Semi-Supervised Graph Structure Learning via Dual Reinforcement of Label and Prior Structure.

Graph neural networks (GNNs) have achieved considerable success in dealing with graph-structured data by the message-passing mechanism. Actually, this mechanism relies on a fundamental assumption that the graph structure along which information propagates is perfect. However, the real-world graphs are inevitably incomplete or noisy, which violates the assumption, thus resulting in limited performance. Therefore, optimizing graph structure for GNNs is indispensable and important. Although current semi-supervised graph structure learning (GSL) methods have achieved a promising performance, the potential of labels and prior graph structure has not been fully exploited yet. Inspired by this, we examine GSL with dual reinforcement of label and prior structure in this article. Specifically, to enhance label utilization, we first propose to construct the prior label-constrained matrices to refine the graph structure by identifying label consistency. Second, to adequately leverage the prior structure to guide GSL, we develop spectral contrastive learning that extracts global properties embedded in the prior graph structure. Moreover, contrastive fusion with prior spatial structure is further adopted, which promotes the learned structure to integrate local spatial information from the prior graph. To extensively evaluate our proposal, we perform sufficient experiments on seven benchmark datasets, where experimental results confirm the effectiveness of our method and the rationality of the learned structure from various aspects.

The Fe-S cluster biosynthesis in Enterococcus faecium is essential for anaerobic growth and gastrointestinal colonization.

The facultative anaerobic Gram-positive bacterium Enterococcus faecium is a ubiquitous member of the human gut microbiota. However, it has gradually evolved into a pathogenic and multidrug resistant lineage that causes nosocomial infections. The establishment of high-level intestinal colonization by enterococci represents a critical step of infection. The majority of current research on Enterococcus has been conducted under aerobic conditions, while limited attention has been given to its physiological characteristics in anaerobic environments, which reflects its natural colonization niche in the gut. In this study, a high-density transposon mutant library containing 26,620 distinct insertion sites was constructed. Tn-seq analysis identified six genes that significantly contribute to growth under anaerobic conditions. Under anaerobic conditions, deletion of sufB (encoding Fe-S cluster assembly protein B) results in more extensive and significant impairments on carbohydrate metabolism compared to aerobic conditions. Consistently, the pathways involved in this utilization-restricted carbohydrates were mostly expressed at significantly lower levels in mutant compared to wild-type under anaerobic conditions. Moreover, deletion of sufB or pflA (encoding pyruvate formate lyase-activating protein A) led to failure of gastrointestinal colonization in mice. These findings contribute to our understanding of the mechanisms by which E. faecium maintains proliferation under anaerobic conditions and establishes colonization in the gut.

Cost-effectiveness analysis of bevacizumab for cerebral radiation necrosis treatment based on real-world utility value in China.

BACKGROUND: Bevacizumab shows superior efficacy in cerebral radiation necrosis (CRN) therapy, but its economic burden remains heavy due to the high drug price. This study aims to evaluate the cost-effectiveness of bevacizumab for CRN treatment from the Chinese payers' perspective. METHODS: A decision tree model was developed to compare the costs and health outcomes of bevacizumab and corticosteroids for CRN therapy. Efficacy and safety data were derived from the NCT01621880 trial, which compared the effectiveness and safety of bevacizumab monotherapy with corticosteroids for CRN in nasopharyngeal cancer patients, and demonstrated that bevacizumab invoked a significantly higher response than corticosteroids (65.5% vs. 31.5%, P < 0.001) with no significant differences in adverse events between two groups. The utility value of the "non-recurrence" status was derived from real-world data. Costs and other utility values were collected from an authoritative Chinese network database and published literature. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was evaluated via one-way and probabilistic sensitivity analyses. RESULTS: Bevacizumab treatment added 0.12 (0.48 vs. 0.36) QALYs compared to corticosteroid therapy, along with incremental costs of $ 2010 ($ 4260 vs. $ 2160). The resultant ICER was $ 16,866/QALY, which was lower than the willingness-to-pay threshold of $ 38,223/QALY in China. The price of bevacizumab, body weight, and the utility value of recurrence status were the key influential parameters for ICER. Probabilistic sensitivity analysis revealed that the probability of bevacizumab being cost-effectiveness was 84.9%. CONCLUSION: Compared with corticosteroids, bevacizumab is an economical option for CRN treatment in China.

Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center.

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

Parallel Dual-Branch Fusion Network for Epileptic Seizure Prediction.

Epilepsy is a prevalent chronic disorder of the central nervous system. The timely and accurate seizure prediction using the scalp Electroencephalography (EEG) signal can make patients adopt reasonable preventive measures before seizures occur and thus reduce harm to patients. In recent years, deep learning-based methods have made significant progress in solving the problem of epileptic seizure prediction. However, most current methods mainly focus on modeling short- or long-term dependence in EEG, while neglecting to consider both. In this study, we propose a Parallel Dual-Branch Fusion Network (PDBFusNet) which aims to combine the complementary advantages of Convolutional Neural Network (CNN) and Transformer. Specifically, the features of the EEG signal are first extracted using Mel Frequency Cepstral Coefficients (MFCC). Then, the extracted features are delivered into the parallel dual-branches to simultaneously capture the short- and long-term dependencies of EEG signal. Further, regarding the Transformer branch, a novel feature fusion module is developed to enhance the ability of utilizing time, frequency, and channel information. To evaluate our proposal, we perform sufficient experiments on the public epileptic EEG dataset CHB-MIT, where the accuracy, sensitivity, specificity and precision are 95.76%, 95.81%, 95.71% and 95.71%, respectively. PDBFusNet shows superior performance compared to state-of-the-art competitors, which confirms the effectiveness of our proposal.

Polygonati Rhizoma: A review on the extraction, purification, structural characterization, biosynthesis of the main secondary metabolites and anti-aging effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizome (PR) is a plant that is extensively widespread in the temperate zones of the Northern Hemisphere. It is a member of the Polygonatum family of Asparagaceae. PR exhibits diverse pharmacological effects and finds applications in ethnopharmacology, serving as a potent tonic for more than two millennia. PR's compounds endow it with various pharmacological properties, including anti-aging, antioxidant, anti-fatigue, anti-inflammatory, and sleep-enhancing effects, as well as therapeutic potential for osteoporosis and age-related diseases. AIM OF THE STUDY: This review seeks to offer a thorough overview of the processing, purification, extraction, structural characterization, and biosynthesis pathways of PR. Furthermore, it delves into the anti-aging mechanism of PR, using organ protection as an entry point. MATERIALS AND METHODS: Information on PR was obtained from scientific databases (Google Scholar, Web of Science, ScienceDirect, SciFinder, PubMed, CNKI) and books, doctoral theses, and master's dissertations. RESULTS: In this investigation, 49 polysaccharides were extracted from PR, and the impact of various processing, extraction, and purification techniques on the structure and activity of these polysaccharides was evaluated. Additionally, 163 saponins and 46 flavonoids were identified, and three key biosynthesis pathways of secondary metabolites were outlined. Notably, PR and Polygonat Rhizomai polysaccharides (PRP) exhibit remarkable protective effects against age-induced injuries to the brain, liver, kidney, intestine, heart, and vessels, thereby promoting longevity and ameliorating the aging process. CONCLUSIONS: PR, a culinary and therapeutic herb, is rich in active components and pharmacological activities. Based on this review, PR plays a meaningful role in lifespan extension and anti-aging, which can be attributed to PRP. Future research should delve deeper into the structural aspects of PRP that underlie its anti-aging effects and explore potential synergistic interactions with other compounds. Moreover, exploring the potential applications of PR in functional foods and pharmaceutical formulations is recommended to advance the development of industries and resources focused on healthy aging.

Lenvatinib plus pembrolizumab in the patients with advanced previously treated endometrial cancer: A cost-effectiveness analysis in the United States and in China.

PURPOSE: To investigate the cost-effectiveness of lenvatinib plus pembrolizumab (LP) compared to chemotherapy as a second-line treatment for advanced endometrial cancer (EC) from the United States and Chinese payers' perspective. METHODS: In this economic evaluation, a partitioned survival model was constructed from the perspective of the United States and Chinese payers. The survival data were derived from the clinical trial (309-KEYNOTE-775), while costs and utility values were sourced from databases and published literature. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were estimated. The robustness of the model was evaluated through sensitivity analyses, and price adjustment scenario analyses was also performed. RESULTS: Base-case analysis indicated that LP wouldn't be cost-effective in the United States at the WTP threshold of $200 000, with improved effectiveness of 0.75 QALYs and an additional cost of $398596.81 (ICER $531392.20). While LP was cost-effective in China, with improved effectiveness of 0.75 QALYs and an increased overall cost of $62270.44 (ICER $83016.29). Sensitivity analyses revealed that the above results were stable. The scenario analyses results indicated that LP was cost-effective in the United States when the prices of lenvatinib and pembrolizumab were simultaneously reduced by 61.95% ($26.5361/mg for lenvatinib and $19.1532/mg for pembrolizumab). CONCLUSION: LP isn't cost-effective in the patients with advanced previously treated endometrial cancer in the United States, whereas it is cost-effective in China. The evidence-based pricing strategy provided by this study could benefit decision-makers in making optimal decisions and clinicians in general clinical practice. More evidence about budget impact and affordability for patients is needed.

Natural Disinfection-like Process Unveiled in Soil Microenvironments by Enzyme-Catalyzed Chlorination.

Substantial natural chlorination processes are a growing concern in diverse terrestrial ecosystems, occurring through abiotic redox reactions or biological enzymatic reactions. Among these, exoenzymatically mediated chlorination is suggested to be an important pathway for producing organochlorines and converting chloride ions (Cl-) to reactive chlorine species (RCS) in the presence of reactive oxygen species like hydrogen peroxide (H2O2). However, the role of natural enzymatic chlorination in antibacterial activity occurring in soil microenvironments remains unexplored. Here, we conceptualized that heme-containing chloroperoxidase (CPO)-catalyzed chlorination functions as a naturally occurring disinfection process in soils. Combining antimicrobial experiments and microfluidic chip-based fluorescence imaging, we showed that the enzymatic chlorination process exhibited significantly enhanced antibacterial activity against Escherichia coli and Bacillus subtilis compared to H2O2. This enhancement was primarily attributed to in situ-formed RCS. Based on semiquantitative imaging of RCS distribution using a fluorescence probe, the effective distance of this antibacterial effect was estimated to be approximately 2 mm. Ultrahigh-resolution mass spectrometry analysis showed over 97% similarity between chlorine-containing formulas from CPO-catalyzed chlorination and abiotic chlorination (by sodium hypochlorite) of model dissolved organic matter, indicating a natural source of disinfection byproduct analogues. Our findings unveil a novel natural disinfection process in soils mediated by indigenous enzymes, which effectively links chlorine-carbon interactions and reactive species dynamics.

Analgesic efficacy of local infiltration anaesthesia versus femoral nerve block in alleviating postoperative wound pain following total knee arthroplasty: A systematic review and meta-analysis.

Total knee arthroplasty (TKA) often involves significant postoperative pain, necessitating effective analgesia. This meta-analysis compares the analgesic efficacy of local infiltration anaesthesia (LIA) and femoral nerve block (FNB) in managing postoperative wound pain following TKA. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was structured around the PICO framework, assessing studies that directly compared LIA and FNB in TKA patients. A comprehensive search across PubMed, Embase, Web of Science and the Cochrane Library was conducted without time restrictions. Studies were included based on specific criteria such as participant demographics, study design and outcomes like pain scores and opioid consumption. Quality assessment utilized the Cochrane Collaboration's risk of bias tool. The statistical approach was determined based on heterogeneity, with the choice of fixed- or random-effects models guided by the I2 statistic. Sensitivity analysis and evaluation of publication bias using funnel plots and Egger's linear regression test were also conducted. From an initial pool of 1275 articles, eight studies met the inclusion criteria. These studies conducted in various countries from 2007 to 2016. The meta-analysis showed no significant difference in resting and movement-related Visual Analogue Scale scores post-TKA between the LIA and FNB groups. However, LIA was associated with significantly lower opioid consumption. The quality assessment revealed a low risk of bias in most studies, and the sensitivity analysis confirmed the stability of these findings. There was no significant publication bias detected. Both LIA and FNB are effective in controlling postoperative pain in TKA patients, but LIA offers the advantage of lower opioid consumption. Its simplicity, cost-effectiveness and opioid-sparing nature make LIA the recommended choice for postoperative analgesia in knee replacement surgeries.

Treatment-related pneumonitis after thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 monoclonal antibodies in advanced esophageal squamous cell carcinoma.

PURPOSE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD­1 mAbs and 41 patients received sequential radiotherapy with anti-PD­1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8-2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD­1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. CONCLUSION: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD­1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD­1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.

Evaluating the impact of ultrasound-guided subsheath versus extrasheath sciatic nerve block on postoperative wound pain in tibial and foot surgeries: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluate the impact of ultrasound-guided subsheath versus extrasheath sciatic nerve blocks on postoperative wound pain in tibial and foot surgeries, crucial for effective pain management and patient recovery. Adhering to PRISMA guidelines, this study used a PICO framework, focusing on patients undergoing tibial and foot surgeries and comparing the efficacy and safety of subsheath and extrasheath sciatic nerve blocks. The literature search spanned four databases without time restrictions, assessing various outcomes like success rate, onset time, duration of analgesia and complication rates. Quality assessment employed the Cochrane Collaboration's risk of bias tool, and statistical analyses included heterogeneity assessment, fixed-effect and random-effects models, sensitivity analysis and publication bias evaluation using funnel plots and Egger's linear regression test. From an initial pool of 1213 articles, six met the inclusion criteria. The subsheath group showed a significantly higher success rate of complete sensory blockade within 30 min compared with the extrasheath group (OR = 5.39; 95% CI: 2.82-10.28; p < 0.01). No significant differences were found in procedure duration or incidence of nerve-related complications between the two techniques. The subsheath approach also demonstrated a quicker onset time of sensory blockade (MD = -8.57; 95% CI: -11.27 to -5.88; p < 0.01). Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected. Ultrasound-guided subsheath sciatic nerve blocks are more effective than extrasheath blocks in achieving rapid and complete sensory blockade for tibial and foot surgeries, with a quicker onset time and comparable safety profile. Subsheath injections are thus recommended as a preferred method for anaesthesia and postoperative pain management in these surgical procedures, enhancing overall patient outcomes.