This research aimed to identify risk factors including individual characteristics and environment circumstances related to different types of school bullying (physical, relational, verbal, sexual, and possession bullying) among middle school students in China. Cases were the respondents reporting perpetrating bullying behaviors three or more times in the past year. One control was selected for each case from those participants who were not involved in school bullying in the past 12 months. Data were collected between April 2019 and May 2019 in China. After considering potential confounding variables including gender, grade level, and school, multivariable conditional logistic regression analysis was performed based on the univariate logistic analysis including 1,594 adolescents. According to conditional logistic regression analysis, alcohol use and lack of emotional management and control were the significant individual characteristics positively associated with involvement in school bullying. Alcohol use was related to all five types of school bullying perpetration. Poor relationships between family members, father’s alcohol use, and parental neglect were strong risk factors for relational bullying. Lack of a sense of safety and absence of trusted people were associated with physical, relational, and verbal bullying perpetration. Results of this study provide evidence about risk factors for school bullying and have implications for potential policies to reduce bullying. Effective policies and programs need to take individual characteristics (social-emotional skills, anger control), family (parent training in conflict resolution, appropriate disciplining), peer and school factors (promoting prosocial networks, zero tolerance for bullying, appropriate disciplining policies against students who bully others, teacher training on building positive teacher–student relationships and positive discipling techniques) into consideration in order to develop effective prevention programs.
Background
Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy.
Methods
Genomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM).
Results
ATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455–0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596–1.362, P = 0.712).
Conclusions
ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.
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