Explore the vast range of titles available.

Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma (RCC). Tumor‐infiltrating immune cells (TIICs) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIICs in RCC and further reveal the independent prognostic values of TIICs. CIBERSORT, an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIICs and immune checkpoint modulators with overall survival (OS). We found that CD8+ T cells were associated with prolonged OS (hazard ratio [HR] = 0.09, 95% confidence interval [CI].01‐.53; P = 0.03) in chromophobe carcinoma (KICH). A higher proportion of regulatory T cells was associated with a worse outcome (HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma (KIRC). In renal papillary cell carcinoma (KIRP), M1 macrophages were associated with a favorable outcome (HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome (HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA4 and LAG3 were associated with a poor prognosis in KIRC, and IDO1 and PD‐L2 were associated with a poor prognosis in KIRP. This study indicates TIICs are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development. We described the immune landscape in detail, revealing the distinct immune infiltration patterns of different subtypes and stages of RCC. We further revealed relationships between TIIC and molecular subtypes, tumor stages, recurrent genomic alterations and survival in RCC. Our work advances the understanding of immune response meanwhile reveals potential targets and biomarkers for immunotherapy development.

To review the research on fear of childbirth, analyze and evaluate the publications by means of bibliometric analysis, and provide suggestions and scopes for future study. Web of Science, PubMed, Embase and the Cochrane Library databases. There is an increasing interest in the research in fear of childbirth during the past two decades. This study has demonstrated that the Swedish authors have a leading role on this topic. Researchers especially in countries with high birth rates, need to promote research projects in this field as it is an important public health issue.

Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18–65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2–T3 vs T4), and recurrent nodal stage (N0 vs N1–N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3–53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference –23% [95% CI –39 to –7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.

Background The use of immune checkpoint inhibitors (ICIs) combined with chemotherapy constitutes the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, elderly patients are underrepresented in the majority of related clinical trials. Patients and methods This retrospective study included RM-NPC patients aged 65 years or older who received immunotherapy between January 2015 and February 2022. Cox regression models were utilized to compare the outcomes. Comorbidity assessments (ACE-27, CCI, and ACCI) were used for the geriatric evaluation. Results Among the 95 of 243 patients included in this analysis (71 men), the median follow-up time was 29.3 months. Patients receiving local therapy had longer progression-free survival (PFS) (HR 0.352; 95% CI: 0.145–0.853; p  = .021). No significant differences in survival outcomes or toxicity profiles were observed between age groups or among the ICI agent groups. Conclusions The findings suggest that immunotherapy is efficacious and safe for treating RM-NPC in elderly patients. The combination of ICIs and local therapy significantly prolonged survival and could be an option for this vulnerable population.

Dysregulation of R-loop homeostasis is closely related to various human diseases, including cancer. However, the causality of aberrant R-loops in tumor progression remains unclear. In this study, using single-cell RNA-sequencing datasets from lung adenocarcinoma (LUAD), we constructed an R-loop scoring model to characterize the R-loop state according to the identified R-loop regulators related to EGFR mutations, tissue origins, and TNM stage. We then evaluated the relationships of the R-loop score with the tumor microenvironment (TME) and treatment response. Furthermore, the potential roles of FANCI-mediated R-loops in LUAD were explored using a series of in vitro experiments. Results showed that malignant cells with low R-loop scores displayed glycolysis and epithelial–mesenchymal transition pathway activation and immune escape promotion, thereby hampering the antitumor therapeutic effects. Cell communication analysis suggested that low R-loop scores contributed to T cell exhaustion. We subsequently validated the prognostic value of R-loop scores by using bulk transcriptome datasets across 33 tumor types. The R-loop scoring model well predicted patients’ therapeutic response to targeted therapy, chemotherapy, or immunotherapy in 32 independent cohorts. Remarkably, changes in R-loop distribution mediated by FANCI deficiency blocked the activity of Ras signaling pathway, suppressing tumor-cell proliferation and dissemination. In conclusion, this study reveals the underlying molecular mechanism of metabolic reprogramming and T cell exhaustion under R-loop score patterns, and the changes in R-loops mediated by R-loop regulators resulting in tumor progression. Therefore, incorporating anticancer methods based on R-loop or R-loop regulators into the treatment schemes of precision medicine may be beneficial.

Heart sound auscultation plays a crucial role in the early diagnosis of cardiovascular diseases. In recent years, great achievements have been made in the automatic classification of heart sounds, but most methods are based on segmentation features and traditional classifiers and do not fully exploit existing deep networks. This paper proposes a cardiac audio classification method based on image expression of multidimensional features (CACIEMDF). First, a 102-dimensional feature vector is designed by combining the characteristics of heart sound data in the time domain, frequency domain and statistical domain. Based on the feature vector, a two-dimensional feature projection space is constructed by PCA dimensionality reduction and the convex hull algorithm, and 102 pairs of coordinate representations of the feature vector in the two-dimensional space are calculated. Each one-dimensional component of the feature vector corresponds to a pair of 2D coordinate representations. Finally, the one-dimensional feature component value and its divergence into categories are used to fill the three channels of a color image, and a Gaussian model is used to dye the image to enrich its content. The color image is sent to a deep network such as ResNet50 for classification. In this paper, three public heart sound datasets are fused, and experiments are conducted using the above methods. The results show that for the two-classification/five-classification task of heart sounds, the method in this paper can achieve a classification accuracy of 95.68%/94.53% when combined with the current deep network.

Background Adenosine monophosphate-activated protein kinase (AMPK) is associated with the development of liver hepatocellular carcinoma (LIHC). AMPKα2, an α2 subunit of AMPK, is encoded by PRKAA2 , and functions as the catalytic core of AMPK. However, the role of AMPKα2 in the LIHC tumor immune environment is unclear. Methods RNA-seq data were obtained from the Cancer Genome Atlas and Genotype-Tissue Expression databases. Using the single-cell RNA-sequencing dataset for LIHC obtained from the China National Genebank Database, the communication between malignant cells and T cells in response to different PRKAA2 expression patterns was evaluated. In addition, the association between PRKAA2 expression and T-cell evolution during tumor progression was explored using Pseudotime analysis, and the role of PRKAA2 in metabolic reprogramming was explored using the R “ scMetabolis ” package. Functional experiments were performed in LIHC HepG2 cells. Results AMPK subunits were expressed in tissue-specific and substrate-specific patterns. PRKAA2 was highly expressed in LIHC tissues and was associated with poor patient prognosis. Tumors with high PRKAA2 expression displayed an immune cold phenotype. High PRKAA2 expression significantly promoted LIHC immune escape. This result is supported by the following evidence: 1) the inhibition of major histocompatibility complex class I (MHC-I) expression through the regulation of interferon-gamma activity in malignant cells; 2) the promotion of CD8+ T-cell exhaustion and the formation of CD4+ Treg cells in T cells; 3) altered interactions between malignant cells and T cells in the tumor immune environment; and 4) induction of metabolic reprogramming in malignant cells. Conclusions Our study indicate that PRKAA2 may contribute to LIHC progression by promoting metabolic reprogramming and tumor immune escape through theoretical analysis, which offers a theoretical foundation for developing PRKAA2 -based strategies for personalized LIHC treatment.

Background Gastric cancer (GC) is a malignant tumour originating from the gastric mucosa epithelium that seriously threatens human health. DCLK1, miR-15b and lncRNA SNHG1 play potential roles in the occurrence of GC, but the mechanism remains unclear. Methods Gene expression of DCLK1, miR-15b and lncRNA SNHG1 was investigated by qRT-PCR. Protein expression was detected by Western blotting. Migration and invasion of gastric cancer cells was tested by a Transwell assay and wound healing assay. Cell proliferation was measured by an MTT assay. Finally, the correctness of the prediction results was confirmed by a dual-luciferase reporter assay. Results The expression of DCLK1, Notch1, and SNHG1 was increased in GC tissues, while the expression of miR-15b was decreased. Overexpression of lncRNA SNHG1 promoted the expression of DCLK1 and Nothc1 in GC cells. Moreover, miR-15b targeted DCLK1 to regulate Notch1 expression and inhibited the EMT process in GC cells. SNHG1 enhanced the effects of DCLK1/Notch1 on the EMT process through regulating miR-15b expression. Conclusion SNHG1 enhances the EMT process in GC cells through DCLK1-mediated Notch1 pathway, which can be a potential target for treating GC.

Post-radiation nasopharyngeal necrosis (PRNN) is a severe complication following re-irradiation in patients with recurrent nasopharyngeal carcinoma (NPC). This study aimed to explore the association between nasopharyngeal microbiota and PRNN in patients with recurrent NPC undergoing re-irradiation and to evaluate the predictive value of the microbiota for PRNN. This retrospective study collected data from 113 patients with recurrent NPC who underwent re-irradiation at the Sun Yat-sen University Cancer Center (SYSUCC) between January 2020 and November 2022. Patients were divided into necrosis and non-necrosis groups based on the development of necrosis after re-irradiation. 5R 16S rRNA sequencing of nasopharyngeal biopsy tissues conducted before re-irradiation was used to assess microbiota composition, diversity, and functional predictions. Clinical features and selected microbial markers were used in a random forest model to predict the occurrence of PRNN. Of the 113 patients with recurrent NPC who underwent re-irradiation, 60 developed PRNN, while 53 did not. Proteobacteria and Firmicutes were the dominant phyla in the nasopharyngeal microbiota of all the patients with recurrent NPC. The necrosis group exhibited significantly higher alpha diversity and distinct beta diversity than the non-necrosis group did. A predictive model that combined clinical features (gross tumor volume [GTV]) with microbiome characteristics achieved an AUC of 87.9% in the training set and 86.9% in the test set, demonstrating robust predictive performance. Nasopharyngeal microbial diversity prior to re-irradiation was significantly higher in the necrosis group. Our predictive model, integrating clinical and microbial features, demonstrated strong performance in predicting PRNN and offers a promising tool for early intervention and prevention strategies.