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10.3389/fonc.2019.01452
|
Association Between the Microsatellite Instability Status and the Efficacy of Postoperative Adjuvant Chemoradiotherapy in Patients With Gastric Cancer
|
Purpose: The effect of microsatellite instability (MSI) on the response to radiotherapy remains unknown. The aim of this study was to investigate the association between the MSI status and the outcomes of gastric cancer (GC) treated by surgical resection with or without postoperative adjuvant chemoradiotherapy. Methods: The records of patients who underwent surgical resection of stage IB–III GC with or without postoperative adjuvant chemoradiotherapy were retrospectively retrieved from the Affiliated Hospital of Jiangsu University (n = 89), The Cancer Genome Atlas (n = 202), and the Asian Cancer Research Group (n = 138). The primary endpoint was overall survival (OS). Results: The MSI status had no significant influence on OS in all cohorts. Compared with surgery alone, adjuvant chemoradiotherapy improved or tended to improve OS of patients with stage III disease, irrespective of the MSI status, in all cohorts. Among patients with stage Ib/II disease, only those with microsatellite stability (MSS) benefited from chemoradiotherapy in terms of OS, whereas those with MSI showed no improvement in OS. A comparison of gene expression profiles between MSI stage Ib/II GC and MSS stage Ib/II GC revealed that MSI correlated with the overexpression of thymidylate synthetase, a marker of fluoropyrimidine resistance. Furthermore, tumor hypoxia scoring for stage Ib/II lesions showed significantly greater hypoxia in MSI tumors than in MSS tumors. Conclusions: The findings of this study suggest that postoperative adjuvant chemoradiotherapy is effective for stage III GC, regardless of the MSI status. However, MSI may predict a poor response to postoperative adjuvant chemoradiotherapy in patients with stage Ib/II GC.
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2234943X
|
ONCOLOGY
|
10.3389/feduc.2019.00153
|
Developing a Short Form of the Self-Assessment Practices Scale: Psychometric Evidence
|
This research aimed to develop a short form of the Self-assessment Practices Scale (SaPS). Guided by a process model of self-assessment, the SaPS scale was designed to assess the actions students engage in during the self-assessment process. The data used for developing the original 20-item SaPS (SaPS-20), i.e., 1,416 Hong Kong students ranging from Primary 4 to Secondary 3, were reanalyzed, and a 12-item short form (SaPS-SF) was developed. Factor analysis and Rasch analysis were applied in complementary ways to examine the psychometric properties of the SaPS-SF. The results showed that factor structure of the original scale held in the SaPS-SF, and all items fitted the Rasch model requirements sufficiently and measured the constructs as theorized. The findings presented in this study facilitate the measurement of self-assessment practice in a parsimonious and effective way.
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2504284X
|
EDUCATION
|
10.3389/fonc.2019.01510
|
Non-invasive Molecular Detection of Minimal Residual Disease in Papillary Thyroid Cancer Patients
|
Background: Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy. Serum thyroglobulin (Tg) levels are used to monitor PTC treatment response and recurrences however, in about 25% of the cases the sensitivity of this method is compromised due to either the presence of neutralizing anti-Tg antibodies (TgAb) or the absence of Tg in less differentiated tumors. Up to 80% of PTC tumors harbor the c.1799T>A hotspot mutation in the BRAF gene (BRAFV600E). Here, we assessed the potential use of plasma cell-free BRAFV600E mutant tumor DNA (ctDNA) levels in determining the minimal residual tumor status of PTC patients. Methods: Patients were classified as either having persistent disease (PD) or no evidence of disease (NED) based on clinicopathological assessments. Tumor BRAFV600E status was determined by both direct sequencing and digital PCR. Plasma total cell-free BRAFV600 wild type DNA (cfDNA) and ctDNA fractions circulating in the plasma of PTC patients were determined by an emulsion based-digital PCR and total ctDNA was quantified by 3D digital PCR. The total ctDNA levels (copies/ml) were then compared to patients' clinicopathological features. Results: About 74% (28/38) of tumors harbored the BRAFV600E mutation. Percent plasma ctDNA fractions for PD patients with BRAFV600E tumors ranged from 0 to 2.07%, whereas absolute plasma ctDNA copies ranged from 0 to 62 copies. The ctDNA levels accurately detected tumor burden of PTC patients whose tumors harbored BRAFV600E; median plasma ctDNA copy numbers were significantly higher (Wilcoxon test, p = 0.03) in patients with metastasis (MET) (20 copies/ml) compared to patients with non-metastatic (non-MET) tumors (1 copy/ml). The plasma ctDNA levels (copies/ml) accurately determined the disease status of PTC patients with sensitivity of 86% and specificity of 90% as compared to 78% sensitivity and 65% specificity determined by serum Tg levels (ng/ml) with areas under the curves (AUC) of 0.88 and 0.71, respectively. Intriguingly, plasma total cfDNA levels were significantly higher in patients with no evidence of residual disease (NED) compared to persistent disease (PD) patients. Conclusions: Our study supports the clinical applicability of plasma ctDNA as biomarker to determine the residual tumor status and tumor burden of PTC patients.
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2234943X
|
ONCOLOGY
|
10.3390/ejihpe10010029
|
Measuring Heart Rate Variability Using Commercially Available Devices in Healthy Children: A Validity and Reliability Study
|
Heart rate variability (HRV) is an accepted method for determining autonomic nervous system activity and cardiovascular risk in various populations. This study assessed the validity and reliability of a commercially available finger photoplethysmography (PPG) system for measuring pediatric HRV in a real-world setting. Sixteen healthy children (4.06 ± 0.58 years) were recruited. The PPG system was compared to the Polar H10 heart rate (HR) sensor validated against ECG (gold standard) for HRV measurement. Seated short-term resting R-R intervals were recorded simultaneously using both systems. Recordings were performed on 3 days at the participants’ school. Paired t-tests, effect sizes and Bland–Altman analyses determined the validity of the PPG system. The relative and absolute reliability of both systems were calculated. No HRV parameters were valid for the PPG system. Polar H10 yielded moderate (0.50–0.75) to good (0.75–0.90) relative reliability with R-R intervals and the standard deviation of instantaneous and continuous R-R variability ratio showing the best results (ICCs = 0.84). Polar H10 displayed better absolute reliability with the root mean square of successive differences, R-R intervals and HR showing the lowest values (TEM% < 12%). The use of the Polar H10 and not the PPG system is encouraged for HRV measurement of young children in an educational real-world setting.
|
22549625
|
PSYCHOLOGY
|
10.3390/cancers12010182
|
Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma
|
Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child–Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259, p = 0.001). For patients with baseline AFP ≥10 ng/mL, significantly higher ORR (63.6% vs. 10.2%, p < 0.001) and disease control rate (81.8% vs. 14.3%, p < 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child–Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child–Pugh class determines survival by ICI treatment.
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20726694
|
ONCOLOGY
|
10.3390/cancers12010223
|
MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer
|
Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates with ESR1 and luminal genes GATA3 and FOXA1 expression and better prognosis, while low MAGI1 levels correlates with higher histological grade, more aggressive phenotype and worse prognosis. Experimentally, MAGI1 downregulation in the ER+ human BC cells MCF7 impairs ER expression and signaling, promotes cell proliferation, and reduces apoptosis and epithelial differentiation. MAGI1 downregulation in the ER+ murine BC cell line 67NR accelerates primary tumor growth and enhances experimental lung metastasis formation. MAGI1 expression is upregulated by estrogen/ER, downregulated by prostaglandin E2/COX-2axis, and negatively correlates with inflammation in ER+/HER2− BC patients. Taken together, we show that MAGI1 is a new potential tumor suppressor in ER+/HER2− breast cancer with possible prognostic value for the identification of patients at high-risk of relapse within this subset.
|
20726694
|
ONCOLOGY
|
10.3389/fpsyg.2019.03033
|
Life History and Multi-Partner Mating: A Novel Explanation for Moral Stigma Against Consensual Non-monogamy
|
Life history theory (LHT) predicts that individuals vary in their sexual, reproductive, parental, familial, and social behavior according to the physical and social challenges imposed upon them throughout development. LHT provides a framework for understanding why non-monogamy may be the target of significant moral condemnation: individuals who habitually form multiple romantic or sexual partnerships may pursue riskier, more competitive interpersonal strategies that strain social cooperation. We compared several indices of life history (i.e., the Mini-K, the High-K Strategy Scale, pubertal timing, sociosexuality, disease avoidance, and risk-taking) between individuals practicing monogamous and consensually non-monogamous (CNM) romantic relationships. Across several measures, CNM individuals reported a faster life history strategy than monogamous individuals, and women in CNM relationships reported earlier pubertal development. CNM individuals also reported more social and ethical risk-taking, less aversion to germs, and greater interest in short-term mating (and less interest in long-term mating) than monogamous individuals. From these data, we discuss a model to explain how moral stigma toward non-monogamy evolved and how these attitudes may be mismatched to the modern environment. Specifically, we argue that the culture of sexual ethics that pervades contemporary CNM communities (e.g., polyamory, swinging) may attenuate risky interpersonal behaviors (e.g., violent intrasexual competition, retributive jealousy, partner/child abandonment, disease transmission) that are relatively more common among those who pursue multi-partner mating.
|
16641078
|
PSYCHOLOGY
|
10.3389/frai.2019.00032
|
Mysteries, Epistemological Modesty, and Artificial Intelligence in Surgery
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Mysteries, Epistemological Modesty, and Artificial Intelligence in Surgery
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26248212
|
AI
|
10.3389/fpsyg.2019.03023
|
The Emotional Stroop Effect Is Modulated by the Biological Salience and Motivational Intensity Inherent in Stimuli
|
Prior research has found significant emotional Stroop effects for negative stimuli, but the results have been inconsistent for positive stimuli. Combining an evolutionary perspective of emotion with the motivational dimensional model of affect, we speculated that the emotional Stroop effect of a stimulus may be influenced by the biological salience and inherent motivational intensity of the stimulus. In the present study, we examined this issue with two experiments. The results indicated that both low- and high-withdrawal-motivation negative stimuli produced a robust emotional Stroop effect; however, the high-withdrawal-motivation negative stimuli produced a stronger emotional Stroop effect than the low-withdrawal-motivation negative stimuli. Regarding positive stimuli, only the high-approach-motivated positive stimuli produced the emotional Stroop effect, unlike the low-approach-motivation positive stimuli. These findings suggest that the emotional Stroop effect is modulated by the biological salience of stimuli and by the motivational intensity inherent in the stimuli. Biological salience and motivational intensity play an additive effect in the emotional Stroop effect.
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16641078
|
PSYCHOLOGY
|
10.3389/fonc.2019.01575
|
A Novel LncRNA, AC091729.7 Promotes Sinonasal Squamous Cell Carcinomas Proliferation and Invasion Through Binding SRSF2
|
Long non-coding RNAs (lncRNAs) play important roles in various biological progresses of carcinogenesis. However, the function of lncRNAs in human sinonasal squamous cell carcinoma (SNSCC) remains greatly unclear. In the current study, lncRNA AC091729.7 expression was examined in SNSCC samples by using microarray, RNA in situ hybridization (ISH) and real-time fluorescence quantitative PCR (qRT-PCR). Cell viability, colony-formation, wound-healing, and transwell assays were applied to SNSCC cells. Xenograft mouse models were employed to evaluate the role of AC091729.7 in growth of SNSCC in vivo. Human protein microarray (HuprotTM Protoarray) and RNA immunoprecipitation (RIP) were used for identifying AC091729.7 binding proteins in SNSCC. Results showed AC091729.7 was upregulated and closely connected with the survival of the SNSCC patients. Knockdown of AC091729.7 suppressed SNSCC cell migration, proliferation, invasion in vitro. Furthermore, downregulation of AC091729.7 could inhibit the growth of SNSCC in vivo. Moreover, Human protein microarray and RIP suggested that AC091729.7 directly combine with the serine/arginine rich splicing factor 2 (SRSF2). Our results suggest that in the cell progression of SNSCC, lncRNA AC091729.7 plays a carcinogenic role and serves as a novel biomarker and latent curative target in SNSCC patients.
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2234943X
|
ONCOLOGY
|
10.3389/feduc.2020.00002
|
Definitions of Formative Assessment Need to Make a Distinction Between a Psychometric Understanding of Assessment and “Evaluative Judgment”
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Definitions of Formative Assessment Need to Make a Distinction Between a Psychometric Understanding of Assessment and “Evaluative Judgment”
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2504284X
|
EDUCATION
|
10.3390/cancers12020325
|
Mutation Analysis of Colorectal and Gastric Carcinomas Originating from Adenomas: Insights into Genomic Evolution Associated with Malignant Progression
|
Small malignant tumor foci arising from benign lesions are rare but offer a unique opportunity to investigate the genomic evolution that occurs during malignant transformation. In this study, we analyzed 11 colorectal and 10 gastric adenoma–carcinoma pairs, each of which represented malignant tumors (carcinomas) embedded in benign lesions (adenomas) found in the same patient. Whole-exome sequencing revealed that mutation abundance was variable across different cases, but comparable between adenoma–carcinoma pairs. When mutations were classified as adenoma-specific, carcinoma-specific, or common, adenoma-specific mutations were more enriched with subclonal mutations than were carcinoma-specific mutations, indicative of a perturbation in mutational subclonal architecture (such as selective sweep) during malignant transformation. Among the recurrent mutations in colorectal cancers, APC and KRAS mutations were common between adenomas and carcinomas, indicative of their early occurrence during genomic evolution. TP53 mutations were often observed as adenoma-specific and therefore likely not associated with the emergence of malignant clones. Clonality-based enrichment analysis revealed that subclonal mutations of extracellular matrix genes in adenomas are more likely to be clonal in carcinomas, indicating potential roles for these genes in malignant transformation. Compared with colorectal cancers, gastric cancers showed more lesion-specific mutations than common mutations and higher levels of discordance in copy number profiles between matched adenomas and carcinomas, which may explain the elevated evolutionary dynamics and heterogeneity of gastric cancers compared to colorectal cancers. Taken together, this study demonstrates that co-existing benign and malignant lesions enable the evolution-based categorization of genomic alterations that may reveal clinically important biomarkers in colorectal and gastric cancers.
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20726694
|
ONCOLOGY
|
10.1186/s40594-019-0201-4
|
Defining interdisciplinary collaboration based on high school teachers’ beliefs and practices of STEM integration using a complex designed system
|
Background: Teachers’ beliefs play an important role in how teachers think about how students learn, and how content should be organized and taught. Integrated STEM is pushing the boundaries of some of the traditional assumptions in education—disciplined-based courses, courses taught independently by teachers, standards and content-driven, and no collaborative planning time for teachers. Six teachers, located in two high schools, participated in a year-long program to develop interdisciplinary collaboration to implement integrated STEM learning in their courses. A qualitative instrumental case study of the two teams of teachers was conducted to gain insights and understandings of the teachers’ beliefs and instructional practices of STEM integration through interdisciplinary approaches in a complex system (i.e., hydroponics). Results: Themes regarding features, beliefs and practices, and challenges emerged from cross-case analysis of the teachers’ stories, which resulted in two interdisciplinary collaboration models, multi-classroom and extracurricular activity, from each of the teams at each of the two high schools. Multi-classroom and extracurricular activity models had some resemblances, but also had differences. Both cases had the same goals to use real-world problems to help students see STEM connections, learn STEM knowledge and skills, and apply STEM knowledge and skills to solve real-world problems. Conclusions: Based on teachers’ beliefs and their interdisciplinary STEM collaboration practices, three components were identified. Team size, teaching goal, and collaboration structure highly affect a successful interdisciplinary STEM collaboration model in high school settings. The study also contributes to expend the concept of a continuum of STEM approaches to curriculum integration, disciplinary, multidisciplinary, interdisciplinary, and transdisciplinary (Vasquez, Sneider, & Comer, STEM lesson essentials: Integrating science, technology, engineering, and mathematics, 2013), and provides frameworks for structuring a successful interdisciplinary collaboration model in high school settings.
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21967822
|
EDUCATION
|
10.1186/s40359-020-0378-9
|
The clinical effects of school sandplay group therapy on general children with a focus on Korea Child & Youth Personality Test
|
Background: This study intended to examine the comprehensive clinical effects of school sandplay group counseling on the emotions and behaviors of children for the first time in Korea. Methods: To this objective, 10 sessions of in-school sandplay group counseling were administered to 113 fourth- to sixth-graders in an elementary school located in Cheonan city for 12 weeks from March to July 2015. Each small group consisted of 10 to 16 children and the entire 12 sessions were composed of a baseline test, 10 therapy sessions, and a post-test and evaluation session. The study subjects consisted of 56 boys (49.6%) and 57 girls (50.4%). As the evaluation instruments, an epidemiologic questionnaire and the Korea Child & Youth Personality Test were used during the baseline phase and after the termination of the counseling. Results: The comparison of the scores according to the KCYP clinical scales and detailed evaluation scales before and after the 12-week counseling showed an increase in the self-esteem and a significant decline in depression in the elementary students after the counseling. Conclusion: It is deemed that school sandplay group counseling can help elementary school students to solve emotional problems and improve their self-esteem.
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20507283
|
PSYCHOLOGY
|
10.3389/fpsyg.2020.00013
|
Influences of a Luck Game on Offers in Ultimatum and Dictator Games: Is There a Mediation of Emotions?
|
The ultimatum (UG) and dictator (DG) games are two tasks where a sum of money has to be divided between two players: a proposer and a receiver. Following the rational choice theory, proposers should offer the minimum in the UG and nothing in the DG, due to the presence/absence of the receivers’ bargaining power. The fact that people generally make non-negligible offers in both games has suggested divergent explicative hypotheses and has generated extensive research to examine exogenous and endogenous factors underlying such decisions. Among the contextual factors affecting the proposers’ offers, the sense of entitlement or of ownership has been shown to reduce offers significantly. A frequent way to induce the sense of entitlement/ownership has been to assign the role of proposer to the player who apparently has better scored in skill tasks executed before the UG or DG or has more contributed, through a previous luck game, to the amount to be shared. Such manipulations, however, could produce a possible overlapping between “ownership” and “merit,” that in this study we aimed to disentangle. We manipulated the participants’ initial endowment through a luck game, by increasing, decreasing or leaving it unchanged, to investigate whether winnings or losses by chance influenced offers in UG and DG in similar or different ways depending on their respective features. All participants played as proposers but this role was apparently random and disconnected from the outcomes of the luck game. Furthermore, we investigated whether the putative effect of experimental manipulation was mediated by the changes in emotions elicited by the luck game and/or by the emotions and beliefs related to decision-making. We used a non-economic version of the games, in which tokens were divided instead of money. In the study, 300 unpaid undergraduates (M = 152) from different degree programs, aged between 18 and 42 years, participated. The results revealed that the effect of outcome manipulation on offers was moderated by the specific structure of the UG and DG. Instead, emotional reactions barely mediated the effect of the experimental manipulation, suggesting that their role in those decisions is less relevant than is assumed in the literature.
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16641078
|
PSYCHOLOGY
|
10.3390/ejihpe10010031
|
The Organization of Self-Knowledge in Adolescence: Some Contributions Using the Repertory Grid Technique
|
(1) Background: This study aims to explore the usefulness of personal construct psychology as a comprehensive framework and assessment tool to embrace a diversity of self-knowledge organization constructs, and to account for developmental differences across adolescence. (2) Methods: The repertory grid technique was used to measure self-knowledge differentiation, polarization, discrepancies between Actual Self, Ideal Self, and Others, and implicative dilemmas, a particular kind of intrapersonal conflict. Data were collected from two samples of early and late adolescents, respectively. (3) Results: Globally, they showed that the organization of self-knowledge was different in both samples. In particular, older adolescents revealed a less polarized self-knowledge. In addition, they tended to construe higher Actual–Ideal self-discrepancies and to present more internal conflicts. No differences were found between early and late adolescents concerning global differentiation and the discrepancies between the self (Actual and Ideal) and the Others. (4) Conclusions: Despite the limitations of the study (e.g., small sample size, cross-sectional design), these novel results support the suitability of the repertory grid technique to capture developmental changes in self-knowledge organization during adolescence, as well as the explanatory potential of personal construct psychology to advance their understanding.
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22549625
|
PSYCHOLOGY
|
10.3390/cancers12020379
|
Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy
|
Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients’ data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data.
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20726694
|
ONCOLOGY
|
10.3390/ai1010005
|
Detection of Anomalies in Large-Scale Cyberattacks Using Fuzzy Neural Networks
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The fuzzy neural networks are hybrid structures that can act in several contexts of the pattern classification, including the detection of failures and anomalous behaviors. This paper discusses the use of an artificial intelligence model based on the association between fuzzy logic and training of artificial neural networks to recognize anomalies in transactions involved in the context of computer networks and cyberattacks. In addition to verifying the accuracy of the model, fuzzy rules were obtained through knowledge from the massive datasets to form expert systems. The acquired rules allow the creation of intelligent systems in high-level languages with a robust level of identification of anomalies in Internet transactions, and the accuracy of the results of the test confirms that the fuzzy neural networks can act in anomaly detection in high-security attacks in computer networks.
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26732688
|
AI
|
10.3389/fpsyg.2020.00123
|
Virtual Reality for the Assessment of Everyday Cognitive Functions in Older Adults: An Evaluation of the Virtual Reality Action Test and Two Interaction Devices in a 91-Year-Old Woman
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Performance-based functional tests for the evaluation of daily living activities demonstrate strong psychometric properties and solve many of the limitations associated with self- and informant-report questionnaires. Virtual reality (VR) technology, which has gained interest as an effective medium for administering interventions in the context of healthcare, has the potential to minimize the time-demands associated with the administration and scoring of performance-based assessments. To date, efforts to develop VR systems for assessment of everyday function in older adults generally have relied on non-immersive systems. The aim of the present study was to evaluate the feasibility of an immersive VR environment for the assessment of everyday function in older adults. We present a detailed case report of an elderly woman who performed an everyday activity in an immersive VR context (Virtual Reality Action Test) with two different types of interaction devices (controller vs. sensor). VR performance was compared to performance of the same task with real objects outside of the VR system (Real Action Test). Comparisons were made on several dimensions, including (1) quality of task performance (e.g., order of task steps, errors, use and speed of hand movements); (2) subjective impression (e.g., attitudes), and (3) physiological markers of stress. Subjective impressions of performance with the different controllers also were compared for presence, cybersickness, and usability. Results showed that the participant was capable of using controllers and sensors to manipulate objects in a purposeful and goal-directed manner in the immersive VR paradigm. She performed the everyday task similarly across all conditions. She reported no cybersickness and even indicated that interactions in the VR environment were pleasant and relaxing. Thus, immersive VR is a feasible approach for function assessment even with older adults who might have very limited computer experience, no prior VR exposure, average educational experiences, and mild cognitive difficulties. Because of inherent limitations of single case reports (e.g., unknown generalizability, potential practice effects, etc.), group studies are needed to establish the full psychometric properties of the Virtual Reality Action Test.
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16641078
|
PSYCHOLOGY
|
10.3389/fpsyg.2020.00133
|
Trajectories of Development and Socialization of Trans Brazilian Youth Through Self-Portraits
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The aim of this research was to explore the meanings of childhood memory established by young people who identify themselves as trans. In a chauvinistic country such as Brazil, sexual socialization of non-cisgender youth is beset by unique challenges, such as discrimination and violence. This study was based on the proposal of a self-portrait method as a content trigger in interviews with three trans young women who reported their life stories. We analyzed data using the oral story technique, through which the described themes came up. The results presented developmental narratives related to gender issue from childhood, which reflected on the experience on youth. Reports of discrimination based on the image of others (family, school, and community) about the gender development of the participants and their relationship with their bodies stand out. We see the importance of reflecting on life history memories in trans identity in order to give meaning to this experience. The influence of heteronormative and sexist Brazilian culture is noticed in the participants’ reports.
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16641078
|
PSYCHOLOGY
|
10.1186/s40359-020-0383-z
|
The relationship between personality traits and marital satisfaction: a systematic review and meta-analysis
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Background: Personality traits can be used to predict an individual’s behaviors in different life situations, including marital life situations. Marital satisfaction that is influenced by different factors is a criterion used to assess couples’ relationship quality. The goal of the present study was to review Iranian studies on the correlation between personality traits and marital satisfaction.Methods: In this systematic review, all the related Iranian studies in international databases, including Google Scholar, PubMed, Web of Science (ISI) and Scopus, and national databases, including Scientific Information Database (SID) and MagIran were reviewed. The following keywords and also combinations of them were used to search the databases: “Marital satisfaction,” “Personality traits,” “Personality factors,” “Big five model of personality,” and “Iran.”Results: A total of 18 correlational studies, without any time limitation, with a total sample of 4049, were reviewed. The following correlation coefficients were found between marital satisfaction and personality traits: r = − 0.439 with neuroticism (95% Confidence Interval [CI]: 0.27–0.60), r = 0.833 with extraversion (95% CI: 0.77–0.88), r = 0.777 with openness (95% CI: 0.70–0.84), r = 0.855 with agreeableness (95% CI: 0.80–0.90), and r = 0.90 with conscientiousness (95% CI: 0.84–0.95).Conclusions: Couples high in Neuroticism experience lower levels of marital satisfaction, and couples high in Conscientiousness are more satisfied with their marital life.
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20507283
|
PSYCHOLOGY
|
10.1186/s40594-019-0199-7
|
The use and effectiveness of colorful, contextualized, student-made material for elementary mathematics instruction
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Background: There is anecdotal evidence that many elementary teachers integrate mathematics lessons and art activities by having students first make colorful, rich material that is subsequently used in an instructional activity. However, it is unclear whether such activities effectively promote learning and transfer of mathematical concepts. The goal of the present research was to examine the use and effectiveness of such “math-and-art” activities on children’s ability to acquire basic fraction knowledge. We report the results of a survey of practicing elementary school teachers in the United States, their use of activities involving physical material, and the resources they use for ideas to supplement the standard curriculum. Two experiments examined first-grade students’ learning, transfer, and recognition of fraction knowledge from rich, contextualized material versus simple, generic material. Results: The survey results confirm that many U.S. teachers use math-and-art activities and are often inspired by informal sources, such as Pinterest and YouTube. Experiment 1 examined the effectiveness of colorful, contextualized student-constructed material (paper pizzas) versus simple, pre-made material (monochromatic paper circles) in an instructional activity on fractions. Students who used the pre-made circles scored higher than those who used the student-made pizzas on pre-instruction tests of basic fraction knowledge, immediate tests of learning, and delayed tests of transfer. Experiment 2 tested students’ ability to spontaneously write fractions to describe proportions of pizzas and circles. Students who answered generic circle questions first were markedly more accurate than those who answered pizza questions first. Conclusions: These findings suggest that rich, contextualized representations, including those made by the student, can hinder students’ learning and transfer of mathematical concepts. We are not suggesting that teachers never integrate mathematics and colorful, contextualized material, and activities. We do suggest that elementary students’ mathematics learning can benefit when initial instruction involves simple, generic, pre-made material and opportunities for students to make and use colorful, contextualized representations come later.
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21967822
|
EDUCATION
|
10.3389/feduc.2020.00009
|
Difficulty of Summarization Items for Japanese Learners: Effects of Passages, Distractors, and Response Formats
|
This study aims to examine factors affecting the difficulty of summarization items for Japanese learners. In the process of item development, creating a connection between cognitive features related to target construct and the difficulty of test items is necessary to define the abilities to be measured. Previous studies have mainly focused on local reading comprehension, while this study addressed summarization skills at the paragraph level. The study originally developed items for an experiment that elicited three macrorules of the paragraph and text: deletion, generalization, and integration. This study evaluated the influence of passages, distractor characteristics central to summarization processes, and response formats on item difficulty, using item difficulty modeling. When editing distractors, characteristics of L2 learners' summarization were carefully reviewed and reflected. The participants included 150 freshmen from Japan, who were asked to answer experimental summarization items. The results of the linear logistic test model (LLTM) indicated that the main source of difficulty in summarization items was distractor characteristics. In particular, summaries with unnecessary information or lacking necessary information increased the level of difficulty. In addition, summaries with detailed information, such as episodes and examples, and with a viewpoint different from the author's, also increased difficulty. The effect of passage differences was found to be minimal. A difference in response formats moderately affected item difficulty, and the extended-matching format was slightly more difficult than the conventional multiple-choice format. This study suggested that test developers and item writers should pay attention to distractor development, to limit students' errors when measuring summarization skills of L2 learners.
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2504284X
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EDUCATION
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10.3389/feduc.2019.00165
|
Contrast and Assimilation Effects on Self-Evaluation of Performance and Task Interest in a Sample of Elementary School Children
|
Social comparison processes and the social position within a school class already play a major role in performance evaluation as early as in elementary school. The influence of contrast and assimilation effects on self-evaluation of performance as well as task interest has been widely researched in observational studies under the labels big-fish-little-pond and basking-in-reflected-glory effect. This study examined the influence of similar contrast and assimilation effects in an experimental paradigm. Fifth and sixth grade students (n = 230) completed a computer-based learning task during which they received social comparative feedback based on 2 × 2 experimentally manipulated feedback conditions: social position (high vs. low) and peer performance (high vs. low). Results show a more positive development of task interest and self-evaluation of performance in both the high social position and the high peer performance condition. When applied to the school setting, results of this study suggest that students who already perform well in comparison to their peer group are also the ones who profit most from social comparative feedback, given that they are the ones who usually receive the corresponding positive performance feedback.
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2504284X
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EDUCATION
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10.3389/fpsyg.2020.00143
|
Metacognitive Therapy for Adjustment Disorder in a Patient With Newly Diagnosed Pulmonary Arterial Hypertension: A Case Report
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Adjustment disorders (ADs) belong to the worldwide most diagnosed mental disorders and are particularly frequent in patients with an underlying physical illness. Pulmonary arterial hypertension (PAH) is a severe and disabling disease, which significantly impacts on quality of life and has high mortality rates. The authors here present the case of a young female who developed a severe adjustment disorder with both anxious and depressive symptoms after a diagnosis of PAH requiring intensive care treatment due to right heart failure. Psychosocial functioning was severely impaired, and physical health reduced. Following hemodynamic stabilization and the establishment of PAH treatment, the patient was admitted to the Department of Psychiatry, Social Psychiatry and Psychotherapy and received metacognitive therapy (MCT). AD with mixed anxiety and depressed mood was diagnosed according to DSM-V criteria. At the start of treatment, she reported significant mental distress, indicated by a total sum score of the Hospital Anxiety and Depression Scale (HADS) of 20 points. The 6-min walking distance was only 358 m before the patient was exhausted. She then was treated with MCT without further psychopharmacological drugs. After only four MCT sessions, she fully remitted from AD which was accompanied by an 11-point reduction in the HADS (to 9 points). MCT specific scores also improved (MCQ-30 sum score decreased from 77 to 35). Notably, physical capacity improved as well, documented by an improved walking distance (439 m; +22%). This is the first case of a patient with AD in the context of PAH treated with MCT. The case report suggests that MCT is a possible psychotherapeutic treatment option for AD in the context of a potentially life-threatening disease. The study design does not permit an attribution of outcome to MCT but it suggests MCT is a potentially viable and acceptable treatment option.
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16641078
|
PSYCHOLOGY
|
10.3389/fpsyg.2020.00225
|
Southerners Are Wiser Than Northerners Regarding Interpersonal Conflicts in China
|
Initial evidence suggests that cultural differences have consequences for wise reasoning (perspective taking, consideration of change and alternatives, intellectual humility, search for compromise, and adopting an outsider’s vantage point), with more reports of wise reasoning about interpersonal conflicts among Japanese (as compared to American) young and middle-aged adults. Similarly, we found that people from the rice-farming area of southern China also exhibited greater wise reasoning when they encountered conflicts with a friend or in the workplace than those from the wheat-farming area of northern China (N = 487, 25 provinces). The relationship between rice farming and wise reasoning was mediated by loyalty/nepotism. This research advances study of the relationship between wisdom and culture. It also provides evidence for the influence of social-ecological factors on wisdom and culture.
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16641078
|
PSYCHOLOGY
|
10.3389/fpsyg.2020.00038
|
How Does Work Motivation Impact Employees’ Investment at Work and Their Job Engagement? A Moderated-Moderation Perspective Through an International Lens
|
This paper aims at shedding light on the effects that intrinsic and extrinsic motivation, as predictors, have on heavy work investment of time and effort and on job engagement. Using a questionnaire survey, this study conducted a moderated-moderation analysis, considering two conditional effects—worker’s status (working students vs. non-student employees) and country (Israel vs. Japan)—as potential moderators, since there are clear cultural differences between these countries. Data were gathered from 242 Israeli and 171 Japanese participants. The analyses revealed that worker’s status moderates the effects of intrinsic and extrinsic motivation on heavy work investment of time and effort and on job engagement and that the moderating effects were conditioned by country differences. Theoretical and practical implications and future research suggestions are discussed.
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16641078
|
PSYCHOLOGY
|
10.3390/cancers12020503
|
A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment
|
In this study, for the first time, we precisely assembled the poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate into a mixed micellar system for the embedment of the anticancer drug doxorubicin. Importantly, the intracellular drug-releasing behaviors could be controlled by changing the secondary structures of poly-γ-benzyl-l-glutamate via the precise regulation of the buffer’s pH value. Under neutral conditions, the micellar architectures were stabilized by both α-helix secondary structures and the microcrystalline structures. Under acidic conditions (pH 4.0), the interior structures transformed into a coil state with a disordered alignment, inducing the release of the loaded drug. A remarkable cytotoxicity of the Dox-loaded mixed micelles was exhibited toward human lung cancer cells in vitro. The internalizing capability into the cancer cells, as well as the intracellular drug-releasing behaviors, were also identified and observed. The secondary structures containing Dox-loaded mixed micelles had an outstanding antitumor efficacy in human lung cancer A549 cells-bearing nude mice, while little toxicities occurred or interfered with the hepatic or renal functions after the treatments. Thus, these pH-tunable α-helix-containing mixed micelles are innovative and promising for controlled intracellular anticancer drug delivery.
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20726694
|
ONCOLOGY
|
10.3389/feduc.2020.00018
|
Three Flute Players’ Lived Experiences of Dalcroze Eurhythmics in Preparing Contemporary Music for Performance
|
This qualitative study presents an interpretative phenomenological analysis of the lived experiences of three flute players who practice Dalcroze Eurhythmics, an approach to teaching, learning, and understanding music through exploring various music-movement relationships in social, creative, and rigorous ways. Our research seeks to understand how these individuals make sense of their lived experiences of Dalcroze Eurhythmics in learning, rehearsing, and performing contemporary music. Data collected through semi-structured interviews were analyzed and interpreted to create codes and categories in each data set. A cross-case analysis brought to light eight main themes: Body and breath; The body as a ‘way in’; Learning through the body overcomes specific technical difficulties; An embodied relationship with the score; Deeper knowledge and connection to music; Clarifying own interpretations; Communication with the audience; A bigger picture beyond the instrument. This study provides new insights into how learning through Dalcroze Eurhythmics can help individuals prepare repertoire for performance. As such, it may be of use to Dalcroze students and teachers, to flute performers and teachers, and to teachers and performers of other instruments who wish to explore the potential of Dalcroze Eurhythmics in learning, rehearsing, and performing contemporary music. The analysis also reveals insights that may be relevant to other repertoires.
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2504284X
|
EDUCATION
|
10.3389/fonc.2020.00192
|
Clinico-Immunological Profile of a 67-Year-Old Woman Affected by HER2-Positive Breast Cancer and Autoimmune Dermatomyositis
|
A patient with HER2-positive early breast cancer (BC) developed dermatomyositis (DM), which disappeared after the first administration of adjuvant trastuzumab. No HER2 overexpression/amplification was observed in DM skin biopsies. Both BC and skin immune infiltrates were composed mostly of CD3+ T-lymphocytes. Interestingly, tumor-infiltrating lymphocytes expressed PD-1, which was negligible in skin-infiltrating lymphocytes, while both BC cells and keratinocytes were PD-L1-positive. High serum levels of endogenous anti-HER2 antibodies were detected, confirming the induction of a HER2-specific adaptive immune response. It may be argued that HER2-specific T-lymphocytes cross-reacted with one or more unknown skin antigens, causing DM. Trastuzumab may have silenced skin cross-reaction by eliminating any residual HER2-positive micrometastatic disease and, thus, inducing DM remission.
|
2234943X
|
ONCOLOGY
|
10.3389/fonc.2020.00212
|
Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma
|
Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC.
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2234943X
|
ONCOLOGY
|
10.3390/educsci10030046
|
An Experiential Online Training Approach for Underrepresented Engineering and Technology Students
|
Workforce pipelines are essential to sustain a productive workforce in an increasingly competitive, high-tech environment. Advanced automation, sensors, materials and data analytics will increase the need for highly skilled workers in the manufacturing (and manufactured construction) sector. Attracting and developing the next-generation workforce is not without its challenges; however, students are often deficient in technical skills and generally have negative perceptions about manufacturing and construction. As a result, new education and training models have been developed to provide instruction at all levels of the educational system, with a focus on both traditional students and non-traditional students, including ethnic minorities, women, veterans, disabled persons and older adult learners. This study focused specifically on certain underrepresented students in STEM programs offered at community colleges in the Great Plains region of the U.S. An available online training program by the Society of Manufacturing Engineers was used as a contextualized online training tool. The Learning Management System embedded in this online training tool was used to gather student data. Conducting multiple regression analyses on the test outcomes, completion rates, and improvement between post-test and pre-test scores showed that female participants achieved greater improvement between pre- and post-test scores than males, and achieved higher rates of credentialing compared to all other demographic groups. African American participants achieved greatest improvement between pre- and post-test scores than all other ethnic groups while Hispanics achieved higher rates of module completion. Additionally, this study also examines the background related to contextualized teaching and learning, as well as the effectiveness of this delivery method for these underrepresented populations.
|
22277102
|
EDUCATION
|
10.1186/s40594-020-00206-7
|
Exploring STEM postsecondary instructors’ accounts of instructional planning and revisions
|
Background: Local and national initiatives to improve the learning experiences of students enrolled in Science, Technology, Engineering, and Mathematics (STEM) courses have been on-going for a couple of decades with a heightened momentum within the last 10 years. However, recent large-scale studies have demonstrated that transmission of information is still the primary mode of instruction in STEM courses across the undergraduate curriculum. The limited impact of instructional change reform efforts can be partly explained by the one-sided focus of educational research on the development of evidence-based instructional practices and production of evidence demonstrating their impact on student learning. This has been done at the expense of understanding faculty members’ instructional practices and mindsets about teaching and learning that underlie their practices. This study addresses this gap in the literature by characterizing STEM instructors’ instructional intentions and reflections on their teaching performance for a week of instruction. Data was collected through semi-structured interviews with 42 STEM faculty members from one doctorate-granting institution in the USA. Results: STEM instructors in this study had teacher-centric mindsets with respect to their instructional planning (e.g., content-focused learning goals, lecture is seen as an engagement strategy). We found that these instructors mostly saw formative assessment tools as engagement strategy rather than tools to monitor student learning. Reflections on their level of satisfaction with their week of teaching focused heavily on content coverage and personal feelings and minimally considered student learning. Finally, we found that pedagogical discontent was not a driver of planned course revisions. Conclusions: This study identifies mismatches between STEM instructors’ teaching mindsets and current approaches to instructional change. STEM instructors in this study paid minimal attention to student learning when considering course-level revisions and many of their reflections were anchored in their personal feelings. However, instructional reform strategies often attempt to convince faculty of a new approach by demonstrating its impact on student learning. The misalignment identified in this study further highlights the need to better characterize STEM instructors’ cognition around teaching so that reform efforts can better meet them where they are.
|
21967822
|
EDUCATION
|
10.3390/ai1010006
|
R-KG: A Novel Method for Implementing a Robot Intelligent Service
|
Aiming to solve the problem of environmental information being difficult to characterize when an intelligent service is used, knowledge graphs are used to express environmental information when performing intelligent services. Here, we specially design a kind of knowledge graph for environment expression referred to as a robot knowledge graph (R-KG). The main work of a R-KG is to integrate the diverse semantic information in the environment and pay attention to the relationship at the instance level. Also, through the efficient knowledge organization of a R-KG, robots can fully understand the environment. The R-KG firstly integrates knowledge from different sources to form a unified and standardized representation of a knowledge graph. Then, the deep logical relationship hidden in the knowledge graph is explored. To this end, a knowledge reasoning model based on a Markov logic network is proposed to realize the self-developmental ability of the knowledge graph and to further enrich it. Finally, as the strength of environment expression directly affects the efficiency of robots performing services, in order to verify the efficiency of the R-KG, it is used here as the semantic map that can be directly used by a robot for performing intelligent services. The final results prove that the R-KG can effectively express environmental information.
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26732688
|
AI
|
10.1186/s40594-020-00205-8
|
Conceptual framework of STEM based on Japanese subject principles
|
Background: School education should improve science, technology, engineering, and mathematics (STEM) ability not only in science and mathematics but also in technology and engineering. However, practice and research are being conducted without clear definitions and methods for STEM education. Moreover, the positioning and characteristics of the technology included in each STEM field are unclear. Therefore, it is necessary to propose an appropriate framework for practice of STEM from the viewpoint of technology education. In response to this need, this commentary proposes a conceptual framework for the appropriate practice of STEM education. Results: First, we referred to the perspectives and thinking styles of the fields of science, technology, and mathematics in the Japanese curriculum to specify the approach of the education system to each subject included in STEM. Next, to determine the concept of engineering in STEM education, we referred to the definition of engineering presented in Japan, the USA, and the UK. We positioned engineering, which means creating structures, processes, systems, etc., as a practical STEM activity and attempted to relate it to the unique perspectives and thinking styles of mathematics, science, and technology. Conclusion: We proposed a conceptual framework for the appropriate practice of STEM education based on the principles of subjects in the Japanese curriculum. The conceptual framework suggests that a means to improve the practice of STEM education is to retain the principles of science, technology, and mathematics in the activity of engineering. It can be inferred that the key point for practicing STEM education is to examine and design the appropriate order and combination of the learning process and activities based on the proposed conceptual framework. Although this framework is theoretical, it can be useful in determining an adequate practice of STEM education and clarifying the relationship between STEM education and technology education.
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21967822
|
EDUCATION
|
10.3390/ejihpe10010037
|
The Role of Field Training in STEM Education: Theoretical and Practical Limitations of Scalability
|
In this article, we consider the features of the perception of student information in science, technology, engineering, and mathematics (STEM) education, in order to draw the attention of researchers to the topic of learning in practice through field training. The article shows the results of these studies in Russia and the Commonwealth of Independent States (CIS countries: Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, and Uzbekistan, as an example) to reflect the global trends. For this purpose, we examined the expectations of students in Russia and the CIS countries from training related to lectures and field training. We created a questionnaire and distributed it in three Moscow-based universities (Moscow State University of Geodesy and Cartography—MIIGAiK, Moscow Aviation Institute—MAI, and Moscow City University—MCU). Our key assumption is that field practices in Russian universities are qualitatively different from the phenomenon described in European literature, where digital or remote field practices have already emerged. The results obtained through the survey show the tendency of students’ perceptions to fulfill practical duties (in a laboratory with instruments of field training) in STEM education.
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22549625
|
PSYCHOLOGY
|
10.3390/cancers12030640
|
Proton Pump Inhibitors Reduce Pancreatic Adenocarcinoma Progression by Selectively Targeting H+, K+-ATPases in Pancreatic Cancer and Stellate Cells
|
Pancreatic duct cells are equipped with acid/base transporters important for exocrine secretion. Pancreatic ductal adenocarcinoma (PDAC) cells may utilize such transporters to acidify extracellular tumor microenvironment, creating a niche favoring cell proliferation, fibrosis and resistance to chemotherapy—all contributing to the notoriously bad prognosis of this disease. Here, we report that gastric and non-gastric H+, K+-ATPases (coded by ATP4A and ATP12A) are overexpressed in human and murine pancreatic cancer and that we can target them specifically with proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) in in vitro models of PDAC. Focusing on pantoprazole, we show that it significantly reduced human cancer cell proliferation by inhibiting cellular H+ extrusion, increasing K+ conductance and promoting cyclin D1-dependent cell cycle arrest and preventing STAT3 activation. Pantoprazole also decreased collagen secretion from pancreatic stellate cells. Importantly, in vivo studies show that pantoprazole treatment of tumor-bearing mice reduced tumor size, fibrosis and expression of angiogenic markers. This work provides the first evidence that H+, K+-ATPases contribute to PDAC progression and that these can be targeted by inhibitors of these pumps, thus proving a promising therapeutic strategy.
|
20726694
|
ONCOLOGY
|
10.3389/fonc.2020.00324
|
Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk
|
Regardless of the promising results of certain immune checkpoint blockers, current immunotherapeutics have met a bottleneck concerning response rate, toxicity, and resistance in lung cancer patients. Accumulating evidence forecasts that the crosstalk between tumor and immune cells takes center stage in cancer development by modulating tumor malignancy, immune cell infiltration, and immune evasion in the tumor microenvironment (TME). Cytokines and chemokines secreted by this crosstalk play a major role in cancer development, progression, and therapeutic management. An increased infiltration of Tumor-associated macrophages (TAMs) was observed in most of the human cancers, including lung cancer. In this review, we emphasize the role of cytokines and chemokines in TAM-tumor cell crosstalk in the lung TME. Given the role of cytokines and chemokines in immunomodulation, we propose that TAM-derived cytokines and chemokines govern the cancer-promoting immune responses in the TME and offer a new immunotherapeutic option for lung cancer treatment.
|
2234943X
|
ONCOLOGY
|
10.1186/s40594-020-00209-4
|
Effects of school climate and teacher self-efficacy on job satisfaction of mostly STEM teachers: a structural multigroup invariance approach
|
Background: Identification and retention of effective teachers in STEM education play cardinal roles in teacher recruitment exercises worldwide. Studies on factors that characterize effective teachers have therefore gained popularity in recent times. Teacher self-efficacy, job satisfaction and school climate are among other factors that have attracted global attention. Thus, proper understanding of the relations between these factors is equally important. The purpose of this study is to validate and cross-validate a model of direct/indirect effects of school climate and teacher self-efficacy on job satisfaction. Results: The data used for the current study are extracted from a publicly available data of Teaching and Learning International Survey (TALIS) 2018 survey. Structural equation modeling approach was used in the analyses coupled with robust maximum likelihood to ensure accurate estimations in the models. The results of the validated models show a strong direct impact of school climate on job satisfaction, a direct impact of teacher self-efficacy on job satisfaction and a mediating effect of teacher self-efficacy between school climate and job satisfaction. This model exhibits structural invariance in factor loadings, intercepts and regression weights across two independent samples from a population of 3951 lower secondary school teachers in Norway. Conclusion: The findings of this study do provide empirical evidence for the relations between teacher self-efficacy, job satisfaction and school climate among Norwegian lower secondary school teachers. The cross-validation of these relations was also established using an independent sample to enhance generalization of the findings. Two methodological observations concerning recoding of some items as well as an addition of item cross-loading in the measurement model of the job satisfaction scales are raised and addressed. It is therefore recommended that researchers who will be using TALIS 2018 data should take note of these observations.
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21967822
|
EDUCATION
|
10.1186/s40594-020-00207-6
|
Research and trends in STEM education: a systematic review of journal publications
|
With the rapid increase in the number of scholarly publications on STEM education in recent years, reviews of the status and trends in STEM education research internationally support the development of the field. For this review, we conducted a systematic analysis of 798 articles in STEM education published between 2000 and the end of 2018 in 36 journals to get an overview about developments in STEM education scholarship. We examined those selected journal publications both quantitatively and qualitatively, including the number of articles published, journals in which the articles were published, authorship nationality, and research topic and methods over the years. The results show that research in STEM education is increasing in importance internationally and that the identity of STEM education journals is becoming clearer over time.
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21967822
|
EDUCATION
|
10.3389/fpsyg.2020.00356
|
A Multiple-Baseline Evaluation of Acceptance and Commitment Therapy Focused on Repetitive Negative Thinking for Comorbid Generalized Anxiety Disorder and Depression
|
Repetitive negative thinking (RNT) is a core feature of generalized anxiety disorder (GAD) and depression. Recently, some studies have shown promising results with brief protocols of acceptance and commitment therapy (ACT) focused on RNT in the treatment of emotional disorders in adults. The current study analyzes the effect of an individual, 3-session, RNT-focused ACT protocol in the treatment of severe and comorbid GAD and depression. Six adults meeting criteria for both disorders and showing severe symptoms of at least one of them participated in the study. A delayed multiple-baseline design was implemented. All participants completed a 5-week baseline without showing improvement trends in emotional symptoms (Depression Anxiety and Stress Scale – 21; DASS-21) and pathological worry (Penn State Worry Questionnaire; PSWQ). The ACT protocol was then implemented, and a 3-month follow-up was conducted. Five of the six participants showed clinically significant changes in the DASS-21 and the PSWQ. The standardized mean difference effect sizes for single-case experimental design were very large for emotional symptoms (d = 3.34), pathological worry (d = 4.52), experiential avoidance (d = 3.46), cognitive fusion (d = 3.90), repetitive thinking (d = 4.52), and valued living (d = 0.92 and d = 1.98). No adverse events were observed. Brief, RNT-focused ACT protocols for treating comorbid GAD and depression deserve further empirical tests.
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16641078
|
PSYCHOLOGY
|
10.1186/s40594-020-00210-x
|
Integrating science and engineering practices: outcomes from a collaborative professional development
|
Background: The Next Generation Science Standards accentuate engineering design along with scientific inquiry, emphasizing the relationship between scientific investigations and engineering design in solving problems and devising new ideas and technologies. The goal is for students to realize the importance of science and engineering in innovation and in solving many of today’s challenges. The Next Generation Science Standards contends that a working knowledge and practicality of engineering design prepares students for embracing the challenges of the future. To support students in developing these capabilities, teachers are tasked with the responsibility of facilitating science instruction that integrates science and engineering practices. This is a challenge since a majority of them have little to no understanding of engineering applications.Results: An interdisciplinary team, consisting of science education and mechanical engineering faculty and doctoral students from each discipline, and science, mathematics, and career and technical curriculum supervisors, collaborated with middle school science, mathematics, and career and technical education teachers to develop a framework for integrating engineering practices into their curricula. The exploratory nature of the project, and instructional outcomes with their students, supported teachers in developing an understanding and value for science and engineering practices. As a result, they were motivated to critique and revise their practices, aiming to develop and implement instruction that they perceived as beneficial to their students.Conclusion: With the surge in emphasis on preparing K-12 students for the STEM workforce, initiatives devoted to exposing teachers and students to STEM applications have also increased. The findings from this study could be useful for informing these initiatives, since they reveal the learning experiences of the teachers while processing instructional strategies for integrating science and engineering practices into their curriculum. The findings highlight factors that motivated these teachers to reform their instructional practices, as well as their deliberations while endeavoring to assimilate the strategies into their curricular activities.
|
21967822
|
EDUCATION
|
10.1186/s40594-020-00208-5
|
Rubrics to assess critical thinking and information processing in undergraduate STEM courses
|
Background: Process skills such as critical thinking and information processing are commonly stated outcomes for STEM undergraduate degree programs, but instructors often do not explicitly assess these skills in their courses. Students are more likely to develop these crucial skills if there is constructive alignment between an instructor’s intended learning outcomes, the tasks that the instructor and students perform, and the assessment tools that the instructor uses. Rubrics for each process skill can enhance this alignment by creating a shared understanding of process skills between instructors and students. Rubrics can also enable instructors to reflect on their teaching practices with regard to developing their students’ process skills and facilitating feedback to students to identify areas for improvement. Results: Here, we provide rubrics that can be used to assess critical thinking and information processing in STEM undergraduate classrooms and to provide students with formative feedback. As part of the Enhancing Learning by Improving Process Skills in STEM (ELIPSS) Project, rubrics were developed to assess these two skills in STEM undergraduate students’ written work. The rubrics were implemented in multiple STEM disciplines, class sizes, course levels, and institution types to ensure they were practical for everyday classroom use. Instructors reported via surveys that the rubrics supported assessment of students’ written work in multiple STEM learning environments. Graduate teaching assistants also indicated that they could effectively use the rubrics to assess student work and that the rubrics clarified the instructor’s expectations for how they should assess students. Students reported that they understood the content of the rubrics and could use the feedback provided by the rubric to change their future performance. Conclusion: The ELIPSS rubrics allowed instructors to explicitly assess the critical thinking and information processing skills that they wanted their students to develop in their courses. The instructors were able to clarify their expectations for both their teaching assistants and students and provide consistent feedback to students about their performance. Supporting the adoption of active-learning pedagogies should also include changes to assessment strategies to measure the skills that are developed as students engage in more meaningful learning experiences. Tools such as the ELIPSS rubrics provide a resource for instructors to better align assessments with intended learning outcomes.
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21967822
|
EDUCATION
|
10.1186/s40359-020-0391-z
|
The use of a psychological testing instrument as an indicator of dissatisfaction with aesthetic dental treatment – a preliminary study
|
Background: The use of psychological testing to indicate the potential for dissatisfaction with dental treatment has many potential patient and clinician benefits but has been rarely investigated. The study aimed to explore the use of the Symptom Checklist-90-Revised (SCL-90-R) psychological testing instrument in describing the relationship between pre-treatment psychological traits and aesthetic restorative treatment satisfaction. Methods: Thirty patients requiring aesthetic restorative dental treatment completed three questionnaires, namely 1) a pre-treatment expectation assessment, 2) an SCL-90-R analysis pre-treatment and 3) an outcome assessment post-treatment to assess patient’s expectations and satisfaction of the proposed dental treatment relating to function, aesthetics, comfort and tissue preservation. Logistic regression models were used to assess the impact of psychological variables on patient satisfaction after adjusting for baseline expectations (P < 0.05). Results: The satisfaction for the aesthetic component of treatment was significantly associated with psychoticism and positive symptom distress index. The satisfaction for the comfort component of treatment was significantly associated with obsessive compulsive symptoms, depression and anxiety. Following adjustment for baseline expectation, tissue preservation satisfaction was associated with somatization, obsessive compulsive, interpersonal sensitivity, depression and global severity index. No baseline psychological measures were significantly associated with chewing satisfaction. Conclusions: The SCL-90-R shows initial promise in assisting clinicians to identify and understanding patients who have a high risk of dissatisfaction with aesthetic dental treatment. The ability to indicate aesthetic restorative treatment dissatisfaction is of great benefit to clinicians in maximising success and mitigating risk.
|
20507283
|
PSYCHOLOGY
|
10.3389/frai.2020.00009
|
Toward a Taxonomy for Adaptive Data Visualization in Analytics Applications
|
Data analytics as a field is currently at a crucial point in its development, as a commoditization takes place in the context of increasing amounts of data, more user diversity, and automated analysis solutions, the latter potentially eliminating the need for expert analysts. A central hypothesis of the present paper is that data visualizations should be adapted to both the user and the context. This idea was initially addressed in Study 1, which demonstrated substantial interindividual variability among a group of experts when freely choosing an option to visualize data sets. To lay the theoretical groundwork for a systematic, taxonomic approach, a user model combining user traits, states, strategies, and actions was proposed and further evaluated empirically in Studies 2 and 3. The results implied that for adapting to user traits, statistical expertise is a relevant dimension that should be considered. Additionally, for adapting to user states different user intentions such as monitoring and analysis should be accounted for. These results were used to develop a taxonomy which adapts visualization recommendations to these (and other) factors. A preliminary attempt to validate the taxonomy in Study 4 tested its visualization recommendations with a group of experts. While the corresponding results were somewhat ambiguous overall, some aspects nevertheless supported the claim that a user-adaptive data visualization approach based on the principles outlined in the taxonomy can indeed be useful. While the present approach to user adaptivity is still in its infancy and should be extended (e.g., by testing more participants), the general approach appears to be very promising.
|
26248212
|
AI
|
10.3390/educsci10030081
|
Teacher Training in Intercultural Education: Teacher Perceptions
|
Background: The aim of the present study was to evaluate teacher perceptions on the training received in intercultural education. Methods: The article presents a quantitative, non- experimental and ex-post-facto type of research; directed to inquire about the perceptions of the teachers of primary education in Andalusia (Spain) in relation to the intercultural training received. Based on the descriptive survey method, two questionnaires were administered to a sample composed of 320 students and 80 teachers. Results: The results show certain strengths of the training teacher programs in the field of interculturality (encouragement of reflection, participation and collaboration …), as well as weaknesses (decontextualization, inflexibility, primacy of theoretical learning, non-transversal character, etc.). Conclusions: Despite strengths, intercultural teacher training continues to be a challenge in Andalusia.
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22277102
|
EDUCATION
|
10.3390/cancers12030745
|
A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy
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The chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cells to elicit attack by NK cells. This study measured ADAM9 mRNA levels in blood samples of advanced HCC patients (n = 10). In newly diagnosed patients (n = 5), the plasma ADAM9 mRNA level was significantly higher than that in healthy controls (3.001 versus 1.00, p < 0.05). Among four patients treated with nivolumab therapy, two patients with clinical response to nivolumab showed significant decreases in fold changes of serum ADAM9 mRNA level from 573.98 to 262.58 and from 323.88 to 85.52 (p < 0.05); however, two patients with no response to nivolumab did not. Using the Cancer Genome Atlas database, we found that higher expression of ADAM9 in tumor tissues was associated with poorer survival of HCC patients (log-rank p = 0.00039), while ADAM10 and ADAM17 exhibited no such association. In addition, ADAM9 expression showed a positive correlation with the expression of inhibitory checkpoint molecules. This study, though small in sample size, clearly suggested that ADAM9 mRNA might serve as biomarker predicting clinical response and that the ADAM9-MICA-NKG2D system can be a good therapeutic target for HCC immunotherapy. Future studies are warranted to validate these findings.
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20726694
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ONCOLOGY
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10.3390/cancers12030755
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Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
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Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93–28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.
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20726694
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ONCOLOGY
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10.3389/fonc.2020.00377
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Editorial: Precision/Personalized Pediatric Oncology and Immune Therapies: Rather Customize Than Randomize
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Editorial on the Research Topic Precision/Personalized Pediatric Oncology and Immune Therapies: Rather Customize Than Randomize Personalization of treatment based on biological markers is being utilized in clinical medicine with increasing frequency. This trend, despite an effort to identify possible common patterns, reflects the reality that no two patients are alike, and no single clinical course is identical; not even within a group of seemingly similar patients (1). There are numerous clinical variations related to host or environment-dependent factors. Numerous examples of these interpersonal differences have been recognized with drugs such as pain-control medications, heart medications, or antimicrobials. The differences have been attributed to increased pharmacometabolic capacity, to different individual microbiomes and to genetic differences between individuals (2). The latter has led to development of an entirely new specialty—pharmacogenomics. While this clinical heterogeneity is well-appreciated in most major medical specialties, clinical oncology seems to represent, surprisingly enough, one of the exceptions (3, 4). Individualized treatments aim to optimize patient outcomes based on specific knowledge about diseases and their biological heterogeneity (5). This individualization of therapy is being adopted even in adult oncology where, at least traditionally, new therapeutic directions depended on success in large randomized clinical trials. Even in cancers where the numbers of adult patients are sufficient for large randomized double-blind clinical trials, the recent trends are to select the most suitable, genetically homogeneous, target population. This trend has been more inherent to pediatrics, where malignancies are implicitly considered rare diseases. However, the smaller populations and a personalized approach, has led to a very small number of drugs being approved for pediatric indications. The small number of patients and more personalized combinations of drugs tended to complicate statistical analysis and created problems for providing evidence of treatment efficacy in children with rare malignancies (Kyr et al.). When a large homogeneous population can be used—a randomized, double blind, placebo controlled trial should remain the gold standard. However, this is rarely possible considering cancer heterogeneity and interpersonal differences in drug response. In pediatrics, the numbers of patients are relatively small and the diseases heterogeneous. The process of randomization and blinding were originally developed to protect the subjects and the investigators from pre-existing subjective preferences for a procedure or a compound under evaluation (6, 7). Randomization was intended to minimalize the effect of confounders, to achieve comparable groups and to permit calculation of an unbiased estimate of the treatment effect. While the use of “blinding” in order to eliminate bias is obvious, there is another important tool that makes randomized trials powerful with regard to rendering reliable and unbiased results. It is the balancing effect between investigated groups, especially with respect unknown covariates that cannot be easily eliminated through model adjustments nor stratification. As stressed above, randomization requires sufficient number of patients and adequate sample size to work. A test sample >200 is said to be less likely to be imbalanced for an important covariate (8). But in rare diseases, where the sample sizes are small (rarely more than a hundred), the usefulness of randomization for balancing of the groups is lost. Similarly, randomized, double blind, placebo-controlled trials may not be suitable for populations that are selected on a common, but infrequent genetic alteration(s). Those groups are also quite small. While the gold standard of clinical trials, a randomized, double blind, placebo controlled trial, may have made logical sense in the era before genomics, it may need to be modified for the era informed by testing for individualized traits and smaller groups. The concept of time-dependent variations is equally important (9). As documented in numerous recent publications, variations within an individual and implicitly, within the individual's macroscopic tumor, occur at velocity rates that cannot be measured by any contemporary techniques (10). It is this variability that constitutes a fundamental concern with the use of treatment group randomization. For a set of individuals being randomized using current rules, a critical prior assumption is made that all randomized individuals are, and will remain, biologically homogenous, and any further events can only be related to the time point of randomization. A further assumption is then made that no change within the set of investigated subjects occurs during the study period except the changes due to treatment. This is not true for cancers, which are known to evolve through continuously accumulating additional genomic alterations through mutations. Consequently, even if randomization was performed at baseline, the randomization effect is lost in any repeated evaluation during subsequent phases of such trials (11). Single patient trial designs or “N = 1” trials (12) are an alternative to population-based clinical trials, but a broad clinical application of this approach is hindered by the absence of a standardized work-up. Current practices are based on physician-specific or institution-enabled assessments of the biological characteristics of the patient and of the cancer tissue. This usually occurs in the form of a multidisciplinary institutional expert consensus referred to as “tumor boards” (13). This personalized treatment approach allows for consideration of disease heterogeneity as well as of time-dependent variations. This clinical plasticity, allows for treatment to be modified at various phases of the patient's journey based on disease course or on the patient's pharmacometabolic capacity to tolerate the selected treatment. The much-needed standardization of the pre-treatment workup of a patient selected to undergo personalized therapy would enable collection of outcomes from these “N = 1” trials in pediatric cancer across many institutions, enable statistical analysis, and provide evidence for changing therapeutic paradigms. Another issue arising in rare diseases, and therefore personalized pediatric oncology, is the identification of future target population likely to benefit from a trial result—the so called “patient horizon” (14). Patient horizon is either the number of patients in the trial, or the number who have the condition under treatment. This well-known concept is rarely utilized. To improve understanding of this concept let us take an extreme situation where all patients from the target population were randomized in 1:1 ratio for effective and ineffective treatment. In this case half of the patients are forced to receive an ineffective treatment as a price for knowing the absolute truth about the relative treatment efficacy between the two treatments. Yet, the same result could be obtained by giving either of the treatment randomly without any knowledge. An optimal size of a trial balances both extremes and maximizes the number of patients who benefit. The exact number of patients may not be known, but the order of magnitude of the optimal number can be calculated using the square root of the patient horizon size for a simple trial design. For example, for a finite population of 1,000 subjects, the optimal size of a trial is a few tenths. Considering disease rarity, especially in the era of molecular medicine, the issue of the target population size (the patient horizon) becomes relevant not in pediatric oncology, but in medicine in general (14). There are two principal issues to be addressed in current cancer medicine pertaining to: (i) Regulatory mechanisms of drug approval and market authorization. (ii) Evaluation of real-life clinical efficacy. A newly proposed drug approval marketing authorization pathway shall require an initial “Candidate Medicinal Product Safety Evaluation” (CMPSE, currently Phase I) and subsequent “Dose Defining Study” (DDS, currently Phase II). As we explained above a current medicinal product approval pathway is mechanistically “drug-centric” as the present practice relies on the ability of a Phase III clinical trial to provide evidence that the addition of a single compound to a standard treatment regimen is of clinical benefit leading to marketing authorization. This approach has become so biased that most resulting Phase III registration trial data do not provide clinically meaningful benefit (3); on top of that, testing for “me-too” drugs toward endpoints as “substantial equivalence or non-inferiority” is vastly contributing. Furthermore, it disregards the clinical need for different pathways for approval of medicines intended for use (A) in the entire world population (e.g., vaccines, antipyretics, pain killers, etc.) and for those intended for (B) specific subpopulations (e.g., LDL-C marker based treatments). In the latter setting, clinical laboratory diagnostics (CDx) are used as a guide or companion to a medicinal product to determine its applicability to a subject. A regulatory approval of medications targeting (C) somatic mutations, and/or (D) diseases that follow Mendelian inheritance or germline mutation (e.g., tyrosinemia type I. and the drug nitisinone) requires a special approval pathway and expedited translation to clinical practice. Summing up from a regulatory point of view, the testing phases CMPSE Phase I + DDS Phase II would allow for conditional medicinal product (pre)approval. Real-life clinical practice-based evaluation should then focus on designing “patient-centric” treatment strategies. Considering there are about 300 active drugs in oncology, and the number of 2 drugs combinations is about 45,000, or 4.4 million combinations for 3 drug combinations, Phase I testing for all these drug combinations is neither feasible nor realistic. New models such as: (i) identification of smaller pediatric cancer patient cohorts likely to benefit from a specific treatment because they have the relevant gene alteration(s), or (ii) the increasing use of multilayer profiling (markers) to diagnose, classify and monitor response in pediatric cancers (Fedorova et al.; Polaskova et al.) are therefore gaining in popularity. There is a need to validate combination treatment strategies, not just individual drugs or individual biomarkers. Attention should be directed at studying drug dosing in respective preclinical models and at identifying optimal biological dose rather than persist with the present maximum-tolerated dose. With most targeted agents, a target occupancy dose, i.e., dose required to stop/minimize pathway phosphorylation and RP2D /dose used in clinical setting (15) is the more appropriate identifier of a clinically relevant dose. As noted in many pre-clinical studies, combinations of targeted agents are often synergistic, and potentiate the effects of chemotherapy. A very good example of how combination therapy dosing can negatively influence the overall success of an innovative drug is the Mylotarg (gemtuzumab ozogamicin, alias GO) story. Gemtuzumab ozogamicin is a recombinant humanized IgG4 kappa antibody that is used to treat CD33 positive AML. It is conjugated with calicheamicin derivative, a cytotoxic antitumor antibiotic. The drug was initially tested in a randomized controlled trial leading to FDA approval via accelerated review in May 2000. However, the drug had intolerable toxicity and mortality at the 9 mg/m2 dose, and was voluntarily withdrawn from the market on 15th October 2010. It was subsequently tested at a much lower drug dose (3 mg/m2 instead of 9 mg/m2) and was shown to be just as effective with greatly improved safety profile. GO was therefore re-approved by the FDA on 1st September 2017 at lower dose (16). Taken together, if a new compound allowed to enter the real-life clinical practice-based evaluation (i.e., CMPSE + DDS passed) brings clinically meaningful benefit, this will lead to the full marketing authorization and consequently, reimbursement of such a novel compound. The use of chemotherapy in combination with a targeted biological agent is a commonly employed approach for enhancing the ability of chemotherapy to fight cancer. Commonly, the assumption that the inhibitory effect of the biological agent would be additive to the effect achieved by traditional chemotherapy or radiation is made. However, because of the synergistic action, the addition of a targeted biologic agent to a maximum tolerated dose (MTD) of chemotherapy, may make an already maximally toxic regimen almost lethal. In most cases, any benefit of tumor response ends up being concealed by unacceptable toxicities, and no overall survival benefit is seen. Yet, because the present design of clinical trials permits modification of only one variable between the two study arms, the dose of chemotherapy in the experimental treatment arm is rarely modified. The use of metronomic chemotherapy, with its goal of long-term “tumor control,” lower toxicity, and prevention of tumor progression (rather than immediate reduction in tumor size), may represent a more realistic strategy for testing targeted and immune therapies as add on to chemotherapy (13). However, because this low toxicity regimen can have a delayed onset of radiologically visible effect, it is often abandoned too early for a patient to benefit. An example of how biomarker assessment can help document the effects of targeted therapy earlier than it could be documented radiologically is provided in this issue (Polaskova et al.) discussing three patients with multiply relapsed Burkitt lymphoma treated with personalized therapy and their response being monitored using target phosphorylation. In summary, data for real-life evidence-based medicine addressing patient-focused clinical efficacy can be derived from time-dependent single-case designs. The new comprehensive efficacy evaluation model we present here, should be focused on treatment strategies using drug combinations rather than testing a single-compound within a randomized setting. We should modify the Phase III wherever feasible. The drug approval pathway should consist of “Candidate Medicinal Product Safety Evaluation” (previously Phase I) and “Dose Defining Study” (previously Phase II). This will bypass the often futile end-of-life enrollments in single drug clinical trials and bring about substantial cost reductions in development and implementation of new medicinal anticancer compounds to the market. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. LM2018125, AZV MZCR 16-33209A, 16-34083A, LQ1605, LO1604, LO1413, and LQ1601 projects from the National Program of Sustainability II (MEYS). 1. Liu K, Meng XL. There is individualized treatment. Why not individualized inference? Annu Rev Stat Its Appl. (2016) 3:79–111. doi: 10.1146/annurev-statistics-010814-020310 CrossRef Full Text | Google Scholar 2. Roden DM, McLeod HL, Relling MV, Williams MS, Mensah GA, Peterson JF, et al. Pharmacogenomics. Lancet. (2019) 394:521–32. doi: 10.1016/S0140-6736(19)31276-0 PubMed Abstract | CrossRef Full Text | Google Scholar 3. Davis C, Naci H, Gurpinar E, Poplavska E, Pinto A, Aggarwal A. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ. (2017) 359:j4530. doi: 10.1136/bmj.j4530 PubMed Abstract | CrossRef Full Text | Google Scholar 4. New Studies Question Whether Novel Anti-Cancer Drugs Are Worth Their Extra Cost [ESMO 2019 Press Release]. (2019). Available online at: (accessed January 9, 2020). 5. Allison KH, Sledge GW. Heterogeneity and cancer. Oncology. (2014) 28:2–3. PubMed Abstract | Google Scholar 6. Yoshioka A. Use of randomisation in the Medical Research Council's clinical trial of streptomycin in pulmonary tuberculosis in the 1940s. BMJ. (1998) 317:1220–3. doi: 10.1136/bmj.317.7167.1220 PubMed Abstract | CrossRef Full Text | Google Scholar 7. Bartholomew M. James Lind's treatise of the scurvy (1753). Postgrad Med J. (2002) 78:695–96. doi: 10.1136/pmj.78.925.695 PubMed Abstract | CrossRef Full Text | Google Scholar 8. Lachin JM. Properties of simple randomization in clinical trials. Control Clin Trials. (1988) 9:312–26. doi: 10.1016/0197-2456(88)90046-3 PubMed Abstract | CrossRef Full Text | Google Scholar 9. Demlova R, Zdrazilova-Dubska L, Sterba J, Stanta G, Valik D. Host-dependent variables: The missing link to personalized medicine. Eur J Surg Oncol. (2018) 44:1289–94. doi: 10.1016/j.ejso.2018.04.014 PubMed Abstract | CrossRef Full Text | Google Scholar 10. Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HYK, Chen R, et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. (2012) 148:1293–307. doi: 10.1016/j.cell.2012.02.009 PubMed Abstract | CrossRef Full Text | Google Scholar 11. Lindsey JK, Lambert P. On the appropriateness of marginal models for repeated measurements in clinical trials. Stat Med. (1998) 17:447–69. doi: 10.1002/(SICI)1097-0258(19980228)17:43.0.CO;2-G PubMed Abstract | CrossRef Full Text | Google Scholar 12. Nikles J, Mitchell G. N-of-1 trials in medical contexts. In: Nikles J, Mitchell G, editors. The Essential Guide to N-of-1 Trials in Health. Dordrecht: Springer Netherlands (2015). p. 43–55. doi: 10.1007/978-94-017-7200-6 CrossRef Full Text | Google Scholar 13. Klement GL, Arkun K, Valik D, Roffidal T, Hashemi A, Klement C, et al. Future paradigms for precision oncology. Oncotarget. (2016) 7:46813–31. doi: 10.18632/oncotarget.9488 PubMed Abstract | CrossRef Full Text | Google Scholar 14. Stallard N, Miller F, Day S, Hee SW, Madan J, Zohar S, et al. Determination of the optimal sample size for a clinical trial accounting for the population size. Biometrical J. (2017) 59:609–25. doi: 10.1002/bimj.201500228 PubMed Abstract | CrossRef Full Text | Google Scholar 15. Le Tourneau C, Gan HK, Razak ARA, Paoletti X. Efficiency of new dose escalation designs in dose-finding phase I trials of molecularly targeted agents. PLoS ONE. (2012) 7:e51039. doi: 10.1371/journal.pone.0051039 PubMed Abstract | CrossRef Full Text | Google Scholar 16. Umukoro C. A Start, Stop, GO Story in AML – Gemtuzumab Ozogamicin (Mylotarg®). (2017) Available online at: (accessed January 9, 2020). Keywords: personalized medicine, precision oncology, pediatric oncology, trial models, drug models, personalized precision pediatric oncology, clinical trial designs Citation: Kýr M, Klement GL, Zdrazilova-Dubska L, Demlova R, Valik D, Slaby O, Slavc I and Sterba J (2020) Editorial: Precision/Personalized Pediatric Oncology and Immune Therapies:...
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2234943X
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ONCOLOGY
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10.3389/fpsyg.2020.00524
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Onlife Extremism: Dynamic Integration of Digital and Physical Spaces in Radicalization
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This article argues that one should consider online and offline radicalization in an integrated way. Occasionally, the design of some counter-measure initiatives treats the internet and the “real” world as two separate and independent realms. New information communication technologies (ICTs) allow extremists to fuse digital and physical settings. As a result, our research contends that radicalization takes place in onlife spaces: hybrid environments that incorporate elements from individuals’ online and offline experiences. This study substantiates this claim, and it examines how algorithms structure information on social media by tracking users’ online and offline activities. Then, it analyzes how the Islamic State promoted onlife radicalization. We focus on how the Islamic State used Telegram, specific media techniques, and videos to connect the Web to the territories it controlled in Syria. Ultimately, the article contributes to the recalibration of the current debate on the relationship between online and offline radicalization on a theoretical level and suggests, on a practical level, potential counter measures.
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16641078
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PSYCHOLOGY
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10.3389/fpsyg.2020.00443
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Discrepancy in Ratings of Shared Decision Making Between Patients and Health Professionals: A Cross Sectional Study in Mental Health Care
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Background: A defined goal in mental health care is to increase the opportunities for patients to more actively participate in their treatment. This goal includes integrating aspects of user empowerment and shared decision-making (SDM) into treatment courses. To achieve this goal, more knowledge is needed about how patients and therapists perceive this integration. Objective: To explore patient experiences of SDM, to describe differences between patient and therapist experiences, and to identify patient factors that might reduce SDM experiences for patients compared to the experiences of their therapists. Methods: This cross-sectional study included 992 patients that had appointments with 267 therapists at Sørlandet Hospital, Division of Mental Health during a 1-week period. Both patients and therapists completed the CollaboRATE questionnaire, which was used to rate SDM experiences. Patients reported demographic and treatment-related information. Therapists provided clinical information. Results: The analysis included 953 patient-therapist responder pairs that completed the CollaboRATE questionnaire. The mean SDM score was 80.7 (SD 20.8) among patients, and 86.6 (SD 12.1) among therapists. Females and patients that did not use medication for mental health disorders reported higher SDM scores than males and patients that used psychiatric medications (83.3 vs. 77.7; p < 0.001 and 82.6 vs. 79.8; p = 0.03, respectively). Patients with diagnoses involving psychotic symptoms reported lower SDM scores than all the other patients (66.8 vs. 82.3; p < 0.001). The probability that a patient would report lower SDM scores than their therapist was highest among patients that received involuntary treatment (OR 3.2, p = 0.02), patients with treatment durations longer than 2.2 years (OR 1.9, p = 0.001), and patients that required day care or in-patient care (OR 3.2, p = 0.01 and OR 3.2, p < 0.001, respectively). Conclusion: We showed that both therapists and patients reported good SDM experiences in decisional situations, which indicated that SDM was implemented well. However, the SDM scores reported by in-patients and patients with prolonged or involuntary treatments were significantly lower than scores reported by their therapists. Our findings suggested that it remains a struggle in mental health care to establish a common understanding between patients and therapists in decisional processes regarding treatments for some patient groups.
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16641078
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PSYCHOLOGY
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10.1007/s00432-020-03190-1
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Attitude of cancer patients from online self-help groups towards physical activity
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Purpose Physical activity (PA) is important for cancer patients during and after therapy with respect to reducing side effects and improving quality of life. The aim of the study was to examine how physically active German cancer patients are and to identify predictors for PA. In addition, patients were asked about their attitude towards PA. Methods A questionnaire was passed on to members of self-help groups. Multiple regression analyses were run to examine possible predictors such as self-efficacy, patient activation, gender, previous PA, therapy status, and age for PA. Results 62% of the participants followed the official recommendations by the American Cancer Society for weekly aerobic activity. Multiple regression analyses could confirm age as a predictor for total PA. Higher self-efficacy and patient activation were associated with lower disease burden and a more positive attitude towards PA. Conclusion This study contributes to the minor knowledge about PA among cancer patients. The examined group showed that there is potential for improvement regarding PA, although the majority had a positive attitude towards PA. Because of the small sample size existing of online self-help group members, results should be taken with caution.
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14321335
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ONCOLOGY
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10.3389/fonc.2020.00416
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Inhibition of microRNA-155 Reduces Neuropathic Pain During Chemotherapeutic Bortezomib via Engagement of Neuroinflammation
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As a chemotherapeutic agent, bortezomib (BTZ) is used for the treatment of multiple myeloma with adverse effect of painful peripheral neuropathy. Our current study was to determine the inhibitory effects of blocking microRNA-155 (miR-155) signal on BTZ-induced neuropathic pain and the underlying mechanisms. We employed real time RT-PCR and western blot analysis to examine the miR-155 and expression of pro-inflammatory tumor necrosis factor-alpha receptor (TNFR1) in the dorsal horn of the spinal cord. Its downstream signals p38-MAPK and JNK and transient receptor potential ankyrin 1 (TRPA1) were also determined. Mechanical pain and cold sensitivity were assessed by behavioral test. In result, inhibition of miR-155 significantly attenuated mechanical allodynia and thermal hyperalgesia in BTZ rats, which was accompanied with decreasing expression of TNFR1, p38-MAPK, JNK, and TRPA1. In contrast, miRNA-155 mimics amplified TNFR1-TRPA1 pathway and augmented mechanical pain and cold sensitivity. In addition, mechanical and thermal hypersensitivity induced by miRNA-155 mimics were attenuated after blocking TNFR1, p38-MAPK, JNK, and TRPA1. Overall, we show the key role of miR-155 in modifying BTZ-induced neuropathic pain through TNFR1-TRPA1 pathway, suggesting that miR-155 is a potential target in preventing neuropathic pain development during intervention of BTZ.
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2234943X
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ONCOLOGY
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10.3389/fpsyg.2020.00562
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The Gold Standard and the Pyrite Principle: Toward a Supplemental Frame of Reference
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In medicine and social sciences, the phrase “gold standard” is often used to characterize an object or procedure described as unequivocally the best in its genre, against which all others should be compared. Examples of this usage are readily available in rigorously peer-reviewed publications, touted by test publishers, and appear in descriptions of methodologies by social science researchers. The phrase does not accurately describe commonly accepted measures, tests, and instruments. Instead, the descriptor can be ambiguous and misleading. This paper presents an overview of the history of the gold standard and its current applications to medicine and the social sciences. We question the use of the phrase “the gold standard” and suggest the additional operational use of a “pyrite principle” as a less presumptuous frame of reference. In thinking about validity and standards, the pyrite principle permits an understanding of standards as authoritative rather than fixed constructs in behavioral and health sciences.
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16641078
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PSYCHOLOGY
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10.3390/educsci10040105
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Analysis of Courses and Teacher Training Programs on Playful Methodology in Andalusia (Spain)
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In this study we analyzed the primary teaching and training experiences that observe play as a didactic resource to facilitate learning, highlighting fundamental elements and characteristics. A descriptive analysis of the different programs and contents with respect to playful methodology proposed by the Ministry of Education of Andalusian Government (Spain) is presented. The purpose of this type of descriptive idiographic research is to define, classify, catalogue, or characterize the experiences of innovation and projects on ludic methodology. The results show a total of 217 experiences and programs that deal with the use of playful methodology in the classroom. The results conclude that there are training resources interested and involved in the training of teachers in relation to play as a didactic resource. This type of training is carried out outside the university environment and has the characteristics of permanent training.
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22277102
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EDUCATION
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10.3390/ai1020008
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Artificial Intelligence (AI) or Intelligence Augmentation (IA): What Is the Future?
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Artificial intelligence (AI) is a rapidly growing technological phenomenon that all industries wish to exploit to benefit from efficiency gains and cost reductions. At the macrolevel, AI appears to be capable of replacing humans by undertaking intelligent tasks that were once limited to the human mind. However, another school of thought suggests that instead of being a replacement for the human mind, AI can be used for intelligence augmentation (IA). Accordingly, our research seeks to address these different views, their implications, and potential risks in an age of increased artificial awareness. We show that the ultimate goal of humankind is to achieve IA through the exploitation of AI. Moreover, we articulate the urgent need for ethical frameworks that define how AI should be used to trigger the next level of IA.
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26732688
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AI
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10.3389/fpsyg.2020.00669
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Math Anxiety and Working Memory Updating: Difficulties in Retrieving Numerical Information From Working Memory
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This study aimed to determine whether math anxiety was related to working memory (WM) updating performance and, specifically, to the retrieval and substitution components of updating. A set of WM updating (WMU) tasks that involve different retrieval and substitution requirements were administered to 114 university students. In addition, participants completed a math anxiety assessment on two occasions: 1–2 weeks before and immediately prior to task administration to increase the likelihood of observing the relationship between math anxiety and updating performance. The results showed a relationship between math anxiety scores and updating performance. Math anxious individuals took longer and made more errors, especially on tasks that required retrieving information from WM. These results suggest that math anxious individuals are less efficient when it comes to accessing numerical information in WM. Consequently, they may struggle with math-related tasks that involve retrieving numerical information from WM.
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16641078
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PSYCHOLOGY
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10.3389/fonc.2020.00528
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Response: Commentary: The Impact of the Time Interval Between Radiation and Hyperthermia on Clinical Outcome in Patients With Locally Advanced Cervical Cancer
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Response: Commentary: The Impact of the Time Interval Between Radiation and Hyperthermia on Clinical Outcome in Patients With Locally Advanced Cervical Cancer
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2234943X
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ONCOLOGY
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10.1186/s40594-020-00211-w
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Increasing high school teachers self-efficacy for integrated STEM instruction through a collaborative community of practice
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Background: Teachers can have a significant impact on student interest and learning in science, technology, engineering, and math (STEM) subjects and careers. Teacher self-efficacy can also significantly affect student learning. Researchers investigated the effects of teacher professional development and integrated STEM curriculum development on teacher self-efficacy. Participants in the study included high school science and engineering technology teachers enrolled in a National Science Foundation–ITEST project called Teachers and Researchers Advancing Integrated Lessons in STEM (TRAILS). The TRAILS program sought to prepare teachers to integrate STEM content using engineering design, biomimicry, science inquiry, and 3D printing as pedagogical approaches. Teachers learned within a community of practice working alongside industry partners and college faculty. The purpose of the study was to investigate the impact of the 70 h of professional development to train three cohorts of teachers over 3 years on teacher self-efficacy. The research design utilized a quasi-experimental nonequivalent control group approach, including an experimental group and an untreated control group.Results: Measurements on beliefs about teacher self-efficacy were collected on pretest, posttest, and delayed posttest survey assessments. Researchers analyzed the T-STEM survey results for teaching self-efficacy using the Wilcoxson signed-rank test for detecting significant differences. Science teachers showed a significant increase in teacher self-efficacy comparing the pretest and delayed posttest scores after TRAILS professional development and STEM lesson implementation (p=.001, effect size = .95). Additionally, significant differences between groups (science experimental vs science control group teachers) using the Wilcoxon rank-sum test were detected from pretest to posttest (p= .033, effect size = .46), posttest to delayed posttest (p= .029, effect size = .47), and pretest to delayed posttest (p= .005, effect size = .64). There were no significant differences detected in the control group. Engineering technology teachers showed no significant differences between the pretest, posttest, and delayed posttest self-efficacy scores.Conclusions: The results indicate the science teachers’ self-efficacy increased after professional development and after lesson implementation. Potential implications from this research suggest that the science teacher participants benefited greatly from learning within a community of practice, engaging in science practices, and using science knowledge to solve a real-world problem (engineering design).
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21967822
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EDUCATION
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10.3389/fonc.2020.00558
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Association of Body Composition With Survival and Treatment Efficacy in Castration-Resistant Prostate Cancer
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Objectives: The association of body composition with survival and the efficacy of first-line treatment was investigated in patients with castration-resistant prostate cancer (CRPC). Methods: The records of CRPC patients treated with docetaxel or androgen receptor signaling inhibitors (ARSi) between 2005 and 2018 were reviewed. Skeletal muscle index (SMI), visceral fat index, and subcutaneous fat index were evaluated using pretreatment computed tomography images. Results: Of 230 eligible patients, 144 received docetaxel, and 86 received ARSi as the first-line treatment for CRPC. The SMIhi (based on median values) group had higher prostate-specific antigen (PSA) progression-free survival (median 13.5 vs. 8.3 months, p = 0.030), radiologic progression-free survival (14.9 vs. 9.1 months, p < 0.001), and overall survival (24.1 vs. 16.9 months, p = 0.015) than the SMIlo group. In docetaxel-treated patients, the SMIhi group had higher PSA progression-free survival (13.5 vs. 5.9 months, p = 0.016) and radiologic progression-free survival (14.6 vs. 6.7 months, p < 0.001) than the SMIlo group. However, PSA progression-free survival and radiologic progression-free survival were comparable between the two groups in ARSi-treated patients. SMI was independently associated with the risk of radiologic progression in patients treated with docetaxel but not in those treated with ARSi. Conclusions: High skeletal muscle mass may be associated with reduced risk of disease progression and mortality in patients with CRPC. However, the significance of these relationships is limited in patients treated with docetaxel. These results suggest that assessing skeletal muscle mass may be worthwhile when selecting treatments for CRPC; however, further prospective validation and large-scale studies are needed.
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2234943X
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ONCOLOGY
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10.3389/fonc.2020.00475
|
Delivery and Biosafety of Oncolytic Virotherapy
|
In recent years, oncolytic virotherapy has emerged as a promising anticancer therapy. Oncolytic viruses destroy cancer cells, without damaging normal tissues, through virus self-replication and antitumor immunity responses, showing great potential for cancer treatment. However, the clinical guidelines for administering oncolytic virotherapy remain unclear. Delivery routes for oncolytic virotherapy to patients vary in existing studies, depending on the tumor sites and the objective of studies. Moreover, the biosafety of oncolytic virotherapy, including mainly uncontrolled adverse events and long-term complications, remains a serious concern that needs to be accurately measured. This review provides a comprehensive and detailed overview of the delivery and biosafety of oncolytic virotherapy.
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2234943X
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ONCOLOGY
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10.3390/cancers12041003
|
Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs
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Immunotherapeutic and targeted drugs improved survival of patients with metastatic melanoma. There is, however, a lack of evidence regarding their healthcare costs in clinical practice. The aim of our study was to provide insight into real-world healthcare costs of patients with metastatic cutaneous melanoma. Data were obtained from the Dutch Melanoma Treatment Registry for patients who were registered between July 2012 and December 2018. Mean total/monthly costs per patient were reported for all patients, patients who did not receive systemic therapy, and patients who received systemic therapy. Furthermore, mean episode/monthly costs per line of therapy and drug were reported for patients who received systemic therapy. Mean total/monthly costs were € 89,240/€ 6809: € 7988/€ 2483 for patients who did not receive systemic therapy (n = 784) and € 105,078/€ 7652 for patients who received systemic therapy (n = 4022). Mean episode/monthly costs were the highest for nivolumab plus ipilimumab (€ 79,675/€ 16,976), ipilimumab monotherapy (€ 79,110/€ 17,252), and dabrafenib plus trametinib (€ 77,053/€ 12,015). Dacarbazine yielded the lowest mean episode/monthly costs (€ 6564/€ 2027). Our study showed that immunotherapeutic and targeted drugs had a large impact on real-world healthcare costs. As new drugs continue entering the treatment landscape for (metastatic) melanoma, it remains crucial to monitor whether the benefits of these drugs outweigh their costs.
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20726694
|
ONCOLOGY
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10.3389/frai.2020.00023
|
PECLIDES Neuro: A Personalisable Clinical Decision Support System for Neurological Diseases
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Neurodegenerative diseases such as Alzheimer's and Parkinson's impact millions of people worldwide. Early diagnosis has proven to greatly increase the chances of slowing down the diseases' progression. Correct diagnosis often relies on the analysis of large amounts of patient data, and thus lends itself well to support from machine learning algorithms, which are able to learn from past diagnosis and see clearly through the complex interactions of a patient's symptoms and data. Unfortunately, many contemporary machine learning techniques fail to reveal details about how they reach their conclusions, a property considered fundamental when providing a diagnosis. Here we introduce our Personalisable Clinical Decision Support System (PECLIDES), an algorithmic process formulated to address this specific fault in diagnosis detection. PECLIDES provides a clear insight into the decision-making process leading to a diagnosis, making it a gray box model. Our algorithm enriches the fundamental work of Masheyekhi and Gras in data integration, personal medicine, usability, visualization, and interactivity. Our decision support system is an operation of translational medicine. It is based on random forests, is personalisable and allows a clear insight into the decision-making process. A well-structured rule set is created and every rule of the decision-making process can be observed by the user (physician). Furthermore, the user has an impact on the creation of the final rule set and the algorithm allows the comparison of different diseases as well as regional differences in the same disease. The algorithm is applicable to various decision problems. In this paper we will evaluate it on diagnosing neurological diseases and therefore refer to the algorithm as PECLIDES Neuro1.
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26248212
|
AI
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10.3389/feduc.2020.00038
|
The MARquette Visualization Lab (MARVL): An Immersive Virtual Environment for Research, Teaching and Collaboration
|
The MARquette Visualization Lab (MARVL) is a large-scale immersive virtual environment for research, teaching, collaboration and outreach at our mid-sized liberal arts university. MARVL consists of multiple display surfaces including an extra wide front wall and floor, and two side walls. This resource includes stereoscopic viewing, motion tracking and space for a large audience. MARVL’s versatile configuration facilitates viewing of content by 30 people, while also projecting on the entire width of the floor. This feature uniquely facilitates comparative or separate content visible simultaneously via “split mode” operation (two 3-sided environments), as well as detailed motion for applications such as gait analysis and performing arts. Since establishing the lab, its members have received numerous queries and requests pertaining to how system attributes and applications were determined, suggesting these and related decisions remain a challenge nearly three decades since the first CAVE was constructed. This paper provides an overview of MARVL including the processes used in identifying a diverse group of cross campus users, understanding their collective vision for potential use, and synthesizing this information to create the resource described above. The subsequent design, qualitative and quantitative approaches to vendor selection, and software decisions are then discussed. Steps implemented for dealing with simulator sickness and latency are presented along with current approaches being implemented for project development with end users. Finally, we present results from the use of MARVL by several end users identified in the early planning stage, and recent upgrades to the system.
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2504284X
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EDUCATION
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10.1186/s40594-020-00219-2
|
Factors influencing participation of underrepresented students in STEM fields: matched mentors and mindsets
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Background: Women and ethnic minorities remain underrepresented in science, technology, engineering, and math (STEM) fields. The goal of this pilot study is to better understand the beliefs and experiences of underrepresented US students pursuing STEM. Our focus was to gain insights into their mentorship experiences and preferences regarding having mentors who are gender and ethnicity matched. Environmental and psychological factors associated with participants’ decision to pursue STEM, such as family influences, academic mindsets, and attitudes towards STEM, were also studied. Methods: We developed a survey tool based on published literature and established instruments, including measures of STEM belonging, science identity, and growth mindset, as well as measures assessing students’ views on their STEM participation. We surveyed members of a STEM-focused non-profit who were in college, graduate school, or were recent graduates. Results: Forty-eight adults currently pursuing STEM responded to the survey. The majority (71%) were female and nearly all (96%) identified as an ethnic minority. Most reported knowing someone of their same gender (68%) or ethnicity (66%) with a STEM career who served as a role model. The majority (54%) stated that meeting a STEM professional of their own gender and ethnicity would be effective encouragement to pursue STEM. A similar percentage (56%) believed that media exposure to gender- and ethnicity-matched STEM professionals would be effective encouragement. Most (73%) demonstrated a growth mindset and had strong family support to pursue STEM (68%). Only two-thirds (66%) felt they belonged in STEM careers, and 30% agreed that people in their STEM classes are a lot like them. Conclusion: This study contributes additional information on the views and experiences of diverse students actively pursuing STEM. Most participants indicated the importance of meeting and being mentored in STEM by those of their same gender and ethnicity, either in person or through media. Future educational efforts to increase STEM diversity should consider students’ mentorship preferences and facilitate interactions with matched-background mentors accordingly, with consideration given to the use of media. Educators should focus on inclusive learning by highlighting the accomplishments of diverse STEM professionals, to help strengthen feelings of STEM belonging.
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21967822
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EDUCATION
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10.3389/fpsyg.2020.00632
|
“I Invest by Following Lead Investors!” The Role of Lead Investors in Fundraising Performance of Equity Crowdfunding
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Psychological factors play a critical role in affecting investor decisions. This study explores how lead investors influence following investors psychologically, thus affecting fundraising performance of equity crowdfunding. We draw upon the signaling theory and observational learning theory to argue that following investors could be induced to invest in a project if they observe the proportion of funding by lead investors in the funding target to be high, that the lead investors have rich investment experience, and that the lead investors can offer help to the projects. To test our hypotheses, we analyze a sample of 215 projects from a Chinese equity crowdfunding platform. The results reveal that the proportion of lead investor investment in the funding target and their investment experience are positively related to fundraising performance. However, the help offered by lead investors toward the projects has no impact on funding performance. Theoretical and practical implications are discussed.
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16641078
|
PSYCHOLOGY
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10.1186/s40594-020-00214-7
|
Correlations between modes of student cognitive engagement and instructional practices in undergraduate STEM courses
|
Background: Within STEM education, research on instructional practices has focused on ways to increase student engagement and thereby reap the associated benefits of increased learning, persistence, and academic success. These meaningful-learning goals have been tied most specifically to cognitive engagement, a construct that is often difficult for instructors to assess on their own. While it has been shown that certain instructional practices are tied to higher cognitive engagement in students, tools to measure instructional practices and student engagement have remained largely isolated in their development and use. Results: This research uses previously developed instruments to simultaneously assess modes of cognitive engagement in students (Student Course Cognitive Engagement Instrument [SCCEI]) and instructional practices (Postsecondary Instructional Practices Survey [PIPS]) within a course. A sample of 19 STEM courses was recruited to participate in this study, with instructors and students each self-reporting data. Results from the instructor and students in each course were scored, and ANOVA and partial correlation analysis were conducted on the sample. ANOVA indicated the significance of and classroom structure on student engagement. From the correlation analysis, a significant relationship was found between four student-reported modes of cognitive engagement and instructor-reported teaching practices. Conclusions: With an understanding of student engagement response to classroom structure, instructors may consider their teaching environment when implementing instructional practices. Moreover, Interactivity with Peers, the deepest mode of cognitive engagement suggested by previous research, was correlated with instructional practices in our study, suggesting that instructors may be able to shape their students’ learning by encouraging collaboration in the classroom. We also found that assessment played a role in students’ cognitive engagement; this indicates that instructors may wish to thoughtfully consider their methods of assessment to facilitate modes of cognitive engagement associated with deeper learning of course material. By understanding factor correlations, the PIPS and SCCEI can be used in tandem to understand impacts of instructional practices on student cognitive engagement within a course. We conclude that there is a need for ongoing research to study the interplay of instructional practices and student cognitive engagement as instruments are developed to measure such phenomena.
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21967822
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EDUCATION
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10.3390/ai1020010
|
Deep Learning Based Wildfire Event Object Detection from 4K Aerial Images Acquired by UAS
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Unmanned Aerial Systems, hereafter referred to as UAS, are of great use in hazard events such as wildfire due to their ability to provide high-resolution video imagery over areas deemed too dangerous for manned aircraft and ground crews. This aerial perspective allows for identification of ground-based hazards such as spot fires and fire lines, and to communicate this information with fire fighting crews. Current technology relies on visual interpretation of UAS imagery, with little to no computer-assisted automatic detection. With the help of big labeled data and the significant increase of computing power, deep learning has seen great successes on object detection with fixed patterns, such as people and vehicles. However, little has been done for objects, such as spot fires, with amorphous and irregular shapes. Additional challenges arise when data are collected via UAS as high-resolution aerial images or videos; an ample solution must provide reasonable accuracy with low delays. In this paper, we examined 4K ( 3840 × 2160 ) videos collected by UAS from a controlled burn and created a set of labeled video sets to be shared for public use. We introduce a coarse-to-fine framework to auto-detect wildfires that are sparse, small, and irregularly-shaped. The coarse detector adaptively selects the sub-regions that are likely to contain the objects of interest while the fine detector passes only the details of the sub-regions, rather than the entire 4K region, for further scrutiny. The proposed two-phase learning therefore greatly reduced time overhead and is capable of maintaining high accuracy. Compared against the real-time one-stage object backbone of YoloV3, the proposed methods improved the mean average precision(mAP) from 0 . 29 to 0 . 67 , with an average inference speed of 7.44 frames per second. Limitations and future work are discussed with regard to the design and the experiment results.
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26732688
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AI
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10.3389/frai.2020.00024
|
Learning to Play the Chess Variant Crazyhouse Above World Champion Level With Deep Neural Networks and Human Data
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Deep neural networks have been successfully applied in learning the board games Go, chess, and shogi without prior knowledge by making use of reinforcement learning. Although starting from zero knowledge has been shown to yield impressive results, it is associated with high computationally costs especially for complex games. With this paper, we present CrazyAra which is a neural network based engine solely trained in supervised manner for the chess variant crazyhouse. Crazyhouse is a game with a higher branching factor than chess and there is only limited data of lower quality available compared to AlphaGo. Therefore, we focus on improving efficiency in multiple aspects while relying on low computational resources. These improvements include modifications in the neural network design and training configuration, the introduction of a data normalization step and a more sample efficient Monte-Carlo tree search which has a lower chance to blunder. After training on 569537 human games for 1.5 days we achieve a move prediction accuracy of 60.4%. During development, versions of CrazyAra played professional human players. Most notably, CrazyAra achieved a four to one win over 2017 crazyhouse world champion Justin Tan (aka LM Jann Lee) who is more than 400 Elo higher rated compared to the average player in our training set. Furthermore, we test the playing strength of CrazyAra on CPU against all participants of the second Crazyhouse Computer Championships 2017, winning against twelve of the thirteen participants. Finally, for CrazyAraFish we continue training our model on generated engine games. In 10 long-time control matches playing Stockfish 10, CrazyAraFish wins three games and draws one out of 10 matches.
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26248212
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AI
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10.3390/cancers12051099
|
The Role of miRNA for the Treatment of MGMT Unmethylated Glioblastoma Multiforme
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Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.
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20726694
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ONCOLOGY
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10.3389/fonc.2020.00658
|
More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy?
|
The bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a mitochondrial one-carbon folate metabolic enzyme whose role in cancer was not known until recently. MTHFD2 is highly expressed in embryos and a wide range of tumors but has low or absent expression in most adult differentiated tissues. Elevated MTHFD2 expression is associated with poor prognosis in both hematological and solid malignancy. Its depletion leads to suppression of multiple malignant phenotypes including proliferation, invasion, migration, and induction of cancer cell death. The non-metabolic functions of this enzyme, especially in cancers, have thus generated considerable research interests. This review summarizes current knowledge on both the metabolic functions and non-enzymatic roles of MTHFD2. Its expression, potential functions, and regulatory mechanism in cancers are highlighted. The development of MTHFD2 inhibitors and their implications in pre-clinical models are also discussed.
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2234943X
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ONCOLOGY
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10.3389/fonc.2020.00641
|
Shaping Up the Tumor Microenvironment With Cellular Fibronectin
|
Normal tissue homeostasis and architecture restrain tumor growth. Thus for a tumor to develop and spread, malignant cells must overcome growth-repressive inputs from surrounding tissue and escape immune surveillance mechanisms that curb cancer progression. This is achieved by promoting the conversion of a physiological microenvironment to a pro-tumoral state and it requires a constant dialog between malignant cells and ostensibly normal cells of adjacent tissue. Pro-tumoral reprogramming of the stroma is accompanied by an upregulation of certain extracellular matrix (ECM) proteins and their cognate receptors. Fibronectin (FN) is one such component of the tumor matrisome. This large multidomain glycoprotein dimer expressed over a wide range of human cancers is assembled by cell-driven forces into a fibrillar array that provides an obligate scaffold for the deposition of other matrix proteins and binding sites for functionalization by soluble factors in the tumor microenvironment. Encoded by a single gene, FN regulates the proliferation, motile behavior and fate of multiple cell types, largely through mechanisms that involve integrin-mediated signaling. These processes are coordinated by distinct isoforms of FN, collectively known as cellular FN (as opposed to circulating plasma FN) that arise through alternative splicing of the FN1 gene. Cellular FN isoforms differ in their solubility, receptor binding ability and spatiotemporal expression, and that exert functions that have yet to be fully defined. FN induction at tumor sites constitutes an important step in the acquisition of biological capabilities required for several cancer hallmarks by sustaining proliferative signaling, promoting angiogenesis, facilitating invasion and metastasis, modulating growth suppressor activity and regulating anti-tumoral immunity. In this review, we will first provide an overview of ECM reprogramming through tumor-stroma crosstalk then focus on the role of cellular FN in tumor progression with respect to these hallmarks. Last, we will discuss the impact of dysregulated ECM on clinical efficacy of classical (radio-/chemo-) therapies and emerging treatments that target immune checkpoints and explore how our growing knowledge of the tumor ECM and the central role of FN can be leveraged for therapeutic benefit.
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2234943X
|
ONCOLOGY
|
10.3390/cancers12051141
|
Molecular Signatures of JMJD10/MINA53 in Gastric Cancer
|
The JMJD10 gene and its encoded protein MYC-induced nuclear antigen (MINA53) are associated with multiple cancers. Besides having both an oncogenic and tumor suppressor function, the intricate role of JMJD10 in cancer is complex as it depends on the cancer type. In particular, the functional role of JMJD10/MINA53 in gastric cancer has been poorly understood. In this study, we have unraveled the molecular signatures and functional roles of JMJD10/MINA53 in gastric cancer by multiple approaches, i.e., multi-omics bioinformatics study, analysis of human gastric cancer tissues, and studies in vitro using knockdown or overexpression strategies in gastric cancer cell lines. The results indicated that the JMJD10 gene and MINA53 protein are commonly overexpressed in cancer patients. JMJD10/MINA53 is involved in the regulation of proliferation and survival of gastric cancer by controlling cell cycle gene expression. These processes are highly associated with MINA53 enzymatic activity in the regulation of H3K9me3 methylation status and controlling activation of AP-1 signaling pathways. This highlights the oncogenic role of JMJD10/MINA53 in gastric cancer and opens the opportunity to develop therapeutic targeting of JMJD10/MINA53 in gastric cancer.
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20726694
|
ONCOLOGY
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10.1007/s00432-020-03218-6
|
Active HPV infection and its influence on survival in head and neck squamous-cell cancer
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Purpose: HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients.Methods: Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors.Results: Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%,p = 0.000; DFS 93.0% vs. 53.35%,p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence.Conclusions: High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.
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14321335
|
ONCOLOGY
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10.3389/frai.2020.00028
|
Predicting Biomass and Yield in a Tomato Phenotyping Experiment Using UAV Imagery and Random Forest
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Biomass and yield are key variables for assessing the production and performance of agricultural systems. Modeling and predicting the biomass and yield of individual plants at the farm scale represents a major challenge in precision agriculture, particularly when salinity and other abiotic stresses may play a role. Here, we evaluate a diversity panel of the wild tomato species (Solanum pimpinellifolium) through both field and unmanned aerial vehicle (UAV)-based phenotyping of 600 control and 600 salt-treated plants. The study objective was to predict fresh shoot mass, tomato fruit numbers, and yield mass at harvest based on a range of variables derived from the UAV imagery. UAV-based red–green–blue (RGB) imageries collected 1, 2, 4, 6, 7, and 8 weeks before harvest were also used to determine if prediction accuracies varied between control and salt-treated plants. Multispectral UAV-based imagery was also collected 1 and 2 weeks prior to harvest to further explore predictive insights. In order to estimate the end of season biomass and yield, a random forest machine learning approach was implemented using UAV-imagery-derived predictors as input variables. Shape features derived from the UAV, such as plant area, border length, width, and length, were found to have the highest importance in the predictions, followed by vegetation indices and the entropy texture measure. The multispectral UAV imagery collected 2 weeks prior to harvest produced the highest explained variances for fresh shoot mass (87.95%), fruit numbers (63.88%), and yield mass per plant (66.51%). The RGB UAV imagery produced very similar results to those of the multispectral UAV dataset, with the explained variance reducing as a function of increasing time to harvest. The results showed that predicting the yield of salt-stressed plants produced higher accuracies when the models excluded control plants, whereas predicting the yield of control plants was not affected by the inclusion of salt-stressed plants within the models. This research demonstrates that it is possible to predict the average biomass and yield up to 8 weeks prior to harvest within 4.23% of field-based measurements and up to 4 weeks prior to harvest at the individual plant level. Results from this work may be useful in providing guidance for yield forecasting of healthy and salt-stressed tomato plants, which in turn may inform growing practices, logistical planning, and sales operations.
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26248212
|
AI
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10.3389/frai.2020.00034
|
On Consequentialism and Fairness
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Recent work on fairness in machine learning has primarily emphasized how to define, quantify, and encourage “fair” outcomes. Less attention has been paid, however, to the ethical foundations which underlie such efforts. Among the ethical perspectives that should be taken into consideration is consequentialism, the position that, roughly speaking, outcomes are all that matter. Although consequentialism is not free from difficulties, and although it does not necessarily provide a tractable way of choosing actions (because of the combined problems of uncertainty, subjectivity, and aggregation), it nevertheless provides a powerful foundation from which to critique the existing literature on machine learning fairness. Moreover, it brings to the fore some of the tradeoffs involved, including the problem of who counts, the pros and cons of using a policy, and the relative value of the distant future. In this paper we provide a consequentialist critique of common definitions of fairness within machine learning, as well as a machine learning perspective on consequentialism. We conclude with a broader discussion of the issues of learning and randomization, which have important implications for the ethics of automated decision making systems.
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26248212
|
AI
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10.3390/educsci10050134
|
The Impact of Learning Strategies and Future Orientation on Academic Success: The Moderating Role of Academic Self-Efficacy among Italian Undergraduate Students
|
Promoting academic success among undergraduate students is crucial for tackling the need to foster employability competencies. Low levels of academic attainment in higher education, along with the increasing number of persons participating in tertiary education, represent crucial trends, which need to be studied in order to develop efficient retention practices. The current study aimed to investigate the relationship between relevant factors that can foster academic success: learning strategies, future orientation, and academic self-efficacy. To this purpose, a longitudinal study was performed on a sample of N = 87 undergraduate students from one of the largest Italian universities (63.4% males, 74.2% enrolled in the first year). Participants filled in an online questionnaire at two different time points, with a time lag of 12 months. Results of a moderated mediation model indicated that the relationship between learning strategies at Time 1 (T1) and Grade Point Average (GPA) at Time 2 (T2) was mediated by students’ future orientation. Moreover, this association was moderated by T1 academic self-efficacy. These results suggest that learning strategies positively influence GPA through an enhanced future orientation, in particular when students report high or medium levels of self-efficacy. The current findings invite a thorough review of training interventions for improving academic achievement.
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22277102
|
EDUCATION
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10.1007/s00432-020-03225-7
|
Prognostic significance of VEGF and components of the plasminogen activator system in endometrial cancer
|
Objective The plasminogen activator system (PAS) and vascular endothelial growth factor (VEGF) are important in the carcinogenesis and play a key role in cancer invasion and mediating metastasis of carcinomas. The aim of the study was to evaluate the correlation of serum levels of VEGF and components of the PAS with clinicopathological risk factors and outcome in patients with endometrial cancer (EC). Methods Preoperative blood was collected from 173 patients treated for EC between 1999 and 2009. Serum concentrations of VEGF, urokinase plasminogen activator (uPA) tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1) and -2 (PAI-2) were assessed by enzyme-linked immunosorbent assays (ELISA). Results Serum levels of VEGF and components of the PAS were significantly associated with stage of the disease, tumor histology, tumor grade, myometrial invasion (MI), presence of lymphovascular space invasion (LVSI) and lymph node metastases (LNM). Preoperative serum levels of PAI-1 and -2 and tPA were higher in patients who experienced a recurrence than in patients who remained disease free (p < 0.01). PAI-1 and -2 and tPA were significantly independent prognostic factors for DFS with a HR of 3.85 (95% CI 1.84–8.07), 3.90 (95% CI 1.75–8.66) and 2.53 (95% CI 1.16–5.55), respectively. PAI-1 and tPA turned out to be independent prognostic factors for OS, with a HR of 2.09 (95% CI 1.08–4.05) and 2.16 (95% CI 1.06–4.44), respectively. Conclusion Serum levels of VEGF and components of the PAS at primary diagnosis were associated with well-known clinicopathological risk factors such as; FIGO stage, tumor histology, tumor grade, MI, LVSI and LNM. High concentrations of PAI-1 and-2 and tPA are independent factors for poor prognosis in patients with endometrial cancer.
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14321335
|
ONCOLOGY
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10.3390/educsci10050137
|
Tales from within: Gifted Students’ Lived Experiences with Teaching Practices in Regular Classrooms
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Gifted students in regular classrooms have fewer opportunities to develop activities that are based on their characteristics as learners and address their needs; however, many of them spend most of their school time in these classrooms. The results presented here were part of a 2-year qualitative project that analyzed 12 Chilean gifted students’ lived experiences in regular classrooms by exploring the factors that foster and hinder their learning through the use of photos, focus groups, and interviews. The results showed students’ discontent with the national curriculum and teaching practices related to rigidity, lack of meaning, and unchallenging assessments. Nevertheless, positive experiences were reported related to teaching strategies, especially when they add novelty and move away from traditional approaches. Waiting experiences were common, but were often seen by students as opportunities for creative production. Methods for engaging gifted students in their learning are highlighted.
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22277102
|
EDUCATION
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10.3390/ai1020012
|
Cities of the Future? The Potential Impact of Artificial Intelligence
|
Artificial intelligence (AI), like many revolutionary technologies in human history, will have a profound impact on societies. From this viewpoint, we analyze the combined effects of AI to raise important questions about the future form and function of cities. Combining knowledge from computer science, urban planning, and economics while reflecting on academic and business perspectives, we propose that the future of cities is far from being a determined one and cities may evolve into ghost towns if the deployment of AI is not carefully controlled. This viewpoint presents a fundamentally different argument, because it expresses a real concern over the future of cities in contrast to the many publications who exclusively assume city populations will increase predicated on the neoliberal urban growth paradigm that has for centuries attracted humans to cities in search of work.
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26732688
|
AI
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10.1186/s40594-020-00222-7
|
Reducing withdrawal and failure rates in introductory programming with subgoal labeled worked examples
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Background: Programming a computer is an increasingly valuable skill, but dropout and failure rates in introductory programming courses are regularly as high as 50%. Like many fields, programming requires students to learn complex problem-solving procedures from instructors who tend to have tacit knowledge about low-level procedures that they have automatized. The subgoal learning framework has been used in programming and other fields to breakdown procedural problem solving into smaller pieces that novices can grasp more easily, but it has only been used in short-term interventions. In this study, the subgoal learning framework was implemented throughout a semester-long introductory programming course to explore its longitudinal effects. Of 265 students in multiple sections of the course, half received subgoal-oriented instruction while the other half received typical instruction. Results: Learning subgoals consistently improved performance on quizzes, which were formative and given within a week of learning a new procedure, but not on exams, which were summative. While exam performance was not statistically better, the subgoal group had lower variance in exam scores and fewer students dropped or failed the course than in the control group. To better understand the learning process, we examined students’ responses to open-ended questions that asked them to explain the problem-solving process. Furthermore, we explored characteristics of learners to determine how subgoal learning affected students at risk of dropout or failure. Conclusions: Students in an introductory programming course performed better on initial assessments when they received instructions that used our intervention, subgoal labels. Though the students did not perform better than the control group on exams on average, they were less likely to get failing grades or to drop the course. Overall, subgoal labels seemed especially effective for students who might otherwise struggle to pass or complete the course.
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21967822
|
EDUCATION
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10.3389/fonc.2020.00757
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Integration of Digital Pathologic and Transcriptomic Analyses Connects Tumor-Infiltrating Lymphocyte Spatial Density With Clinical Response to BRAF Inhibitors
|
Metastatic melanoma is one of the most immunogenic malignancies due to its high rate of mutations and neoantigen formation. Response to BRAF inhibitors (BRAFi) may be determined by intratumoral immune activation within melanoma metastases. To evaluate whether CD8+ T cell infiltration and distribution within melanoma metastases can predict clinical response to BRAFi, we developed a methodology to integrate immunohistochemistry with automated image analysis of CD8+ T cell position. CD8+ distribution patterns were correlated with gene expression data to identify and quantify “hot” areas within a tumor. Furthermore, the relative activation of CD8+cells, based on transcriptomic analysis, and their relationship to other CD8+ T cells and non-CD8+ cells within the tumor suggested a less crowded distribution of cells around activated CD8+ T cells. Furthermore, the relative activation of these CD8+ T cells was associated with improved clinical outcomes and decreased tumor cell proliferation. This study demonstrates the potential of digital pathomics to incorporate immune cell spatial distribution within metastases and RNAseq analysis to predict clinical response to BRAF inhibition in metastatic melanoma.
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2234943X
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ONCOLOGY
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10.3389/frai.2020.00031
|
Bringing Big Data to Bear in Environmental Public Health: Challenges and Recommendations
|
Understanding the role that the environment plays in influencing public health often involves collecting and studying large, complex data sets. There have been a number of private and public efforts to gather sufficient information and confront significant unknowns in the field of environmental public health, yet there is a persistent and largely unmet need for findable, accessible, interoperable, and reusable (FAIR) data. Even when data are readily available, the ability to create, analyze, and draw conclusions from these data using emerging computational tools, such as augmented and artificial intelligence (AI) and machine learning, requires technical skills not currently implemented on a programmatic level across research hubs and academic institutions. We argue that collaborative efforts in data curation and storage, scientific computing, and training are of paramount importance to empower researchers within environmental sciences and the broader public health community to apply AI approaches and fully realize their potential. Leaders in the field were asked to prioritize challenges in incorporating big data in environmental public health research: inconsistent implementation of FAIR principles in data collection and sharing, a lack of skilled data scientists and appropriate cyber-infrastructures, and limited understanding of possibilities and communication of benefits were among those identified. These issues are discussed, and actionable recommendations are provided.
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26248212
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AI
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10.3390/cancers12051273
|
Preclinical Efficacy and Involvement of AKT, mTOR, and ERK Kinases in the Mechanism of Sulforaphane against Endometrial Cancer
|
Sulforaphane exerts anti-cancer activity against multiple cancer types. Our objective was to evaluate utility of sulforaphane for endometrial cancer therapy. Sulforaphane reduced viability of endometrial cancer cell lines in association with the G2/M cell cycle arrest and cell division cycle protein 2 (Cdc2) phosphorylation, and intrinsic apoptosis. Inhibition of anchorage-independent growth, invasion, and migration of the cell lines was associated with sulforaphane-induced alterations in epithelial-to-mesenchymal transition (EMT) markers of increased E-cadherin and decreased N-cadherin and vimentin expression. Proteomic analysis identified alterations in AKT, mTOR, and ERK kinases in the networks of sulforaphane effects in the Ishikawa endometrial cancer cell line. Western blots confirmed sulforaphane inhibition of AKT, mTOR, and induction of ERK with alterations in downstream signaling. AKT and mTOR inhibitors reduced endometrial cancer cell line viability and prevented further reduction by sulforaphane. Accumulation of nuclear phosphorylated ERK was associated with reduced sensitivity to the ERK inhibitor and its interference with sulforaphane activity. Sulforaphane induced apoptosis-associated growth inhibition of Ishikawa xenograft tumors to a greater extent than paclitaxel, with no evidence of toxicity. These results verify sulforaphane’s potential as a non-toxic treatment candidate for endometrial cancer and identify AKT, mTOR, and ERK kinases in the mechanism of action with interference in the mechanism by nuclear phosphorylated ERK.
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20726694
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ONCOLOGY
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10.1186/s40594-020-00217-4
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Measuring university students’ interest in biology: evaluation of an instrument targeting Hidi and Renninger’s individual interest
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Background: Boosting students’ disciplinary interest has long been considered an important mechanism to increase student success and retention in STEM education. Yet, interest is a complex construct and can mean different things to different people, and many of the existing interest questionnaires do not identify a specific theoretical framework underlying their items. To demonstrate that curricular interventions targeting students’ interest are effective, educators need a theoretically based instrument to measure interest. The aim of this study was to develop an instrument measuring undergraduate students’ interest in the discipline of biology and collect initial validity evidence supporting the proposed use. The instrument structure is based on Hidi and Renninger’s (Educational Psychologist 41:111–127, 2006) conceptualization of individual interest, and the intended use is to evaluate changes in the biology interests of the US undergraduate students pursuing STEM degrees. To provide evidence of validity, the instrument was completed by 446 biology majors and 489 non-biology majors at two R1 universities. Exploratory and confirmatory factor analyses were applied to evaluate the internal structure of the instrument.Results: The final three-factor instrument supported by these analyses includes 6 items representing positive feelings towards biology, 5 items representing personal value of biology, and 8 items representing reengagement in biology-related activities. Measurement invariance across biology and non-biology majors was established and subsequent comparisons of these populations demonstrated that biology majors report significantly higher positive feelings, personal value, and reengagement in biology-related activities compared to non-biology majors.Conclusions: The study findings support the use of the instrument to gain a broad understanding of students’ individual interest in biology. With minor adaptions, the instrument could also be evaluated for use in other STEM disciplines and for use by other populations.
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21967822
|
EDUCATION
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10.3389/fonc.2020.00633
|
Long Non-coding RNA AK025387 Promotes Cell Migration and Invasion of Gastric Cancer
|
Gastric cancer is one of the most common cancers in the world, and long non-coding RNAs (lncRNAs) play a crucial role in proliferation, metastasis, and invasion of gastric cancer. However, there are very few researches focusing on the effects of lncRNAs on metastatic gastric cancer. In this research, we identify one kind of lncRNA, called AK025387, which is highly expressed in metastatic gastric cancer samples compared with non-metastatic gastric cancer samples. The expression of AK025387 is significantly positively correlated with lymph node metastasis. The in situ hybridization demonstrates that AK025387 is located in both nucleus and cytoplasm, but mostly in cytoplasm. AK025387 promotes gastric cancer cells migratory and invasive ability, but it inhibits apoptosis in vitro. Furthermore, AK025387 regulates Raf-1, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated kinase (ERK) and is involved in mitogen-activated protein kinase (MAPK) signaling pathway to perform its biological functions. We conclude that AK025387 is highly expressed in metastatic gastric cancer, and its biological functions suggest the potential of AK025387 to be a biomarker of metastatic gastric cancer.
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2234943X
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ONCOLOGY
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10.3389/fonc.2020.00786
|
Development and Validation of a Comprehensive Multivariate Dosimetric Model for Predicting Late Genitourinary Toxicity Following Prostate Cancer Stereotactic Body Radiotherapy
|
Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3–98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.
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2234943X
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ONCOLOGY
|
10.3389/fonc.2020.00788
|
The Landscape of Iron Metabolism-Related and Methylated Genes in the Prognosis Prediction of Clear Cell Renal Cell Carcinoma
|
Background: Clear cell renal cell carcinoma (ccRCC) is characteristics of resistance to chemotherapy and radiotherapy. The prognosis of ccRCC was dismay with immense diversity. Iron metabolism disturbance is a common phenomenon in ccRCC. The purpose of our study is to identify and validate the candidate prognostic gene signature of iron metabolism and methylation closely related to the poor prognosis of ccRCC through comprehensive bioinformatics analysis in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Methods: The prognostic iron metabolism-related genes were screened according to the overlapping differentially expressed genes (DEGs) from the TCGA database. We built a prognostic model using risk score method to predict OS, each ccRCC patient's risk score was calculated, and the resulting score can divide these patients into two categories according to the cut-point risk score. The prognostic significance of the hub genes was further evaluated with the Kaplan-Meier (KM) survival and Receiver Operating Characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analysis was implemented to evaluate the impact of each variable on OS. Furthermore, the prediction power of the 25 gene signatures has been validated using an independent ccRCC cohort from the GEO database. The Gene Set Enrichment Analysis (GSEA) identified the characteristics of hub related oncogenes. Finally, we utilize Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the co-expression network based on these DEGs. Results: In this study, we identified and validated 25 iron metabolism-related and methylated genes as the prognostic signatures, which differentiated ccRCC patients into high and low risk subgroups. The KM analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 25 gene signatures could largely predict OS and DFS for 1, 3, and 5 years in patients with ccRCC. Conclusions: Taken together, we identified the key iron metabolism-related and methylated genes for ccRCC through a comprehensive bioinformatics analysis. This study provides a reliable and robust gene signature for the prognostic predictor of ccRCC patients and maybe provides a promising treatment strategy for this lethal disease.
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2234943X
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ONCOLOGY
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10.3389/frai.2020.00035
|
Implicit Standardization in a Minority Language Community: Real-Time Syntactic Change among Hasidic Yiddish Writers
|
The recent turn to “big data” from social media corpora has enabled sociolinguists to investigate patterns of language variation and change at unprecedented scales. However, research in this paradigm has been slow to address variable phenomena in minority languages, where data scarcity and the absence of computational tools (e.g., taggers, parsers) often present significant barriers to entry. This article analyzes socio-syntactic variation in one minority language variety, Hasidic Yiddish, focusing on a variable for which tokens can be identified in raw text using purely morphological criteria. In non-finite particle verbs, the overt tense marker tsu (cf. English to, German zu) is variably realized either between the preverbal particle and verb (e.g., oyf-tsu-es-n up-to-eat-INF ‘to eat up’; the conservative variant) or before both elements (tsu oyf-es-n to up-eat-INF; the innovative variant). Nearly 38,000 tokens of non-finite particle verbs were extracted from the popular Hasidic Yiddish discussion forum Kave Shtiebel (the ‘coffee room’; kaveshtiebel.com). A mixed-effects regression analysis reveals that despite a forum-wide favoring effect for the innovative variant, users favor the conservative variant the longer their accounts remain open and active. This process of rapid implicit standardization is supported by ethnographic evidence highlighting the spread of language norms among Hasidic writers on the internet, most of whom did not have the opportunity to express themselves in written Yiddish prior to the advent of social media.
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26248212
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AI
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10.3390/cancers12061425
|
A Phase 1 Study of mTORC1/2 Inhibitor BI 860585 as a Single Agent or with Exemestane or Paclitaxel in Patients with Advanced Solid Tumors
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This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel.
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20726694
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ONCOLOGY
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10.1007/s00432-020-03275-x
|
Appropriate arrangement of cancer treatment after COVID-19 epidemic peaks in China
|
Purpose COVID-19 is causing a lot of problems in health services around the world, especially in medical institutions receiving cancer patients. On March 12, China’s National Health Commission announced that the peak of the COVID-19 epidemic has passed in China. Thus, a proper arrangement of medication, surgery and radiotherapy for patients with cancer is of vital importance after the epidemic peak. Methods A range of measures have been implemented in our center. Specific patients take priority for chemotherapy treatment. The amount of semi-elective and elective surgeries could be gradually increased beyond urgent and emergency surgery. The hypofractionated radiotherapy is recommended in the right circumstances. Results On March 13, our center announced that more than 5000 visits of chemotherapy and radiotherapy are arranged in our outpatient clinics and none of our patients and staffs have been diagnosed with COVID-19 as of March 28, 2020. Conclusion The rational arrangement we make now may be helpful to the future restoration of cancer treatments in other countries.
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14321335
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ONCOLOGY
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10.3389/feduc.2020.00053
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Form-Focused Instruction in the Heritage Language Classroom: Toward Research-Informed Heritage Language Pedagogy
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In the context of adult second language teaching, heritage language speakers have been recognized as a special group of language learners, whose experience with their home language, as well as their motivations for (re)learning it, differ drastically from those of an average learner of a second language. Current heritage language pedagogical approaches focus primarily on the development of communicative (or functional) abilities of the heritage learners and on critical exploration of bilingual practices and identities. However, structural accuracy remains a persistent issue for heritage speakers, who do not always reach higher levels of proficiency in their heritage language (as measured by standard language proficiency tests). In this paper, we use the example of heritage Russian instruction in American college classrooms to argue for the critical role of form-focused instruction in teaching a heritage language, and in particular in bringing heritage learners to greater proficiency. The argument for the importance of form-focused instruction is based on the results of extensive linguistic research combined with insights from the currently available pedagogically oriented research. We formulate and discuss instructional methods that help educators (1) develop heritage learners’ attention to grammatical form, (2) foster heritage learners’ understanding of grammatical concepts, and (3) increase the learners’ metalinguistic awareness. Given consistent parallels across different heritage languages, the methodologies developed for Russian learners can apply to other heritage language classrooms as well, with adjustments based on the sociolinguistic context of particular heritage languages.
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2504284X
|
EDUCATION
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10.3390/ai1020017
|
Improving Daily Peak Flow Forecasts Using Hybrid Fourier-Series Autoregressive Integrated Moving Average and Recurrent Artificial Neural Network Models
|
In multi-purpose reservoirs, to achieve optimal operation, sophisticated models are required to forecast reservoir inflow in both short- and long-horizon times with an acceptable accuracy, particularly for peak flows. In this study, an auto-regressive hybrid model is proposed for long-horizon forecasting of daily reservoir inflow. The model is examined for a one-year horizon forecasting of high-oscillated daily flow time series. First, a Fourier-Series Filtered Autoregressive Integrated Moving Average (FSF-ARIMA) model is applied to forecast linear behavior of daily flow time series. Second, a Recurrent Artificial Neural Network (RANN) model is utilized to forecast FSF-ARIMA model’s residuals. The hybrid model follows the detail of observed flow time variation and forecasted peak flow more accurately than previous models. The proposed model enhances the ability to forecast reservoir inflow, especially in peak flows, compared to previous linear and nonlinear auto-regressive models. The hybrid model has a potential to decrease maximum and average forecasting error by 81% and 80%, respectively. The results of this investigation are useful for stakeholders and water resources managers to schedule optimum operation of multi-purpose reservoirs in controlling floods and generating hydropower.
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26732688
|
AI
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10.3390/cancers12061572
|
Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers
|
Transcription factors encoded by Homeobox (HOX) genes play numerous key functions during early embryonic development and differentiation. Multiple reports have shown that mis-regulation of HOX gene expression plays key roles in the development of cancers. Their expression levels in cancers tend to differ based on tissue and tumor type. Here, we performed a comprehensive analysis comparing HOX gene expression in different cancer types, obtained from The Cancer Genome Atlas (TCGA), with matched healthy tissues, obtained from Genotype-Tissue Expression (GTEx). We identified and quantified differential expression patterns that confirmed previously identified expression changes and highlighted new differential expression signatures. We discovered differential expression patterns that are in line with patient survival data. This comprehensive and quantitative analysis provides a global picture of HOX genes’ differential expression patterns in different cancer types.
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20726694
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ONCOLOGY
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10.3390/educsci10070177
|
Progression of Cognitive-Affective States During Learning in Kindergarteners: Bringing Together Physiological, Observational and Performance Data
|
It has been shown that combining data from multiple sources, such as observations, self-reports, and performance with physiological markers offers better insights into cognitive-affective states during the learning process. Through a study with 12 kindergarteners, we explore the role of utilizing insights from multiple data sources, as a potential arsenal to supplement and complement existing assessments methods in understanding cognitive-affective states across two main pedagogical approaches—constructionist and instructionist—as children explored learning a chosen Science, Technology, Engineering and Mathematics (STEM) concept. We present the trends that emerged across pedagogies from different data sources and illustrate the potential value of additional data channels through case illustrations. We also offer several recommendations for such studies, particularly when collecting physiological data, and summarize key challenges that provide potential avenues for future work.
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22277102
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EDUCATION
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10.3390/cancers12071782
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A Novel Combination Treatment with Honokiol and Rapamycin Effectively Restricts c-Met-Induced Growth of Renal Cancer Cells, and also Inhibits the Expression of Tumor Cell PD-L1 Involved in Immune Escape
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The mTOR inhibitor Rapamycin has tumor inhibitory properties; and it is also used as an immunosuppressive agent after organ transplantation. However, prolonged Rapamycin treatment re-activates Akt and can promote cancer growth. Honokiol is a natural compound with both anti-tumorigenic and anti-inflammatory properties. Here, we assessed the anti-tumor effects of Rapamycin and Honokiol combination in renal cell carcinoma (RCC). Receptor tyrosine kinase c-Met-mediated signaling plays a major role in RCC growth. We observed that compared with Rapamycin alone, Rapamycin + Honokiol combination can effectively down-regulate c-Met-induced Akt phosphorylation in renal cancer cells; and it markedly inhibited Ras activation and cell proliferation and promoted G1 phase cell cycle arrest. The combination treatment significantly induced ROS generation and cancer cell apoptosis even when c-Met is activated. Importantly, Honokiol, but not Rapamycin, decreased c-Met-induced expression of the co-inhibitory molecule PD-L1, implied in the immune escape of renal cancer cells. In mouse renal cancer cells and Balb/c splenocytes co-culture assay, Rapamycin + Honokiol markedly potentiated immune-cell-mediated killing of cancer cells, possibly through the down-regulation of PD-L1. Together, Honokiol can effectively overcome the limitation of Rapamycin treatment alone; and the combination treatment can markedly restrict the growth of RCC, with particular importance to post-transplantation renal cancer.
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20726694
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ONCOLOGY
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10.1007/s00432-020-03298-4
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Aberrant DNA methylation results in altered gene expression in non-alcoholic steatohepatitis-related hepatocellular carcinomas
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Purpose: The aim of this study was to investigate DNA methylation alterations in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinomas (HCCs). Methods: Genome-wide DNA methylation analysis was performed using the Infinium Human Methylation 450 K BeadChip, and levels of mRNA expression were analyzed by quantitative reverse transcription-PCR. Results: Compared to 36 samples of normal control liver tissue (C), DNA methylation alterations were observed on 19,281 probes in 22 samples of cancerous tissue (T) obtained from patients showing histological features compatible with NASH in their non-cancerous liver tissue (N). Among those probes, 1396 were located within CpG islands or their shores and shelves, designed around the transcription start sites of 726 genes. In representative genes, such as DCAF4L2, CKLF, TRIM4, PRC1, UBE2C and TUBA1B, both DNA hypomethylation and mRNA overexpression were observed in T samples relative to C samples, and the levels of DNA methylation and mRNA expression were inversely correlated with each other. DNA hypomethylation occurred even in N samples at the precancerous NASH stage, and this was inherited by or further strengthened in T samples. DNA hypomethylation of DCAF4L2, CKLF and UBE2C was observed in both NASH-related and viral hepatitis-related HCCs, whereas that of TRIM4, PRC1 and TUBA1B occurred in a NASH-related HCC-specific manner. DNA hypomethylation and/or mRNA overexpression of these genes was frequently associated with the necroinflammatory grade of NASH and was correlated with poorer tumor differentiation. Conclusion: DNA methylation alterations may occur under the necroinflammatory conditions characteristic of NASH and participate in NASH-related hepatocarcinogenesis through aberrant expression of tumor-related genes.
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14321335
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ONCOLOGY
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10.3389/fonc.2020.01408
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Risk Factor Analysis of Acute Kidney Injury After Microwave Ablation of Hepatocellular Carcinoma: A Retrospective Study
|
Objectives:Acute kidney injury (AKI) is a recently observed side effect in patients after microwave ablation (MWA) of hepatocellular carcinoma (HCC) and is associated with negative outcomes. The aim of this study is to explore the risk factors of affecting the occurrence of AKI (stages 1b, 2, and 3), because they have a higher mortality rate than patients with AKI (stage 1a) and without AKI. Materials and methods:In this retrospective study, a total of 1,214 patients with HCC who were treated with MWA under ultrasound (US) guidance in our department between January 2005 and November 2017 were enrolled. We evaluated the influence of 20 risk factors. Univariate and multivariate analysis were used for statistical analysis. The possible risk factors of AKI after MWA for HCC were summarized. Results:AKI, AKI (stage 1a), and AKI (stages 1b, 2, and 3) after MWA were found in 34, 15, and 19 patients (2.80, 1.24, and 1.57%), respectively. Among 34 patients with AKI, 10 cases with AKI (stage 1a) and 6 cases with AKI (stages 1b, 2, and 3) recovered before their discharge without any treatment for AKI and 9 cases with AKI (stages 1b, 2, and 3) with further treatment. Four cases who had chronic renal failure before MWA of liver accepted renal dialysis. By univariate analysis, the number of antenna insertions (P= 0.027, OR = 3.3), MWA time >= 20 min (P= 0.029, OR = 4.3), creatinine (Cr)-pre above the upper limit of the reference value (P< 0.001, OR = 35.5), albumin (Alb)-pre (P= 0.030, OR = 0.9), and red blood cell (RBC)-pre (P< 0.001, OR = 0.3) were significant risk factors. By multivariate analysis, Cr-pre >= 110 mu mol/L (P< 0.001, OR = 31.4) and MWA time >= 20 min (P= 0.043 OR = 9.9) were the independent risk factors. Conclusion:AKI (stages 1b, 2, and 3) is a relatively serious complication after MWA for HCC, which is related to MWA time and Cr-pre. It requires attention by clinicians. So it is of great necessity to assess the Cr-pre level and reduce the MWA time to <20 min to minimize the risk of AKI after MWA for HCC.
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2234943X
|
ONCOLOGY
|
10.3389/frai.2020.00070
|
Clustering and Recognition of Spatiotemporal Features Through Interpretable Embedding of Sequence to Sequence Recurrent Neural Networks
|
Encoder-decoder recurrent neural network models (RNN Seq2Seq) have achieved success in ubiquitous areas of computation and applications. They were shown to be effective in modeling data with both temporal and spatial dependencies for translation or prediction tasks. In this study, we propose an embedding approach to visualize and interpret the representation of data by these models. Furthermore, we show that the embedding is an effective method for unsupervised learning and can be utilized to estimate the optimality of model training. In particular, we demonstrate that embedding space projections of the decoder states of RNN Seq2Seq model trained on sequences prediction are organized in clusters capturing similarities and differences in the dynamics of these sequences. Such performance corresponds to an unsupervised clustering of any spatio-temporal features and can be employed for time-dependent problems such as temporal segmentation, clustering of dynamic activity, self-supervised classification, action recognition, failure prediction, etc. We test and demonstrate the application of the embedding methodology to time-sequences of 3D human body poses. We show that the methodology provides a high-quality unsupervised categorization of movements. The source code with examples is available in a Github repository1.
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26248212
|
AI
|
10.3389/fonc.2020.523577
|
Baoyuan Jiedu Decoction Alleviates Cancer-Induced Myotube Atrophy by Regulating Mitochondrial Dynamics Through p38 MAPK/PGC-1α Signaling Pathway
|
Cancer cachexia is a multifactorial syndrome characterized by continuous body wasting and loss of skeletal muscle. Impaired mitochondria function is closely associated with muscle atrophy in cancer cachexia. Our previous study confirmed the effectiveness of Baoyuan Jiedu decoction (BJD) in inhibiting cancer-induced muscle atrophy in an in vivo model. However, little is known about its mechanisms in regulating mitochondria dysfunction. In this study, we evaluated the therapeutic effect and action mechanisms of BJD against atrophy both in the Lewis-conditioned medium induced C2C12 myotube atrophy model and in a BALB/c mice xenograft model using mouse colon cancer C26 cells. The mitochondrial content was tested by 10-Non-ylacridine orange staining. Expressions of related proteins and mRNAs were detected by western blotting (WB) and qPCR, respectively. As a result, 18 major components were identified in BJD by ultra-high performance liquid chromatography-quadrupole (UHPLC-Q) Exactive analysis. As shown in the in vitro results, BJD treatment prevented prominent myotube atrophy and increased the myotube diameter of C2C12 cells. Besides, BJD treatment increased mitochondrial content and ATPase activity. Furthermore, the protein and mRNA expressions that were related to mitochondrial functions and generation such as cytochrome-c oxidase IV, Cytochrome C, nuclear respiratory factor 1, and mitochondrial transcription factor A were significantly increased in BJD treatment compared to the control group. The in vivo results showed that BJD treatment prevented body weight loss and improved the gastrocnemius index in cachexia mice. Moreover, the expressions of Atrogin-1 and muscle RING-finger protein-1 were decreased by BJD treatment. Mechanically, BJD increased the expression of peroxisome proliferator-activated receptor-gamma coactivator 1, and consistently, inhibited the expression of p38 MAPK and its phosphorylation both in vivo and in vitro. Taken together, this study identified that BJD effectively relieved cancer-induced myotube atrophy and provided a potential mechanism for BJD in regulating mitochondrial dynamics through p38 MAPK/PGC-1α signaling pathway.
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2234943X
|
ONCOLOGY
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