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These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the congress.

Many immune checkpoint inhibitors (ICIs) have been approved on the basis of tumor response end points in nonrandomized trials, including objective response rate (ORR) and duration and depth of response. We aimed to assess the validity of these end points as surrogate end points for overall survival (OS) in patients with advanced solid tumors treated with ICIs at trial and treatment arm levels.

ICI trials in advanced solid cancers published between January 1, 2000, and March 31, 2020, were included. Correlations between ORR, durable response (DR) of ≥ 6 months, complete response (CR), and OS were assessed for treatment comparisons (trial-level) and for patients receiving ICI (arm-level), using weighted linear regression.

Sixty-three trials were eligible, including 58 randomized controlled trials and 20 nonrandomized controlled trials (78 ICI arms and 30,815 patients). The majority were phase III (63%), and OS was the most common primary end point (40%). In relative treatment comparisons, correlations betscreening activity of novel agents in early-phase nonrandomized trials.We extend the blindspot model for self-supervised denoising to handle Poisson-Gaussian noise and introduce an improved training scheme that avoids hyperparameters and adapts the denoiser to the test data. Self-supervised models for denoising learn to denoise from only noisy data and do not require corresponding clean images, which are difficult or impossible to acquire in some application areas of interest such as low-light microscopy. We introduce a new training strategy to handle Poisson-Gaussian noise which is the standard noise model for microscope images. Our new strategy eliminates hyperparameters from the loss function, which is important in a self-supervised regime where no ground truth data is available to guide hyperparameter tuning. We show how our denoiser can be adapted to the test data to improve performance. Our evaluations on microscope image denoising benchmarks validate our approach.

Inhibitory neurons in the spinal dorsal horn can be classified based on expression of neurochemical marker genes. However, these marker genes are often expressed throughout the central nervous system, which poses challenges for manipulating genetically identified spinal neurons without undesired off-target effects.

We investigated whether

, previously identified as a highly selective marker of dynorphin-lineage neurons in the dorsal horn, is expressed in other locations within the adult mouse spinal cord, dorsal root ganglia (DRG), or brain. In addition, we sought to molecularly characterize

expressing dorsal horn neurons and investigate whether the disruption of

gene expression affects sensitivity to itch or pain.

In situ hybridization experiments assessed

mRNA expression in the adult mouse spinal cord, DRG, and brain, and its colocalization with

and

in dorsal horn neurons. Knockout mice lacking

expression were compared with littermate controls to assess sensitivity to chloroquine-induced itch and dry skin-mediated chronic itch, as well as heat, cold, or mechanical stimuli.

is selectively expressed in dynorphin-lineage neurons in lamina I-III of the adult mouse spinal cord but not in the brain or DRG. Spinal

-expressing neurons are inhibitory neurons that also express the transcription factor

and the cGMP-dependent phosphodiesterase

knockout mice did not exhibit altered responses to itch or pain.

The selective expression of

within a subpopulation of inhibitory dorsal horn neurons may yield a means to selectively manipulate inhibitory signaling at the level of the spinal cord without effects on the brain.

The selective expression of Gucy2d within a subpopulation of inhibitory dorsal horn neurons may yield a means to selectively manipulate inhibitory signaling at the level of the spinal cord without effects on the brain.Due to the specific hydrothermal conditions of dry-hot valleys, temperature changes caused by the development of large-scale hydropower projects may be more extreme than they are in other regions. In this study, we analyzed these temperature changes at four hydropower stations in both dry-hot and non-dry-hot valleys. Based on the calculated relative temperatures of the downstream river and the areas surrounding the reservoirs, we employed two indices to quantify the influence of the reservoirs on the temperatures of these two regions the downstream river temperature change and the reservoir effect change intensity. Our results are as follows (a) In the downstream rivers, the temperature regulation effect was more pronounced in the wet season; in the regions surrounding the reservoirs, the temperature regulation effect was more pronounced in the dry season. (b) The downstream river temperature in both the dry-hot and wet-hot valleys exhibited noticeable warming in both the wet and dry seasons, while the cold-dry valley was characterized by cooling in the dry season and warming in the wet season. With the exception of the Liyuan station (where the influence of the reservoir on the downstream temperatures only extended to a distance of 9 km from the dam) during the dry season, the existence of the hydropower stations affected the temperatures of the entire downstream region. (c) For the areas surrounding the reservoir, the presence of a hydropower station mainly caused the temperatures in the dry-hot valleys to rise and the temperatures in the non-dry-hot valleys to decrease.Spatial hot spots of COVID-19 infections and fatalities are observed at places exposed to high levels of air pollution across many countries. This study empirically investigates the relationship between exposure to air pollutants that is, sulfur dioxide, nitrogen dioxide, and particulate matter (SO2, NO2, and PM10) and COVID-19 infection at the smallest administrative level (ward) of Mumbai City in India. The paper explores two hypotheses COVID-19 infection is associated with air pollution; the pollutants act as determinants of COVID-19 deaths. Kriging is used to assess the spatial variations of air quality using pollution data, while information on COVID-19 are retrieved from the database of Mumbai municipality. Annual average of PM10 in Mumbai over the past 3 years is much higher than the WHO specified standard across all wards; further, suburbs are more exposed to SO2, and NO2 pollution. Bivariate local indicator of spatial autocorrelation finds significant positive relation between pollution and COVID-19 infected cases in certain suburban wards. Spatial Auto Regressive models suggest that COVID-19 death in Mumbai is distinctly associated with higher exposure to NO2, population density and number of waste water drains. If specific pollutants along with other factors play considerable role in COVID-19 infection, it has strong implications for any mitigation strategy development with an objective to curtail the spreading of the respiratory disease. These findings, first of its kind in India, could prove to be significant pointers toward disease alleviation and better urban living.Impossible figures represent the world in ways it cannot be. DNA Repair inhibitor From the work of M. C. Escher to any popular perception textbook, such experiences show how some principles of mental processing can be so entrenched and inflexible as to produce absurd and even incoherent outcomes that could not occur in reality. However, impossible experiences of this sort are mostly limited to visual perception; are there "impossible figures" for other sensory modalities? Here, we import a known magic trick into the laboratory to report and investigate an impossible experience for somatosensation-one that can be physically felt. We show that, even under full-cue conditions with objects that can be freely inspected, subjects can be made to experience a single object alone as feeling heavier than a group of objects that includes the single object as a member-an impossible and phenomenologically striking experience of weight. Moreover, we suggest that this phenomenon-a special case of the size-weight illusion-reflects a kind of "anti-Bayesian" perceptual updating that amplifies a challenge to rational models of perception and cognition.Astrocytes are dynamic cells residing in the central nervous system exhibiting many diverse functions. Astrocytes quickly change and present unique phenotypes in response to injury or disease. Here, we briefly summarize recent information regarding astrocyte morphology and function and provide brief insight into their phenotypic changes following injury or disease. We also present the utility of in vitro astrocyte cultures and present recent advances in biomaterial development that enable better recapitulation of their in vivo behavior and morphology.Mycobacterium tuberculosis (Mtb) is an intracellular human pathogen that has evolved to survive in a nutrient limited environment within the host for decades. Accordingly, Mtb has developed strategies to acquire scarce nutrients and the mycobacterial transporter systems provide an important route for the import of key energy sources. However, the physiological role of the Mtb transporters and their substrate preference(s) are poorly characterised. Previous studies have established that the Mtb UspC solute-binding domain recognises amino- and phosphorylated-sugars, indicating that the mycobacterial UspABC transporter plays a key role in the import of peptidoglycan precursors. Herein, we have used a wide array of approaches to investigate the role of UspABC in Mycobacterium smegmatis by analysis of mutant strains that either lack the solute binding domain ΔuspC or the entire transport complex ΔuspABC. Analysis of mycobacterial transcripts shows that the uspABC system is functionally expressed in mycobacteria as a contiguous reading frame. Topology mapping confirms an Nin-Cin orientation of the UspAB integral membrane spanning domains. Phenotypic microarray profiling of commercially available sugars suggests, unexpectedly, that the uspC and ΔuspABC mutants had different carbon utilisation profiles and that neither strain utilised glucose-1-phosphate. Furthermore, proteomics analysis showed an alteration in the abundance of proteins involved in sugar and lipid metabolism, crucial for cell envelope synthesis, and we propose that UspABC has an important role in determining the interplay between these pathways.

Coronavirus disease 2019 (COVID-19) has had a global effect on the training of residents of medicine because of what has been required in the pandemic. The field of oncology has not been spared, as prepandemic training schedules have not been available for residents. We conducted an online survey to understand the effect of the pandemic and the effect of online teaching schedules as a measure to help residents of oncology in their training.

An online survey consisting of 31 questions was sent through various social media platforms based on the training pattern before the onset of COVID-19, effect of the pandemic on educational activities, and the effect of online academic activities on residency training and learning. The survey addressed the need for online academics as an alternate mode of teaching. The survey was left open for a period of 4 weeks with participation requests from the various branches of oncology, including radiation, surgical and medical oncology, onco-anesthesia, palliative oncology, neuro-oncology, and so forth.