Distance Estimation Is Influenced by Encoding Conditions

Background:\ud It is well established that foveating a behaviorally relevant part of the visual field improves localization performance as compared to the situation where the gaze is directed elsewhere. Reduced localization performance in the peripheral encoding conditions has been attributed to an eccentricity-dependent increase in positional uncertainty. It is not known, however, whether and how the foveal and peripheral encoding conditions can influence spatial interval estimation. In this study we compare observers' estimates of a distance between two co-planar dots in the condition where they foveate the two sample dots and where they fixate a central dot while viewing the sample dots peripherally.\ud \ud Methodology/Principal Findings:\ud Observers were required to reproduce, after a short delay, a distance between two sample dots based on a stationary reference dot and a movable mouse pointer. When both sample dots are foveated, we find that the distance estimation error is small but consistently increases with the dots-separation size. In comparison, distance judgment in peripheral encoding condition is significantly overestimated for smaller separations and becomes similar to the performance in foveal trials for distances from 10 to 16 degrees.\ud \ud Conclusions/Significance:\ud Although we find improved accuracy of distance estimation in the foveal condition, the fact that the difference is related to the reduction of the estimation bias present in the peripheral conditon, challenges the simple account of reducing the eccentricity-dependent positional uncertainty. Contrary to this, we present evidence for an explanation in terms of neuronal populations activated by the two sample dots and their inhibitory interactions under different visual encoding conditions. We support our claims with simulations that take into account receptive fields size differences between the two encoding conditions

Viral load dynamics in intubated patients with COVID-19 admitted to the intensive care unit

Background: Prolonged viral RNA detection in respiratory samples from patients with COVID-19 has been described, but the clinical relevance remains unclear. We studied the dynamics of SARS-CoV-2 on a group and individual level in intubated ICU patients. Methods: In a cohort of 86 patients, we analysed SARS-CoV-2 RT-PCR results on nasopharyngeal and sputum samples (obtained as part of clinical care twice a week) according to time after intubation. Subsequently, we performed survival analyses. Results: 870 samples were tested by RT-PCR. Overall viral load was highest in the first week (median nasopharynx 3.5. IQR 1.5-4.3; median sputum 4.3. IQR 3.3-5.6) and decreased over time. In 20% of patients a relapsing pattern was observed. Nasopharyngeal and sputum PCR status on day 14 was not significantly associated with survival up to day 60 in this small cohort. Conclusion: In general SARS-CoV-2 RNA levels in respiratory samples in patients with severe COVID-19 decease alter the first week after intubation, but individual SARS-CoV-2 RNA levels can show a relapsing pattern. Larger studies are needed to address the association of clearance of SARS-CoV-2 RNA from respiratory samples with survival, because we observed a trend towards better survival in patients with early clearance from sputum. (C) 2021 The Authors. Published by Elsevier Inc

Germline variant affecting p53β isoforms predisposes to familial cancer

Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition

Retinotopic Mapping of Categorical and Coordinate Spatial Relation Processing in Early Visual Cortex

Spatial relations are commonly divided in two global classes. Categorical relations concern abstract relations which define areas of spatial equivalence, whereas coordinate relations are metric and concern exact distances. Categorical and coordinate relation processing are thought to rely on at least partially separate neurocognitive mechanisms, as reflected by differential lateralization patterns, in particular in the parietal cortex. In this study we address this textbook principle from a new angle. We studied retinotopic activation in early visual cortex, as a reflection of attentional distribution, in a spatial working memory task with either a categorical or a coordinate instruction. Participants were asked to memorize a dot position, with regard to a central cross, and to indicate whether a subsequent dot position matched the first dot position, either categorically (opposite quadrant of the cross) or coordinately (same distance to the centre of the cross). BOLD responses across the retinotopic maps of V1, V2, and V3 indicate that the spatial distribution of cortical activity was different for categorical and coordinate instructions throughout the retention interval; a more local focus was found during categorical processing, whereas focus was more global for coordinate processing. This effect was strongest for V3, approached significance in V2 and was absent in V1. Furthermore, during stimulus presentation the two instructions led to different levels of activation in V3 during stimulus encoding; a stronger increase in activity was found for categorical processing. Together this is the first demonstration that instructions for specific types of spatial relations may yield distinct attentional patterns which are already reflected in activity early in the visual cortex

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Germline variant affecting p53β isoforms predisposes to familial cancer

Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management