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Background: Everolimus is beneficial for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). However, some patients developed drug resistance and the well-established predictor for everolimus efficacy was limited. Objectives: The study was designed to evaluate the efficacy of everolimus in different treatment lines and identify several clinicopathological markers to estimate everolimus efficacy in patients with HR+/HER2− ABC. Design: This was a retrospective and multicenter study. Methods: Between 2014 and 2022, more than 2000 patients with tumors who received everolimus were collected from multiple cancer centers in China (National Cancer Center, Chinese PLA General Hospital, Peking University Cancer Hospital & Institute). A training cohort and two validation cohorts were developed. Results: The training cohort included 338 patients. The median progression-free survival (PFS) for everolimus was 5.6 months, with an objective response rate of 25.1% and a clinical benefit rate of 54.4%. PFS was significantly worse from first-line (1L) to second-line (2L) to third-line (3L), with PFS1L for 13.5 months, PFS2L for 6.1 months, and PFS3L for 4.1 months (p = 2.9e−6, hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.61–0.82). The clinicopathological characteristics, including post-1L everolimus treatment, Ki67 index of more than 40%, more than two metastatic sites at first recurrence, and receiving adjuvant chemotherapy, were independent risk factors for PFS. A predictive model for everolimus efficacy was established using these four factors. In the low-risk group, patients achieved a median PFS of 12.6 months, significantly longer compared to 2.7 months for those in the high-risk group (p = 2.4e−64, HR = 9.41, 95% CI = 7.05–12.56). The area under the curve was 0.96, 0.95, and 0.94 for 6-month, 1-year, and 3-year PFS, respectively. Internal validation cohort (PFS 18.4 vs 3.1 months, p = 3.6e−11, HR = 3.78, 95% CI = 2.49–5.74) and external validation cohort (PFS 13.5 vs 3.1 months, p = 2.9e−10, HR = 11.53, 95% CI = 4.68–28.37) confirmed its power for estimating clinical benefits of everolimus. Conclusion: A predictive model was successfully established to predict survival outcomes for everolimus in patients with HR+/HER2− ABC, which may provide references for the management of everolimus in Chinese patients with HR+/HER2− ABC. [ABSTRACT FROM AUTHOR]

Wilms tumor (WT) is the most common malignant tumor of the urinary system in children. Though the traditional treatment of surgery plus radiotherapy and chemotherapy achieves exciting clinical efficacy, in relapsed and refractory cases, the long-term overall survival rates are poor. Besides, chemotherapy and radiation have serious long-term toxic side effects on children. Cancer immunotherapy is a new tumor therapy that works by activating the body's immune system to allow immune cells to kill tumor cells more efficiently. Currently, cancer immunotherapy has been tested in clinical trials or basic studies in WT. This article reviews the current status of clinical trials and basic research of cancer immunotherapy in WT to promote the application of cancer immunotherapy in WT patients. Article highlights Introduction With the traditional treatment of surgery plus radiotherapy and chemotherapy, the overall survival rate for relapsed and refractory cases, the long-term overall survival rate was are poor. Some cancer immunotherapy strategies have been used in treating Wilms tumor (WT), especially in relapsed and refractory WT cases, and some of them have achieved encouraging effects. Literature search The literature search strategy for writing this review is described. 'Immunotherapy,' 'Biological Therapy?' 'Immune checkpoints?' 'Adoptive?' 'Vaccines' and 'Wilms Tumor' were used as a key words to search the PubMed, Web of Science and Embase databases for related literature. Therapeutic tumor vaccines therapy The mechanism of tumor vaccine treatment, and its application in WT clinical research results and analysis. The effects of the glypican-3 (GPC3) vaccine and NeuGcGM3 simulated vaccine in WT are not ideal, which may be because we didn't choose a suitable tumor-specific antigen to make the vaccine. Immune checkpoint inhibitors therapy The mechanism of immune checkpoint inhibitors therapy, and its application in WT clinical research results and analysis. The effects of pembrolizumab and atezolizumab in WT are not ideal which may be due to the low expression of immune checkpoint in WT. Immune cell therapy The mechanism of Chimeric antigen receptor-modified T cell (CAR-T) therapy and Tumor-associated antigen-specific T cell (TAA-T) therapy, and them application in WT clinical research results and analysis. CAR-T cell therapy has begun clinical trials in children with WT. These clinical trials are in progress, and the results have yet to be counted. In a phase I study (NCT02789228), two WT patients treated with TAA-T hadn't disease progression for more than 15 months and there are no infusion-related adverse events. The results of application of NK in the WT transplanted tumor mouse model. Conclusion & future perspective Combining different immunotherapy strategies and immunotherapy combined with traditional therapy may produce better efficacy for WT treatment. Treatment of relapsed and refractory WT with CAR-T may have a good prospect. [ABSTRACT FROM AUTHOR]

Background: Many patients with enterostomy and their family caregivers experience severe anxiety and fatigue, which affects their participation in normal social activities and family life, resulting in impaired social function. The purpose of this study was to understand the status of social function of patients with enterostomy and their family caregivers;at the same time to analyze the subjective and objective effects of anxiety and fatigue on their social functions. Methods: The self-made general information questionnaire, WHO Social Disability rating Scale, Miao Yu's Multidimensional Fatigue Scale-20 and Zung et al. 's Self-rating Anxiety Scale were used to investigate the general situation, social function, fatigue and anxiety of enterostomy patients and their family caregivers who came to the hospital for treatment from March 28, 2023 to November 30, 2023. SPSS27.0 was used to complete the statistical analysis of the data, and AMOS26.0 was used to establish the structural equation model to complete the subject and object effect analysis. Results: A total of 260 pairs of enterostomy patients and their family caregivers were included in this study. The social function scores of enterostomy patients and their family caregivers were (8.80±3.44) and (6.44±3.60). The anxiety scores were (37.81±7.60) and (34.73±7.50). The fatigue scores were (63.35±12.80) and (51.21±12.38).The results of the subject-object effect analysis reported the subject effect: the anxiety of patients with enterostomy had a significant positive impact on the degree of social dysfunction (β = 0.154, P = 0.015); The fatigue of patients with enterostomy had a significant positive effect on the degree of social dysfunction (β = 0.132, P = 0.034). The anxiety of family caregivers had a significant positive effect on the degree of social dysfunction (β = 0.161, P = 0.023). The fatigue of family caregivers had a significant positive effect on the degree of social dysfunction (β = 0.201, P = 0.005). In terms of object effects: only the fatigue of family caregivers had a significant positive impact on the degree of social dysfunction of enterostomy patients (β = 0.224, P < 0.001), and other ways had no object effects. Conclusion: Patients with enterostomy and their family caregivers have serious social function defects. Clinical medical staff should take care of them as a whole in order to better return to family and society after surgery. [ABSTRACT FROM AUTHOR]

Background: Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods: We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results: Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion: Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment. [ABSTRACT FROM AUTHOR]

In the pursuit of next‐generation ultrahigh‐energy‐density Li−O2 batteries, it is imperative to develop an electrolyte with stability against the strong oxidation environments. N,N‐dimethylacetamide (DMA) is a recognized solvent known for its robust resistance to the highly reactive reduced oxygen species, yet its application in Li−O2 batteries has been constrained due to its poor compatibility with the Li metal anode. In this study, a rationally selected hydrofluoroether diluent, methyl nonafluorobutyl ether (M3), has been introduced into the DMA‐based electrolyte to construct a localized high concentration electrolyte. The stable −CH3 and C−F bonds within the M3 structure could not only augment the fundamental properties of the electrolyte but also fortify its resilience against attacks from O2− and 1O2. Additionally, the strong electron‐withdrawing groups (−F) presented in the M3 diluent could facilitate coordination with the electron‐donating groups (−CH3) in the DMA solvent. This intermolecular interaction promotes more alignments of Li+‐anions with a small amount of M3 addition, leading to the construction of an anion‐derived inorganic‐rich SEI that enhances the stability of the Li anode. As a result, the Li−O2 batteries with the DMA/M3 electrolyte exhibit superior cycling performance at both 30 °C (359th) and −10 °C (120th). [ABSTRACT FROM AUTHOR]

Sea buckthorn has lipid‐lowering properties and is widely used in the development of functional foods. In this study, a probiotic (Lactobacillus plantarum, Lp10211) with cholesterol‐lowering potential and acid and bile salt resistant was screened for the fermentation of sea buckthorn juice. Changes in the active ingredients, such as sugars and phenolics, before and after fermentation, as well as their in vitro lipid‐lowering activities, were compared. The contents of reducing and total sugars decreased substantially after fermentation. Lp10211 primarily utilized fructose for growth and reproduction, with a utilization rate of 76.9%. The phenolic compound content of sea buckthorn juice increased by 37.06% after fermentation and protected the phenolic components from degradation (protocatechuic and p‐coumaric acids) and produced new polyphenol (shikimic acid). Enhanced inhibition of pancreatic lipase activity (95.42%) and cholesterol micellar solubility (59.15%) was evident. The antioxidant properties of the fermentation broth were improved. Notably, Lp10211 preserved the color and reversed browning in sea buckthorn juice. The collective findings indicate that fermentation of sea buckthorn juice by Lp10211 may enhance the functional components and lipid‐lowering activity of sea buckthorn, which may provide a new approach for the development of lipid‐lowering foods. [ABSTRACT FROM AUTHOR]

Background Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2−) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. Patients and Methods The study cohort comprised HR+/HER2−, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. Results The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). Conclusion In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]

Link prediction has a wide range of applications in the study of complex networks, and the current research on link prediction based on single-layer networks has achieved fruitful results, while link prediction methods for multilayer networks have to be further developed. Existing research on link prediction for multilayer networks mainly focuses on multiplexed networks with homogeneous nodes and heterogeneous edges, while there are relatively few studies on general multilayer networks with heterogeneous nodes and edges. In this context, this paper proposes a method for heterogeneous multilayer networks based on motifs for link prediction. The method considers not only the effect of heterogeneity of edges on network links but also the effect of heterogeneous and homogeneous nodes on the existence of links between nodes. In addition, we use the role function of nodes to measure the contribution of nodes to form the motifs with links in different layers of the network, thus enabling the prediction of intra- and inter-layer links on heterogeneous multilayer networks. Finally, we apply the method to several empirical networks and find that our method has better link prediction performance than several other link prediction methods on multilayer networks. [ABSTRACT FROM AUTHOR]