Alterations in treatment intensity and decreased use of radiation therapy have reduced the risk of late treatment-related death in long-term survivors of childhood cancer.
In the 1960s, fewer than ...half the children in whom cancer was diagnosed were still alive 5 years later.
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Now, more than 83% of patients with a childhood cancer in the United States become 5-year survivors of the disease.
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As a result, in 2013 it was estimated that there were more than 420,000 survivors of childhood cancer in the United States and that by the year 2020 this number would surpass 500,000.
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Increased success in the treatment of childhood cancers has been achieved through the systematic conduct of clinical trials to assess the efficacy of multimodal approaches involving combination chemotherapy, . . .
Neurosteroids are endogenous modulators of neuronal excitability and nervous system development and are being developed as anesthetic agents and treatments for psychiatric diseases. While gamma ...amino-butyric acid Type A (GABAA) receptors are the primary molecular targets of neurosteroid action, the structural details of neurosteroid binding to these proteins remain ill defined. We synthesized neurosteroid analogue photolabeling reagents in which the photolabeling groups were placed at three positions around the neurosteroid ring structure, enabling identification of binding sites and mapping of neurosteroid orientation within these sites. Using middle-down mass spectrometry (MS), we identified three clusters of photolabeled residues representing three distinct neurosteroid binding sites in the human α1β3 GABAA receptor. Novel intrasubunit binding sites were identified within the transmembrane helical bundles of both the α1 (labeled residues α1-N408, Y415) and β3 (labeled residue β3-Y442) subunits, adjacent to the extracellular domains (ECDs). An intersubunit site (labeled residues β3-L294 and G308) in the interface between the β3(+) and α1(-) subunits of the GABAA receptor pentamer was also identified. Computational docking studies of neurosteroid to the three sites predicted critical residues contributing to neurosteroid interaction with the GABAA receptors. Electrophysiological studies of receptors with mutations based on these predictions (α1-V227W, N408A/Y411F, and Q242L) indicate that both the α1 intrasubunit and β3-α1 intersubunit sites are critical for neurosteroid action.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in ...whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.
Young children with limited knowledge of formal mathematics can intuitively perform basic arithmetic‐like operations over nonsymbolic, approximate representations of quantity. However, the ...algorithmic rules that guide such nonsymbolic operations are not entirely clear. We asked whether nonsymbolic arithmetic operations have a function‐like structure, like symbolic arithmetic. Children (n = 74 4‐ to ‐8‐year‐olds in Experiment 1; n = 52 7‐ to 8‐year‐olds in Experiment 2) first solved two nonsymbolic arithmetic problems. We then showed children two unequal sets of objects, and asked children which of the two derived solutions should be added to the smaller of the two sets to make them “about the same.” We hypothesized that, if nonsymbolic arithmetic follows similar function rules to symbolic arithmetic, then children should be able to use the solutions of nonsymbolic computations as inputs into another nonsymbolic problem. Contrary to this hypothesis, we found that children were unable to reliably do so, suggesting that these solutions may not operate as independent representations that can be used inputs into other nonsymbolic computations. These results suggest that nonsymbolic and symbolic arithmetic computations are algorithmically distinct, which may limit the extent to which children can leverage nonsymbolic arithmetic intuitions to acquire formal mathematics knowledge.
Children live in a dynamic environment, in which objects continually change locations and move into and out of occlusion. Children must therefore rely on working memory to store information from the ...environment and to update those stored representations as the environment changes. Previous work suggests that the ability to store information in working memory increases through infancy and childhood. However, less is known about the development of the ability to update stored information. Participants were 63 4-7-year-old children (37 girls; 34 caregivers completed optional demographic forms, and those children were reported as Asian one, Asian/White four, Black one, Middle East/Arab one, or White 27; two were Hispanic/Latinx). We asked children to keep track of arrays of hidden items that either remained where they were hidden (static trials) or swapped locations (swap trials) and then to identify from two alternatives which item was hidden in a particular location. We manipulated the number of items in the arrays and the number of times the items swapped locations in order to investigate how increasing storage and updating load impacted children's performance. We found that children's ability to update working memory developed significantly across our age range. Updating appeared to impose a significant one-time cost to working memory performance, regardless of the number of times items swapped. Our results yield new insights into the developmental trajectories of storage and updating in working memory across early childhood.
•Children can reason by exclusion to infer unknown identities in working memory.•The use of reasoning by exclusion also poses additional cognitive demands.•The cognitive cost of reasoning by ...exclusion eases with development.
Reasoning by exclusion allows us to form more complete representations of our environments, “filling in” inaccessible information by ruling out known alternatives. In two experiments (Experiment 1: N = 34 4- to 6-year-olds; Experiment 2: N = 85 4- to 8-year-olds), we examined children’s ability to use reasoning by exclusion to infer the identity of an unknown object and investigated the role of working memory in this ability. Children were asked to encode a set of objects that were then hidden, and after a brief retention interval children were asked to select the identity of the object hidden in one of the locations from two alternatives. On some trials, all the images were visible during encoding, so selecting the correct identity when probed required successful working memory storage and retrieval. On other trials, all but one of the images was visible during encoding, so selecting the correct identity when probed also required maintaining a representation of an unknown object in working memory and then using reasoning by exclusion to fill in the missing information retroactively to complete that representation by ruling out known alternatives. To investigate the working memory cost of exclusive reasoning, we manipulated the working memory demands of the task. Our results suggest that children can use reasoning by exclusion to retroactively assign an identity to an incomplete object representation at least by 4 years of age but that this ability incurs some cognitive cost, which eases with development. These results provide new insights into children’s representational capacities and on the foundational building blocks of fully developed exclusive reasoning.
Children can represent the approximate quantity of sets of items using the Approximate Number System (ANS), and can perform arithmetic-like operations over ANS representations. Previous work has ...shown that the representational precision of the ANS develops substantially during childhood. However, less is known about the development of the
operational
precision of the ANS. We examined developmental change in the precision of the solutions to two non-symbolic arithmetic operations in 4-6-year-old U.S. children. We asked children to represent the quantity of an occluded set (Baseline condition), to compute the sum of two sequentially occluded arrays (Addition condition), or to infer the quantity of an addend after observing an initial array and then the array incremented by the unknown addend (Unknown-addend condition). We measured the precision of the solutions of these operations by asking children to compare their solutions to visible arrays, manipulating the ratio between the true quantity of the solution and the comparison array. We found that the precision of ANS representations that were not the result of operations (in the Baseline condition) was higher than the precision of solutions to ANS operations (in the Addition and Unknown-addend conditions). Further, we found that precision in the Baseline and Addition conditions improved significantly between 4 and 6 years, while precision in the Unknown-Addend condition did not. Our results suggest that ANS operations may inject “noise” into the representations they operate over, and that the development of the precision of different operations may follow different trajectories in childhood.
Since manual detection of brain metastases (BMs) is time consuming, studies have been conducted to automate this process using deep learning. The purpose of this study was to conduct a systematic ...review and meta-analysis of the performance of deep learning models that use magnetic resonance imaging (MRI) to detect BMs in cancer patients. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted until 30 September 2022. Inclusion criteria were: patients with BMs; deep learning using MRI images was applied to detect the BMs; sufficient data were present in terms of detective performance; original research articles. Exclusion criteria were: reviews, letters, guidelines, editorials, or errata; case reports or series with less than 20 patients; studies with overlapping cohorts; insufficient data in terms of detective performance; machine learning was used to detect BMs; articles not written in English. Quality Assessment of Diagnostic Accuracy Studies-2 and Checklist for Artificial Intelligence in Medical Imaging was used to assess the quality. Finally, 24 eligible studies were identified for the quantitative analysis. The pooled proportion of patient-wise and lesion-wise detectability was 89%. Articles should adhere to the checklists more strictly. Deep learning algorithms effectively detect BMs. Pooled analysis of false positive rates could not be estimated due to reporting differences.
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