An Investigation of Factors Affecting Elementary School Students’ BMI Values Based on the System Dynamics Modeling

This study used system dynamics method to investigate the factors affecting elementary school students’ BMI values. The construction of the dynamic model is divided into the qualitative causal loop and the quantitative system dynamics modeling. According to the system dynamics modeling, this study consisted of research on the four dimensions: student’s personal life style, diet-relevant parenting behaviors, advocacy and implementation of school nutrition education, and students’ peer interaction. The results of this study showed that students with more adequate health concepts usually have better eating behaviors and consequently have less chance of becoming obese. In addition, this study also verified that educational attainment and socioeconomic status of parents have a positive correlation with students’ amounts of physical activity, and nutrition education has a prominent influence on changing students’ high-calorie diets

Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD

13 páginas, 7 figurasCurrent clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg.This study was supported by Taiwan Ministry of Science and Technology grants MOST 104-2320-B-002-044-MY3, MOST 106-2320-B-002-046-MY3, and MOST 108-2320-B-002-024-MY3, National Health Research Institutes grants NHRI-EX106-10401BI and NHRI-EX109-10725BI, National Taiwan University grants NTU107L890504 and NTU110L893503 to M.-S. Lee, and National Taiwan University Hospital grants 106-003451, 107-003849, 108-004269, and 109-004720 to C.-C. Ho. This work was also supported by MINECO grants BFU2016-80570-R and RTI2018-098084-B-I00 (AEI/FEDER, UE). The authors would like to thank the Laboratory Animal Core Facility at the College of Medicine, National Taiwan University for their servicesPeer reviewe

An Investigation of Factors Affecting Elementary School Students' BMI Values Based on the System Dynamics Modeling

This study used system dynamics method to investigate the factors affecting elementary school students' BMI values. The construction of the dynamic model is divided into the qualitative causal loop and the quantitative system dynamics modeling. According to the system dynamics modeling, this study consisted of research on the four dimensions: student's personal life style, diet-relevant parenting behaviors, advocacy and implementation of school nutrition education, and students' peer interaction. The results of this study showed that students with more adequate health concepts usually have better eating behaviors and consequently have less chance of becoming obese. In addition, this study also verified that educational attainment and socioeconomic status of parents have a positive correlation with students' amounts of physical activity, and nutrition education has a prominent influence on changing students' high-calorie diets

Neural Network of Body Representation Differs between Transsexuals and Cissexuals

<div><p>Body image is the internal representation of an individual’s own physical appearance. Individuals with gender identity disorder (GID), commonly referred to as transsexuals (TXs), are unable to form a satisfactory body image due to the dissonance between their biological sex and gender identity. We reasoned that changes in the resting-state functional connectivity (rsFC) network would neurologically reflect such experiential incongruence in TXs. Using graph theory-based network analysis, we investigated the regional changes of the degree centrality of the rsFC network. The degree centrality is an index of the functional importance of a node in a neural network. We hypothesized that three key regions of the body representation network, i.e., the primary somatosensory cortex, the superior parietal lobule and the insula, would show a higher degree centrality in TXs. Twenty-three pre-treatment TXs (11 male-to-female and 12 female-to-male TXs) as one psychosocial group and 23 age-matched healthy cissexual control subjects (CISs, 11 males and 12 females) were recruited. Resting-state functional magnetic resonance imaging was performed, and binarized rsFC networks were constructed. The TXs demonstrated a significantly higher degree centrality in the bilateral superior parietal lobule and the primary somatosensory cortex. In addition, the connectivity between the right insula and the bilateral primary somatosensory cortices was negatively correlated with the selfness rating of their desired genders. These data indicate that the key components of body representation manifest in TXs as critical function hubs in the rsFC network. The negative association may imply a coping mechanism that dissociates bodily emotion from body image. The changes in the functional connectome may serve as representational markers for the dysphoric bodily self of TXs.</p></div

The between-group difference in the degree centrality of the node of interests (NOIs).

<p>All NOIs showed an increased degree centrality (one-tailed two-sample t-test, TX>CIS) across a range of network densities (1–12%). An asterisk denotes p<0.05.</p

Abbreviations for the anatomical regions defined by the Harvard-Oxford cortical and subcortical atlases.

<p>Formerly termed the Supplementary Motor Cortex.</p

Inclusion and exclusion criteria for the TX and the CIS groups.

<p>Subjects who were in the period ranging from less than 11 days (follicular phase) or more than 17 days after the beginning of their last menses were included. Follow-up phone calls were made to verify the date of the beginning of the next menses. This selection criterion was used on the basis that sudden surges in LH (luteinizing hormone) and FSH (follicle stimulating hormone) at mid-menstrual cycle could affect brain activation patterns.</p

Inclusion and exclusion criteria for the TX group and the CON group.

<p>*Subjects who were in the period ranging from less than 11 days (follicular phase) or more than 17 days after the beginning of their last menses were included. Follow-up phone calls were made to verify the date of the beginning of the next menses. This selection criterion was used on the basis that sudden surges in LH (luteinizing hormone) and FSH (follicle stimulating hormone) at mid-menstrual cycle could affect brain activation patterns.</p

A priori voxel-based and ROI-based correlation analyses.

<p><i>Panel a. Intragroup comparison</i>. Voxel-based correlation analysis was performed by anchoring the VTA as the seed region (defined as a sphere with a 3-mm radius centered at the MNI coordinates [4, −18, −12]) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Georgiadis1" target="_blank">[11]</a>. The a priori ROIs specifically relate to the processing of social exclusion <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Eisenberger1" target="_blank">[13]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Slavich1" target="_blank">[14]</a>, emotional conflict in interpersonal relationships <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Ruz1" target="_blank">[15]</a> and behavioral adjustments in response to punishment <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Wrase1" target="_blank">[16]</a>. VTA-seeded ROI (radius  = 10 mm)-based analysis with a small-volume correction(SVC, controlled for the family-wise error, P = 0.05) was performed based on the connectivity map for H⁻/TXs and fc/CONs. <i>Panel b. Intergroup comparison</i>. The same VTA-seeded ROI-based analysis was performed using the contrast map (H⁻/TXs >fc/CONs) with and without a SVC. [X] indicates the cited reference.</p

Connectional pattern of the node of interests (NOIs).

<p>The nodes with stronger connections (i.e., group connectivity >10%) within each of the NOIs are displayed for the TX and the CIS groups. The nodal size and edge color denote the strength of the group connectivity between a node and the NOI. Stronger group connectivity indicates that a larger number of participants shared the same edge in their binary networks.</p