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in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab.
In this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression.
ClinicalTrials.gov Identifier NCT03594747.
ClinicalTrials.gov Identifier NCT03594747.
RPE injury often induces epithelial to mesenchymal transition (EMT). Although RPE-EMT has been implicated in a variety of retinal diseases, including proliferative vitroretinopathy, neovascular and atrophic AMD, and diabetic retinopathy, it is not well-understood at the molecular level. To contribute to our understanding of EMT in human RPE, we performed a time-course transcriptomic analysis of human stem cell-derived RPE (hRPE) monolayers induced to undergo EMT using 2 independent, yet complementary, model systems.
EMT of human stem cell-derived RPE monolayers was induced by either enzymatic dissociation or modulation of TGF-β signaling. Transcriptomic analysis of cells at different stages of EMT was performed by RNA-sequencing, and select findings were confirmed by reverse transcription quantitative PCR and immunostaining. An ingenuity pathway analysis (IPA) was performed to identify signaling pathways and regulatory networks associated with EMT.
Proteocollagenolytic enzymatic dissociation and cotreatpathways defined by these studies may help to identify targets for the development of novel therapeutic targets for the treatment of retinal disease.
To examine location-specific retinal vascular changes in intermediate age-related macular degeneration (iAMD) using age-matched, high-density en face optical coherence tomography angiography (OCTA) cluster analysis.
En face OCTA images of the 6 × 6 mm macular area were retrospectively acquired from 60 iAMD eyes and 60 age-matched normal eyes and then subdivided into 126 × 126 (47.62 × 47.62 µm) grids within the superficial and deep vascular complex. Grid-wise vessel perfusion (VP) were compared between iAMD and normal eyes from the corresponding 10-yearly age cohort, forming difference plots. Difference plots were further separated by normative topographical map spatial clusters (C1-6), derived from normaldatabase eyes (n = 236, 20-81 years old).
Overall difference plots showed decreased VP in the superficial (-12.19%) and deep vascular complex (-6.44%) of iAMD compared to normal eyes (P < 0.0001 both comparisons). Cluster-based difference plots highlighted nonuniform changes in the superficial vascutocol of iAMD.In 1970, Masahiro Mori proposed the uncanny valley (UV), a region in a human-likeness continuum where an entity risks eliciting a cold, eerie, repellent feeling. Recent studies have shown that this feeling can be elicited by entities modeled not only on humans but also nonhuman animals. The perceptual and cognitive mechanisms underlying the UV effect are not well understood, although many theories have been proposed to explain them. To test the predictions of nine classes of theories, a within-subjects experiment was conducted with 136 participants. The theories' predictions were compared with ratings of 10 classes of stimuli on eeriness and coldness indices. One type of theory, configural processing, predicted eight out of nine significant effects. Atypicality, in its extended form, in which the uncanny valley effect is amplified by the stimulus appearing more human, also predicted eight. Threat avoidance predicted seven; atypicality, perceptual mismatch, and mismatch+ predicted six; category+, novelty avoidance, mate selection, and psychopathy avoidance predicted five; and category uncertainty predicted three. Empathy's main prediction was not supported. Given that the number of significant effects predicted depends partly on our choice of hypotheses, a detailed consideration of each result is advised. We do, however, note the methodological value of examining many competing theories in the same experiment.We address two questions concerning eye guidance during visual search in naturalistic scenes. First, search has been described as a task in which visual salience is unimportant. Here, we revisit this question by using a letter-in-scene search task that minimizes any confounding effects that may arise from scene guidance. Akt inhibitor Second, we investigate how important the different regions of the visual field are for different subprocesses of search (target localization, verification). In Experiment 1, we manipulated both the salience (low vs. high) and the size (small vs. large) of the target letter (a "T"), and we implemented a foveal scotoma (radius 1°) in half of the trials. In Experiment 2, observers searched for high- and low-salience targets either with full vision or with a central or peripheral scotoma (radius 2.5°). In both experiments, we found main effects of salience with better performance for high-salience targets. In Experiment 1, search was faster for large than for small targets, and high-salience helped more for small targets. When searching with a foveal scotoma, performance was relatively unimpaired regardless of the target's salience and size. In Experiment 2, both visual-field manipulations led to search time costs, but the peripheral scotoma was much more detrimental than the central scotoma. Peripheral vision proved to be important for target localization, and central vision for target verification. Salience affected eye movement guidance to the target in both central and peripheral vision. Collectively, the results lend support for search models that incorporate salience for predicting eye-movement behavior.