European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.Fil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: von Karsa, Lawrence. International Agency for Research on Cancer; FranciaFil: Patrick, J.. NHS Cancer Screening Programmes Sheffield; Reino Unido. University of Oxford; Reino UnidoFil: Segnan, N.. International Agency for Research on Cancer; Francia. AO Città della Salute e della Scienza di Torino; ItaliaFil: Atkin, W.. Imperial College London; Reino UnidoFil: Halloran, S.. University of Surrey; Reino UnidoFil: Saito, H.. National Cancer Centre; JapónFil: Sauvaget, C.. International Agency for Research on Cancer; FranciaFil: Scharpantgen, A.. Ministry of Health; LuxemburgoFil: Schmiegel, W.. Ruhr-Universität Bochum; AlemaniaFil: Senore, C.. AO Città della Salute e della Scienza di Torino; ItaliaFil: Siddiqi, M.. Cancer Foundation of India; IndiaFil: Sighoko, D.. University of Chicago; Estados Unidos. Formerly International Agency for Research on Cancer; FranciaFil: Smith, R.. American Cancer Society; Estados UnidosFil: Smith S.. University Hospitals Coventry & Warwickshire NHS Trust; Reino UnidoFil: Suchanek, S.. Charles University; República ChecaFil: Suonio, E.. International Agency for Research on Cancer; FranciaFil: Tong, W.. Chinese Academy of Sciences; República de ChinaFil: Törnberg, S.. Stockholm Gotland Regional Cancer Centre. Department of Cancer Screening; SueciaFil: Van Cutsem, E.. Katholikie Universiteit Leuven; BélgicaFil: Vignatelli, L.. Agenzia Sanitaria e Sociale Regionale; ItaliaFil: Villain, P.. University of Oxford; Reino UnidoFil: Voti, L.. Formerly International Agency for Research on Cancer; Francia. University of Miami; Estados UnidosFil: Watanabe, H.. Niigata University; JapónFil: Watson, J.. University of Oxford; Reino UnidoFil: Winawer, S.. Memorial Sloan–Kettering Cancer Center; Estados UnidosFil: Young, G.. Flinders University. Gastrointestinal Services; AustraliaFil: Zaksas, V.. State Patient Fund; LituaniaFil: Zappa, M.. Cancer Prevention and Research Institute; ItaliaFil: Valori, R.. NHS Endoscopy; Reino Unid

The influence of spatial pattern on visual short-term memory for contrast

Several psychophysical studies of visual short-term memory (VSTM) have shown high-fidelity storage capacity for many properties of visual stimuli. On judgments of the spatial frequency of gratings, for example, discrimination performance does not decrease significantly, even for memory intervals of up to 30 s. For other properties, such as stimulus orientation and contrast, however, such “perfect storage” behavior is not found, although the reasons for this difference remain unresolved. Here, we report two experiments in which we investigated the nature of the representation of stimulus contrast in VSTM using spatially complex, two-dimensional random-noise stimuli. We addressed whether information about contrast per se is retained during the memory interval by using a test stimulus with the same spatial structure but either the same or the opposite local contrast polarity, with respect to the comparison (i.e., remembered) stimulus. We found that discrimination thresholds got steadily worse with increasing duration of the memory interval. Furthermore, performance was better when the test and comparison stimuli had the same local contrast polarity than when they were contrast-reversed. Finally, when a noise mask was introduced during the memory interval, its disruptive effect was maximal when the spatial configuration of its constituent elements was uncorrelated with those of the comparison and test stimuli. These results suggest that VSTMfor contrast is closely tied to the spatial configuration of stimuli and is not transformed into a more abstract representation

Illusory Stimuli Can Be Used to Identify Retinal Blind Spots

Background. Identification of visual field loss in people with retinal disease is not straightforward as people with eye disease are frequently unaware of substantial deficits in their visual field, as a consequence of perceptual completion ("filling-in'') of affected areas. Methodology. We attempted to induce a compelling visual illusion known as the induced twinkle after-effect (TwAE) in eight patients with retinal scotomas. Half of these patients experience filling-in of their scotomas such that they are unaware of the presence of their scotoma, and conventional campimetric techniques can not be used to identify their vision loss. The region of the TwAE was compared to microperimetry maps of the retinal lesion. Principal Findings. Six of our eight participants experienced the TwAE. This effect occurred in three of the four people who filled-in their scotoma. The boundary of the TwAE showed good agreement with the boundary of lesion, as determined by microperimetry. Conclusion. For the first time, we have determined vision loss by asking patients to report the presence of an illusory percept in blind areas, rather than the absence of a real stimulus. This illusory technique is quick, accurate and not subject to the effects of filling-in

The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function of viral components versus the cellular defenses. Non-coding RNAs (ncRNAs) are important cellular modulators, either promoting or preventing the progression of viral infections. Among these ncRNAs, the long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators of the cellular response during infection of human host cells by single stranded RNA viruses. However, the role of host lncRNAs in the infection by human RNA coronaviruses such as SARS-CoV-2 remains uncharacterized. Methods: In the present work, we have performed a transcriptomic study of a cohort of patients with different SARS-CoV-2 viral load and analyzed the involvement of lncRNAs in supporting regulatory networks based on their interaction with RNA-binding proteins (RBPs). Results: Our results revealed the existence of a SARS-CoV-2 infection-dependent pattern of transcriptional up-regulation in which specific lncRNAs are an integral component. To determine the role of these lncRNAs, we performed a functional correlation analysis complemented with the study of the validated interactions between lncRNAs and RBPs. This combination of in silico functional association studies and experimental evidence allowed us to identify a lncRNA signature composed of six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, and U62317.2 - associated with the regulation of SARS-CoV-2 infection. Conclusions: We propose a competition mechanism between the viral RNA genome and the regulatory lncRNAs in the sequestering of specific RBPs that modulates the interferon response and the regulation of RNA surveillance by nonsense-mediated decay (NMD)

A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases

Short-Term Memory Trace in Rapidly Adapting Synapses of Inferior Temporal Cortex

Visual short-term memory tasks depend upon both the inferior temporal cortex (ITC) and the prefrontal cortex (PFC). Activity in some neurons persists after the first (sample) stimulus is shown. This delay-period activity has been proposed as an important mechanism for working memory. In ITC neurons, intervening (nonmatching) stimuli wipe out the delay-period activity; hence, the role of ITC in memory must depend upon a different mechanism. Here, we look for a possible mechanism by contrasting memory effects in two architectonically different parts of ITC: area TE and the perirhinal cortex. We found that a large proportion (80%) of stimulus-selective neurons in area TE of macaque ITCs exhibit a memory effect during the stimulus interval. During a sequential delayed matching-to-sample task (DMS), the noise in the neuronal response to the test image was correlated with the noise in the neuronal response to the sample image. Neurons in perirhinal cortex did not show this correlation. These results led us to hypothesize that area TE contributes to short-term memory by acting as a matched filter. When the sample image appears, each TE neuron captures a static copy of its inputs by rapidly adjusting its synaptic weights to match the strength of their individual inputs. Input signals from subsequent images are multiplied by those synaptic weights, thereby computing a measure of the correlation between the past and present inputs. The total activity in area TE is sufficient to quantify the similarity between the two images. This matched filter theory provides an explanation of what is remembered, where the trace is stored, and how comparison is done across time, all without requiring delay period activity. Simulations of a matched filter model match the experimental results, suggesting that area TE neurons store a synaptic memory trace during short-term visual memory

Prospects in Analytical Atomic Spectrometry

Tendencies in five main branches of atomic spectrometry (absorption, emission, mass, fluorescence and ionization spectrometry) are considered. The first three techniques are the most widespread and universal, with the best sensitivity attributed to atomic mass spectrometry. In the direct elemental analysis of solid samples, the leading roles are now conquered by laser-induced breakdown and laser ablation mass spectrometry, and the related techniques with transfer of the laser ablation products into inductively-coupled plasma. Advances in design of diode lasers and optical parametric oscillators promote developments in fluorescence and ionization spectrometry and also in absorption techniques where uses of optical cavities for increased effective absorption pathlength are expected to expand. Prospects for analytical instrumentation are seen in higher productivity, portability, miniaturization, incorporation of advanced software, automated sample preparation and transition to the multifunctional modular architecture. Steady progress and growth in applications of plasma- and laser-based methods are observed. An interest towards the absolute (standardless) analysis has revived, particularly in the emission spectrometry.Comment: Proofread copy with an added full reference list of 279 citations. A pdf version of the final published review may be requested from Alexander Bol'shakov <[email protected]

Neural Correlates of Visual Motion Prediction

Predicting the trajectories of moving objects in our surroundings is important for many life scenarios, such as driving, walking, reaching, hunting and combat. We determined human subjects’ performance and task-related brain activity in a motion trajectory prediction task. The task required spatial and motion working memory as well as the ability to extrapolate motion information in time to predict future object locations. We showed that the neural circuits associated with motion prediction included frontal, parietal and insular cortex, as well as the thalamus and the visual cortex. Interestingly, deactivation of many of these regions seemed to be more closely related to task performance. The differential activity during motion prediction vs. direct observation was also correlated with task performance. The neural networks involved in our visual motion prediction task are significantly different from those that underlie visual motion memory and imagery. Our results set the stage for the examination of the effects of deficiencies in these networks, such as those caused by aging and mental disorders, on visual motion prediction and its consequences on mobility related daily activities

Role of miR-2392 in driving SARS-CoV-2 infection

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans

Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease

To better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host–microbiome–pathogen interactions