motion-blurred QR code recognition.

Abstract Emergency departments (ED) are complex, triage is a main task in the ED to prioritize patient with limited medical resources who need them most. Machine learning (ML) based ED triage tool, Score for Emergency Risk Prediction (SERP), was previously developed using an interpretable ML framework with single center. We aimed to develop SERP with 3 Korean multicenter cohorts based on common data model (CDM) without data sharing and compare performance with inter-hospital validation design. This retrospective cohort study included all adult emergency visit patients of 3 hospitals in Korea from 2016 to 2017. We adopted CDM for the standardized multicenter research. The outcome of interest was 2-day mortality after the patients’ ED visit. We developed each hospital SERP using interpretable ML framework and validated inter-hospital wisely. We accessed the performance of each hospital’s score based on some metrics considering data imbalance strategy. The study population for each hospital included 87,670, 83,363 and 54,423 ED visits from 2016 to 2017. The 2-day mortality rate were 0.51%, 0.56% and 0.65%. Validation results showed accurate for inter hospital validation which has at least AUROC of 0.899 (0.858–0.940). We developed multicenter based Interpretable ML model using CDM for 2-day mortality prediction and executed Inter-hospital external validation which showed enough high accuracy.

Abstract The separation and purification of C6 cyclic hydrocarbons (benzene, cyclohexene, cyclohexane) represent a critically important but energy intensive process. Developing adsorptive separation technique to replace thermally driven distillation processes holds great promise to significantly reduce energy consumption. Here we report a flexible one-dimensional coordination polymer as an efficient adsorbent to discriminate ternary C6 cyclic hydrocarbons via an ideal molecular sieving mechanism. The compound undergoes fully reversible structural transformation associated with removal/re-coordination of water molecules and between activated and hydrocarbon-loaded forms. It exhibits distinct temperature- and adsorbate-dependent adsorption behavior which facilitates the complete separation of benzene, cyclohexene and cyclohexane from their binary and ternary mixtures, with the record-high uptake ratios for C6H6/C6H12 and C6H10/C6H12 in vapor phase and highest binary and ternary selectivities in liquid phase. In situ infrared spectroscopic analysis and ab initio calculations provide insight into the host-guest interactions and their effect on the preferential adsorption and structural transformation.

Abstract Background In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation. Methods Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR. Results During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04–2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23–5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1–2 ( 0.05). Conclusion High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.

AimsClostridium perfringens is one of the major anaerobic pathogen causing food poisoning and animal enteritis. With the rise of antibiotic resistance and the restrictions of the use of antibiotic growth promoting agents (AGPs) in farming, Clostridium enteritis and food contamination have become more common. It is time-consuming and labor-intensive to confirm the detection by standard culture methods, and it is necessary to develop on-site rapid detection tools. In this study, a combination of recombinase polymerase amplification (RPA) and lateral flow biosensor (LFB) was used to visually detect C. perfringens in chicken meat and milk.Methods and resultsTwo sets of primers were designed for the plc gene of C. perfringens, and the amplification efficiency and specificity of the primers. Selection of primers produces an amplified fragment on which the probe is designed. The probe was combined with the lateral flow biosensor (LFB). The reaction time and temperature of RPA-LFB assay were optimized, and the sensitivity of the assay was assessed. Several common foodborne pathogens were selected to test the specificity of the established method. Chicken and milk samples were artificially inoculated with different concentrations (1 × 102 CFU/mL to 1 × 106 CFU/mL) of C. perfringens, and the detection efficiency of RPA-LFB method and PCR method was compared. RPA-LFB can be completed in 20 min and the results can be read visually by the LFB test strips. The RPA-LFB has acceptable specificity and the lowest detection limit of 100 pg./μL for nucleic acid samples. It was able to stably detect C. perfringens contamination in chicken and milk at the lowest concentration of 1 × 104 CFU/mL and 1 × 103 CFU/mL, respectively.ConclusionIn conclusion, RPA-LFB is specific and sensitive. It is a rapid, simple and easy-to-visualize method for the detection of C. perfringens in food and is suitable for use in field testing work.

The simulation of the predissociation spectrum of the Na2 23Πg∼33Πg←b3Πu (v=14,J=14) transition, observed earlier with the Perturbation Facilitated Optical–Optical Double Resonance (PFOODR) experimental method, is done within the Optimizer project with our Split-operator computational package using Padé approximations for all functions involved in the model. This simulation reproduces the experimental spectrum satisfactory well. The parameters of the model functions involved in the simulations are determined and reported. A brief description of our computational methods and programs is presented.

Abstract Background Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. Methods Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. Results Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. Conclusions Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

The biosynthetic potential of actinobacteria to produce novel natural products is still regarded as immense. In this paper, we correlated a cryptic biosynthetic gene cluster to chemical molecules by genome mining and chemical analyses, leading to the discovery of a new group of catecholate-hydroxamate siderophores, nobachelins, from Nocardiopsis baichengensis DSM 44845. Nobachelin biosynthesis genes are conserved in several bacteria from the family Nocardiopsidaceae. Structurally, nobachelins feature fatty-acylated hydroxy-ornithine and a rare chlorinated catecholate group. Intriguingly, nobachelins rescued Caenorhabditis elegans from Pseudomonas aeruginosa-mediated killing.

In modern electronic warfare, the jamming environment of radar is more complex than ever. The airborne jammer adapts its jamming method based on diverse raid missions and stages. Recently, the reinforcement learning–based radar anti-jamming method has made some progress in the confrontation scenario of single jamming; however, the gap with respect to actual complex multi-jamming scenarios is large. To address this issue, this paper proposes a multi-jamming scenario radar anti-jamming method based on deep reinforcement learning in the complex domain to optimize the anti-jamming strategy of frequency agile radar. First, according to the stage characteristics of the raid mission, noise spot jamming, range deception jamming , and dense false target forwarding jamming models are established. The three jamming sequence strategies were designed to simulate actual jamming scenarios. Second, a reinforcement learning reward function that integrates the signal-to-noise ratio and target trajectory integrity is constructed for the multi-jamming scenario model. Thus, a multi-jamming scenario radar anti-jamming method based on deep reinforcement learning in a complex domain is proposed, which is based on the complex domain characteristics of the jamming signal. Finally, radar anti-jamming simulation experiments are performed based on the three jamming sequence strategies. The results show that the proposed method can effectively deal with the main-lobe jamming problem of complex multi-jamming scenarios under time-sequence conditions. Moreover, the average decision-making accuracy was improved, and the average decision-making time was reduced to 405.3 ms compared with the two classical reinforcement learning algorithms.

Abstract Background The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. Objective To outline the statistical analysis plan for the REVISE trial. Methods REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. Results The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. Conclusions This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. Trial registration www.ClinicalTrials.gov NCT03374800. November 21, 2017.

Abstract Background Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and death. The use of low-molecular-weight heparin (LMWH), despite being the standard of care to prevent VTE, comes with some challenges. Shared decision-making (SDM) interventions are recommended to support patients and clinicians in making preference-sensitive decisions. The quality of the SDM process has been widely assessed with the decisional conflict scale (DCS). Our aim is to report participants’ perspectives of each of the components of an SDM intervention (DASH-TOP) in relation to the different subscales of the DCS. Methods Design: A convergent, parallel, mixed-methods design. Participants: The sample consisted of 22 health care professionals, students of an Applied Clinical Research in Health Sciences (ICACS) master program. Intervention: We randomly divided the participants in three groups: Group 1 received one component (evidence -based information), Group 2 received two components (first component and value elicitation exercises), and Group 3 received all three components (the first two and a decision analysis recommendation) of the SDM intervention. Analysis: For the quantitative strand, we used a non-parametric test to analyze the differences in the DCS subscales between the three groups. For the qualitative strand, we conducted a content analysis using the decisional conflict domains to deductively categorize the responses. Results Groups that received more intervention components experienced less conflict and better decision-making quality, although the differences between groups were not statistically significant. The decision analysis recommendation improved the efficacy with the decision-making process, however there are some challenges when implementing it in clinical practice. The uncertainty subscale showed a high decisional conflict for all three groups; contributing factors included low certainty of the evidence-based information provided and a perceived small effect of the drug to reduce the risk of a VTE event. Conclusions The DASH-TOP intervention reduced decisional conflict in the decision -making process, with decision analysis being the most effective component to improve the quality of the decision. There is a need for more implementation research to improve the delivery of SDM interventions in the clinical encounter.

Abstract Background Shared decision-making is useful to facilitate cancer treatment decisions. However, it is difficult to make treatment decisions when physician and patient preferences are different. This review aimed to summarize and compare the preferences for cancer treatments between physicians and patients. Methods A systematic literature search was conducted on PubMed, Embase, PsycINFO, CINAHL and Scopus. Studies elicited and compared preferences for cancer treatments between physicians and patients were included. Information about the study design and preference measuring attributes or questions were extracted. The available relative rank of every attribute in discrete choice experiment (DCE) studies and answers to preference measuring questions in non-DCE studies were summarized followed by a narrative synthesis to reflect the preference differences. Results Of 12,959 studies identified, 8290 were included in the title and abstract screening and 48 were included in the full text screening. Included 37 studies measured the preferences from six treatment-related aspects: health benefit, adverse effects, treatment process, cost, impact on quality of life, and provider qualification. The trade-off between health benefit and adverse effects was the main focus of the included studies. DCE studies showed patients gave a higher rank on health benefit and treatment process, while physicians gave a higher rank on adverse effects. Non-DCE studies suggested that patients were willing to take a higher risk of adverse effects or lower health benefit than physicians when accepting a treatment. Conclusions Physicians and patients had important preference differences for cancer treatment. More sufficient communication is needed in cancer treatment decision-making.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

Background: Anesthesiology plays a crucial role in perioperative care, critical care, and pain management, impacting patient experiences and clinical outcomes. However, our understanding of the anesthesiology research landscape is limited. Accordingly, we initiated a data-driven analysis through topic modeling to uncover research trends, enabling informed decision-making and fostering progress within the field. Methods: The easyPubMed R package was used to collect 32,300 PubMed abstracts spanning from 2000 to 2022. These abstracts were authored by 737 Anesthesiology Principal Investigators (PIs) who were recipients of National Institute of Health (NIH) funding from 2010 to 2022. Abstracts were preprocessed, vectorized, and analyzed with the state-of-the-art BERTopic algorithm to identify pillar topics and trending subtopics within anesthesiology research. Temporal trends were assessed using the Mann-Kendall test. Results: The publishing journals with most abstracts in this dataset were Anesthesia & Analgesia 1133, Anesthesiology 992, and Pain 671. Eight pillar topics were identified and categorized as basic or clinical sciences based on a hierarchical clustering analysis. Amongst the pillar topics, “Cells & Proteomics” had both the highest annual and total number of abstracts. Interestingly, there was an overall upward trend for all topics spanning the years 2000–2022. However, when focusing on the period from 2015 to 2022, topics “Cells & Proteomics” and “Pulmonology” exhibit a downward trajectory. Additionally, various subtopics were identified, with notable increasing trends in “Aneurysms”, “Covid 19 Pandemic”, and “Artificial intelligence & Machine Learning”. Conclusion: Our work offers a comprehensive analysis of the anesthesiology research landscape by providing insights into pillar topics, and trending subtopics. These findings contribute to a better understanding of anesthesiology research and can guide future directions.

Fermentation is a vital process occurred under the premise of rolling affecting black tea quality. Theoretically, re-rolling during fermentation will remodel the biochemical conditions of tea leaves, and thus influence black tea quality. Herein, we studied the effect of re-rolling on black tea taste and liquor color. Sensory evaluation showed that re-rolling significantly weakened the astringency taste and improved the redness and luminance of liquor. With re-rolling, the color attributes of a* and L* and the contents of theaflavins and thearubigins were significantly improved. Metabolomics analysis showed that the contents of 110 non-volatile compounds were significantly different among black teas with different rolling treatments. In summary, re-rolling accelerated the oxidation of polyphenols into pigments, the hydrolysis of proteins into amino acids, and the metabolism of alkaloids, organic acids, glycosidically-bound volatiles, and lipids during the fermentation period. Our study provided a novel and simple way to improve black tea quality.

Abstract Satellite infrared detectors cannot penetrate clouds, especially precipitating clouds. Improving precipitation estimation accuracy based on infrared brightness temperature has always been important but challenging. In this paper, based on the infrared brightness temperature of the Advanced Geosynchronous Radiation Imager (AGRI) onboard China's Feng‐Yun 4A satellite, we develop and evaluate a new precipitation estimation method. First, using static data, physical characteristics of clouds, cloud image texture features, temporal motion features, and AGRI infrared channel brightness temperature, we construct features for a machine learning model. Then, we develop precipitation estimation methods. Precipitation is estimated in two steps: classification and regression. We employ a random forest classification model to identify whether there is precipitation in a given field of view. If there is precipitation, a multi‐model ensemble regression learning method is used to estimate the areas with this precipitation. The ensemble learning method uses convex optimization to integrate prediction results based on the optimization of hyperparameters of five basic models (i.e., those of random forest, XGBoost, LightGBM, decision tree, and extra tree models). Furthermore, two regression stacking ensemble models—the Least Absolute Shrinkage and Selection Operator (herein referred to as Stacking1‐LASSO) and K‐nearest neighbor (herein referred to as Stacking2‐KNN)—are used to predict the results of the aforementioned basic models. The results of basic models are used as inputs of these two stacking models. Finally, based on the Integrated Multi‐satellitE Retrievals for GPM (IMERG) precipitation product and rain gauge precipitation data, we conduct precipitation estimation experiments and evaluate our methods. The results show that ensemble learning models have greater accuracy in estimating precipitation than the basic models. When using IMERG precipitation as the target precipitation, ensemble learning models can estimate the central area of heavy precipitation during typhoons Ampil and Maria. The ensemble learning estimation effect is better than that of Stacking2‐KNN. Moreover, when rain gauge data is used as the target precipitation, ensemble learning can also estimate the center of heavy precipitation and with good consistency with recorded satellite brightness temperature data.

Abstract Background IMPACT-AF is a prospective, randomized, cluster design trial comparing atrial fibrillation (AF) management with a computerized decision support system (CDS) to usual care (control) in the primary care setting of Nova Scotia, Canada. The objective of this analysis was to compare the resource use and costs between CDS and usual care groups. Methods Case costing data, 12-month self-administered questionnaires, and monthly diaries from IMPACT-AF were used in this analysis. Descriptive statistics were used to compare costs and resource use between groups. All costs are presented in 2021 Canadian dollars and cover the 12-month period of participation in the study. Results A total of 1,145 patients enrolled in the trial. Case costing data were available for 466 participants (41.1%), 12-month self-administered questionnaire data for 635 participants (56.0%) and monthly diary data for 223 participants (19.7%). Emergency department visits and hospitalizations comprised the most expensive component of AF care. Across all three datasets, there were no statistically significant differences in costs or resource use between CDS and usual care groups. Conclusions Although there were no significant differences in resource use or costs among CDS and usual care groups in the IMPACT-AF trial, this study provides insight into the methodology and practical challenges of collecting economic data alongside a trial. Registration Clinicaltrials.gov (registration number: NCT01927367, date of registration: 2013-08-20).

In this paper, we consider the dynamics of a slow-fast Bazykin's model with piecewise-smooth Holling type Ⅰ functional response. We show that the model has Saddle-node bifurcation and Boundary equilibrium bifurcation. Furthermore, it is also proven that the model has a homoclinic cycle, a heteroclinic cycle or two relaxation oscillation cycles for different parameters conditions. These results imply the dynamical behavior of the model is sensitive to the predator competition rate and the initial densities of prey and predators. In order to support the theoretical analysis, we present some phase portraits corresponding to different values of parameters by numerical simulation. These phase portraits include two relaxation oscillation cycles, an unstable relaxation oscillation cycle surrounded by a stable homoclinic cycle; the coexistence of a heteroclinic cycle and an unstable relaxation oscillation cycle. These results reveal far richer and much more complex dynamics compared to the model without different time scale or with smooth Holling type Ⅰ functional response.

ABSTRACT Purpose: To investigate the risk factors associated with adverse outcomes in patients with residual stones after percutaneous nephrolithotomy (PCNL) and to establish a nomogram to predict the probability of adverse outcomes based on these risk factors. Methods: We conducted a retrospective review of 233 patients who underwent PCNL for upper urinary tract calculi and had postoperative residual stones. The patients were divided into two groups according to whether adverse outcomes occurred, and the risk factors for adverse outcomes were explored by univariate and multivariate analyses. Finally, we created a nomogram for predicting the risk of adverse outcomes in patients with residual stones after PCNL. Results: In this study, adverse outcomes occurred in 125 (53.6%) patients. Multivariate logistic regression analysis indicated that the independent risk factors for adverse outcomes were the diameter of the postoperative residual stones (P < 0.001), a positive urine culture (P = 0.022), and previous stone surgery (P = 0.004). The above independent risk factors were used as variables to construct the nomogram. The nomogram model was internally validated. The calculated concordance index was 0.772. The Hosmer– Lemeshow goodness-of-fit test was performed (P > 0.05). The area under the ROC curve of this model was 0.772. Conclusions: Larger diameter of residual stones, positive urine culture, and previous stone surgery were significant predictors associated with adverse outcomes in patients with residual stones after PCNL. Our nomogram could help to assess the risk of adverse outcomes quickly and effectively in patients with residual stones after PCNL

Abstract Background As a new obesity-related index, the weight-adjusted-waist index (WWI) appears to be a good predictor of cardiovascular disease (CVD) in East Asian populations. This study aimed to validate the association between WWI and CVD in United States (US) adults and also evaluate its relationships with the prevalence of specific CVDs. Methods The data were obtained from the 2009–2016 National Health and Nutrition Examination Survey. WWI was calculated as waist circumference divided by the square root of weight, and CVD was ascertained based on self-reported physician diagnoses. Multivariable logistic regression models and subgroup analyses were performed to evaluate the association between WWI and CVD. Results A total of 21,040 participants were included. There was a positive linear relationship between WWI and the odds of CVD (P = 0.310). After adjusting for all covariates, each unit of increased WWI was associated with 48% increased risk of CVD (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.25–1.74). Moreover, compared with the lowest quintile (

Amphibians serve as reliable indicators of ecosystem health and are the most threatened group of vertebrates. Studies on their spatial distribution pattern and threats are crucial to formulate conservation strategies. Gongga Mountains, with a peak at 7509 m a.s.l. and running latitudinally, are in the center of the Hengduan Mountains Range and at the eastern steep edge of the Qinghai–Xizang Plateau, providing heterogeneous habitats and varied niches for amphibians. In this study, we combined 83 days of field work with information from 3894 museum specimens that were collected over the past 80 years, and identified twenty amphibian species belonging to seven families and twelve genera by morphology. Of these species, seven were listed in the threatened categories of the Red List of China’s Biodiversity and thirteen were endemic to China. Ten species were found on the plateau side (western slope) and eleven species were found on the other side close to the Sichuan Basin (eastern slope). Only one species was found on both sides, indicating different community structures horizontally. The species richness was unimodal vertically and peaking at mid elevation on both sides, with the maximum number (ten vs. nine) of species occurring at 3300–3700 vs. 1700–1900 m a.s.l. and in different types of vegetation. The elevation span and body length of species distributed on both slopes did not show significant differences. These findings help to understand the horizontal and vertical distribution pattern of amphibian diversity, laying a foundation for future biogeographical and conservation research in this area.

In the paper, glass ceramics used as architectural materials were prepared based on lead fuming furnace-slag (LFFS) by a synergistic sinter-crystallization method. The effects of Al2O3 addition on the crystallization phase, crystallization kinetics, and mechanical performance of glass ceramics were investigated. The results showed that the phases of the glass ceramics prepared were composed of gehlenite and wollastonite, and crystallization kinetics analysis showed that bulk crystallization dominated the overall crystallization process in the Al2O3 content range from 2% to 8%. The glass transition temperature and the crystallization peak temperature of the glass ceramics generally increased with the increase in the Al2O3 content. Additionally, the crystalline morphology gradually developed from sheet-like to spherical, while the number of pores increased and the bulk density gradually decreased. When the Al2O3 content was 2%, the bending strength of glass ceramics reached its maximum, 75.1 MPa, corresponding to a bulk density of 2.24 g·cm−3. Owing to the high strength and relatively low bulk density, the sintered glass ceramics appear promising for potential applications in lightweight construction tiles.

Chemical communication is an important mode of communication in the courtship and breeding processes of amphibians. In caudates, multiple components of sexual pheromones have been identified and functionally verified. One of these pheromone systems is plethodontid modulating factor (PMF). In anurans, the pheromone called amplexin was found in nuptial pads of ranids and was considered a member of the PMF system, yet its bio-function has not been tested. In this study, we obtained 18 amplexin transcript sequences from nuptial pads of Nidirana pleuraden (Amphibia, Ranidae) by transcriptome sequencing and found that the proteins translated by these transcripts are diversified, hydrophilic, and relatively stable. We also acquired a N. pleuraden amplexin isoform with the highest expression level in the transcriptome analysis through the prokaryotic expression system. Using two different animal behavioral experimental settings, we have tested the bio-function of the recombinant PMF protein (rPMF) in N. pleuraden’s reproduction and found that the rPMF does not attract females but shortens the duration of amplexus significantly. This is the first study to verify the function of the PMF pheromone in Anura, indicating the pervasiveness of chemical communication during breeding in amphibians.

Abstract Objectives Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor‐infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor‐infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods Single‐cell RNA sequencing (scRNA‐seq) data and survival data were obtained from public databases. Twenty‐one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results ScRNA‐seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177− Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177‐overexpressing induced Treg (iTreg) cells had lower levels of PD‐1 than their CD177− counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR‐T) cell therapy.

Abstract Extracellular vesicles and particles (EVPs) are recognized as ideal liquid biopsy tools for cancer detection, and membrane proteins are commonly used EVP biomarkers. However, bulk analysis of EVP membrane protein biomarkers typically fails to meet the clinical requirement for diagnostic accuracy. We investigated the correlation between the membrane protein expression level, the binding kinetics to aptamers and the sizes of EVPs with interferometric plasmonic microscopy (iPM), and demonstrated the implementation of the correlative signature to determine cancer types. Using EVPs collected from both cell model and clinical plasma samples with liver, lung, breast, or prostate cancer, we found that the selective set of membrane protein expression levels of five protein markers and their binding kinetics were highly heterogeneous across various sizes of EVPs, resulting in the low overall accuracy (

Introduction The Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.Methods and analysis REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.Ethics and dissemination All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to – Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.Trial registration number NCT03374800.

Pancreatic cancer has an annual incidence of 2/10,000 in Canada, with a one-year mortality rate greater than 80%. In the absence of a cost-effectiveness analysis in Canada, this study’s objective was to assess the cost-effectiveness of olaparib versus a placebo in adult patients with deleterious or suspected deleterious BRCA metastatic pancreatic adenocarcinoma, who did not show any progression for at least 16 weeks with first-line platinum-based chemotherapy. A partitioned survival model with a 5-year time horizon was adopted to estimate the costs and effectiveness. All of the costs were extracted from the public payer’s available resources, effectiveness data were obtained from the POLO trial, and Canadian studies were used for utility inputs. Probabilistic sensitivity analyses and scenario analyses were performed. The total costs of olaparib and the placebo over five years were CAD 179,477 and CAD 68,569, with overall quality-adjusted life-years (QALYs) of 1.70 and 1.36, respectively. The incremental cost-effectiveness ratio (ICER) of the olaparib group compared with the placebo was CAD 329,517 per QALY. With a commonly cited willingness to pay (WTP) threshold of CAD 50,000 per QALY, the drug does not achieve acceptable cost-effectiveness mainly due to the high price of the medication and insufficient impact on the overall survival of patients with metastatic pancreatic cancer.

Mechanical properties and particle size composition of a lead-zinc ore in Yunnan were determined, and the problems such as low processing capacity of a section ball mill, substandard fineness and unreasonable particle size composition were solved through the contrast test of grinding medium. The experimental results show that the ore is medium hard and soft ore, with uneven distribution, and high bulk density and toughness. When the grinding fineness is 65% of -0.074 mm, the best effect is obtained. Plan of Φ80mm:Φ60mm:Φ40mm :Φ30mm =20:25:25:30 would improve grinding efficiency and grinding fineness, at the same time reduce the grinding grade levels.

Abstract Background TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA). Methods We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA. Results Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS estimate was 3.7 months; EFS was not reported for VEN + HMA or HMA. The ORR was 41% for IC, 65% for VEN + HMA, and 47% for HMA. DoR was 3.5 months for IC, 5.0 months for VEN + HMA, and was not reported for HMA. Conclusions Despite improved responses seen with IC and VEN + HMA compared to HMA, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53m AML, demonstrating a significant need for improved treatment for this difficult-to-treat population.

Indentation size effect (ISE), in general, is observed in shallow indentation tests, which is manifested as an increase (NISE) or decrease (RISE) in hardness with penetration depth decreases. The complicated origin of ISE is dependent on multiple factors, which can be divided into two types, both strain gradient and external factors. It's very difficult to judge which factor is the source for a certain ISE phenomenon. Further, studies on ISE phenomena under the joint of multiple factors are fewer. To date, the classical Nix-Gao model based on strain gradient has been widely recognized, but it's sometimes not suited for all ISE. And most current analytical models on ISE are not yet mature. Therefore, more mechanistic models on ISE are required, especially for RISE. Herein, we critically reviewed several mechanistic models on ISE, focusing on the exploration of RISE, and developed an analytical model incorporating external factors, i.e. surface undulation and indenter tip irregularity, to account for NISE and RISE. We examined the two external factors on the origin responsible for ISE in light of 3D numerical simulations and experimental observations, meanwhile, the combined effect of both factors on ISE was also considered. The effect of both external factors on ISE can be equivalent to a depth deviation δ. The corresponding hardness deviation caused by δ can be theoretically eliminated through correcting the depth deviation. More importantly, only after eliminating the effect of external factors on ISE, one can determine whether the ISE results from strain gradient plasticity. Finally, this paper was summarized and outlooked.

Ginsenosides, agents extracted from an important herb (ginseng), are expected to provide new therapies for endometrium-related diseases. Based on the molecular types of ginsenosides, we reviewed the main pharmacological effects of ginsenosides against endometrium-related diseases (e.g., endometrial cancers, endometriosis, and endometritis). The mechanism of action of ginsenosides involves inducing apoptosis of endometrium-related cells, promoting autophagy of endometrium-related cells, regulating epithelial-mesenchymal transition (EMT) in endometrium-related cells, and activating the immune system to kill cells associated with endometrial diseases. We hope to provide a theoretical foundation for the treatment of endometrium-related diseases by ginsenosides.

Objective This study aimed to explore the predictive value of liver and spleen stiffness measurement based on two-dimensional shear wave elastography for the portal vein pressure in patients with compensatory viral cirrhosis. Methods From January 2017 to August 2019, 107 patients with compensatory viral cirrhosis and 76 patients with viral hepatitis were enrolled as cirrhosis group and hepatitis group, respectively. Patient data were obtained during admission, and this study was a review and analysis of patient data. Liver stiffness measurement (LSM), spleen stiffness measurement (SSM), portal vein diameter and spleen thickness were compared between the two groups, and their diagnostic value for compensatory viral cirrhosis was analyzed. According to the hepatic vein pressure, the cirrhosis group patients were divided into non-hypertensive group (no portal hypertension, hepatic venous pressure gradient (HVPG) < 5 mmHg), mild group (mild portal hypertension, 5 mmHg ≤ HVPG ≤ 10 mmHg) and severe group (clinically significant portal hypertension group, HVPG > 10 mmHg). LSM, SSM, portal vein diameter and spleen thickness of the three groups were compared, and the correlation between SSM and hepatic vein pressure was analyzed. Results LSM, SSM, portal vein diameter and spleen thickness in the cirrhosis group were higher than those in hepatitis group (all P

Introduction Friedreich ataxia (FA) is the most common hereditary ataxia in Europe, characterised by progressively worsening movement and speech impairments with a typical onset before the age of 25 years. The symptoms affect the patients’ health-related quality of life (HRQoL) and psychosocial health. FA leads to an increasing need for care, associated with an economic burden. Little is known about the impact of FA on daily lives and HRQoL. To fill that gap, we will assess patient-reported, psychosocial and economic outcomes using momentary data assessment via a mobile health application (app).Methods and analysis The PROFA Study is a prospective observational study. Patients with FA (n=200) will be recruited at six European study centres (Germany, France and Austria). We will interview patients at baseline in the study centre and subsequently assess the patients’ health at home via mobile health app. Patients will self-report ataxia severity, HRQoL, speech and hearing disabilities, coping strategies and well-being, health services usage, adverse health events and productivity losses due to informal care on a daily to monthly basis on the app for 6 months. Our study aims to (1) validate measurements of HRQoL and psychosocial health, (2) assess the usability of the mobile health app, and (3) use descriptive and multivariate statistics to analyse patient-reported and economic outcomes and the interaction effects between these outcomes. Insights into the app’s usability could be used for future studies using momentary data assessments to measure outcomes of patients with FA.Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of the University Medicine of Greifswald, (BB096/22a, 26 October 2022) and from all local ethics committees of the participating study sites. Findings of the study will be published in peer-reviewed journals, presented at relevant international/national congresses and disseminated to German and French Patient Advocacy Organizations.Trial registration number ClinicalTrials.gov Registry (NCT05943002); Pre-results.

Abstract Background Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. Results We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell–cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. Conclusions Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

Abstract Background Risk prediction models are useful tools in clinical decision-making which help with risk stratification and resource allocations and may lead to a better health care for patients. AutoScore is a machine learning–based automatic clinical score generator for binary outcomes. This study aims to expand the AutoScore framework to provide a tool for interpretable risk prediction for ordinal outcomes. Methods The AutoScore-Ordinal framework is generated using the same 6 modules of the original AutoScore algorithm including variable ranking, variable transformation, score derivation (from proportional odds models), model selection, score fine-tuning, and model evaluation. To illustrate the AutoScore-Ordinal performance, the method was conducted on electronic health records data from the emergency department at Singapore General Hospital over 2008 to 2017. The model was trained on 70% of the data, validated on 10% and tested on the remaining 20%. Results This study included 445,989 inpatient cases, where the distribution of the ordinal outcome was 80.7% alive without 30-day readmission, 12.5% alive with 30-day readmission, and 6.8% died inpatient or by day 30 post discharge. Two point-based risk prediction models were developed using two sets of 8 predictor variables identified by the flexible variable selection procedure. The two models indicated reasonably good performance measured by mean area under the receiver operating characteristic curve (0.758 and 0.793) and generalized c-index (0.737 and 0.760), which were comparable to alternative models. Conclusion AutoScore-Ordinal provides an automated and easy-to-use framework for development and validation of risk prediction models for ordinal outcomes, which can systematically identify potential predictors from high-dimensional data.

Aiming at establishing the transient flow characteristics of gas–liquid two-phase flow in high-undulation water pipelines, based on the bubble distribution law measured using physical tests, the bubble distribution law function was input into the hump-pipe fluid domain model, and CFD numerical simulation was carried out for different flow rates and different air contents. The CLSVOF two-phase flow model and the RNG k-ε turbulence model were used to analyze the flow pattern evolution and pressure pulsation propagation in the process of gas–liquid two-phase flow through a hump pipe. The results show that the bubble size has a lognormal distribution, the equivalent diameter is between 3 mm and 10 mm, and the evolution of the flow pattern in the hump pipe is complex and violent. In the horizontal pipe section, there are three main flow patterns: bubble flow, wavy flow and segment plug flow. In the vertical pipe, there are two main flow patterns, slug flow and churning flow, and the flow pattern is affected by the flow rate and the air content rate. When air bubbles or air pockets in the pipeline flow through a certain area, this leads to a steep increase and decrease in the pressure pulsation amplitude in the region, and the pressure fluctuation is extremely frequent. Compared with the water flow rate, the air content is the main factor affecting the relative pressure pulsation amplitude under the condition of a 0.15-air content operating mode, which is generally approximately two to six times that of the 0-air content operating mode. The results of the research should facilitate the prediction of stagnant gas pipeline system bursts and water hammer protection, providing a theoretical basis and calculation parameters.

Unmanned aerial vehicles (UAVs) multi-area coverage-path planning has a broad range of applications in agricultural mapping and military reconnaissance. Compared to homogeneous UAVs, heterogeneous UAVs have higher application value due to their superior flexibility and efficiency. Nevertheless, variations in performance parameters among heterogeneous UAVs can significantly amplify computational complexity, posing challenges to solving the multi-region coverage path-planning problem. Consequently, this study studies a clustering-based method to tackle the multi-region coverage path-planning problem of heterogeneous UAVs. First, the constraints necessary during the planning process are analyzed, and a planning formula based on an integer linear programming model is established. Subsequently, this problem is decomposed into regional allocation and visiting order optimization subproblems. This study proposes a novel clustering algorithm that utilizes centroid iteration and spatiotemporal similarity to allocate regions and adopts the nearest-to-end policy to optimize the visiting order. Additionally, a distance-based bilateral shortest-selection strategy is proposed to generate region-scanning trajectories, which serve as trajectory references for real flight. Simulation results in this study prove the effective performance of the proposed clustering algorithm and region-scanning strategy.

Steel balls as traditional grinding media are prone to excessive fines generation and high energy consumption. Therefore, in light of this problem, the authors investigated another media—ceramic balls based on the output characteristics of fine particles. This study discusses the effect of ceramic balls on the change of the particle size distribution, zero-order output characteristics, micro-strain, and collision energy in ground products. The results showed that for −10 μm particle size, ceramic balls have a smaller production rate than steel balls. In addition, when the filling rate of ceramic balls is 40%, the yield of −10 μm is reduced compared to steel balls. Therefore, ceramic balls greatly reduced the overgeneration of fines. Additionally, the micro-strain rate of ceramic ball grinding with time is 67% lower than that of steel ball grinding. Furthermore, ceramic balls cannot only mitigate excessive fines generation but also effectively reduce energy consumption.

Ochratoxins, a common class of mycotoxin in capsicum, and techniques and methods for the determination of mycotoxins in spices have been increasingly developed in recent years. An innovative and eco-friendly method of dispersive liquid–liquid microextraction (DLLME) was demonstrated in this study, based on a synthesized deep eutectic solvent (DES) combined with LC-MS/MS, for the quantification and analysis of two ochratoxins in capsicum. The DES-DLLME method parameters entail selecting the DES type (thymol:decanoic acid, molar ratio 1:1) and DES volume (100 μL). The volume of water (3 mL) and salt concentration (0 g) undergo optimization following a step-by-step approach to achieve optimal target substance extraction efficiency. The matrix effect associated with the direct detection of the target substance in capsicum was significantly reduced in this study by the addition of isotopic internal standards corresponding to the target substance. This facilitated optimal conditions wherein quantitative analysis using LC-MS/MS revealed a linear range of 0.50–250.00 µg/mL, with all two curves calibrated with internal standards showing correlation coefficients (r2) greater than 0.9995. The method’s limits of detection (LODs) and limits of quantification (LOQs) fell in the ranges of 0.14–0.45 μg/kg and 0.45–1.45 μg/kg, respectively. The method’s spiked recoveries ranged from 81.97 to 105.17%, indicating its sensitivity and accuracy. The environmental friendliness of the technique was assessed using two green assessment tools, AGREE and complexGAPI, and the results showed that the technique was more in line with the concept of sustainable development compared to other techniques for detecting ochratoxins in capsicum. Overall, this study provides a new approach for the determination of mycotoxins in a complex food matrix such as capsicum and other spices using DES and also contributes to the application of green analytical chemistry methods in the food industry.

Abstract The 2019 novel coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is ongoing, and has necessitated scientific efforts in disease diagnosis, treatment, and prevention. Interestingly, extracellular vesicles (EVs) have been crucial in these developments. EVs are a collection of various nanovesicles which are delimited by a lipid bilayer. They are enriched in proteins, nucleic acids, lipids, and metabolites, and naturally released from different cells. Their natural material transport properties, inherent long‐term recycling ability, excellent biocompatibility, editable targeting, and inheritance of parental cell properties make EVs one of the most promising next‐generation drug delivery nanocarriers and active biologics. During the COVID‐19 pandemic, many efforts have been made to exploit the payload of natural EVs for the treatment of COVID‐19. Furthermore, strategies that use engineered EVs to manufacture vaccines and neutralization traps have produced excellent efficacy in animal experiments and clinical trials. Here, the recent literature on the application of EVs in COVID‐19 diagnosis, treatment, damage repair, and prevention is reviewed. And the therapeutic value, application strategies, safety, and biotoxicity in the production and clinical applications of EV agents for COVID‐19 treatment, as well as inspiration for using EVs to block and eliminate novel viruses are discussed.

Backgroundhypertension is one of the major preventable risk factors for numerous diseases. The role of vitamin E in blood pressure (BP) has been controversial. We aimed to investigate the relationship between gamma-tocopherol serum concentration (GTSC) and BPMethodsData from 15,687 US adults from the National Health and Nutrition Examination Survey (NHANES) were analyzed. The correlations of GTSC with systolic BP (SBP), diastolic BP (DBP), and prevalence of hypertension were investigated by multivariate logistic regression models, generalized summation models, and fitted smoothing curves. Subgroup analyses were performed to investigate possible effect modifiers between them.ResultsWith each natural log increase in GTSC, SBP, and DBP increased by 1.28 mmHg (β 1.28, 95% CI 0.71–1.84) and 1.15 mmHg (β 1.15, 95% CI 0.72–1.57), respectively, both P for trend

Summary: The AutoScore framework can automatically generate data-driven clinical scores in various clinical applications. Here, we present a protocol for developing clinical scoring systems for binary, survival, and ordinal outcomes using the open-source AutoScore package. We describe steps for package installation, detailed data processing and checking, and variable ranking. We then explain how to iterate through steps for variable selection, score generation, fine-tuning, and evaluation to generate understandable and explainable scoring systems using data-driven evidence and clinical knowledge.For complete details on the use and execution of this protocol, please refer to Xie et al. (2020),1 Xie et al. (2022)2, Saffari et al. (2022)3 and the online tutorial https://nliulab.github.io/AutoScore/. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Assessing health-related quality of life (HRQoL) among persons with dementia poses several challenges due to cognitive decline and limited perception. As a result, proxy ratings by family members or health professionals are used. The EQ-5D is the most commonly used generic and preference-based HRQoL instrument. Methodological drawbacks of the three-level version (EQ-5D-3L) prompted the development of the five-level version (EQ-5D-5L) by expanding the range in the domains. However, no comparison of the psychometric properties of both versions and different proxy ratings exist so far. Therefore, the objective of this study was to compare the psychometric properties of the EQ-5D-5L and EQ-5D-3L by application of different proxy ratings in dementia. Methods The EQ-5D-3L and -5L were completed by n = 52 family caregivers and one care manager at baseline and three and six months later. In total, 106 caregiver and 133 care manager proxy ratings were completed. The EQ-5D-3L and 5L were evaluated in terms of acceptability (missing values), agreement, ceiling effects, redistribution properties and inconsistency, and informativity (Shannon, H', and Shannon Evenness, J', indices) as well as convergent and discriminative validity. Results Mean proxy index scores were higher for the 5L than the 3L. Missing values occurred less frequently in both proxy ratings and versions (