ARHGAP4 as a Prognostic Biomarker for Colon Liver Metastases After Surgical Resection.

BACKGROUND/AIM: To select and stratify patients for optimal treatment plans is challenging. Identification of cancer-related biomarkers that serve as predictors for prognosis and treatment response is essential to better predict treatment outcome and find future targets for therapy. Previous data has suggested ARHGAP4 as a relevant biomarker in colorectal cancer (CRC). The purpose of this study was to assess how ARHGAP4 expression affected patients undergoing surgery for colon liver metastasis (CLM) in terms of overall survival (OS). PATIENTS AND METHODS: A total of 251 patients undergoing resection of CLM from 2006 to 2017 were included. Corresponding resected tumor specimens were examined for ARHGAP4 expression levels by immunohistochemistry (IHC). The correlation between ARHGAP4 expression and postoperative survival was analyzed. RESULTS: High expression levels of ARHGAP4 were seen in 60% of patients. High expression levels of ARHGAP4 were correlated with adverse prognosis after hepatectomy due to CLM. Survival data generated using Cox proportional hazard model showed a statistically significant difference between high and low ARHGAP4 expression groups by univariate (HR=1.5, 95% CI=1.1-2.2) and multivariate (HR=1.5, 95% CI=1.0-2.1) analysis. In multivariate Cox regression, high ARHGAP4 expression, preoperative CEA levels and presence of vascular invasion by pathological examinations were independent predictive factors of overall survival. CONCLUSION: ARHGAP4 is a novel prognostic biomarker after resection of CLM.

L-type Amino Acid Transporter 1 as a Therapeutic Target in Pancreatic Cancer.

Metabolic rewiring is a key feature of cancer cells to support the demands of growth and proliferation. The metabolism of amino acids is altered in many cancers, including pancreatic cancer. The cellular uptake of amino acids is regulated by amino acid transporters, such as L-type amino acid transporter 1 (LAT1). Accumulating evidence suggests that LAT1 is overexpressed in pancreatic cancer and confers a poor prognosis. Here we discuss the prospects of utilizing LAT1 as a novel target for pancreatic cancer therapy.

Surveillance after resection of pancreatic ductal adenocarcinoma: How to do it and what are the benefits?

BACKGROUND AND OBJECTIVE: Surveillance following resection with curative intent of pancreatic cancer varies widely, and supporting evidence is limited. Recurrence is although frequent, not at least during the first 2 years. Surveillance may be costly, but evidence on how this influences overall survival is not fully elucidated. METHODS, RESULTS: There are reports implying that signs of biological recurrence (increasing CA 19-9) precede radiologically demonstrated recurrence by months. CONCLUSIONS: The possibility of initiating salvage therapy earlier is discussed, potentially based on improved future biomarker panels.

Neurocognitive mechanisms of co-occurring math difficulties in dyslexia: Differences in executive function and visuospatial processing.

Children with dyslexia frequently also struggle with math. However, studies of reading disability (RD) rarely assess math skill, and the neurocognitive mechanisms underlying co-occurring reading and math disability (RD+MD) are not clear. The current study aimed to identify behavioral and neurocognitive factors associated with co-occurring MD among 86 children with RD. Within this sample, 43% had co-occurring RD+MD and 22% demonstrated a possible vulnerability in math, while 35% had no math difficulties (RD-Only). We investigated whether RD-Only and RD+MD students differed behaviorally in their phonological awareness, reading skills, or executive functions, as well as in the brain mechanisms underlying word reading and visuospatial working memory using functional magnetic resonance imaging (fMRI). The RD+MD group did not differ from RD-Only on behavioral or brain measures of phonological awareness related to speech or print. However, the RD+MD group demonstrated significantly worse working memory and processing speed performance than the RD-Only group. The RD+MD group also exhibited reduced brain activations for visuospatial working memory relative to RD-Only. Exploratory brain-behavior correlations along a broad spectrum of math ability revealed that stronger math skills were associated with greater activation in bilateral visual cortex. These converging neuro-behavioral findings suggest that poor executive functions in general, including differences in visuospatial working memory, are specifically associated with co-occurring MD in the context of RD. RESEARCH HIGHLIGHTS: Children with reading disabilities (RD) frequently have a co-occurring math disability (MD), but the mechanisms behind this high comorbidity are not well understood. We examined differences in phonological awareness, reading skills, and executive function between children with RD only versus co-occurring RD+MD using behavioral and fMRI measures. Children with RD only versus RD+MD did not differ in their phonological processing, either behaviorally or in the brain. RD+MD was associated with additional behavioral difficulties in working memory, and reduced visual cortex activation during a visuospatial working memory task.

Developmental dyscalculia is not associated with atypical brain activation: A univariate fMRI study of arithmetic, magnitude processing, and visuospatial working memory.

Functional neuroimaging serves as a tool to better understand the cerebral correlates of atypical behaviors, such as learning difficulties. While significant advances have been made in characterizing the neural correlates of reading difficulties (developmental dyslexia), comparatively little is known about the neurobiological correlates of mathematical learning difficulties, such as developmental dyscalculia (DD). Furthermore, the available neuroimaging studies of DD are characterized by small sample sizes and variable inclusion criteria, which make it problematic to compare across studies. In addition, studies to date have focused on identifying single deficits in neuronal processing among children with DD (e.g., mental arithmetic), rather than probing differences in brain function across different processing domains that are known to be affected in children with DD. Here, we seek to address the limitations of prior investigations. Specifically, we used functional magnetic resonance imaging (fMRI) to probe brain differences between children with and without persistent DD; 68 children (8-10 years old, 30 with DD) participated in an fMRI study designed to investigate group differences in the functional neuroanatomy associated with commonly reported behavioral deficits in children with DD: basic number processing, mental arithmetic and visuo-spatial working memory (VSWM). Behavioral data revealed that children with DD were less accurate than their typically achieving (TA) peers for the basic number processing and arithmetic tasks. No behavioral differences were found for the tasks measuring VSWM. A pre-registered, whole-brain, voxelwise univariate analysis of the fMRI data from the entire sample of children (DD and TA) revealed areas commonly associated with the three tasks (basic number processing, mental arithmetic, and VSWM). However, the examination of differences in brain activation between children with and without DD revealed no consistent group differences in brain activation. In view of these null results, we ran exploratory, Bayesian analyses on the data to quantify the amount of evidence for no group differences. This analysis provides supporting evidence for no group differences across all three tasks. We present the largest fMRI study comparing children with and without persistent DD to date. We found no group differences in brain activation using univariate, frequentist analyses. Moreover, Bayesian analyses revealed evidence for the null hypothesis of no group differences. These findings contradict previous literature and reveal the need to investigate the neural basis of DD using multivariate and network-based approaches to brain imaging.

Elementary school teachers' perspectives about learning during the COVID-19 pandemic.

How did school closures affect student access to education and learning rates during the COVID-19 pandemic? How did teachers adapt to the new instructional contexts? To answer these questions, we distributed an online survey to Elementary School teachers (N = 911) in the United States and Canada at the end of the 2020-2021 school year. Around 85.8% of participants engaged in remote instruction, and nearly half had no previous experience teaching online. Overall, this transition was challenging for most teachers and more than 50% considered they were not as effective in the classroom during remote instruction and reported not being able to deliver all the curriculum expected for their grade. Despite the widespread access to digital technologies in our sample, nearly 65% of teachers observed a drop in class attendance. More than 50% of participants observed a decline in students' academic performance, a growth in the gaps between low and high-performing students, and predicted long-term adverse effects. We also observed consistent effects of SES in teachers' reports. The proportion of teachers reporting a drop in performance increases from 40% in classrooms with high-income students, to more than 70% in classrooms with low-income students. Students in lower-income households were almost twice less likely to have teachers with previous experience teaching online and almost twice less likely to receive support from adults with homeschooling. Overall, our data suggest the effects of the pandemic were not equally distributed.

White matter correlates of reading subskills in children with and without reading disability.

Individual differences in reading ability are associated with characteristics of white matter microstructure in the brain. However, previous studies have largely measured reading as a single construct, resulting in difficulty characterizing the role of structural connectivity in discrete subskills of reading. The present study used diffusion tensor imaging to examine how white matter microstructure, measured by fractional anisotropy (FA), relates to individual differences in reading subskills in children aged 8 to 14 (n = 65). Findings showed positive correlations between FA of the left arcuate fasciculus and measures of single word reading and rapid naming abilities. Negative correlations were observed between FA of the right inferior longitudinal fasciculus and bilateral uncinate fasciculi, and reading subskills, particularly reading comprehension. The results suggest that although reading subskills rely to some extent on shared tracts, there are also distinct characteristics of white matter microstructure supporting different components of reading ability in children.

Task features change the relation between math anxiety and number line estimation performance with rational numbers: Two large-scale online studies.

Math performance is negatively related to math anxiety (MA), though MA may impact certain math skills more than others. We investigated whether the relation between MA and math performance is affected by task features, such as number type (e.g., fractions, whole numbers, percentages), number format (symbolic vs. nonsymbolic), and ratio component size (small vs. large). Across two large-scale studies (combined n = 3,822), the MA-performance relation was strongest for large whole numbers and fractions, and stronger for symbolic than nonsymbolic fractions. The MA-performance relation was also stronger for smaller relative to larger components, and MA relating to specific number types may be a better predictor of performance than general MA for certain tasks. The relation between MA and estimation performance changes depending on task features, which suggests that MA may relate to certain math skills more than others, which may have implications for how people reason with numerical information and may inform future interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of school-level and area-level socio-economic factors on elementary school student COVID-19 infections: a population-based observational study.

OBJECTIVES: To estimate the variability of the cumulative incidence of SARS-CoV-2 infections among elementary school students attributable to individual schools and/or their geographic areas, and to ascertain whether socio-economic characteristics of school populations and/or geographic areas may be predictive of this variability. DESIGN: Population-based observational study of SARS-CoV-2 infections among elementary school children. SETTING: 3994 publicly funded elementary schools in 491 forward sortation areas (designated geographic unit based on first three characters of Canadian postal code), Ontario, Canada, September 2020 to April 2021. PARTICIPANTS: All students attending publicly funded elementary schools with a positive molecular test for SARS-CoV-2 reported by the Ontario Ministry of Education. MAIN OUTCOME MEASURES: Cumulative incidence of laboratory-confirmed elementary school student SARS-CoV-2 infections in Ontario, 2020-21 school year. RESULTS: A multilevel modelling approach was used to estimate the effects of socio-economic factors at the school and area levels on the cumulative incidence of elementary school student SARS-CoV-2 infections. At the school level (level 1), the proportion of the student body from low-income households was positively associated with cumulative incidence (ß=0.083, p<0.001). At the area level (level 2), all dimensions of marginalisation were significantly related to cumulative incidence. Ethnic concentration (ß=0.454, p<0.001), residential instability (ß=0.356, p<0.001) and material deprivation (ß=0.212, p<0.001) were positively related, while dependency (ß=-0.204, p<0.001) was negatively related. Area-related marginalisation variables explained 57.6% of area variability in cumulative incidence. School-related variables explained 1.2% of school variability in cumulative incidence. CONCLUSIONS: The socio-economic characteristics of the geographic area of schools were more important in accounting for the cumulative incidence of SARS-CoV-2 elementary school student infections than individual school characteristics. Schools in marginalised areas should be prioritised for infection prevention measures and education continuity and recovery plans.

A million is more than a thousand: Children's acquisition of very large number words.

Very large numbers words such as "hundred," "thousand," "million," "billion," and "trillion" pose a learning problem for children because they are sparse in everyday speech and children's experience with extremely large quantities is scarce. In this study, we examine when children acquire the relative ordering of very large number words as a first step toward understanding their acquisition. In Study 1, a hundred and twenty-five 5-8-year-olds participated in a verbal number comparison task involving very large number words. We found that children can judge which of two very large numbers is more as early as age 6, prior to entering first grade. In Study 2, we provided a descriptive analysis on the usage of very large number words using the CHILDES database. We found that the relative frequency of large number words does not change across the years, with "hundred" uttered more frequently than others by an order of magnitude. We also found that adults were more likely to use large number words to reference units of quantification for money, weight, and time, than for discrete, physical entities. Together, these results show that children construct a numerical scale for large number words prior to learning their precise cardinal meanings, and highlight how frequency and context may support their acquisition. Our results have pedagogical implications and highlight a need to investigate how children acquire meanings for number words that reference quantities beyond our everyday experience.

Model-based screening for pancreatic cancer in Sweden.

BACKGROUND: Detecting pancreatic cancer at an earlier stage may contribute to an increased survival. Patients with stage I pancreatic cancer have a 5-year survival rate of 36%, while stage IV patients have a 5-year survival rate of 1% in Sweden. Research into novel blood-based biomarkers for pancreatic cancer is highly intensive and innovative, but has yet to result in any routine screening test. The aim of this study was to evaluate the specificity and sensitivity of a hypothetical blood test for pancreatic cancer used for screening purposes and the economic aspects of testing. METHOD: A model of a screening test was created, with varying specificity and sensitivity both set at 80%, 85%, 90%, 95% or 99% and applied to selected risk groups. Excessive costs of false positive screening outcomes, QALYs, ICERs and total costs were calculated. RESULTS: Individuals with family history and genetic mutations associated with pancreatic cancer, new-onset diabetes ≥50 years of age and early symptoms had the highest positive predictive values and ICERs beneath the willingness-to-pay-level of EUR 100,000/QALY. Screening of the general population and smokers resulted in a high rate of false positive cases and extensive extra costs. CONCLUSIONS: General screening for pancreatic cancer is not cost-effective, while screening of certain high-risk groups may be economically justified given the availability of a high-performing blood-based test.

Histopathological investigation of colon liver metastases - which factors affect survival after surgery?

INTRODUCTION: Novel therapeutic options have improved prognosis for patients with colonic liver metastases (CLM) over the last decades. Despite this, the challenge to select and stratify patients for optimal treatment regimen persists. This study aimed to evaluate established and novel histopathological features and investigate the impact on overall survival (OS) and recurrence in patients undergoing surgery for CLM. METHODS: Two hundred and sixty patients who underwent resection of CLM with curative intent 2006-2017 were included in the study. Clinicopathological characteristics were retrieved from patient medical records. The following histopathological parameters were investigated: vascular/lymphatic invasion, perineural invasion, tumor regression grade (TRG), tumor growth pattern, pseudocapsule and acellular mucin. Histopathological traits were correlated to OS. RESULTS: Vascular and lymphatic invasion, as well as perineural invasion, significantly correlated with an adverse prognosis hazard ratio (HR) = 1.7, 95% confidence interval (CI) 1.23-2.40 and HR = 1.7, 95% CI 1.20-2.51, respectively. Results retrieved from the study could not propose any novel explorative histopathological features (TRG, tumor growth pattern, pseudocapsule and acellular mucin) to be of significant value as comes correlation with patient OS. DISCUSSION: Classical histopathological characteristics of previously reported influence on survival were confirmed, while more novel factors that has been proposed, like tumor growth pattern, tumor regression and grade and presence of a pseudocapsule, were not. Further studies are thus needed to identify better ways of understanding the impact of tumor microenvironment and tumor biology on patient outcome and not at least for stratification and improved treatment response.

The role of the angular gyrus in arithmetic processing: a literature review.

Since the pioneering work of the early 20th century neuropsychologists, the angular gyrus (AG), particularly in the left hemisphere, has been associated with numerical and mathematical processing. The association between the AG and numerical and mathematical processing has been substantiated by neuroimaging research. In the present review article, we will examine what is currently known about the role of the AG in numerical and mathematical processing with a particular focus on arithmetic. Specifically, we will examine the role of the AG in the retrieval of arithmetic facts in both typically developing children and adults. The review article will consider alternative accounts that posit that the involvement of the AG is not specific to arithmetic processing and will consider how numerical and mathematical processing and their association with the AG overlap with other neurocognitive processes. The review closes with a discussion of future directions to further characterize the relationship between the angular gyrus and arithmetic processing.

Investigating the relationships between temporal and spatial ratio estimation and magnitude discrimination using structural equation modeling: Evidence for a common ratio processing system.

Humans perceive ratios of spatial and temporal magnitudes, such as length and duration. Previous studies have shown that spatial ratios may be processed by a common ratio processing system. The aim of the current study was to determine whether ratio processing is a domain-general ability and consequently involves common processing of temporal and spatial magnitudes. Two hundred seventy-five participants completed a battery of spatial and temporal ratio estimation and magnitude discrimination tasks online. Structural equation modeling was used to analyze the relationship between ratio processing across domains while controlling for absolute magnitude discrimination ability. The four-factor higher order model, consisting of spatial and temporal magnitude and ratio processing latent variables, showed adequate local and global fit, χ²(44) = 41.41, p = .626, root mean square error of approximation = .000. We found a significant relationship (r = .63) between spatial and temporal ratio processing, suggesting that ratio processing may be a domain-general ability. Additionally, absolute magnitude processing explained a large part (60-66%) of the variance in both spatial and temporal ratio processing factors. Overall, findings suggest that representation of spatial and temporal ratios is highly related and points toward a common ratio processing mechanism across different types of magnitudes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The neural correlates of retrieval and procedural strategies in mental arithmetic: A functional neuroimaging meta-analysis.

Mental arithmetic is a complex skill of great importance for later academic and life success. Many neuroimaging studies and several meta-analyses have aimed to identify the neural correlates of mental arithmetic. Previous meta-analyses of arithmetic grouped all problem types into a single meta-analytic map, despite evidence suggesting that different types of arithmetic problems are solved using different strategies. We used activation likelihood estimation (ALE) to conduct quantitative meta-analyses of mental arithmetic neuroimaging (n = 31) studies, and subsequently grouped contrasts from the 31 studies into problems that are typically solved using retrieval strategies (retrieval problems) (n = 18) and problems that are typically solved using procedural strategies (procedural problems) (n = 19). Foci were compiled to generate probabilistic maps of activation for mental arithmetic (i.e., all problem types), retrieval problems, and procedural problems. Conjunction and contrast analyses were conducted to examine overlapping and distinct activation for retrieval and procedural problems. The conjunction analysis revealed overlapping activation for retrieval and procedural problems in the bilateral inferior parietal lobules, regions typically associated with magnitude processing. Contrast analyses revealed specific activation in the left angular gyrus for retrieval problems and specific activation in the inferior frontal gyrus and cingulate gyrus for procedural problems. These findings indicate that the neural bases of arithmetic systematically differs according to problem type, providing new insights into the dynamic and task-dependent neural underpinnings of the calculating brain.

Surgical resection of pancreatic cancer with synchronous hepatic oligometastases: Real benefit or selection bias?

In this editorial, we review the evidence for liver resection in patients with oligometastatic pancreatic cancer.