Awareness of the process and limitations involved in search filter development is essential to make an informed decision on the applicability and validity of search filters. The findings of this review indicate a considerable agenda for future research, in particular, to improve the quality of reporting of search filters and to inform users on their use and application. Based on the review, guidance in the appraisal process of search filters is given in the form of a checklist.

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In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility. We demonstrate that fascin is not detectable in normal colonic epithelium, but is dramatically up-regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could participate in tumor invasive behavior, we developed a cell culture model to examine the effect of fascin expression on the adhesive interactions, invasiveness, and differentiation of colonic epithelial cells. We report marked effects on the organization of cell-surface protrusions, actin cytoskeleton, and focal adhesions in the absence of alterations in the protein levels of the major components of these structures. These effects correlate with alterations in cell movements on two-dimensional matrix, and increased invasiveness in three-dimensional matrix. The cells also show increased proliferation and decreased capacity for normal glandular differentiation in collagen gels. We propose that up-regulation of fascin, by promoting the formation of protrusive, actin-based, cell-motility structures, could be a significant component in the acquisition of invasive phe- Epithelial cell differentiation is fundamentally influenced by cell-matrix and cell-cell interactions. [1][2][3] In colonic epithelial cells, both the integrin and cadherin superfamilies of adhesion molecules are important contributors to the establishment of cell polarity and epithelial cell differentiation, and have been shown to play a role in the control of colorectal differentiation in tumor cells. 4,5 This is partly achieved through the formation of intracellular protein assemblies that anchor cytoskeletal actin filaments at defined areas within the cell membrane. In epithelial cells, these zones correspond to integrin-dependent focal adhesions and cadherin-containing adherens junctions and desmosomes. 6 These assemblies also function as important links in the integration of multiple cell signaling pathways. 3 Cell-matrix and cell-cell adhesive interactions normally stabilize the epithelial cell layer and maintain the cells in a nonmigratory state. However, the malignant conversion of epithelial cells involves a phenotypic switch to a migratory state that enables tumor invasion beyond the basement membrane and metastasis. The process of cell migration is poorly understood in epithelial cells, but studies in many types of carcinoma cells have documented increased formation of cell protrusions at cell margins, release of cell-cell contacts, and group movement of sheets of cells. In the models of cell motility that have been developed from studies of fibroblasts, protru...

IMPORTANCE Binocular amblyopia treatment using contrast-rebalanced stimuli showed promise in laboratory studies and requires clinical trial investigation in a home-based setting.OBJECTIVE To compare the effectiveness of a binocular video game with a placebo video game for improving visual functions in older children and adults. DESIGN, SETTING, AND PARTICIPANTSThe Binocular Treatment of Amblyopia Using Videogames clinical trial was a multicenter, double-masked, randomized clinical trial. Between March 2014 and June 2016, 115 participants 7 years and older with unilateral amblyopia (amblyopic eye visual acuity, 0.30-1.00 logMAR; Snellen equivalent, 20/40-20/200) due to anisometropia, strabismus, or both were recruited. Eligible participants were allocated with equal chance to receive either the active or the placebo video game, with minimization stratified by age group (child, age 7 to 12 years; teenager, age 13 to 17 years; and adult, 18 years and older).INTERVENTIONS Falling-blocks video games played at home on an iPod Touch for 1 hour per day for 6 weeks. The active video game had game elements split between eyes with a dichoptic contrast offset (mean [SD] initial fellow eye contrast, 0.23 [0.14]). The placebo video game presented identical images to both eyes. MAIN OUTCOMES AND MEASURESChange in amblyopic eye visual acuity at 6 weeks. Secondary outcomes included compliance, stereoacuity, and interocular suppression. Participants and clinicians who measured outcomes were masked to treatment allocation. RESULTSOf the 115 included participants, 65 (56.5%) were male and 83 (72.2%) were white, and the mean (SD) age at randomization was 21.5 (13.6) years. There were 89 participants (77.4%) who had prior occlusion. The mean (SD) amblyopic eye visual acuity improved 0.06 (0.12) logMAR from baseline in the active group (n = 56) and 0.07 (0.10) logMAR in the placebo group (n = 59). The mean treatment difference between groups, adjusted for baseline visual acuity and age group, was −0.02 logMAR (95% CI, −0.06 to 0.02; P = .25). Compliance with more than 25% of prescribed game play was achieved by 36 participants (64%) in the active group and by 49 (83%) in the placebo group. At 6 weeks, 36 participants (64%) in the active group achieved fellow eye contrast greater than 0.9 in the binocular video game. No group differences were observed for any secondary outcomes. Adverse effects included 3 reports of transient asthenopia. CONCLUSIONS AND RELEVANCEThe specific home-based binocular falling-blocks video game used in this clinical trial did not improve visual outcomes more than the placebo video game despite increases in fellow eye contrast during game play. More engaging video games with considerations for compliance may improve effectiveness.