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Exposure to ozone (O3) is associated with stroke incidence and mortality. However, whether long-term exposure to O3 is associated with post-stroke neurological disability remains unknown. This study investigated the relationship based on the longitudinal analysis of China National Stroke Screening Survey (CNSSS), which included 65,778 records of stroke patients. All of the analyzed patients were followed-up at least twice. Stroke disability was assessed using the modified Rankin scale (mRS). Long-term exposure was assessed by the peak-season or annual mean of maximum 8-h O3 concentrations for 365 days before the mRS measurement. We used fixed-effect models to evaluate the associations between O3 and mRS score, with adjustment for multiple confounders, and found a 10 µg/m3 increase in peak-season O3 concentration was associated with a 0.0186 (95% confidence interval [CI] 0.0115–0.0256) increment in the mRS score. The association was robust in various subpopulations. For secondary outcomes, for each 10 µg/m3 increment in peak-season O3, the odds ratio of an increased mRS score (vs. unchanged or decreased mRS score) increased by 23% (95% CI 9–37%). A nonlinear analysis showed a sublinear association between O3 exposure and risk for post-stroke disability. A saturation effect was observed at an O3 concentration of more than ~120 μg/m3. Our study adds to evidence that long-term exposure to O3 increases the risk of neurological disability after stroke.

Resistance to Immune Checkpoint Blockade (ICB) constitutes the current limiting factor for the optimal implementation of this novel therapy, which otherwise demonstrates durable responses with acceptable toxicity scores. This limitation is exacerbated by a lack of robust biomarkers. In this study, we have dissected the basal TME composition at the gene expression and cellular levels that predict response to Nivolumab and prognosis. BCR, TCR and HLA profiling were employed for further characterization of the molecular variables associated with response. The findings were validated using a single-cell RNA-seq data of metastatic melanoma patients treated with ICB, and by multispectral immunofluorescence. Finally, machine learning was employed to construct a prediction algorithm that was validated across eight metastatic melanoma cohorts treated with ICB. Using this strategy, we have unmasked a major role played by basal intratumoral Plasma cells expressing high levels of IGKC in efficacy. IGKC, differentially expressed in good responders, was also identified within the Top response-related BCR clonotypes, together with IGK variants. These results were validated at gene, cellular and protein levels; CD138+ Plasma-like and Plasma cells were more abundant in good responders and correlated with the same RNA-seq-defined fraction. Finally, we generated a 15-gene prediction model that outperformed the current reference score in eight ICB-treated metastatic melanoma cohorts. The evidenced major contribution of basal intratumoral IGKC and Plasma cells in good response and outcome in ICB in metastatic melanoma is a groundbreaking finding in the field beyond the role of T lymphocytes.

Previous studies have reported that intra-urban variability of NO2 concentrations is even higher than inter-urban variability. In recent years, an increasing number of studies have developed satellite-derived land use regression (LUR) models to predict ground-level NO2 concentrations, though only a few have been conducted at a city scale. In this study, we developed a satellite-derived LUR model to predict seasonal NO2 concentrations at a city scale by including satellite-retrieved NO2 tropospheric column density, population density, traffic indicators, and NOx emission data. The R2 of model fitting and 10-fold cross validation were 0.70 and 0.61 for the satellite-derived seasonal LUR model, respectively. The satellite-based LUR model captured seasonal patterns and fine gradients of NO2 variations at a 100 m × 100 m resolution and demonstrated that NO2 pollution in winter is 1.46 times higher than that in summer. NO2 concentrations declined significantly with increasing distance from roads and with increasing distance from the city center. In Suzhou, 84% of the total population lived in areas with NO2 concentrations exceeding the annual-mean standard at 40 μg/m3 in 2014. This study demonstrated that satellite-retrieved data could help increase the accuracy and temporal resolution of the traditional LUR models at a city scale. This application could support exposure assessment at a high resolution for future epidemiological studies and policy development pertaining to air quality control.

It is well recognized that exposure to fine particulate matter (PM2.5) affects health adversely, yet few studies from South America have documented such associations due to the sparsity of PM2.5 measurements. Lima’s topography and aging vehicular fleet results in severe air pollution with limited amounts of monitors to effectively quantify PM2.5 levels for epidemiologic studies. We developed an advanced machine learning model to estimate daily PM2.5 concentrations at a 1 km2 spatial resolution in Lima, Peru from 2010 to 2016. We combined aerosol optical depth (AOD), meteorological fields from the European Centre for Medium-Range Weather Forecasts (ECMWF), parameters from the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), and land use variables to fit a random forest model against ground measurements from 16 monitoring stations. Overall cross-validation R2 (and root mean square prediction error, RMSE) for the random forest model was 0.70 (5.97 μg/m3). Mean PM2.5 for ground measurements was 24.7 μg/m3 while mean estimated PM2.5 was 24.9 μg/m3 in the cross-validation dataset. The mean difference between ground and predicted measurements was −0.09 μg/m3 (Std.Dev. = 5.97 μg/m3), with 94.5% of observations falling within 2 standard deviations of the difference indicating good agreement between ground measurements and predicted estimates. Surface downwards solar radiation, temperature, relative humidity, and AOD were the most important predictors, while percent urbanization, albedo, and cloud fraction were the least important predictors. Comparison of monthly mean measurements between ground and predicted PM2.5 shows good precision and accuracy from our model. Furthermore, mean annual maps of PM2.5 show consistent lower concentrations in the coast and higher concentrations in the mountains, resulting from prevailing coastal winds blown from the Pacific Ocean in the west. Our model allows for construction of long-term historical daily PM2.5 measurements at 1 km2 spatial resolution to support future epidemiological studies.