The Neurodiversity Attitudes Questionnaire: Development and Initial Validation.

LAY ABSTRACT: Neurodiversity refers to the idea that brain differences (including disabilities) are valuable and should be accepted. Attitudes toward neurodiversity can have real-life impacts on the lives of neurodivergent people (those whose brains do not fit society's "standard"). These impacts can include effects on daily interactions, as well as how professionals such as teachers and doctors deliver services to neurodivergent people. In order to identify negative attitudes toward neurodiversity and potentially improve them, we first need to measure these attitudes. This article describes the development of the Neurodiversity Attitudes Questionnaire (NDAQ). NDAQ development included revision of questionnaire items based on feedback from experts and neurodivergent people, systematically evaluating the way participants responded to questionnaire items, and analysis of how the NDAQ items are grouped into different factors. A preliminary analysis with 351 individuals mostly living in the United States who were currently working or planning to work in a helping profession (e.g. doctors, teachers, therapists, and so on) indicates that the NDAQ measures attitudes toward neurodiversity, is well understood by participants, and fits a five-factor structure. While the NDAQ represents the first instrument designed to specifically assess attitudes toward the broad idea of neurodiversity, further work is still needed.

MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D.

INTRODUCTION: We previously reported the significant upregulation of eight circulating exosomal microRNAs (miRNAs) in patients with diabetic kidney disease (DKD). However, their specific roles and molecular mechanisms in the kidney remain unknown. Among the eight miRNAs, we evaluated the effects of miR-5010-5p on renal tubular epithelial cells under diabetic conditions in this study. RESEARCH DESIGN AND METHODS: We transfected the renal tubular epithelial cell line, HK-2, with an miR-5010-5p mimic using recombinant plasmids. The target gene of hsa-miR-5010-5p was identified using a dual-luciferase assay. Cell viability was assessed via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Moreover, mRNA and protein expression levels were determined via real-time PCR and western blotting, respectively. RESULTS: High glucose levels did not significantly affect the intracellular expression of miR-5010-5p in HK-2 cells. Transfection of the miR-5010-5p mimic caused no change in cell viability. However, miR-5010-5p-transfected HK-2 cells exhibited significantly decreased expression levels of inflammatory cytokines, such as the monocyte chemoattractant protein-1, interleukin-1ß, and tumor necrosis factor-ɑ, under high-glucose conditions. These changes were accompanied by the restored expression of phosphorylated AMP-activated protein kinase (AMPK) and decreased phosphorylation of nuclear factor-kappa B. Dual-luciferase assay revealed that miR-5010-5p targeted the gene, protein phosphatase 2 regulatory subunit B delta (PPP2R2D), a subunit of protein phosphatase 2A, which modulates AMPK phosphorylation. CONCLUSIONS: Our findings suggest that increased miR-5010-5p expression reduces high glucose-induced inflammatory responses in renal tubular epithelial cells via the regulation of the target gene, PPP2R2D, which modulates AMPK phosphorylation. Therefore, miR-5010-5p may be a promising therapeutic target for DKD.

An efficient 3-approximation algorithm for the Steiner tree problem with the minimum number of Steiner points and bounded edge length.

We present improved algorithms for the Steiner tree problem with the minimum number of Steiner points and bounded edge length. Given n terminal points in a 2D Euclidean plane and an edge length bound, the problem asks to construct a spanning tree of n terminal points with minimal Steiner points such that every edge length of the spanning tree is within the given bound. This problem is known to be NP-hard and has practical applications such as relay node placements in wireless networks, wavelength-division multiplexing(WDM) optimal network design, and VLSI design. The best-known deterministic approximation algorithm has O(n3) running time with an approximation ratio of 3. This paper proposes an efficient approximation algorithm using the Voronoi diagram that guarantees an approximation ratio of 3 in O(n log n) time. We also present the first exact algorithm to find an optimal Steiner tree for given three terminal points in constant time. Using this exact algorithm, we improve the 3-approximation algorithm with better performance regarding the number of required Steiner points in O(n log n) time.

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1.

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of ß-catenin through ß-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked ß-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.

ALIS: Learning Affective Causality Behind Daily Activities From a Wearable Life-Log System.

Human emotions and behaviors are reciprocal components that shape each other in everyday life. While the past research on each element has made use of various physiological sensors in many ways, their interactive relationship in the context of daily life has not yet been explored. In this work, we present a wearable affective life-log system (ALIS) that is robust as well as easy to use in daily life to accurately detect emotional changes and determine the cause-and-effect relationship between emotions and emotional situations in users' lives. The proposed system records how a user feels in certain situations during long-term activities using physiological sensors. Based on the long-term monitoring, the system analyzes how the contexts of the user's life affect his/her emotional changes and builds causal structures between emotions and observable behaviors in daily situations. Furthermore, we demonstrate that the proposed system enables us to build causal structures to find individual sources of mental relief suited to negative situations in school life.

Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway.

Itraconazole, an FDA-approved antifungal, has antitumor activity against a variety of cancers. We sought to determine the effects of itraconazole on esophageal cancer and elucidate its mechanism of action. Itraconazole inhibited cell proliferation and induced G1-phase cell-cycle arrest in esophageal squamous cell carcinoma and adenocarcinoma cell lines. Using an unbiased kinase array, we found that itraconazole downregulated protein kinase AKT phosphorylation in OE33 esophageal adenocarcinoma cells. Itraconazole also decreased phosphorylation of downstream ribosomal protein S6, transcriptional expression of the upstream receptor tyrosine kinase HER2, and phosphorylation of upstream PI3K in esophageal cancer cells. Lapatinib, a tyrosine kinase inhibitor that targets HER2, and siRNA-mediated knockdown of HER2 similarly suppressed cancer cell growth in vitro Itraconazole significantly inhibited growth of OE33-derived flank xenografts in mice with detectable levels of itraconazole and its primary metabolite, hydroxyitraconazole, in esophagi and tumors. HER2 total protein and phosphorylation of AKT and S6 proteins were decreased in xenografts from itraconazole-treated mice compared to xenografts from placebo-treated mice. In an early phase I clinical trial (NCT02749513) in patients with esophageal cancer, itraconazole decreased HER2 total protein expression and phosphorylation of AKT and S6 proteins in tumors. These data demonstrate that itraconazole has potent antitumor properties in esophageal cancer, partially through blockade of HER2/AKT signaling.

Immature platelets as a biomarker for disease severity and mortality in COVID-19 patients.

COVID-19, caused by SARS-CoV-2, is a contagious life-threatening viral disease that has killed more than three million people worldwide to date. Attempts have been made to identify biomarker(s) to stratify disease severity and improve treatment and resource allocation. Patients with SARS-COV-2 infection manifest with a higher inflammatory response and platelet hyperreactivity; this raises the question of the role of thrombopoiesis in COVID-19 infection. Immature platelet fraction (IPF, %) and immature platelet counts (IPC, ×109 /l) can be used to assess thrombopoiesis. This study investigates whether the level of thrombopoiesis correlates with COVID-19 severity. A large cohort of 678 well-characterized COVID-19 patients was analyzed, including 658 (97%) hospitalized and 139 (21%) admitted to the intensive care unit (ICU). Elevated percentage IPF at presentation was predictive of length of hospitalization (P < 0·01) and ICU admission (P < 0·05). Additionally, percentage IPF at the peak was significantly higher among ICU patients than non-ICU patients (6·9 ± 5·1 vs 5·3 ± 8·4, P < 0·01) and among deceased patients than recovered patients (7·9 ± 6·3 vs 5·4 ± 7·8, P < 0·01). Furthermore, IPC at the peak was significantly higher among ICU patients than non-ICU patients (18·5 ± 16·2 vs. 13·2 ± 8·3, P < 0·05) and among patients on a ventilator than those not (22·1 ± 20·1 vs.13·4 ± 8·4, P < 0·05). Our study demonstrated that elevated initial and peak values of percentage IPF and IPC might serve as prognostic biomarkers for COVID-19 progression to severe conditions.

A-Situ: a computational framework for affective labeling from psychological behaviors in real-life situations.

This paper presents a computational framework for providing affective labels to real-life situations, called A-Situ. We first define an affective situation, as a specific arrangement of affective entities relevant to emotion elicitation in a situation. Then, the affective situation is represented as a set of labels in the valence-arousal emotion space. Based on psychological behaviors in response to a situation, the proposed framework quantifies the expected emotion evoked by the interaction with a stimulus event. The accumulated result in a spatiotemporal situation is represented as a polynomial curve called the affective curve, which bridges the semantic gap between cognitive and affective perception in real-world situations. We show the efficacy of the curve for reliable emotion labeling in real-world experiments, respectively concerning (1) a comparison between the results from our system and existing explicit assessments for measuring emotion, (2) physiological distinctiveness in emotional states, and (3) physiological characteristics correlated to continuous labels. The efficiency of affective curves to discriminate emotional states is evaluated through subject-dependent classification performance using bicoherence features to represent discrete affective states in the valence-arousal space. Furthermore, electroencephalography-based statistical analysis revealed the physiological correlates of the affective curves.

Tussilagone promotes osteoclast apoptosis and prevents estrogen deficiency-induced osteoporosis in mice.

Osteoporosis is a degenerative disease characterized by reduced bone mass, in which deregulated bone remodeling by osteoclasts and osteoblasts is a main pathogenesis. Although recently tussilagone, a major active component of flower buds of Tussilago farfara, has been shown to inhibit osteoclastogenesis, its effect on estrogen deficiency-induced osteoporosis remains unknown. This study examined the effect of tussilagone on bone loss in ovariectomized mice and further explored its impact on osteoclast apoptosis and osteoblast formation in addition to osteoclastogenesis. Tussilagone suppression of osteoclastogenesis was confirmed in bone marrow derived macrophages, which was observed with the 1/10 concentration of that of the previous study. As demonstrated by ApoPercentage dye staining and Western blotting, tussilagone enhanced apoptosis in differentiated osteoclasts by increasing estrogen receptor α and Fas ligand expression. On the contrary, either osteoblast differentiation or mineralization was not affected by tussilagone. Lastly, administering tussilagone to mice for 6 weeks prevented trabecular microarchitecture impairment in ovariectomized mice compared to vehicle control groups. These findings suggest that tussilagone or Tussilago farfara prevents osteoporotic bone loss by suppressing osteoclast differentiation and inducing osteoclast apoptosis, and that it may therefore offer a possible remedy against resorptive bone diseases.

Effects of Lotus (Nelumbo nucifera) Leaf on Quality and Antioxidant Activity of Yogurt during Refrigerated Storage.

The supplementation with natural ingredients that are rich in polyphenols could improve the quality and functionality of yogurt. Lotus leaf (LL) are abundant in phenolic compounds. We aimed to investigate the effects of LL powder on the quality properties, total phenolic content (TPC), and antioxidant activity of yogurt. Yogurt was supplemented with four different concentrations (0%, 0.2%, 0.5%, and 1%) of LL powder and evaluated for 14 d refrigerated storage. During storage, the titratable acidity (TA) of all LL yogurt groups was higher than that of the control (p<0.05). The L* and a* values decreased by LL addition to the yogurts, while the b* values increased. All LL yogurt groups indicated better viscosity than that of control, and among them, 0.2% LL yogurts had the highest viscosity without significant decrease until the end of the storage duration. The addition of LL into yogurt enhanced the water-holding capacity (WHC) by at least 1.5-fold than that of control for the entire storage duration. The TPC of yogurts gradually increased with the addition of LL (p<0.05) and continued to increase during storage; the 1% LL yogurt at 14 d showed the highest value of 61.94±1.68 µg GAE/g. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity and reducing power of the yogurts were also significantly enhanced with increasing LL concentrations (p<0.05). These results suggest that lotus leaf may be useful as a natural ingredient for improving the quality and antioxidant activity of yogurt.

Automatic tooth segmentation of dental mesh using a transverse plane.

This paper proposes an automatic method to separate the gingiva and individual teeth from a dental mesh. We define a transverse plane that produces a cross-section of tooth lingual and labial surfaces, preserving the shape of individual teeth. The upper vertices from the transverse plane, which belong to the tooth, are projected onto the transverse plane, and partitioned into individual teeth. We apply region growing to the remaining non-segmented parts to determine the cluster the vertices belong to, and the proposed approach is fully automatic, i.e., segmentation does not require user interaction for feature point search or tooth boundary markers. The proposed segmentation method is applied to several dental mesh models to demonstrate its robustness.

The Cut-off Values of Surrogate Measures for Insulin Sensitivity in a Healthy Population in Korea according to the Korean National Health and Nutrition Examination Survey (KNHANES) 2007-2010.

BACKGROUND: This study aimed to identify the gender-specific characteristics of the surrogate measures of insulin resistance and to establish valid cut-off values for metabolic abnormalities in a representative sample in Korea. METHODS: Data were collected from the datasets of the Korean National Health and Nutrition Examination Survey between 2007 and 2010. The total number of eligible participants was 10,997. We used three measures of insulin resistance: the homeostasis model assessment-insulin resistance (HOMA-IR), McAuley index, and triglyceride and glucose (TyG) index. The estimated cut-off values were determined using the highest score of the Youden index. RESULTS: The area under the curve (AUC) of the HOMA-IR, McAuley index, and TyG index were 0.737 (95% confidence interval [CI], 0.725-0.750), 0.861 (95% CI, 0.853-0.870), and 0.877 (95% CI, 0.868-0.885), respectively. The cut-off values of the HOMA-IR were 2.20 in men, 2.55 in premenopausal women, and 2.03 in postmenopausal women, and those of the McAuley index were 6.4 in men and 6.6 in premenopausal and postmenopausal women. For the TyG index, the cut-off values were 4.76 in men and 4.71 in premenopausal and postmenopausal women. CONCLUSION: In conclusion, the present study provides the valid cut-off values of the indirect surrogate measures of insulin sensitivity. These values may be used as reference for insulin sensitivity in a clinical setting and may provide a simple and supplementary method for identifying populations at risk of insulin resistance.

Assessment of Korean consumer exposure to sodium saccharin, aspartame and stevioside.

The dietary intakes of sodium saccharin, aspartame and stevioside were estimated on the basis of food consumption data of the Korean consumer and the concentration of sweeteners in processed foods. Results were compared with the acceptable daily intake (ADI) of sweeteners. Among the 28 food categories for which the application of sodium saccharin, aspartame and stevioside is permitted in Korea, they were detected in 5, 12 and 13 categories, respectively. The estimated daily intake (EDI) of sodium saccharin and aspartame were high in infants and children, whereas the EDI of stevioside was high in adolescents and adults. The most highly consumed sweetener was aspartame, and the highest EDI/ADI ratio was found for sodium saccharin. The main food categories contributing to sweetener consumption were beverages, including alcoholic beverages. For most Korean consumers, the EDIs were no greater than 20% of their corresponding ADI; however, the EDI of sodium saccharin for conservative consumers aged 1-2 years reached 60% of their ADI.

Assessment of exposure of Korean consumers to acesulfame K and sucralose using a stepwise approach.

Using a stepwise assessment of the exposure of Korean consumers to acesulfame K and sucralose, theoretical maximum daily intakes of the sweeteners were calculated using the Budget screening method, which resulted in values greater than the acceptable daily intakes (ADIs). Accordingly, the daily intakes of the sweeteners based on food consumption data and concentrations determined by instrumental analysis of 605 food samples were estimated for the more refined approach. The estimated daily intakes (EDIs) of all ordinary consumers were lower than the ADI, which was considered safe. However, for infants and 95th percentile high-level consumers (especially those who choose sucralose-containing foods), the EDIs of sucralose were very close to and higher than the ADI. Therefore, the sucralose concentration in sweetened beverages should be reduced; this would benefit the health of both high-level consumers and infants.