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Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors--cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2)--and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors., Introduction Glioblastoma (GBM) is the most common and lethal brain cancer in adults and one of the least immunogenic tumors (1). Recent work has revealed striking immune dysregulation and functional [...]

A new global dataset of annually averaged ultrafine particle (UFP) concentrations at the Earth's surface for the years 2015–2017 has been developed through numerical simulations using the ECHAM/MESSy Atmospheric Chemistry model (EMAC). We present total and size-resolved concentrations along with their interannual variability. Size distributions of emitted particles from the contributing source sectors have been derived based on literature reports. The model results of UFP concentrations are evaluated using particle size distribution and particle number concentration measurements from available datasets and the literature. While we obtain reasonable agreement between the model results and observations (logarithmic-scale correlation of r=0.76 for non-remote, polluted regions), the highest values of observed, street-level UFP concentrations are systematically underestimated, whereas in rural environments close to urban areas the model generally overestimates observed UFP concentrations. As the relatively coarse global model does not resolve concentration gradients in urban centres and industrial UFP hotspots, high-resolution data of anthropogenic emissions are used to account for such differences in each model grid box, obtaining UFP concentrations with unprecedented 0.1∘×0.1∘ horizontal resolution at the Earth's surface. This observation-guided downscaling further improves the agreement with observations, leading to an increase in the logarithmic-scale correlation between observed and simulated UFP concentrations to r=0.84 in polluted environments (and 0.95 in all regions), a decrease in the root mean squared logarithmic error (from 0.57 to 0.43), and removal of discrepancies associated with air quality and population density gradients within the model grid boxes. The model results are made publicly available for studies on public health and other impacts of atmospheric UFPs, as well as for intercomparison with other regional and global models and datasets. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the effectiveness of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) with three, monthly, intravitreal bevacizumab (IVB) injections for refractory diabetic macular edema. Materials and Methods: This was a prospective, randomized, comparative, interventional study. Forty-four patients were enrolled and randomized in two groups. Twenty-two eyes enrolled in Group I received three IVB injections at monthly interval. Twenty-two eyes were enrolled in Group II which underwent PPV with ILM removal. The primary outcomes measured were: (1) Best corrected logMAR visual acuity (BCVA) using Snellen′s visual acuity chart. (2) Central macular thickness (CMT) on optical coherence tomography. The secondary outcome measures were: Complication rates like (1) progression of lens opacities, (2) high intraocular pressure needing further treatment/procedure, (3) development of vitreous hemorrhage related to the procedure employed, (4) retinal detachment and (5) severe inflammation/endophthalmitis. Results: In Group I (IVB): 3 (13.6%) eyes showed no change in BCVA; 3 (13.6%) eyes reported decrease in BCVA and 16 (72.8%) eyes showed improvement in BCVA; (P = 0.0181). In Group II (PPV): 4 (18.2%) eyes showed no change in BCVA; 5 (22.7%) eyes showed decrease and 13 (59.1%) eyes showed improvement in BCVA (P = 0.0281). Mean decrease in CMT in IVB group was 108.45 μ, whereas mean decrease in CMT in PPV group was 161.36 μ. No major complications were seen in either group. Conclusion: Posttreatment decrease in CMT was more in PPV group and vision improvement more in IVB group. However, no statistically significant difference between the two methods was found.