Single-digit Numbers Research Articles

Abstract 2688: The landscape of precision cancer combination therapy: a single-cell perspective

Abstract The availability of single-cell transcriptomics data opens new opportunities for rational design of combination cancer treatments in a systematic manner. Mining such data, we explore the landscape of optimal combination therapy targets in solid tumors (including brain, head and neck, melanoma, lung, breast and colon cancers). To this end, we developed MadHitter (https://github.com/ruppinlab/madhitter), which analyzes tumor single-cell transcriptomics data using combinatorial algorithms to identify precision combination of treatment targets that are predicted to maximize the killing of cancer cells while minimizing the killing of noncancerous ones. We started with a predefined set of 533 proteins that are lowly abundant across healthy tissues and thus may have low off-tumor targeting and toxicity if targeted via chimeric antigen receptors (CAR) T cell therapy. In most cancer types analyzed, we find that combinations composed of a single-digit number of targets are sufficient to kill at least 80% of the tumor cells while killing at most 10% of the non-tumor cells in each patient. We identify targets that are shared across datasets of the same cancer type (e.g., TNR) or across different cancer types (the SOX family, MAGE family, and KRT16). Next, we expanded our search for a set of 1269 known cell surface receptors, which may be precisely targeted by antibody or nanoparticles delivering a toxin into cells via receptor mediated endocytosis. The resulting optimal target sets are encouragingly also in the single-digit size. The gene PTPRZ1, a tyrosine phosphatase receptor, is frequently found in the optimal combinations for brain and head and neck cancers, and EGFR is a high-coverage target in multiple tumor types. Notably, requiring more stringent levels of cancer killing, the number of targets that need to be combined rises sharply in both search spaces described above. In sum, this analysis provides the first systematic characterization of potential combinatorial targets in solid tumors, uncovering promising future targets for both CAR therapy and conjugated toxin delivering antibodies and nanoparticles. Citation Format: Saba Ahmadi, Pattara Sukprasert, Rahulsimham Vegesna, Sanju Sinha, Natalie Artzi, Samir Khuller, Alejandro A. Schäffer, Eytan Ruppin. The landscape of precision cancer combination therapy: a single-cell perspective [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2688.

The Brave New Digital World: The Value of Published Work Today is Multifactorial; it is in the Heart of the Paper, not an Abstract Meaningless Single-Digit Number.

The Brave New Digital World: The Value of Published Work Today is Multifactorial; it is in the Heart of the Paper, not an Abstract Meaningless Single-Digit Number.

In Reply: Dismantling the Apocalypse Narrative: The Myth of the COVID-19 Stroke.

In Reply: Dismantling the Apocalypse Narrative: The Myth of the COVID-19 Stroke.

Modified Chorological Coded Data Compression Methodology for Wireless Sensor Networks

Wireless Sensor Network (WSN) is a fast evolving current technology which is being employed in various applications. Despite its wide usage, WSNs have a few challenges to overcome to be called as an ideal technology. Some of the challenges are battery life time, memory storage and deployment issues. Batteries are the primary source of power supply to WSN and one of the major challenges is the energy constraint. This paper aims to propose a few techniques to better the energy efficiency of the sensor networks by saving sensor energy using data compression methodology. In this paper, a modified chorological coded data compression methodology is proposed (MCDC). This algorithm deals with assigning the sequence value to the given input information. If the assigned sequence value is a double digit number, it is converted in to single digit number. Double digit numbers and single digit numbers are combined. Separate location tables are generated for all double digit and single digit numbers. This procedure continues until all the sequence values are changed in to single digit number. Then the final single digit is assign with an equivalent Sequence Code (SC). MCDC algorithm is compared with DELTA compression and RUNLENGTH compression and a better compression ratio was achieved when compared with DELTA compression and RUNLENGTH compression algorithms.

The comparative lyrics of Paranar, Mamoolanar and Marudan Ilanaganar are the external stories of the songs

288 Historical Notes on the 400 - Songs in Akanaguru Only 149 songs are featured. Of these, Paranar - 30 songs, Mamulanar - 27 songs, Madurai Maruthan Illanganar - 10 songs, only about near than half of the (67) songs have been sung. The other 82 songs were sung by 50 Poets (Akananur - 117 is not known by the name of the Poet). And they have all sung single-digit numbers. These are the above tips, these three poets’ high numbers of the Historical Notes sung in akapadals Why? Kurunthogai, in natrinai Than In akananuru Why is that number so high? Is there any relationship between the songs in Pattuppāṭṭu and this one? Such questions arise. The purpose of this article is to seek explanations for these questions.

Numerical Processing in the Stroop Task of Working Memory

Messages from different dimensions conveyed by a single-digit number are complex. Sometimes people need to focus on the most practical and relevant ones and ignore the others. We designed a working memory version of numerical Stroop task to figure out whether attended numerical information could be automatically encoded and kept in working memory system even when they are unrelated to the task. It turns out that irrelevant numerical information could be encoded in working memory and even interferes with physical judgments. However, in the similar procedures physical information didn’t show such power. The asymmetric results indicated that numerical information in the Stroop task of working memory enjoys distinct priority during processing.

Designing a Rich Numeracy Task in Early Childhood Mathematics Education: Teaching Addition in a Kindergarten in Macao

This paper presents an overview of the first cycle of collaborative action research of a kindergarten teacher who with the help of a university researcher, has designed a rich tool-based numeracy task for K3 children at a kindergarten in Macao. The rich numeracy task coupled with a tailor-made physical tool allows the children to investigate a model of addition with the manipulation of the critical selection of number cards by paying attention to a combination of corresponding numbers. Major data sources were documents, classroom observation, reflective dialogues between the two classroom teachers and with the university researcher. The results indicate that this rich tool-based task not only facilitates children’s numeracy development but also promotes the development of other domains, such as social and linguistic development. Mathematical concepts, such as sum of three single digit numbers, are prominently emerged in the implementation of the rich numeracy task. This first cycle illustrates that the purposive design of rich tasks, coupled with appropriate artefacts for kindergarten children, is beneficial for promoting children’s comprehensive development. It can also serve as an example to create rich numeracy tasks in early childhood mathematics education for kindergarten teachers to develop teaching strategies corresponding to the education reform in Macao.

The neurophysiological relationship between number anxiety and the EEG gamma-band

ABSTRACT The development of math anxiety is thought to originate at a young age, as a form of number anxiety, but has not been investigated extensively. Research has shown greater levels of EEG gamma-band activity are experienced during threat perception and attentional bias. This has been identified in high math anxious individuals when confronted with math-based tasks, but has not yet been explored for number anxiety specifically. Single-digit numbers and letters were presented to 15 high and 15 low math anxious participants, who were required to observe the stimuli. High math anxious participants displayed significantly greater levels of gamma activity during number observation compared to letter observation. Findings suggest high math anxious individuals may have a threat-related response to observation of simple numerical stimuli. Further behavioural investigations are needed, but high math anxious individuals may display avoidance towards number and math due to a threat response associated with increased gamma activity.

Distinct strategies for estimating the temporal average of numerical and perceptual information

Humans can estimate global trends in dynamic information presented either as perceptual features or as symbolic codes such as numbers. Previous studies on temporal statistics estimation have shown that observers judge the temporal average of visual attributes according to information from the last few frames of the presentation sequence (in what is referred to as the recency effect). Here, we investigated how humans estimate the temporal average of number vs. orientation using identical stimuli for the two tasks. In Experiment 1, a randomly-selected single-digit number was serially presented at orientations randomly varying over time. In Experiment 2, a texture comprising a random number of Gabor elements was shown at orientations randomly varying over time. In both experiments, observers judged the temporal averages of the numerical values and orientations in separate blocks. Results showed that observers judging the temporal average of orientation relied upon information from later frames as predicted by a typical model of perceptual decision making. By contrast, for the judgement of numerical values, we found that the impacts of each temporal frame were constant or varied little across temporal frames regardless of whether the numerical information was given as digits or by the number of texture elements. The results are interpreted as evidence that distinct computational strategies may be involved in estimating the temporal averages of perceptual features and numerical information.

Electric Field–Induced Release and Measurement (EFIRM): Characterization and Technical Validation of a Novel Liquid Biopsy Platform in Plasma and Saliva

Electric field-induced release and measurement (EFIRM) is a novel, plate-based, liquid biopsy platform capable of detecting circulating tumor DNA containing EGFR mutations directly from saliva and plasma in both early- and late-stage patients with non-small-cell lung cancer. We investigated the properties of the target molecule for EFIRM and determined that the platform preferentially detects single-stranded DNA molecules. We then investigated the properties of the EFIRM assay and determined the linearity, linear range, precision, and limit of detection for six different EGFR variants (the four most common g.Exon19del variants), p.T790M, and p.L858R). The limit of detection was in single-digit copy number for the latter two mutations, and the limit of detection for Exon19del was 5000 copies. Following these investigations, technical validations were performed for four separate EFIRM liquid biopsy assays, qualitative and quantitative assays for both saliva and plasma. We conclude that EFIRM liquid biopsy is an assay platform that interrogates a biomarker not targeted by any other extant platform (namely, circulating single-stranded DNA molecules). The assay has acceptable performance characteristics in both quantitative and qualitative assays on both saliva and plasma.

T28. BENEFITS AND HARMS OF ANTIPSYCHOTICS IN THE TREATMENT OF CHILDREN AND ADOLESCENTS WITH SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

BackgroundChildhood and adolescent schizophrenia is a severe and debilitating disorder associated with long-term impairments in functioning, poor physical health, and reduced life expectancy. Compared with adult-onset schizophrenia, childhood and adolescent schizophrenia may be a more severe disorder, negatively influencing social, cognitive and psychological development, educational achievements and life-long occupational functioning. Therefore, treatment of childhood and adolescent schizophrenia is highly important and presents a major therapeutic challenge. The aim of this systematic review and meta-analysis was to assess whether antipsychotics (APs) have different clinical benefits and harms profiles in acute treatment of childhood and adolescent schizophrenia.MethodsWe conducted systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) assessing efficacy and adverse effects of APs in acute childhood and adolescent schizophrenia to compare clinical benefits and harms. An electronic search was conducted without language restrictions using Embase, Scopus, MEDLINE/PubMed, the Cochrane library, and the US National Institutes of Health clinical trials registry (http://www.clinicaltrials.gov). The electronic search was supplemented by a hand search of reference lists of relevant studies and reviews. The primary efficacy outcome examined was treatment response. The primary safety/tolerability was assessed based on discontinuation due to adverse event.In order to visualize the risk and benefit tradeoff of each AP, risk ratios (RRs) were plotted on two-dimensional graph for the primary efficacy and safety/tolerability outcomes.ResultsTen studies were selected, comprising of 2,271 patients across eight active interventions (aripiprazole, asenapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) and placebo. The mean intervention duration was 6.4 weeks (range 6–8 weeks). Lurasidone, asenapine and risperidone had significantly higher response rate (RR = 1.54, 95% CI = 1.21 to 1.95, p<0.001; RR = 1.38, 95% CI = 1.02 to 1.85, p=0.035; and RR = 1.71, 95% CI = 1.39 to 2.11, p<0.001, respectively) compared with placebo.These three antipsychotics also had significant single digit numbers needed to treat (NNT = 5, 4, and 8, respectively). All APs did not significantly separate from placebo in discontinuation rate due to adverse event compared with placebo (RR = 0.47 to 5.42). Aripiprazole had the significant number needed to harm (NNH = 25). On a two-dimensional graph plot of efficacy and safety/tolerability, lurasidone showed the most desirable profile for the risk / benefit tradeoff balance among all antipsychotics.DiscussionResults from this meta-analysis illustrate that there are significant differences in benefits and harms among APs in the treatment of childhood and adolescent schizophrenia. Medications choice needs to be carefully evaluated to achieve optimal clinical benefit while minimizing burden of side effects for the patients.

Embodied numerical representations and their association with multi-digit arithmetic performance.

There is a well-documented association between fingers and numbers, which was claimed to stem from the use of finger-based strategies for counting and calculating during childhood. Recently, it has been argued that this may lead to a concomitant activation of finger-based alongside other numerical representations when encountering single-digit numbers. Indeed, the occurrence of such a co-activation is supported by observed influences of finger counting habits on different numerical tasks, including single-digit arithmetic problem solving. In this study, we pursued the question whether the influence of finger-based representations on arithmetic generalizes to multi-digit arithmetic by investigating the association between the recognition of canonical and non-canonical finger patterns and multi-digit arithmetic in adults. Results indicated that canonical finger-based numerical representations were significantly associated with addition performance only, whereas non-canonical finger-based representations were associated significantly with all four arithmetic operations. We argue that, because non-canonical patterns do not benefit from the iconicity of canonical patterns, their magnitude may need to be constructed through magnitude manipulation which may in turn increase associations with mental arithmetic. In sum, our findings provide converging evidence for a functional association between finger-based representations and arithmetic performance.

Game-Based Training to Promote Arithmetic Fluency

The research team designed and evaluated a mobile game to promote rapid retrieval of arithmetic facts among a group of children aged 7-8 years (n=97). The design of the game was based on principles drawn from research literature in mathematical cognition, game-based learning, and game design. The game trains basic number knowledge within a motivating context. It tested an implication of theory of automatization of arithmetic facts that training of recognition of multiples of single-digit numbers should lead to greater fluency in solving multiplication and division problems. A quasi-experimental design was employed to test whether the game improves retrieval of arithmetic facts. Children played the game in their classrooms for 20 minutes a day for 2 weeks. Comparisons between pre- and post-tests showed that the game playing group outperformed controls with a medium to large effect size (> 0.6). These results suggest an improvement in arithmetic fluency equivalent to around 7 months’ progress and provide rare empirical evidence supporting transfer of game-based training to a pencil-and-paper test. The findings are consistent with a connectionist theory of arithmetic skill, by showing that improved recognition of multiples contributes to multiplication and division skill. The theoretical and practical implications of these findings are discussed.

Aging effects on symbolic number comparison: No deceleration of numerical information retrieval but more conservative decision-making.

Whereas many cognitive tasks show pronounced aging effects, even in healthy older adults, other tasks seem more resilient to aging. A small number of recent studies suggests that number comparison is possibly one of the abilities that remain unaltered across the life span. We investigated the ability to compare single-digit numbers in young (19-39 years; n = 39) and healthy older (65-79 years; n = 39) adults in considerable detail, analyzing accuracy as well as mean and variance of their response time, together with several other well-established hallmarks of numerical comparison. Using a recent comprehensive process model that parsimoniously accounts quantitatively for many aspects of number comparison (Reike & Schwarz, 2016), we address two fundamental problems in the comparison of older to young adults in numerical comparison tasks: (a) to adequately correct speed measures for different levels of accuracy (older participants were significantly more accurate than young participants), and (b) to distinguish between general sensory and motor slowing on the one hand, as opposed to a specific age-related decline in the efficiency to retrieve and compare numerical magnitude representations. Our results represent strong evidence that healthy older adults compare magnitudes as efficiently as young adults, when the measure of efficiency is uncontaminated by strategic speed-accuracy trade-offs and by sensory and motor stages that are not related to numerical comparison per se. At the same time, older adults aim at a significantly higher accuracy level (risk aversion), which necessarily prolongs processing time, and they also show the well-documented general decline in sensory and/or motor functions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Characteristics of teaching and learning single-digit whole number multiplication in china: the case of the nine-times table

This study investigates the teaching and learning of single-digit whole number multiplication in China. Analysis of data from documents, classroom teaching, and semi-structured interviews revealed three salient characteristics of emphasizing oral calculation, calculation speed, and understanding across standards, textbook and classroom practices. It also showed how mathematics teachers enact these features in their teaching practice to help students develop their computational skills. The study particularly elaborates the role played by the nine-times table, or Chengfa Kou Jue Table (CKJ Table) in teaching practices, as well as how teachers treat memorization of CKJ and how understanding of operations contributes to their better understanding the relationship between the two in the teaching process.

Establishing and Running a Three-dimensional and Advanced Imaging Laboratory.

Multidetector CT technology has advanced during the past 2 decades from single-digit numbers of sections to 320-section CT scanners. The ability to perform three-dimensional (3D) postprocessing of acquired data has accompanied this technical progress. Multiple considerations are involved in developing and deploying a 3D and advanced imaging laboratory to provide postprocessing for both CT and MRI examinations. Establishing and running a 3D laboratory requires administrators to buy into the process and also requires regular input from radiologists and other stakeholders. Technologists with prior 3D experience are rare, and extensive immersive training is typically required. Laboratory space and equipment must be maintained and updated regularly to continue to meet stakeholders' needs. Postprocessing protocols must be established and reviewed periodically. Quality control is also necessary to ensure that postprocessing outputs adhere to the protocols. Laboratory technologists can also provide postprocessing support for research examinations and can lend their technical expertise to research projects. Regular review of laboratory productivity is essential to ensure longevity and availability of necessary resources (human, environmental, and technical). As the technologies for the imaging equipment, the picture archiving and communication system, and postprocessing continue to advance, the role of the 3D laboratory will also evolve to include other services. This evolution will affect ongoing training of technologists, as well as the requirements when new technologists are hired. The 3D laboratory is often positioned to take on novel technology and augment radiologists' workflow as new modalities and techniques enter the clinical workflow. ©RSNA, 2018.

Tracking the continuous dynamics of numerical processing: A brief review and editorial

Many recent studies in numerical cognition have moved beyond the use of purely chronometric techniques in favor of methods which track the continuous dynamics of numerical processing. Two examples of such techniques include eye tracking and hand tracking (or computer mouse tracking). To reflect this increased concentration on continuous methods, we have collected a group of 5 articles that utilize these techniques to answer some contemporary questions in numerical cognition. In this editorial, we discuss the two paradigms and provide a brief review of some of the work in numerical cognition that has profited from the use of these techniques. For both methods, we discuss the past research through the frameworks of single digit number processing, multidigit number processing, and mental arithmetic processing. We conclude with a discussion of the papers that have been contributed to this special section and point to some possible future directions for researchers interested in tracking the continuous dynamics of numerical processing.

P111. Exploring the effects of transcranial direct current stimulation on cognitive control training

Introduction The dorsolateral prefrontal cortex (dlPFC) is a brain structure responsible for working memory performance and cognitive control (CC). CC, critically underlying goal-directed behaviour, has been shown to be impaired in depression and to be associated with reduced activity of the dlPFC ( Fitzgerald and Laird, 2008 ). Transcranial direct current stimulation (tDCS) of this brain area can modify the neuronal response and therefore CC, and has already shown potential for CC malleability: both amelioration as well as impairment ( [Wolkenstein and Plewnia, 2013] , [Plewnia et al., 2015a] , [Plewnia et al., 2015b] ). Within this study series we systematically investigate the effects of tDCS on a CC training in healthy participants by varying stimulation parameters regarding intensity, polarity and laterality. Methods Over the course of 8 sessions within 4 weeks and a follow-up session 3 months later participants perform a modified adaptive paced auditory serial addition task (PASAT) during which they hear a series of single digit numbers and are instructed to add the most recent digit to the third to last digit (n + n − 2). Digit presentation speed is adapted to performance with the goal to challenge CC by inducing stress and frustration during the experiment. TDCS is applied for 19 min during each training session. The first two test groups receive stimulation of the left dlPFC with 1 and 2 mA respectively, the third and fourth group are treated likewise except for stimulation being shifted to the right dlPFC. Each group is furthermore divided into subjects receiving either anodal, cathodal or sham tDCS. Preliminary results and conclusion Within the first study group, subjects who received anodal stimulation (1 mA) to the left dlPFC showed significant performance gains during PASAT training compared to cathodal (1 mA) and sham stimulation, suggesting that improvement was aided by plasticity enhancement of CC induced by tDCS. Outlook Data for the remaining three groups (2 mA, left dlPFC; 1 and 2 mA, right dlPFC) is currently being gathered. Collection will be finished by the end of the year, ensuing final analysis of the comprehensive data set by the beginning of 2018.

Setting, rheology and packing density of biomass fly ash/Portland cement mixtures

Paper deals with rheological properties and packing density of fresh mixtures of Portland cement and biomass fly ash. Water demand of paste of normal consistency increases with increase of replacement level of biomass fly ash for Portland cement. Up to 5 wt. % contents of biomass fly ash yield stress and plastic viscosity values decrease, while at contents higher than 5 wt. %, the opposite trend was revealed. Biomass fly ash compared to Portland cement has proportionally lower content of particles with size of tens and first single digit numbers of microns. Deficiency in this region at higher contents of biomass fly ash in cement mixtures results in deflection from ideal packing density curve.

Incidence and Mortality Patterns of Acute Myeloid Leukemia in Belgrade, Serbia (1999⁻2013).

Introduction: To assess incidence and mortality trends of acute myeloid leukemia (AML) in Belgrade (Serbia) in a 15-year period (from 1999 to 2013). Material and Methods: Data were obtained from the Cancer Registry of Serbia, Institute of Public Health of Serbia. Standardized incidence and mortality rates per 100,000 inhabitants were calculated by direct standardization method using World Standard Population. Analysis of raw data indicated single-digit numbers per year and per 5-year age cohorts. Therefore, we merged years of diagnosis to three-year intervals, creating so-called “moving averages”. We also merged study population to 10-year age cohorts. Results: Both incidence and mortality rates increased with age, i.e., the lowest rates were observed in the youngest age groups and the highest rates were observed in oldest age groups. In all age groups, except the youngest (15–24 years), AML incidence was statistically significantly higher in men compared with women. Average age-adjusted incidence was 2.73/100,000 (95% confidence interval (CI) 2.28–3.71). Average age-adjusted mortality was 1.81/100,000 (95% CI 1.30–2.26). Overall, there were no significant changes in incidence trend. Age-adjusted incidence rates had increasing tendency among men aged 65–74 years (B = 0.80, standard error (SE) = 0.11; p = 0.005) and in total population aged 65–74 years (B = 0.41, SE = 0.09; p = 0.023). Increasing tendency in incidence of AML among women was observed in age group >75 years (B = 0.63, SE = 0.14; p = 0.019). No changes of mortality trend were observed. Conclusion: There was no significant change in trends of AML from 1999 to 2013 in the population of Belgrade.