Fascin promotes lung cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression.

Fascin is a pro-metastatic actin-bundling protein that is upregulated in all metastatic carcinomas. Fascin promotes cancer cell migration and invasion by facilitating membrane protrusions, such as filopodia and invadopodia. Aerobic glycolysis is a key feature of cancer metabolism and provides critical intermediate metabolites for tumor growth. Here, we report that fascin increases glycolysis in lung cancer to promote tumor growth and metastasis. Fascin promotes glycolytic flux by increasing the expression and activities of phosphofructose-kinases 1 and 2 (PFK1 and 2). Fascin mediates glycolytic functions via activation of yes-associated protein 1 (YAP1) through its canonical actin-bundling activity by promoting the binding of YAP1 to a TEAD1/4 binding motif located 30 bp upstream of the PFKFB3 transcription start site to activate its transcription. Examination of the TCGA database suggests that the fascin-YAP1-PFKFB3 axis is likely conserved across different types of cancers. Importantly, pharmacological inhibitors of fascin suppressed YAP1-PFKFB3 signaling and glycolysis in cancer cell lines, organoid cultures, and xenograft metastasis models. Taken together, our data reveal that the glycolytic function of fascin is essential for the promotion of lung cancer growth and metabolism, and suggest that pharmacological inhibitors of fascin may be used to reprogram cancer metabolism in lung and potentially other cancers with fascin upregulation.

Speaking Haptically: From Phonemes to Phrases With a Mobile Haptic Communication System.

In this article, we present three studies involving WhatsHap, a mobile system designed to deliver speech as vibrations on the forearm with minimal hardware demands and practice time. After only 4.2 h of training on a 24-haptic phoneme vocabulary and on how to combine these to form words, participants were able to generalize their phoneme identification skills to the understanding of untrained English words, correctly identifying 65% of words in phrases rendered with a user-controlled interval between words, and up to 59% with a fixed interval. Ultimately, participants were able to complete 88% of simple communicative tasks that elicited spontaneous speech and semi-structured bidirectional conversation using the apparatus. We conclude by providing insights as to how such a system may ultimately be used for communication under more natural conditions.

Narcissism and Reactions to a Self-Esteem Insult: An Experiment Using Predictions from Self-Report and the Rorschach Task.

We used self-reported narcissistic grandiosity and vulnerability and a component derived from 11 potential grandiosity and narcissism variables (GNVs) coded from Rorschach behavior to predict fluctuations in self-esteem and their links to anger and defensive reactions. We assessed state mood, state self-esteem, and performance attributions in 105 college students who underwent a self-esteem manipulation involving success followed by failure on cognitive testing. Self-reported grandiosity predicted the disavowal of effortful ability as a factor in failure, but we did not replicate other previously reported findings for this variable. Self-reported vulnerability predicted oscillations in self-reported mood and self-esteem. The GNV scale predicted spontaneously expressed hostility and externalization following self-esteem insult, and attributions mediated its relationship with anger expressed after failure. We discuss implications of these results and recommend additional replication research.

Assessing Narcissism Using Rorschach-Based Imagery and Behavior Validated by Clinician Reports: Studies With Adult Patients and Nonpatients.

We evaluate 11 Rorschach variables with potential for assessing grandiosity and narcissism. Seven of these variables were drawn from previous literature: Omnipotence, Idealization, Reflection, Personal Knowledge Justification, Exhibitionism, Magic, and Elevated Mood States; four were developed for this research: Expanded Personal Reference, Narcissistic Devaluation, Narcissistic Deflation, and Narcissistic Denial. Using Rorschach protocols from American normative adults and Italian adult outpatients, the dimensional structure of these variables was evaluated by principal components analysis, and validity was tested by correlations with clinician ratings of narcissism on two scales from the Shedler-Westen Assessment Procedure-200 that were made after at least five sessions with the primary clinician. A cohesive dimension was found in both data sets defined by Expanded Personal Reference, Personal Knowledge Justification, Omnipotence, and Idealization, and it was meaningfully correlated with the clinician ratings of narcissism ( M r = .41). Implications of the findings include the applicability of these variables in clinical practice and research for assessing narcissistic personality dynamics.

Canadian Normative Data for Minimal Assessment of Cognitive Function in Multiple Sclerosis.

OBJECTIVE: The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus-based collection of neuropsychological tests that evaluate cognitive functioning in individuals with multiple sclerosis (MS). The tests are typically scored using each respective published test manual, leaving the examiner to make interpretations from norms derived from different American populations. Given demographic differences, this may lead to misinterpretation of findings in Canadians. Our goal was to establish both discrete and regression-based normative data for the MACFIMS based on a largely co-normed Canadian population to allow for improved psychometric interpretation. METHODS: MACFIMS data sets were aggregated from across three different Canadian cities (Ottawa, Toronto, and London), yielding a total of 330 healthy control participants from four different studies evaluating cognition in individuals with MS. Given the variety of contributing studies, there was variability in terms of the number of participants completing each measure. RESULTS: Both age-based discrete normative data and demographically adjusted (sex, age, and education) regression-based formulae were established. The demographic variables varied in their contribution to each MACFIMS test in the regression models, predicting 0 to 18% of the variance. CONCLUSIONS: Provision of these regression-based formulae will allow for more accurate interpretation of Canadian-derived MACFIMS scores by allowing clinicians to correct for all relevant demographic variables simultaneously, leading to improved clinical decision making for individuals with multiple sclerosis.