ABSTRACT
Purpose: This study was conducted to reexamine the question of whether children treated for anisometropic amblyopia have contour integration deficits. To do so, we used psychophysical methods that require global contour processing while minimizing the influence of low-level deficits: visibility, shape perception, and positional uncertainty. Methods: Thirteen children with anisometropic amblyopia (age: 10.1 ± 1.8 years) and thirteen visually normal children (age: 10.8 ± 2.0 years) participated in this study. The stimuli were closed figures made up of Gabor patches either in noise or on a blank field. The contrast thresholds to detect a circular contour on a blank field, as well as the thresholds of aspect ratio and contour element number to discriminate a circular or elliptical contour in noise, were measured at Gabor spatial frequencies of 1.5, 3, and 6 cpd for amblyopic eyes (AEs), fellow eyes (FEs), and normal control eyes. Visual acuities and contrast sensitivity functions for AEs and FEs and the Randot stereoacuity were measured before testing. Results: The AEs showed contrast deficits and degraded shape perception compared to the FEs at higher spatial frequencies (6 cpd). When the influence of abnormal contrast sensitivity and shape perception were minimized, the AEs showed contour integration deficits at spatial frequencies 3 and 6 cpd. These deficits were not related to basic losses in contrast sensitivity and acuity, stereoacuity, and visual crowding. Besides, no significant difference was found between the fellow eyes of the amblyopic children and the normal control eyes in the performance of contour integration. Conclusion: After eliminating or compensating for the low-level deficits, children treated for anisometropic amblyopia still show contour integration deficits, primarily at higher spatial frequencies, which might reflect the deficits in global processing caused by amblyopia. Contour integration deficits are likely independent of spatial vision deficits. Refractive correction and/or occlusion therapies may not be sufficient to fully restore contour integration deficits, which indicates the need for the development of clinical treatments to recover these deficits.
ABSTRACT
Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer due to its lack of treatment options. Patients with TNBC frequently develop resistance to chemotherapy. As epigenetic-based antineoplastic drugs, histone deacetylase inhibitors (HDACis) have achieved particular efficacy in lymphoma but are less efficacious in solid tumors, and the resistance mechanism remains poorly understood. In this study, the GSE129944 microarray dataset from the Gene Expression Omnibus database was downloaded, and fold changes at the transcriptome level of a TNBC line (MDA-MB-231) after treatment with belinostat were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify the critical biological processes. Construction and analysis of the protein-protein interaction (PPI) network were performed to screen candidate genes related to cancer prognosis. A total of 465 DEGs were identified, including 240 downregulated and 225 upregulated genes. The cytokine-cytokine receptor pathway was identified as being significantly changed. Furthermore, the expression of CXCL1 was implicated as a favorable factor in the overall survival of breast cancer patients. With in vitro approaches, we also showed that belinostat could induce the expression of CXCL1 in another 2 TNBC cell lines (BT-549 and HCC-1937). We speculate that belinostat-induced CXCL1 expression could be one of the results of the stress clone evolution of cells after HDACi treatment. These findings provide new insights into clone evolution during HDACi treatment, which might guide us to a novel perspective that various mutation-targeted treatments should be implemented during the whole treatment cycle.
