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Abnormal visual experience during a sensitive period of development disrupts neuronal circuitry in the visual cortex and results in abnormal spatial vision or amblyopia. Here we examined whether playing video games can induce plasticity in the visual system of adults with amblyopia. Specifically 20 adults with amblyopia (age 15-61 y; visual acuity: 20/25-20/480, with no manifest ocular disease or nystagmus) were recruited and allocated into three intervention groups: action videogame group (n = 10), non-action videogame group (n = 3), and crossover control group (n = 7). Our experiments show that playing video games (both action and non-action games) for a short period of time (40-80 h, 2 h/d) using the amblyopic eye results in a substantial improvement in a wide range of fundamental visual functions, from low-level to high-level, including visual acuity (33%), positional acuity (16%), spatial attention (37%), and stereopsis (54%). Using a cross-over experimental design (first 20 h: occlusion therapy, and the next 40 h: videogame therapy), we can conclude that the improvement cannot be explained simply by eye patching alone. We quantified the limits and the time course of visual plasticity induced by video-game experience. The recovery in visual acuity that we observed is at least 5-fold faster than would be expected from occlusion therapy in childhood amblyopia. We used positional noise and modelling to reveal the neural mechanisms underlying the visual improvements in terms of decreased spatial distortion (7%) and increased processing efficiency (33%). Our study had several limitations: small sample size, lack of randomization, and differences in numbers between groups. A large-scale randomized clinical study is needed to confirm the therapeutic value of video-game treatment in clinical situations. Nonetheless, taken as a pilot study, this work suggests that video-game play may provide important principles for treating amblyopia, and perhaps other cortical dysfunctions. ClinicalTrials.gov NCT01223716.

To evaluate the optical performance of blue-light filtering spectacle lenses and investigate whether a reduction in blue light transmission affects visual performance and sleep quality. Experiment 1: The relative changes in phototoxicity, scotopic sensitivity, and melatonin suppression of five blue-light filtering plano spectacle lenses were calculated based on their spectral transmittances measured by a spectrophotometer. Experiment 2: A pseudo-randomized controlled study was conducted to evaluate the clinical performance of two blue-light filtering spectacle lenses (BF: blue-filtering anti-reflection coating; BT: brown-tinted) with a regular clear lens (AR) serving as a control. A total of eighty computer users were recruited from two age cohorts (young adults: 18-30 yrs, middle-aged adults: 40-55 yrs). Contrast sensitivity under standard and glare conditions, and colour discrimination were measured using standard clinical tests. After one month of lens wear, subjective ratings of lens performance were collected by questionnaire. All tested blue-light filtering spectacle lenses theoretically reduced the calculated phototoxicity by 10.6% to 23.6%. Although use of the blue-light filters also decreased scotopic sensitivity by 2.4% to 9.6%, and melatonin suppression by 5.8% to 15.0%, over 70% of the participants could not detect these optical changes. Our clinical tests revealed no significant decrease in contrast sensitivity either with (95% confidence intervals [CI]: AR-BT [-0.05, 0.05]; AR-BF [-0.05, 0.06]; BT-BF [-0.06, 0.06]) or without glare (95% CI: AR-BT [-0.01, 0.03]; AR-BF [-0.01, 0.03]; BT-BF [-0.02, 0.02]) and colour discrimination (95% CI: AR-BT [-9.07, 1.02]; AR-BF [-7.06, 4.46]; BT-BF [-3.12, 8.57]). Blue-light filtering spectacle lenses can partially filter high-energy short-wavelength light without substantially degrading visual performance and sleep quality. These lenses may serve as a supplementary option for protecting the retina from potential blue-light hazard. ClinicalTrials.gov NCT02821403.

Playing three-dimensional (3D) video games enhances stereo acuity (i.e., the precision of stereopsis) in young adults with normal vision Here we asked whether the improvement in stereoacuity was the result of a reduced disparity pedestal, as indicated by a decreased subjective depth bias (i.e., the accuracy of stereopsis). Twenty-one healthy young participants with normal vision and limited previous video game experience, none had played 3D video games, played first-person-shooter action stereoscopic 3D video games for a total of 40 h. Depth detection performance was measured using random dot stereograms before and after the video game intervention. We found that playing stereoscopic 3D video games boosts the precision, but not the accuracy of depth perception, suggesting that the enhanced stereoacuity did not result from reducing the effects of a disparity pedestal. These types of video games have potential therapeutic applications for improving stereo vision in patients with binocular vision anomalies.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette–Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7–73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4–95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9–68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 . In a single-arm phase 2 trial evaluating intravesical delivery of the oncolytic adenovirus cretostimogene grenadenorepvec with systemic anti-PD-1 in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ, the complete response rate at 12 months was 57.1%, meeting the primary endpoint.

Since the introduction of radical prostatectomy by Hugh Hampton Young in 1905, this surgery has undergone constant evolution. With increasing appreciation for the impact of functional preservation on cancer survivorship, urologists have been steadfast in their pursuit of precision surgery to eradicate cancer while maximally preserving the surrounding anatomical structures. In the 1990s and 2000s, the introduction of laparoscopic and robotic prostatectomy brought about welcome improvements including decreased intra-operative blood loss, decreased postoperative pain, shorter hospital length of stay, and faster recovery. Recognizing that focality of prostate cancer lends itself well to precision surgery, robotic surgeons have attempted to exploit the enhanced vision and dexterity provided by the instrument to further improve outcomes. Over the last decade, new techniques have been introduced to help reduce the incidence of incontinence and erectile dysfunction, the 2 most often encountered complications following prostatectomy.

The field of valleytronics has promised greater control of electronic and spintronic systems with an additional valley degree of freedom. However, conventional and two-dimensional valleytronic systems pose practical challenges in the utilization of this valley degree of freedom. Here we show experimental evidences of the valley effect in a bulk, ambient, and bias-free model system of Tin(II) sulfide. We elucidate the direct access and identification of different sets of valleys, based primarily on the selectivity in absorption and emission of linearly polarized light by optical reflection/transmission and photoluminescence measurements, and demonstrate strong optical dichroic anisotropy of up to 600% and nominal polarization degrees of up to 96% for the two valleys with band-gap values 1.28 and 1.48 eV, respectively; the ease of valley selection further manifested in their non-degenerate nature. Such discovery enables a new platform for better access and control of valley polarization. Valleytronics leverages the valley degree of freedom to engineer light-matter interaction. Here, the authors demonstrate a room temperature, bias-free valley effect in bulk SnS by means of spectroscopic measurements, previously unattainable using atomically thin transition metal dichalcogenides.

The response to neoadjuvant treatment can be used to stratify individuals with muscle-invasive bladder cancer according to their risk of progression, enabling bladder-sparing approaches for some — and heralding a shift from the existing one-size-fits-all approach.

Experience-dependent plasticity is closely linked with the development of sensory function; however, there is also growing evidence for plasticity in the adult visual system. This review re-examines the notion of a sensitive period for the treatment of amblyopia in the light of recent experimental and clinical evidence for neural plasticity. One recently proposed method for improving the effectiveness and efficiency of treatment that has received considerable attention is 'perceptual learning'. Specifically, both children and adults with amblyopia can improve their perceptual performance through extensive practice on a challenging visual task. The results suggest that perceptual learning may be effective in improving a range of visual performance and, importantly, the improvements may transfer to visual acuity. Recent studies have sought to explore the limits and time course of perceptual learning as an adjunct to occlusion and to investigate the neural mechanisms underlying the visual improvement. These findings, along with the results of new clinical trials, suggest that it might be time to reconsider our notions about neural plasticity in amblyopia.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

There is emerging evidence that the adaptive anti-tumor activity may be orchestrated by secondary lymphoid organ-like aggregates residing in the tumor microenvironment. Known as tertiary lymphoid structures, these lymphoid aggregates serve as key outposts for lymphocyte recruitment, priming and activation. They have been linked to favorable outcomes in many tumor types, and more recently, have been shown to be effective predictors of response to immune checkpoint blockade. We have previously described a 12-chemokine (12-CK) transcriptional score which recapitulates an overwhelming enrichment for immune-related and inflammation-related genes in colorectal carcinoma. Subsequently, the 12-CK score was found to prognosticate favorable survival in multiple tumors types including melanoma, breast cancer, and bladder cancer. In the current study, we summarize the discovery and validation of the 12-CK score in various tumor types, its relationship to TLSs found within the tumor microenvironment, and explore its potential role as both a prognostic and predictive marker in the treatment of various cancers.