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1.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35131942

RESUMEN

Math anxiety is a common affective disorder in students that is characterized by intrusive thoughts that disrupt critical cognitive resources required for math problem-solving. Consistent associations between math anxiety and math achievement have been observed across countries and age groups, placing math anxiety among other important correlates of math achievement, such as socioeconomic status and magnitude representation ability. However, studies examining math anxiety's relation to achievement have largely focused on the effect of students' own math anxiety (individual effect), while little is known regarding the effect of math anxiety in students' educational context (contextual effect). Using three international studies of achievement (n = 1,175,515), we estimated both the individual and contextual effects of math anxiety across the globe. Results suggest that while there are consistent individual effects in virtually all countries examined, the contextual effects are varied, with only approximately half of the countries exhibiting a contextual effect. Additionally, we reveal that teacher confidence in teaching math is associated with a reduction of the individual effect, and country's level of uncertainty avoidance is related to a lessening of the contextual effect. Finally, we uncovered multiple predictors of math anxiety; notably, student perception of teacher competence was negative related with math anxiety, and parental homework involvement was positively related with math anxiety. Taken together, these results suggest that there are significant between-country differences in how math anxiety may be related with math achievement and suggest that education and cultural contexts as important considerations in understanding math anxiety's effects on achievement.


Asunto(s)
Logro , Ansiedad , Matemática , Niño , Bases de Datos Factuales , Femenino , Humanos , Masculino
2.
Cancer Control ; 31: 10732748241251583, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38683590

RESUMEN

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.


Asunto(s)
Transportador de Aminoácidos Neutros Grandes 1 , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Terapia Molecular Dirigida/métodos
3.
Dev Sci ; 27(2): e13443, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37675857

RESUMEN

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.


Asunto(s)
Dislexia , Discapacidades para el Aprendizaje , Niño , Humanos , Función Ejecutiva , Encéfalo , Memoria a Corto Plazo
4.
Hum Brain Mapp ; 44(1): 229-244, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36121072

RESUMEN

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.


Asunto(s)
Encéfalo , Solución de Problemas , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Solución de Problemas/fisiología , Corteza Prefrontal , Neuroimagen , Neuroimagen Funcional , Mapeo Encefálico , Imagen por Resonancia Magnética
5.
Hum Brain Mapp ; 44(18): 6308-6325, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37909347

RESUMEN

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.


Asunto(s)
Discalculia , Memoria a Corto Plazo , Niño , Humanos , Memoria a Corto Plazo/fisiología , Imagen por Resonancia Magnética , Discalculia/diagnóstico por imagen , Discalculia/complicaciones , Teorema de Bayes , Encéfalo/diagnóstico por imagen
6.
Scand J Gastroenterol ; 58(5): 534-541, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36440687

RESUMEN

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.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pancreáticas , Humanos , Detección Precoz del Cáncer/métodos , Suecia/epidemiología , Análisis Costo-Beneficio , Valor Predictivo de las Pruebas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Años de Vida Ajustados por Calidad de Vida , Tamizaje Masivo
7.
Scand J Gastroenterol ; 58(6): 627-633, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36440692

RESUMEN

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.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias del Recto , Humanos , Hepatectomía/métodos , Estadificación de Neoplasias , Neoplasias del Colon/cirugía , Neoplasias del Colon/patología , Pronóstico , Neoplasias Hepáticas/patología , Neoplasias del Recto/cirugía , Mucinas , Neoplasias Colorrectales/patología , Tasa de Supervivencia , Estudios Retrospectivos , Microambiente Tumoral
8.
Dev Sci ; 26(1): e13246, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35170832

RESUMEN

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.


Asunto(s)
Aprendizaje , Habla , Niño , Adulto , Humanos
9.
Scand J Gastroenterol ; 57(10): 1169-1177, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35477331

RESUMEN

BACKGROUND: Pancreatic cancer has been and still is associated with a very poor prognosis. This is due to a lack of major breakthroughs with respect to early diagnosis, prognostication, prediction, as well as novel, targeted therapies. The benefits of surgery and chemotherapy are evident, but the fact that only some 10% of all patients have early, localized disease highlights the unmet need for new early detection methods. An improved understanding of tumor biology and the development of molecular markers detectable both in the circulation and in cancer tissues may underlie the development of new tools for optimizing both diagnosis and treatment. MATERIAL AND METHODS: Review of the literature. RESULTS AND CONCLUSION: If we do not improve precision oncology for pancreatic ductal adenocarcinoma, the prognosis will still remain dismal and the" burden" on society will increase substantially.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/terapia , Detección Precoz del Cáncer , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/terapia , Medicina de Precisión , Neoplasias Pancreáticas
10.
Dev Sci ; 25(3): e13211, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34889002

RESUMEN

Which dimension of a set of objects is more salient to young children: number or size? The 'Build-A-Train' task was developed and used to examine whether children spontaneously use a number or physical size approach on an un-cued matching task. In the Build-A-Train task, an experimenter assembles a train using one to five blocks of a particular length and asks the child to build the same train. The child's blocks differ in length from the experimenter's blocks, causing the child to build a train that matches based on either the number of blocks or length of the train, as it is not possible to match on both. One hundred and nineteen children between 2 years 2 months and 6 years 0 months of age (M = 4.05, SD = 0.84) completed the Build-A-Train task, and the Give-a-Number task, a classic task used to assess children's conceptual knowledge of verbal number words. Across train lengths and verbal number knowledge levels, children used a number approach more than a size approach on the Build-A-Train task. However, children were especially likely to use a number approach over a size approach when they knew the verbal number word that corresponded to the quantity of blocks in the train, particularly for quantities smaller than four. Therefore, children's attention to number relates to their knowledge of verbal number words. The Build-A-Train task and findings from the current study set a foundation for future longitudinal research to investigate the causal relationship between children's acquisition of symbolic mathematical concepts and attention to number.


Asunto(s)
Desarrollo Infantil , Conocimiento , Niño , Preescolar , Humanos , Conceptos Matemáticos
11.
Dev Sci ; 25(3): e13194, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34800342

RESUMEN

Children's ability to discriminate nonsymbolic number (e.g., the number of items in a set) is a commonly studied predictor of later math skills. Number discrimination improves throughout development, but what drives this improvement is unclear. Competing theories suggest that it may be due to a sharpening numerical representation or an improved ability to pay attention to number and filter out non-numerical information. We investigate this issue by studying change in children's performance (N = 65) on a nonsymbolic number comparison task, where children decide which of two dot arrays has more dots, from the middle to the end of 1st grade (mean age at time 1 = 6.85 years old). In this task, visual properties of the dot arrays such as surface area are either congruent (the more numerous array has more surface area) or incongruent. Children rely more on executive functions during incongruent trials, so improvements in each congruency condition provide information about the underlying cognitive mechanisms. We found that accuracy rates increased similarly for both conditions, indicating a sharpening sense of numerical magnitude, not simply improved attention to the numerical task dimension. Symbolic number skills predicted change in congruent trials, but executive function did not predict change in either condition. No factor predicted change in math achievement. Together, these findings suggest that nonsymbolic number processing undergoes development related to existing symbolic number skills, development that appears not to be driving math gains during this period. Children's ability to discriminate nonsymbolic number improves throughout development. Competing theories suggest improvement due to sharpening magnitude representations or changes in attention and inhibition. The current study investigates change in nonsymbolic number comparison performance during first grade and whether symbolic number skills, math skills, or executive function predict change. Children's performance increased across visual control conditions (i.e., congruent or incongruent with number) suggesting an overall sharpening of number processing. Symbolic number skills predicted change in nonsymbolic number comparison performance.


Asunto(s)
Logro , Función Ejecutiva , Niño , Humanos , Inhibición Psicológica , Matemática
12.
J Cogn Neurosci ; 33(6): 1003-1019, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-34428783

RESUMEN

Visuospatial working memory (VSWM) plays an important role in arithmetic problem solving, and the relationship between these two skills is thought to change over development. Even though neuroimaging studies have demonstrated that VSWM and arithmetic both recruit frontoparietal networks, inferences about common neural substrates have largely been made by comparisons across studies. Little work has examined how brain activation for VSWM and arithmetic converge within the same participants and whether there are age-related changes in the overlap of these neural networks. In this study, we examined how brain activity for VSWM and arithmetic overlap in 38 children and 26 adults. Although both children and adults recruited the intraparietal sulcus (IPS) for VSWM and arithmetic, children showed more focal activation within the right IPS, whereas adults recruited the bilateral IPS, superior frontal sulcus/middle frontal gyrus, and right insula. A comparison of the two groups revealed that adults recruited a more left-lateralized network of frontoparietal regions for VSWM and arithmetic compared with children. Together, these findings suggest possible neurocognitive mechanisms underlying the strong relationship between VSWM and arithmetic and provide evidence that the association between VSWM and arithmetic networks changes with age.


Asunto(s)
Encéfalo , Memoria a Corto Plazo , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Niño , Humanos , Matemática , Solución de Problemas
13.
J Cogn Neurosci ; 34(1): 16-33, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-34705042

RESUMEN

This fMRI study aimed at unraveling the neural basis of learning alphabet arithmetic facts, as a proxy of the transition from slow and effortful procedural counting-based processing to fast and effortless processing as it occurs in learning addition arithmetic facts. Neural changes were tracked while participants solved alphabet arithmetic problems in a verification task (e.g., F + 4 = J). Problems were repeated across four learning blocks. Two neural networks with opposed learning-related changes were identified. Activity in a network consisting of basal ganglia and parieto-frontal areas decreased with learning, which is in line with a reduction of the involvement of procedure-based processing. Conversely, activity in a network involving the left angular gyrus and, to a lesser extent, the hippocampus gradually increases with learning, evidencing the gradual involvement of retrieval-based processing. Connectivity analyses gave insight in the functional relationship between the two networks. Despite the opposing learning-related trajectories, it was found that both networks become more integrated. Taking alphabet arithmetic as a proxy for learning arithmetic, the present results have implications for current theories of learning arithmetic facts and can give direction to future developments.


Asunto(s)
Aprendizaje , Solución de Problemas , Humanos , Imagen por Resonancia Magnética , Matemática , Redes Neurales de la Computación , Lóbulo Parietal
14.
Acta Oncol ; 60(7): 866-871, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33729903

RESUMEN

BACKGROUND: Pancreatic cancer is predicted to become the second most common cause of cancer-related death by 2030. The objective of this study was to estimate the economic burden of pancreatic cancer for the years 2018 and 2030 based on changing demographics and incidence rates in Sweden. METHOD: The incidence of pancreatic cancer in Sweden and additional relevant data were obtained from official statistics. A linear regression model and the mean incidence rates 2008-2018 were applied to calculate the incidence in 2030. An economic model based on the human capital method was created to calculate the indirect cost of pancreatic cancer in 2018 and 2030. Costs associated with surgery, radiology, oncology, and palliative care constituted the direct costs. A sensitivity analysis was performed. RESULTS: The incidence of pancreatic cancer in Sweden in the year 2018 was 1352 patients and projected to between 1554 (+15%) and 1736 (+28%) in 2030. The total cost was calculated to €125 million in 2018 and between €210 million (+68%) and €225 million (+80%) in 2030. The indirect cost in the ≤65-year-old group was €328,344 in 2018 and between €380,738 and €382,109 per individual in 2030. CONCLUSIONS: The economic burden of pancreatic cancer is expected to increase in Sweden by 2030 due to the increasing incidence of the disease and changing demographics. Pancreatic cancer is a growing health care problem in urgent need of advancements in prevention, early detection, treatment, and control of the disease.


Asunto(s)
Costo de Enfermedad , Neoplasias Pancreáticas , Anciano , Predicción , Costos de la Atención en Salud , Humanos , Neoplasias Pancreáticas/epidemiología , Suecia/epidemiología
15.
Neuroimage ; 214: 116716, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32151762

RESUMEN

A region in the posterior inferior temporal gyrus (pITG) is thought to be specialized for processing Arabic numerals, but fMRI studies that compared passive viewing of numerals to other character types (e.g., letters and novel characters) have not found evidence of numeral preference in the pITG. However, recent studies showed that the engagement of the pITG is modulated by attention and task contexts, suggesting that passive viewing paradigms may be ill-suited for examining numeral specialization in the pITG. It is possible, however, that even if the strengths of responses to different category types are similar, the distributed response patterns (i.e., neural representations) in a candidate numeral-preferring pITG region ("pITG-numerals") may reveal categorical distinctions, even during passive viewing. Using representational similarity analyses with three datasets that share the same task paradigm and stimulus sets (total N â€‹= â€‹88), we tested whether the neural representations of digits, letters, and novel characters in pITG-numerals were organized according to visual form and/or conceptual categories (e.g., familiar versus novel, numbers versus others). Small-scale frequentist and Bayesian meta-analyses of our dataset-specific findings revealed that the organization of neural representations in pITG-numerals is unlikely to be described by differences in abstract shape, but can be described by a categorical "digits versus letters" distinction, or even a "digits versus others" distinction (suggesting greater numeral sensitivity). Evidence of greater numeral sensitivity during passive viewing suggest that pITG-numerals is likely part of a neural pathway that has been developed for automatic processing of objects with potential numerical relevance. Given that numerals and letters do not differ categorically in terms of shape, categorical distinction in pITG-numerals during passive viewing must reflect ontogenetic differentiation of symbol set representations based on repeated usage of numbers and letters in differing task contexts.


Asunto(s)
Corteza Cerebral/fisiología , Reconocimiento Visual de Modelos/fisiología , Adulto , Mapeo Encefálico/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Adulto Joven
16.
Hum Brain Mapp ; 41(16): 4562-4573, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32701218

RESUMEN

In contrast to a substantial body of research on the neural basis of cognitive performance in several academic domains, less is known about how the brain generates metacognitive (MC) awareness of such performance. The existing work on the neurobiological underpinnings of metacognition has almost exclusively been done in adults and has largely focused on lower level cognitive processing domains, such as perceptual decision-making. Extending this body of evidence, we investigated MC monitoring by asking children to solve arithmetic problems, an educationally relevant higher-order process, while providing concurrent MC reports during fMRI acquisition. Results are reported on 50 primary school children aged 9-10 years old. The current study is the first to demonstrate that brain activity during MC monitoring, relative to the control task, increased in the left inferior frontal gyrus in children. This brain activity further correlated with children's arithmetic development over a 3-year time period. These data are in line with the frequently suggested, yet never empirically tested, hypothesis that activity in the prefrontal cortex during arithmetic is related to the higher-order process of MC monitoring.


Asunto(s)
Mapeo Encefálico , Desarrollo Infantil/fisiología , Función Ejecutiva/fisiología , Imagen por Resonancia Magnética , Conceptos Matemáticos , Metacognición/fisiología , Corteza Prefrontal/fisiología , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/crecimiento & desarrollo
17.
Hum Brain Mapp ; 41(6): 1591-1610, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-31854024

RESUMEN

How are number symbols (e.g., Arabic digits) represented in the brain? Functional resonance imaging adaptation (fMRI-A) research has indicated that the intraparietal sulcus (IPS) exhibits a decrease in activation with the repeated presentation of the same number, that is followed by a rebound effect with the presentation of a new number. This rebound effect is modulated by the numerical ratio or difference between presented numbers. It has been suggested that this ratio-dependent rebound effect is reflective of a link between the symbolic numerical representation system and an approximate magnitude system. Experiment 1 used fMRI-A to investigate an alternative hypothesis: that the rebound effect observed in the IPS is related to the ordinal relationships between symbols (e.g., 3 comes before 4; C after B). In Experiment 1, adult participants exhibited the predicted distance-dependent parametric rebound effect bilaterally in the IPS for number symbols during a number adaptation task, however, the same effect was not found anywhere in the brain in response to letters. When numbers were contrasted with letters (numbers > letters), the left intraparietal lobule remained significant. Experiment 2 demonstrated that letter stimuli used in Experiment 1 generated a behavioral distance effect during an active ordinality task, despite the lack of a neural distance effect using fMRI-A. The current study does not support the hypothesis that general ordinal mechanisms underpin the neural parametric recovery effect in the IPS in response to number symbols. Additional research is needed to further our understanding of mechanisms underlying symbolic numerical representation in the brain.


Asunto(s)
Adaptación Psicológica/fisiología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiología , Lectura , Adulto , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Lenguaje , Imagen por Resonancia Magnética , Masculino , Matemática , Desempeño Psicomotor/fisiología , Adulto Joven
18.
J Transl Med ; 18(1): 77, 2020 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-32054505

RESUMEN

BACKGROUND: Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue. METHODS: YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP-TEAD interaction, including Super-TDU, Verteporfin and CA3. RESULTS: Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E-06). Prognostic analysis of YAP1 demonstrated a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224-2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299-2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction. CONCLUSIONS: Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Neoplasias Pancreáticas , Factores de Transcripción , Proteínas Adaptadoras Transductoras de Señales/análisis , Proteínas Adaptadoras Transductoras de Señales/sangre , Carcinogénesis , Matriz Extracelular , Humanos , Neoplasias Pancreáticas/genética , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Transcripción/análisis , Factores de Transcripción/sangre , Microambiente Tumoral , Proteínas Señalizadoras YAP
19.
Dev Sci ; 23(2): e12897, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31448505

RESUMEN

Research demonstrating that infants discriminate between small (e.g., 1 vs. 3 dots) and large numerosities (e.g., 8 vs. 16 dots) is central to theories concerning the origins of human numerical abilities. To date, there has been no quantitative meta-analysis of the infant numerical competency data. Here, we quantitatively synthesize the evidential value of the available literature on infant numerosity discrimination using a meta-analytic tool called p-curve. In p-curve the distribution of available p-values is analyzed to determine whether the published literature examining particular hypotheses contains evidential value. p-curves demonstrated evidential value for the hypotheses that infants can discriminate between both small and large unimodal and cross-modal numerosities. However, the analyses also revealed that the published data on infants' ability to discriminate between large numerosities is less robust and statistically powered than the data on their ability to discriminate small numerosities. We argue there is a need for adequately powered replication studies to enable stronger inferences in order to use infant data to ground theories concerning the ontogenesis of numerical cognition.


Asunto(s)
Cognición , Aprendizaje Discriminativo , Conceptos Matemáticos , Femenino , Humanos , Lactante , Masculino , Distribuciones Estadísticas
20.
Dev Sci ; 23(2): e12884, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31271687

RESUMEN

A long-standing debate in the field of numerical cognition concerns the degree to which symbolic and non-symbolic processing are related over the course of development. Of particular interest is the possibility that this link depends on the range of quantities in question. Behavioral and neuroimaging research with adults suggests that symbolic and non-symbolic quantities may be processed more similarly within, relative to outside of, the subitizing range. However, it remains unclear whether this unique link exists in young children at the outset of formal education. Further, no study has yet taken numerical size into account when investigating the longitudinal influence of these skills. To address these questions, we investigated the relation between symbolic and non-symbolic processing inside versus outside the subitizing range, both cross-sectionally and longitudinally, in 540 kindergarteners. Cross-sectionally, we found a consistently stronger relation between symbolic and non-symbolic number processing within versus outside the subitizing range at both the beginning and end of kindergarten. We also show evidence for a bidirectional relation over the course of kindergarten between formats within the subitizing range, and a unidirectional relation (symbolic â†’ non-symbolic) for quantities outside of the subitizing range. These findings extend current theories on symbolic and non-symbolic magnitude development by suggesting that non-symbolic processing may in fact play a role in the development of symbolic number abilities, but that this influence may be limited to quantities within the subitizing range.


Asunto(s)
Cognición/fisiología , Matemática , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Neuroimagen , Instituciones Académicas
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