Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B-cell lymphoma.

Enhancers are regulatory regions of DNA, which play a key role in cell-type specific differentiation and development. Most active enhancers are transcribed into enhancer RNA (eRNA) that can regulate transcription of target genes by means of in cis as well as in trans action. eRNA stabilize contacts between distal genomic regions and mediate the interaction of DNA with master transcription factors. Here, we characterized an enhancer eRNA, GECPAR (germinal center proliferative adapter RNA), which is specifically transcribed in normal and neoplastic germinal center B cells from the super-enhancer of POU2AF1, a key regulatory gene of the germinal center reaction. Using diffuse large B-cell lymphoma cell line models, we demonstrated the tumor suppressor activity of GECPAR, which is mediated via its transcriptional regulation of proliferation and differentiation genes, particularly MYC and the Wnt pathway.

Apatinib, a novel VEGFR-2 tyrosine kinase inhibitor, for relapsed and refractory nasopharyngeal carcinoma: data from an open-label, single-arm, exploratory study.

Purpose Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has shown promising efficacy against several solid cancers, but evidence of its efficacy against relapsed and refractory nasopharyngeal carcinoma is limited. We investigated the efficacy and safety of apatinib for relapsed and refractory nasopharyngeal carcinoma in an open-label, single-arm, phase II clinical trial. Fifty-one patients with relapsed and refractory nasopharyngeal carcinoma in the First Affiliated Hospital, Zhengzhou University, who met the inclusion criteria were enrolled in the study. All patients received apatinib at an initial dose of 500 mg daily (1 cycle = 28 days). The primary and secondary endpoints were overall response rate, progression-free survival, and overall survival. We evaluated treatment effects and recorded apatinib-related adverse events by performing regular follow-ups and workup. The overall response rate (complete and partial responses) was 31.37% (16/51). The median overall survival and progression-free survival were 16 (95% CI, 9.32-22.68) and 9 months (95% CI, 5.24-12.76), respectively. Most patients tolerated treatment-related adverse events of grades 1 and 2; hypertension (29, 56.86%), proteinuria (25, 49.02%), and hand-foot syndrome (27, 52.94%) were the most common adverse events. There were no treatment-related deaths. Apatinib showed good efficacy and safety in patients with relapsed and refractory NPC.

Predicting the onset of overweight in Chinese high school students: a machine-learning approach in a one-year prospective cohort study.

OBJECTIVE: This study aimed to develop and evaluate machine-learning models for predicting the onset of overweight in adolescents aged 14‒17, utilizing easily collectible personal information. METHODS: This study was a one-year prospective cohort study. Baseline data were collected through anthropometric measurements and questionnaires, and the incidence of overweight was calculated one year later via anthropometric measurements. Predictive factors were selected through univariate analysis. Six machine-learning models were developed for predicting the onset of overweight. The SHapley Additive exPlanations (SHAP) was used for global and local interpretation of the models. RESULTS: Out of 1,241 adolescents, 204 (16.4%) were identified as overweight after one year. Nineteen features were associated with the overweight incidence in univariable analysis. Participants were randomly divided into a training group and a testing group in a 7:3 ratio. The Light Gradient Boosting Machine (LGBM) algorithm achieved outperformed other models, achieving the following metrics: Accuracy (0.956), Recall (0.812), Specificity (0.983), F1-score (0.855), AUC (0.961). Importance ranking revealed that the top 11 minimal feature set can maintain the stability of model performance. CONCLUSIONS: The onset of overweight in adolescents was accurately predicted using easily collectible personal information. The LGBM-based model exhibited superior performance. Oversampling technique notably improved model performance. The model interpretation technique provided innovative strategies for managing adolescent overweight/obesity.

Processing directional information in stimuli inhibits the spatial association of luminance levels.

Previous studies have found that the spatial-numerical association of the response codes (SNARC) effect automatically occurred when processing both numbers and non-symbolic magnitudes. However, this conclusion was challenged by several recent studies that found no SNARC effect when processing non-symbolic magnitudes with a directional cue. In the present study, we hypothesized that automatic spatial association of non-symbolic magnitudes would be inhibited by directional cues; thus, we utilized left and right arrow stimuli with different luminance levels to systematically investigate the spatial association of luminance. To ensure that participants could effectively discriminate the luminance stimuli, we first replicated the SNARC effect in Experiment 1, by presenting rectangles with different luminance levels. Then, arrows with the same luminance levels as the rectangles were randomly presented to participants on the centre of a screen; participants completed direction classification (Experiment 2), colour classification (Experiment 3), or luminance classification (Experiment 4) tasks with these arrow stimuli. We found that (1) the SNARC effect was present when processing rectangles with different luminance levels (Experiment 1); however, (2) the Simon-like effect rather than the spatial association of luminance was observed when processing arrows with different luminance levels in the luminance-irrelevant classification tasks (Experiments 2 and 3) and the luminance-relevant classification task (Experiment 4). These results indicate that processing of a directional cue inhibited the spatial association of luminance in both luminance-relevant and luminance-irrelevant classification tasks.

Prognostic analysis of CD5 expression in double-hit diffuse large B-cell lymphoma and effectiveness comparison in patients treated with dose-adjusted EPOCH plus rituximab/R-CHOP regimens.

OBJECTIVES: To compare the efficacy of rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) with traditional rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimens in CD5+ double-hit lymphoma (DHL) and to evaluate prognostic factors. METHODS: We retrospectively studied 139 patients with newly diagnosed DHL/THL diffuse large B-cell lymphoma (including 20 cases CD5+ and 119 cases CD5-), 87 cases were MYC/BCL2 DHL, 30 cases were MYC/BCL6 DHL, 22 cases were THL. MYC, BCL2 and BCL6 rearrangements were examined by fluorescence in-situ hybridization. CD5 is detected by immunohistochemistry (IHC). RESULTS: The objective response rate (ORR) difference between CD5+ and CD5- was significant (80.0% vs 63.8%, P=0.003). The median follow-up time was 18 months (range: 4-39 months). Progression-free survival (PFS) of CD5+ group was significantly worse than that of CD5- (28.1% vs 59.0%, P=0.028), while no significant difference was observed in overall survival (OS) (32.1% vs 59.9%, P=0.057). Compared with the two regimens, the 2-year survival rate of DA-EPOCH-R group was significantly superior than that of R-CHOP (63.6% vs 45.4%, P=0.034 for PFS; 67.4% vs 47.8%, P=0.038 for OS). Besides, CD5+ patients receiving DA-EPOCH-R had survival benefits compared with R-CHOP in PFS (85.7% vs 23.0%, P=0.029), but there was no statistical difference in OS (87.7% vs 34.4.0%, P=0.064). However, in DA-EPOCH-R protocol, there was no significant difference between CD5+ DHL (MYC/BCl2 and MYC/BCL6) and triple-hit lymphoma (P=0.776 for PFS; P=0.728 for OS). Multivariate analysis showed that CD5+ treatment regimen and disease stage were independent prognostic factors. CONCLUSION: Our retrospective study shows that CD5+ has a poorer prognosis than CD5- patients. Based on its improved lifetime and good tolerance on CD5+ patients, which is expected to become the first-line treatment for high-risk DLBCL types based on more clinical research.