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To win in sports competitions, in addition to excellent sports skills, coping strategies in the face of various competition situations are also critical for success. Therefore, cultivating students' diverse, creative and flexible tactical application abilities is an important educational goal in sports training. However, in the online component of blended training in sports, conventional instructional approaches are teacher-centred and hardly ever adopt the consolidated approaches to creative problem solving used in other fields. This results in limited opportunities for students to discover the problems and apply their creative thinking tendencies for problem solving. Hence, the present study proposed applying a consolidated creative problem-solving approach in the online phase of blended training initiatives in order to cultivate students' higher-order thinking skills. To verify the effectiveness of this approach, a convenience grouping-based quasi-experiment design was adopted. A 10-week teaching experiment was conducted in a billiards training course. A total of 79 students were recruited in this study; they were divided into one CPS-BL group with 41 students and one conventional blended learning (C-BL) group with 38 students. The results showed that the CPS-BL approach could significantly enhance students' billiards striking strategies, creative thinking tendencies and problem-solving skills.

Abstract Background The six core competencies of ACGME - patient care (PC), medical knowledge (MK), systems-based practice (SBP), practice-based learning and improvement (PBLI), professionalism (PROF), and interpersonal and communication skills (ICS) - represent domains in which physicians must ultimately demonstrate competence. Although the ACGME’s six core competencies have been applied in Taiwan with the milestone project, the application of the six core competences in the Family Medicine milestones for residency training have not yet been established. Methods We recruited 61 family medicine physicians from 25 hospitals from four major geographic areas for a Delphi round one survey and 72 physicians from 27 hospitals for a Delphi round two survey. With 5-point scales, the Cronbach’s alphas for both importance and fitness were 0.98 in round one. In round two, the Cronbach’s alphas were 0.86 and 0.83 for importance and fitness. The mode and quartile deviation in Delphi method, importance-performance analysis (IPA), and importance-performance matrix analysis (IPMA) were used for three stages IPA process. Results In IPA, a total of 72.7% (16/22) of the sub-competencies exhibited high importance and fitness, with a mean score ≥ 4.7; the exceptions were PC-1 (cares for acutely ill or injured patients), MK-2 (critical thinking skills in patient care), SBP-1 (cost-conscious medical care), PBLI-3 (improves systems), PROF-3 (humanism/cultural proficiency), and ICS-4 (utilizes technology). In IPMA, the performance value of six core competencies for FMM-Taiwan was 92.6 when considering the importance and fitness indices of the 22 sub-competencies. Conclusions The accordance of the ACGME’s milestones to Taiwan was acceptable to good and related milestones could been developed for residency training.

Abstract Background Assessing the current status and identifying the mechanisms threatening endangered plants are significant challenges and fundamental to biodiversity conservation, particularly for protecting Tertiary relict trees and plant species with extremely small populations (PSESP). Ulmus elongata (Ulmus, Ulmaceae) with high values for the ornamental application, is a Tertiary relict tree species and one of the members from PSESP in China. Currently, the wild populations of U. elongata have been threatened by excessive deforestation and urbanization, but limited knowledges of its genetic diversity seriously hinder conservation efforts. Therefore, a further study on the genetic diversity and drivers of genetic pattern in U. elongata is crucial for preserving genetic resources and can serve as a reference for other Tertiary relict plants and PSESP under climate change. Results Here, a total of 12 populations from 70 individuals of U. elongata were collected covering its geographical distribution in China. Utilizing chloroplast genome datasets, we found that U. elongata exhibited remarkably low nucleotide diversity and gene flow (π = 0.00013, Nm = 0.03). Analysis of molecular variance (AMOVA) showed that genetic variation in U. elongata occurs mainly between eight clades (60.95%). The Mantel tests indicated a significant correlation between genetic differentiation and geographical distances (r = 0.3777, p

Actinobacillus pleuropneumoniae infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the antimicrobial susceptibilities and probe the resistome of A. pleuropneumoniae in Taiwan. Herein, 133 isolates were retrospectively collected; upon initial screening, 38 samples were subjected to next-generation sequencing (NGS). Over the period 2017–2022, the lowest frequencies of resistant isolates were found for ceftiofur, cephalexin, cephalothin, and enrofloxacin, while the highest frequencies of resistant isolates were found for oxytetracycline, streptomycin, doxycycline, ampicillin, amoxicillin, kanamycin, and florfenicol. Furthermore, most isolates (71.4%) showed multiple drug resistance. NGS-based resistome analysis revealed aminoglycoside- and tetracycline-related genes at the highest prevalence, followed by genes related to beta-lactam, sulfamethoxazole, florphenicol, and macrolide. A plasmid replicon (repUS47) and insertion sequences (IS10R and ISVAp11) were identified in resistant isolates. Notably, the multiple resistance roles of the insertion sequence IS10R were widely proposed in human medicine; however, this is the first time IS10R has been reported in veterinary medicine. Concordance analysis revealed a high consistency of phenotypic and genotypic susceptibility to florphenicol, tilmicosin, doxycycline, and oxytetracycline. The current study reports the antimicrobial characterization of A. pleuropneumoniae for the first time in Taiwan using NGS.

Abstract Background Pathogenic infections can significantly impact the health of livestock. Traditionally, antibiotic growth promoters (AGPs) have been used in feed to enhance growth performance and disease control. However, concerns regarding antibiotic resistance have led to the exploration of traditional herbal medicine as a natural alternative, guided by the principle of medicine-food homology. The Taguchi method was employed to optimize the culture formula for cordycepin production, an active component of Cordyceps militaris (C. militaris). The influences of C. militaris supplementing solid-state fermentation (CMSSF) in feed on the growth performance and immune responses of grower pigs were evaluated in the present study. Results The C. militaris ethanol extract (CME) displayed potent free radical scavenging activity against 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) after undergoing fermentation. Additionally, the antibacterial testing revealed that CME effectively inhibits the growth of common pig pathogens such as Glaesserella parasuis, Pasteurella multocida, Staphylococcus hyicus, and Streptococcus suis. In lipopolysaccharide (LPS)-treated intestinal porcine enterocyte cell line (IPEC-J2), CME significantly suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6. In addition, higher antioxidative activity was detected as indicated by elevated concentration of superoxide dismutase (SOD) in pig serum. The levels of immunoglobulin M (IgM), IgA, and IgG antibodies, as well as classical swine fever virus (CSFV) antibodies (S/P ratio) in serum were all increased. Growth performance of pigs fed with dietary CMSSF supplementation was improved in comparison with the control. Conclusions Results demonstrated that CMSSF has the potential to be used as a natural growth promoter to enhance immunity, antioxidation, as well as overall health and growth performance of grower pigs.

To develop high activity Auricularia auricula polysaccharide yogurt, Auricularia cornea var. Li. polysaccharides was used as the material to determine its basic components and rheological properties, and the production process of ACP yogurt was optimized by one-way comparative experiments and orthogonal experiments. Moreover, the effect of ACP on the quality of yogurt was investigated in order to develop high-activity Auricularia cornea polysaccharides yogurt. The results showed that: The total sugar, glucuronic acid and protein contents of ACP were 82.21%±2.40%, 11.95%±1.28% and 2.36%±0.10%, respectively. The rheological properties showed that the polysaccharides solution exhibited both liquid and solid characteristics, with good viscoelasticity and potential application as a thickener and gelling agent. What's more, ACP could promote the fermentation of yogurt, increase the number of viable lactic acid bacteria, increase the acidity, and reduce the pH. Low-concentration ACP (0.02%~0.08%) could increase the water-holding capacity of yogurt, improve the tissue condition and stability of yogurt, and reduce whey precipitation. With the amount of ACP added was 0.04%, the yogurt showed the greatest water-holding capacity, hardness, consistency, cohesiveness and viscosity, and the best sensory quality. With the ACP addition amount was 0.06%, the number of viable lactic acid bacteria in yogurt was the largest and the acidity was the highest. The optimal production process of ACP yogurt was to add 0.04% ACP, 6% sucrose, and 0.1% starter culture of fresh milk, ferment at 42 ℃ for 7 hours, and refrigerate at 4 ℃ for 24 hours. The yogurt produced had higher viable bacterial count, better sensory quality and textural properties than ordinary yogurt. This research explored the effect of ACP on lactic acid bacteria fermentation and yogurt quality, in order to provide a scientific theoretical basis for improving the health care performance and quality of yogurt and broadening the application scope of Auricularia cornea var. Li..

Abstract Background Porcine pathogenic Escherichia coli (E. coli), the globally recognized important pathogen, causes significant economic loss in the field. Enterotoxigenic E. coli (ETEC) causes porcine neonatal and post-weaning diarrhea (PWD), frequently carrying F4 adhesin, F18 adhesin, Heat-Stable toxin (ST), and Heat-Labile toxin (LT). Shiga Toxin-Producing E. coli (STEC) produces F18 adhesin and Shiga toxin type 2e (stx2e), majorly leading to systemic endothelial cell damage and edema disease. In this study, hemolytic pathogenic hybrid STEC/ETEC strains carrying ST and LT genes of ETEC and the Stx2e gene of STEC isolated from pigs with PWD in Taiwan were identified. The pathogenicity of a Taiwan hybrid STEC/ETEC strain was evaluated by oral inoculation in post-weaning pigs. Results Next generation sequencing and multilocus sequence typing of two hybrid Taiwan porcine STEC/ETEC isolates indicated that these two isolates were closely related to the ST88 porcine hybrid STEC/ETEC isolated from pigs with watery diarrhea. Furthermore, the two hybrid Taiwan porcine STEC/ETEC isolates also displayed combinations of multiple resistance genes encoding mechanisms for target modification and antibiotic inactivation. Animal experiments confirmed that the Taiwan hybrid STEC/ETEC could cause watery diarrhea in post-weaning pigs with no signs of edema disease and minimal histopathological lesions. Conclusion To the best of the authors’ knowledge, the present study is the first study demonstrating intestinal pathogenicity of the hybrid STEC/ETEC in pigs. The result suggests that the hybrid STEC/ETEC should be considered as a new emerging pathogen and a new target for vaccine development.

Abstract Engineering the electronic band structures upon doping is crucial to improve the thermoelectric performance of materials. Understanding how dopants influence the electronic states near the Fermi level is thus a prerequisite to precisely tune band structures. Here, we demonstrate that the Sn-s states in SnTe contribute to the density of states at the top of the valence band. This is a consequence of the half-filled p-p σ-bond (metavalent bonding) and its resulting symmetry of the orbital phases at the valence band maximum (L point of the Brillouin zone). This insight provides a recipe for identifying superior dopants. The overlap between the dopant s- and the Te p-state is maximized, if the spatial overlap of both orbitals is maximized and their energetic difference is minimized. This simple design rule has enabled us to screen out Al as a very efficient dopant to enhance the local density of states for SnTe. In conjunction with doping Sb to tune the carrier concentration and alloying with AgBiTe2 to promote band convergence, as well as introducing dislocations to impede phonon propagation, a record-high average ZT of 1.15 between 300 and 873 K and a large ZT of 0.36 at 300 K is achieved in Sn0.8Al0.08Sb0.15Te-4%AgBiTe2.

Abstract Background Keloids are currently challenging to treat because they recur after resection which may affect patients’ quality of life. At present, no universal consensus on treatment regimen has been established. Thus, finding new molecular mechanisms underlying keloid formation is imminent. This study aimed to explore the function of secreted protein acidic and cysteine rich (SPARC) on keloids and its behind exact mechanisms. Methods The expression of SPARC, p38γ, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), α-SMA, and Ki67 in patients with keloid and bleomycin (BLM)-induced fibrosis mice was assessed utilizing western blot, qRT-PCR, and immunohistochemical staining. After transfected with pcDNA-SPARC, si-SPARC-1#, si-SPARC-2#, and si-p38γ, and treated with glycolytic inhibitor (2-DG) or p38 inhibitor (SB203580), CCK-8, EdU, transwell, and western blot were utilized for assessing the proliferation, migration, and collagen production of keloid fibroblasts (KFs). Results SPARC, p38γ, and PFKFB3 were highly expressed in patients with keloid and BLM-induced fibrosis mice. SPARC promoted the proliferation, migration, and collagen production of KFs via inducing glycolysis. Moreover, SPARC could activate p38γ signaling to stabilize PFKFB3 protein expression in KFs. Next, we demonstrated that SPARC promoted the proliferation, migration, collagen production, and glycolysis of KFs via regulating p38γ signaling. In addition, in BLM-induced fibrosis mice, inhibition of p38γ and PFKFB3 relieved skin fibrosis. Conclusions Our findings indicated that SPARC could activate p38γ pathway to stabilize the expression of PFKFB3, and thus promote the glycolysis of KFs and the progression of keloid.

The technological requirements of low-power and high-fidelity color displays have been instrumental in driving research into advanced coloration technologies. At the forefront of these developments is the implementation of dye-free approaches, which overcome previous constraints related to color resolution and fading. Resonant dielectric nanostructures have emerged as a promising paradigm, showing great potential for high efficiency, high color saturation, wide gamut palette, and image reproduction. However, they still face limitations related to color accuracy, purity, and simultaneous brightness tunability. Here, we demonstrate an all-dielectric metasurface empowered by photonic bound states in the continuum (BICs), which supports sharp resonances throughout the visible spectral range, ideally suited for producing a wide range of structural colors. The metasurface design consists of TiO2 ellipses with carefully controlled sizes and geometrical asymmetry, allowing versatile and on-demand variation of the brightness and hue of the output colors, respectively.

Abstract Background Our research endeavored to develop a robust predictive signature grounded in super-enhancer-related genes (SERGs), with the dual objectives of forecasting survival outcomes and evaluating the tumor immune microenvironment (TiME) in hepatocellular carcinoma (HCC). Methods HCC RNA-sequencing data were retrieved from The Cancer Genome Atlas (TCGA), and 365 patients were randomly assigned to training or testing sets in 1:1 ratio. SERGs of HCC were downloaded from Super-Enhancer Database (SEdb). On the basis of training set, a SERGs signature was identified, and its prognostic value was confirmed by internal and external validation (GSE14520) sets. We subsequently examined the model for potential functional enrichment and the degree of tumor immune infiltration. Additionally, we carried out in vitro experiments to delve into the biological functions of CBX2 gene. Results An SE-related prognostic model including CBX2, TPX2, EFNA3, DNASE1L3 and SOCS2 was established and validated. According to this risk model, patients in the high-risk group had a significantly worse prognosis, and their immune cell infiltration was significantly different from that of low-risk group. Moreover, the high-risk group exhibited a significant enrichment of tumor-associated pathological pathways. The SERGs signature can generally be utilized to screen HCC patients who are likely to respond to immunotherapy, as there is a positive correlation between the risk score and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Furthermore, the downregulation of the CBX2 gene expression was found to inhibit HCC cell viability, migration, and cell cycle progression, while simultaneously promoting apoptosis. Conclusions We developed a novel HCC prognostic model utilizing SERGs, indicating that patients with high-risk score not only face a poorer prognosis but also may exhibit a diminished therapeutic response to immune checkpoint inhibitors (ICIs). This model is designed to tailor personalized treatment strategies to the individual needs of each patient, thereby improving the overall clinical outcomes for HCC patients. Furthermore, CBX2 is a promising candidate for therapeutic intervention in HCC.

Abstract Colitis-associated colorectal cancer (CAC) frequently develops in patients with inflammatory bowel disease (IBD) who have been exposed to a prolonged state of chronic inflammation. The investigation of pharmacological agents and their mechanisms to prevent precancerous lesions and inhibit their progression remains a significant focus and challenge in CAC research. Previous studies have demonstrated that vitexin effectively mitigates CAC, however, its precise mechanism of action warrants further exploration. This study reveals that the absence of the Vitamin D receptor (VDR) accelerates the progression from chronic colitis to colorectal cancer. Our findings indicate that vitexin can specifically target the VDR protein, facilitating its translocation into the cell nucleus to exert transcriptional activity. Additionally, through a co-culture model of macrophages and cancer cells, we observed that vitexin promotes the polarization of macrophages towards the M1 phenotype, a process that is dependent on VDR. Furthermore, ChIP-seq analysis revealed that vitexin regulates the transcriptional activation of phenazine biosynthesis-like domain protein (PBLD) via VDR. ChIP assays and dual luciferase reporter assays were employed to identify the functional PBLD regulatory region, confirming that the VDR/PBLD pathway is critical for vitexin-mediated regulation of macrophage polarization. Finally, in a mouse model with myeloid VDR gene knockout, we found that the protective effects of vitexin were abolished in mid-stage CAC. In summary, our study establishes that vitexin targets VDR and modulates macrophage polarization through the VDR/PBLD pathway, thereby alleviating the transition from chronic colitis to colorectal cancer.

Purpose: We investigated the effects of classroom-based physical activity (CBPA) interventions on academic performance and assessed the impact of different CBPA elements on academic performance. Methods: Relevant experimental studies in four databases were searched from their inception to September 2022. Random effects models were used to compute standardized mean differences (SMDs) and 95% confidence intervals. Results: A total of 13 studies were included. CBPA interventions could improve academic performance in children and adolescents (SMD = 0.17, p = 0.02). For the CBPA elements, low frequency (no more than three times per week; SMD = 0.19, p = 0.01), moderate intensity (SMD = 0.19, p = 0.01), long time (more than 20 min in each intervention; SMD = 0.14, p = 0.05), integrated physical activity (SMD = 0.18, p = 0.04), no more than 400 metabolic equivalents of energy-min/week (SMD = 0.33, p = .001), and more than 8-week interventions (SMD = 0.19, p = 0.04) tended to improve academic performance. Conclusions: CBPA may improve academic performance in children and adolescents. CBPA elements also have an impact on academic performance.

The derivation of water quality criteria (WQC) for antibiotics is influenced by the inclusion of various organisms' toxicity data, including microbial data, though no definitive conclusions have been reached. This study focuses on sulfonamide antibiotics, common in the Yangtze River Delta (YRD), to assess the influences of different organisms' toxicity data on determining WQCs and subsequent evaluation of ecological risks. A total of 263 toxicity data points from eight sulfonamides, including sulfamethoxazole (SMX) and sulfamethazine (SM2), were selected to derive WQCs using Species Sensitivity Distribution (SSD) methods. Three WQC types were calculated: based on native species (WQC-n), a combination of native and non-native species (WQC-nn), and a combination of species and microorganisms (WQC-nnm). While WQC-nn showed minimal differences from WQC-n, the inclusion of microbial data resulted in more conservative short-term WQCs (SWQC-nnm), calculated as 256.90 μg/L for SMX and 196.09 μg/L for SM2, approximately half of SWQC-nn values (435.20 μg/L for SMX and 491.11 μg/L for SM2). Monitoring data from the past 15 years in the YRD revealed a 133 % increase in ecological risks when using LWQC-nnm compared to LWQC-n and LWQC-nn, particularly under the worst-case pollution scenarios. However, there was a slight temporal decline in overall ecological risks. The study concludes that incorporating microbial toxicity data results in more protective WQCs and underscores the need for further research to develop WQCs that safeguard sensitive organisms and better reflect real-world exposure scenarios, e.g., the mixture exposure.

Bisphenols (BPs), prevalent endocrine disruptors in daily life, have been widely studied in vitro for their potential to cause liver diseases, including liver cancer. However, there is a dearth of research exploring BP levels in clinical populations with liver issues. This study comprehensively analyzed the distribution and characteristics of ten BPs in paired serum, blood, and urine samples from 197 hepatocellular carcinoma (HCC) patients and 100 non-HCC patients. The study investigated the impact of sociodemographic factors, such as gender, BMI (Body Mass Index), age, drinking, and smoking habits, on BP distribution. Additionally, it analyzed the relationship between BPs and three liver function biomarkers: γ-glutamyl transferase (GGT), alanine aminotransferase (ALT) and alpha-fetoprotein (AFP). Notably, some BP levels were higher in non-HCC patients compared to HCC patients across all three sample types. For HCC patients, the BP concentrations followed the order of serum (29.12 ng/mL) > blood (18.36 ng/mL) > urine (14.91 ng/mL), whereas for non-HCC patients, the order was urine (30.79 ng/mL) > serum (29.51 ng/mL) > blood (24.34 ng/mL). Moreover, BP levels in all patient samples, regardless of HCC status, increased with age. Among HCC patients, females were found to have a higher exposure to BPs compared to males, while the opposite trend was observed in non-HCC patients. Furthermore, the study revealed positive correlations between BPs and liver function indicators, such as ALT and BPAF, BPAP, BPBP; GGT and BPF; and AFP and BPF. These findings suggest a potential association between BPs and liver disease. This comprehensive analysis of BP concentrations in bio-samples from liver disease patients provides valuable insights into the relationship between BPs and liver disease in clinical settings, serving as a reference for future research and clinical practice.

Abstract Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition of this condition is still not well understood. To fill this gap, we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing. We defined a population of myxoma cells, which exhibited a resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, and adhesion. The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration, along with their enhanced spatial interaction, were found to significantly contribute to the occurrence of embolism. The immune cells surrounding the myxoma exhibit inhibitory characteristics, with impaired function of T cells characterized by the expression of GZMK and TOX, along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC. Furthermore, in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly. In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.

Abstract Background The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. Methods We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. Results 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. Conclusions Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015–2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.

Abstract Introduction The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS). Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3 months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO. Results Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3 months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p

Abstract Accurate positioning of intelligent connected vehicle (ICV) is a key element for the development of cooperative intelligent transportation system. In vehicular networks, lots of state‐related measurements, especially the mutual measurements between ICVs, are shared. It is an advisable strategy to fuse these measurements for a more robust positioning. In this context, an innovative framework, referred to as multisource‐multitarget cooperative positioning (MMCP) is presented. In MMCP, ICVs are local information source, that upload both the states of ICVs estimated by on‐board sensors and the relative vectors between surrounding objects and vehicles to a fusion centre. In the fusion centre, ICVs are selected as the global targets, and the relative vectors are converted into global measurements. Then, the MMCP is modelled into a multi‐target tracking problem with specific targets. This paper proposes a low complexity Gaussian mixture probability hypothesis density (GM‐PHD‐LC) filter to match and fuse the global measurements to further improve the estimation of ICVs. The evaluation results show that our GM‐PHD‐LC can provide 10 Hz positioning services in urban area, and significantly improve the positioning accuracy compared to the standalone global navigation satellite system.

Abstract Colorectal liver metastasis (CRLM) is challenging in the clinical treatment of colorectal cancer. Limited research has been conducted on how CRLM develops. RNA sequencing data were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Four machine learning algorithms were used to screen the hub CRLM-specific genes, including Least Absolute Shrinkage and Selection Operator (Lasso), Random forest, SVM-RFE, and XGboost. The model for identifying CRLM was developed using stepwise logistic regression and was validated using internal and independent datasets. The prognostic value of hub CRLM-specific genes was assessed using the Lasso-Cox method. The in vitro experiments were performed using SW620 cells. The CRLM identification model was developed based on four CRLM-specific genes (SPP1, ZG16, P2RY14, and PRKAR2B), and the model efficacy was validated using GSE41258 and three external cohorts. Five CRLM-specific prognostic hub genes, SPP1, ZG16, P2RY14, CYP2E1, and C5, were identified using the Lasso-Cox algorithm, and a risk score was constructed. The risk score was validated using the GSE39582 cohort. Three genes have both efficacy in identifying CRLM and prognostic value: ZG16, P2RY14, and SPP1. Immune infiltration and enrichment analyses demonstrated that SPP1 was associated with M2 macrophage polarization and extracellular matrix remodeling. In vitro experiments indicated that SPP1 may act as a cancer-promoting factor. The hub CRLM-specific gene SPP1 can help determine the diagnosis, prognosis, and immune infiltration of patients with CRLM.

Abstract To facilitate the regulation of the air‐gap magnetic field of permanent magnet synchronous machines, a novel topology of a high‐speed hybrid excitation synchronous machine (HESM) was presented. The electromagnetic performance of the proposed HESM was evaluated. The air‐gap magnetic field regulation principle was introduced first. Then, a mathematical model of the HESM was established. Based on the characteristics of a 3D magnetic circuit, the HESM equalled three types of 2D magnetic circuit machines in axial parallel superposition, and thus the expressions of inductance parameters were deduced. Subsequently, the voltage regulation performance of the HESM was assessed according to the mathematical model and inductance parameters. The loss and efficiency were calculated. Finally, a HESM prototype was tested and verified.

Abstract Background Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights. Results Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest. Conclusions In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://bc.imb.sinica.edu.tw/SpliceAPP . Source code can be downloaded at https://github.com/hsinnan75/SpliceAPP .

Abstract The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer–Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.

Abstract We investigate the radiation from accelerating electrons with asymptotic constant velocity and their analog signatures as evaporating black holes with left-over remnants. We find high-speed electrons, while having a high temperature, correspond to low-temperature analog remnants.

BackgroundEven in patients with a successful return of spontaneous circulation (ROSC), outcomes after cardiac arrest (CA) remain poor, with some eventually succumbing after several months of treatment. There is a need for early assessment of outcomes in patients with ROSC after CA. Therefore, we developed three models for predicting death within 6 months after CA using early post-arrest factors, performed external validation, and compared their efficiency.MethodsIn this retrospective cohort study, 199 patients aged 18–80 years who experienced either in-hospital cardiac arrest or out-of-hospital cardiac arrest and achieved ROSC were included as the training set. Patients were divided into an “alive” group (95 cases) and a “dead” group (104 cases) according to their survival status 6 months after CA. Demographic data, medical history, and laboratory results were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors. A risk prediction model was constructed using random forest methods, support vector machine (SVM), and a nomogram based on factors with P

Perfluorobutane sulfonate (PFBS) is recognized as a highly persistent environmental contaminant, notorious for its chemical stability and enduring presence in ecosystems. Its propensity for persistence and environmental mobility allows PFBS to infiltrate the human body, predominantly accumulating in the liver where it poses a potential risk for hepatic damage. This investigation aimed to explore the outcomes of PFBS on the physiological functionalities of hepatocytes in vitro. To this end, hepatocytes were exposed to 750 ug/ml PFBS, followed by an analysis of various cellular phenotypes and functionalities, including assessments of cell viability and mitochondrial integrity. The findings indicated that PFBS exposure led to a suppression of cell proliferation and an increase in apoptotic cell death. Moreover, PFBS exposure was found to augment the generation of reactive oxygen species (ROS) and induce significant mitochondrial dysfunction. Gene expression analysis identified significant changes in genes associated with numerous tumor signaling pathways and autophagy signaling pathways. Further examinations revealed an increase in cellular mitophagy following PFBS exposure, coupled with the activation of the mitophagy-associated Drp1/Pink1/Parkin pathway. Inhibition of mitophagy was observed to concurrently amplify cellular damage and inhibit the Drp1/Pink1/Parkin pathway. Together, these findings highlight PFBS’s capacity to inflict hepatocyte injury through mitochondrial disruption, positioning Drp1/Pink1/Parkin-mediated mitophagy as a crucial cellular defense mechanism against PFBS-induced toxicity.

Summary: Heart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery (n = 514) and validation (n = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 μmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 μmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.

Accurate and efficient power flow (PF) analysis is crucial in modern electrical networks’ operation and planning. Therefore, there is a need for scalable algorithms that can provide accurate and fast solutions for both small and large scale power networks. As the power network can be interpreted as a graph, Graph Neural Networks (GNNs) have emerged as a promising approach for improving the accuracy and speed of PF approximations by exploiting information sharing via the underlying graph structure. In this study, we introduce PowerFlowNet, a novel GNN architecture for PF approximation that showcases similar performance with the traditional Newton–Raphson method but achieves it 4 times faster in the IEEE 14-bus system and 48 times faster in the realistic case of the French high voltage network (6470rte). Meanwhile, it significantly outperforms other traditional approximation methods, such as the DC power flow, in terms of performance and execution time; therefore, making PowerFlowNet a highly promising solution for real-world PF analysis. Furthermore, we verify the efficacy of our approach by conducting an in-depth experimental evaluation, thoroughly examining the performance, scalability, interpretability, and architectural dependability of PowerFlowNet. The evaluation provides insights into the behavior and potential applications of GNNs in power system analysis.

The hallmark pathological features of Alzheimer’s disease (AD) consist of senile plaques, which are formed by extracellular β-amyloid (Aβ) deposition, and neurofibrillary tangles, which are formed by the hyperphosphorylation of intra-neuronal tau proteins. With the increase in clinical studies, the in vivo imbalance of iron homeostasis and the dysfunction of synaptic plasticity have been confirmed to be involved in AD pathogenesis. All of these mechanisms are constituted by the abnormal accumulation of misfolded or conformationally altered protein aggregates, which in turn drive AD progression. Proteostatic imbalance has emerged as a key mechanism in the pathogenesis of AD. Ubiquitination modification is a major pathway for maintaining protein homeostasis, and protein degradation is primarily carried out by the ubiquitin-proteasome system (UPS). In this review, we provide an overview of the ubiquitination modification processes and related protein ubiquitination degradation pathways in AD, focusing on the microtubule-associated protein Tau, amyloid precursor protein (APP), divalent metal transporter protein 1 (DMT1), and α-amino-3-hyroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. We also discuss recent advances in ubiquitination-based targeted therapy for AD, with the aim of contributing new ideas to the development of novel therapeutic interventions for AD.

Abstract Background To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. Methods HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. Results The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from − 29.03% to 34.78%. Conclusions CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.