Infliximab for treatment-refractory transverse myelitis following immune therapy and radiation.

BackgroundNeurologic toxicities with immune therapy are rare, but can cause devastating and often permanent injury when they occur. Although there is increasing interest in the potential synergism between immune therapy and radiation, it is possible that such combinations may lead to a greater number or increased severity of immune-related adverse events. We present here a case of extensive and progressive transverse myelitis following combined therapy, which did not improve until treatment with infliximab. This case highlights the unmet need for treatment of adverse events that are refractory to consensus recommendations, and may ultimately require further study and incorporation into future published guidelines.Case presentationWe report a case of a 68-year-old with metastatic melanoma, who developed transverse myelitis in the setting of immune checkpoint blockade and spinal irradiation for vertebral metastases. Despite management according to published consensus guidelines: cessation of immune therapy, high-dose steroids, and plasmapheresis, he continued to deteriorate neurologically, and imaging revealed a progressive and ascending transverse myelitis. The patient was then treated with infliximab, and demonstrated dramatic imaging and modest clinical improvement following the first treatment cycle.ConclusionsThis is the first report describing the successful use of infliximab in immune therapy and radiation-related transverse myelitis that was not responding to recommended therapy. Evaluation of additional treatment options such as infliximab for high-grade immune-related neurologic toxicities is warranted, and may be needed earlier in the disease process to prevent significant morbidity. The adverse effects of immune therapy when used in combination with radiation also require further investigation

Targeting Microglia-Synapse Interactions in Alzheimer's Disease

In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be "resting" (i.e., inactive), are instead strongly implicated in dynamic and plastic processes. Indeed, there is an intimate relationship between microglia and neurons at synapses which modulates activity-dependent functional and structural plasticity through the release of cytokines and growth factors. These roles are indispensable to brain development and cognitive function. Therefore, approaches aimed at maintaining the ramified state of microglia might be critical to ensure normal synaptic plasticity and cognition. On the other hand, inflammatory signals associated with Alzheimer's disease are able to modify the ramified morphology of microglia, thus leading to synapse loss and dysfunction, as well as cognitive impairment. In this context, we highlight microglial TREM2 and CSF1R as emerging targets for disease-modifying therapy in Alzheimer's disease (AD) and other neurodegenerative disorders

Restriction Spectrum Imaging Differentiates True Tumor Progression From Immune-Mediated Pseudoprogression: Case Report of a Patient With Glioblastoma.

Immunotherapy is increasingly used in the treatment of glioblastoma (GBM), with immune checkpoint therapy gaining in popularity given favorable outcomes achieved for other tumors. However, immune-mediated (IM)-pseudoprogression is common, remains poorly characterized, and renders conventional imaging of little utility when evaluating for treatment response. We present the case of a 64-year-old man with GBM who developed pathologically proven IM-pseudoprogression after initiation of a checkpoint inhibitor, and who subsequently developed true tumor progression at a distant location. Based on both qualitative and quantitative analysis, we demonstrate that an advanced diffusion-weighted imaging (DWI) technique called restriction spectrum imaging (RSI) can differentiate IM-pseudoprogression from true progression even when conventional imaging, including standard DWI/apparent diffusion coefficient (ADC), is not informative. These data complement existing literature supporting the ability of RSI to estimate tumor cellularity, which may help to resolve complex diagnostic challenges such as the identification of IM-pseudoprogression

Stationary waves and slowly moving features in the night upper clouds of Venus

At the cloud top level of Venus (65-70 km altitude) the atmosphere rotates 60 times faster than the underlying surface, a phenomenon known as superrotation. Whereas on Venus's dayside the cloud top motions are well determined and Venus general circulation models predict a mean zonal flow at the upper clouds similar on both day and nightside, the nightside circulation remains poorly studied except for the polar region. Here we report global measurements of the nightside circulation at the upper cloud level. We tracked individual features in thermal emission images at 3.8 and 5.0 $\mathrm{\mu m}$ obtained between 2006 and 2008 by the Visible and Infrared Thermal Imaging Spectrometer (VIRTIS-M) onboard Venus Express and in 2015 by ground-based measurements with the Medium-Resolution 0.8-5.5 Micron Spectrograph and Imager (SpeX) at the National Aeronautics and Space Administration Infrared Telescope Facility (NASA/IRTF). The zonal motions range from -110 to -60 m s$^{-1}$, consistent with those found for the dayside but with larger dispersion. Slow motions (-50 to -20 m s$^{-1}$) were also found and remain unexplained. In addition, abundant stationary wave patterns with zonal speeds from -10 to +10 m s$^{-1}$ dominate the night upper clouds and concentrate over the regions of higher surface elevation.Comment: 15 pages, 4 figures, 6 supplementary figure

Distribution of Relaxation Times Based on Lasso Regression: A Tool for High-Resolution Analysis of IMPS Data in Photoelectrochemical Systems

Intensity-modulated photocurrent spectroscopy (IMPS) has been largely employed in semiconductor characterization for solar energy conversion devices to probe the operando behavior with widely available facilities. However, the implementation of IMPS data analysis to complex structures, whether based on the physical rate constant model (RCM) or the assumption-free distribution of relaxation times (DRT), is generally limited to a semi-quantitative description of the charge carrier kinetics of the system. In this study, a new algorithm for the analysis of IMPS data is developed, providing unprecedented time resolution to the investigation of μs to s charge carrier dynamics in semiconductor-based systems used in photoelectrochemistry and photovoltaics. The algorithm, based on the previously developed DRT analysis, is herein modified with a Lasso regression method and available to the reader free of charge. A validation of this new algorithm is performed on a α-Fe2O3 photoanode for photoelectrochemical water splitting, identified as a standard platform in the field, highlighting multiple potential-dependent charge transfer paths, otherwise hidden in the conventional IMPS data analysis

Venus O2 night glow observations with VIRTSI/Venus Express

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Two-year observations of the Jupiter polar regions by JIRAM on board Juno

We observed the evolution of Jupiter's polar cyclonic structures over two years between February 2017 and February 2019, using polar observations by the Jovian InfraRed Auroral Mapper, JIRAM, on the Juno mission. Images and spectra were collected by the instrument in the 5‐μm wavelength range. The images were used to monitor the development of the cyclonic and anticyclonic structures at latitudes higher than 80° both in the northern and the southern hemispheres. Spectroscopic measurements were then used to monitor the abundances of the minor atmospheric constituents water vapor, ammonia, phosphine and germane in the polar regions, where the atmospheric optical depth is less than 1. Finally, we performed a comparative analysis with oceanic cyclones on Earth in an attempt to explain the spectral characteristics of the cyclonic structures we observe in Jupiter's polar atmosphere

Photoelectrochemical Valorization of Biomass Derivatives with Hematite Photoanodes Modified by Cocatalysts

The solar-driven oxidation of biomass to valuable chemicals is rising as a promising anodic reaction in photoelectrochemical cells, replacing the sluggish oxygen evolution reaction and improving the added value of the energy conversion process. Herein, the photooxidation of 5-hydroxymethylfurfural into furan dicarboxylic acid (FDCA) is performed in basic aqueous environment (borate buffer, pH 9.2), with the addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as redox mediator. Because of its good stability, cost-effectiveness, and nontoxicity, titanium-modified hematite (Ti:Fe2O3) photoanodes are investigated to this aim, and their performance is tuned by engineering the semiconductor surface with a thin layer of Co-based cocatalysts, i.e., cobalt iron oxide (CoFeO x ) and cobalt phosphate (CoPi). Interestingly, the electrode modified with CoPi shows improved efficiency and selectivity toward the final product FDCA The source of this enhancement is correlated to the effect of the cocatalyst on the charge carrier dynamics, which is investigated by electrochemical impedance spectroscopy and intensity-modulated photocurrent spectroscopy analysis. In addition, the results of the latter are interpreted through a novel approach called Lasso distribution of relaxation time, revealing that CoPi cocatalyst is effective in the suppression of the recombination processes and in the enhancement of direct hole transfer to TEMPO