Attenuated Replication-Competent Herpes Simplex Virus Expressing an ECM-Modifying Transgene Hyaluronan Synthase 2 of Naked Mole Rat in Oncolytic Gene Therapy.

Herpes simplex virus (HSV) has proven successful in treating human cancer. Since the approval of talimogene laherparepvec (T-VEC) in 2015, HSV has been thoroughly researched to discover novel mechanisms to combat cancer and treat other diseases. Another HSV-based drug, beremagene geperpavec (B-VEC), received approval in 2023 to treat the rare genetic disease dystrophic epidermolysis bullosa, and was also the first clinically approved HSV vector carrying an extracellular matrix (ECM)-modifying transgene. The ECM is a network of macromolecules surrounding cells, which provides support and regulates cell growth and differentiation, the disruption of which is common in cancer. The naked mole rat (NMR) has a thick ECM and a unique mutation in the hyaluronan synthase 2 (HAS2) gene, which has been linked to the high cancer resistance of the species. To study the effect of this mutation in human cancer, we have developed an attenuated, replication-competent HSV vector expressing the NMR-HAS2 gene. The viral replication, transgene expression and cytotoxic effect of the novel vector was studied in glioma cells. Our results show that an attenuated, replication-competent HSV vector expressing a foreign ECM-modifying transgene, namely HAS2, provides an effective tool to study and combat cancer in humans.

Increased volatility in video poker results in more winning players but shorter winning streaks - Evidence from simulations.

Objective and Method: Electronic gambling machines are a prominent cause of significant gambling harms globally. We use simulations of a simplified video poker game to show how changes in game volatility, defined primarily by the size of the main prize, affect patterns of wins and losses as well as winning streaks. Results: We found that in low- and medium volatility games the proportion of winning players quickly drops to zero after about 30 h of play, while in the high volatility game 5% of players are still winning after playing for 100 h. However, the proportion of winning streaks was significantly higher in the low- and medium volatility games compared with high volatility: the simulated players were on a winning streak about 26.3, 25.6 and 18% of the time in the low-, medium- and high volatility games, respectively. Conclusions: Fast-paced video poker with varying volatility levels but identical return-to-player rates and win frequencies can yield highly different result patterns across individuals. These patterns may be counter-intuitive for players and difficult to realize without simulations and visualizations. We argue that the findings have relevance for responsible gambling communication and for building a better understanding of how cognitive biases influence gambling behaviour.

Dissociative experiences reduce online problem gambling treatment effectiveness.

AIMS: To determine whether dissociative experiences moderate online problem gambling treatment effectiveness, and to characterize the temporal persistence of the relationship between dissociation and problem gambling. DESIGN: Repeatedly measured self-report data on a guided online cognitive behavioral therapy for problem gambling collected on four occasions: before treatment, after treatment, and at 6- and 12-month follow-ups. SETTING AND PARTICIPANTS: The data (N = 1243, 59.2% males) were collected in Finland between 2019 and 2021. MEASUREMENTS: The primary outcome variable was the self-reported level of problem gambling. The predictors were the treatment phase and dissociative experiences, their interaction, and the demographic covariates of age, education, income, and gender. FINDINGS: Problem gambling scores and dissociative experiences declined significantly following treatment and remained low through the follow-ups (retention rates: 52.6% [post-treatment], 26.3% [at the 6-month follow-up], and 16.1% [at the 12-month follow-up]). However, the treatment was significantly less effective in reducing problem gambling for individuals who kept experiencing dissociation after the treatment. CONCLUSIONS: Dissociation is an integral sign of problem gambling severity and sustained dissociative experiences may significantly reduce the long-term effectiveness of online problem gambling treatments. Treatment efforts should be customized to account for individual differences in dissociative tendencies, and future research should broaden the study of dissociative experiences to other behavioral addictions.

Predicting online problem gambling treatment discontinuation: New evidence from cross-validated models.

OBJECTIVE: There are tens of millions of problem gamblers in the world, many of whom either do not seek treatment or fail to commit to it. Dropout rates are high, and not enough is known about factors predicting treatment adherence. We focus on an online cognitive behavioral therapy program for severe problem gambling to determine the likelihood of treatment discontinuation at three different treatment phases: pretreatment, before halfway, and before the end of the program. METHOD: Participants were Finnish adults (N = 1,139, 670 males, Mage = 34.5) registered in the program between 2019 and 2021. Using logistic regression and five-fold cross-validated naïve Bayes classification, we predicted discontinuation with demographic-, psychometric-, and other gambling-related variables, including the quality of one's social relations, time spent on the waiting list, and experienced readiness to behavioral change. RESULTS: The models had acceptable predictive ability (area under the curve [AUC] values from .69 to .745; cross-validated balanced classification accuracy = 63.2%). In logistic regressions, treatment discontinuation was prominently associated with younger age (p = .008), lower education (p < .001), not being ready to change gambling behavior (p < .001), problem gambling severity (p < .0001), longer time spent on the treatment waiting list (p < .0001), and fewer close social relationships (p < .001). CONCLUSIONS: We found significant new real-world evidence on factors statistically predicting treatment discontinuation, which is crucial when existing programs are modified to better serve those in need. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Would you exchange your soul for immortality?-existential meaning and afterlife beliefs predict mind upload approval.

Mind upload, or the digital copying of an individual brain and mind, could theoretically allow one to "live forever." If such a technology became available, who would be most likely to approve of it or condemn it? Research has shown that fear of death positively predicts the moral approval of hypothetical mind upload technology, while religiosity may have the opposite effect. We build on these findings, drawing also from work on religiosity and existential mattering as predictors of perceived meaning in one's life. In a cross-sectional study (N = 1,007), we show that existential mattering and afterlife beliefs are negatively associated with moral approval of mind upload technology: people who believe there is a soul or some form of afterlife and who also report a high level of existential mattering, are least likely to morally approve of mind upload technology. Indeed, mind uploading-if it ever becomes feasible-is a form of technology that would fundamentally redraw the existential boundaries of what it means to be human.

Psychometric analysis of the flow short scale translated to Finnish.

Flow is a well-known construct describing the experience of deep absorption in a task, typically demanding but intrinsically motivating, and conducted with high skill. Flow is operationalized by self-report, and various instruments have been developed for this, but none have been made available in the Finnish language in thoroughly validated form. We present a psychometric scale-validation study for the Finnish translation of the Flow Short Scale (FSS). We collected data from 201 Finnish speaking participants using the Prolific Academic platform. We assessed the scale's factorial structure using Mokken scale analysis, Parallel Analysis, Very Simple Structures analysis and a standard Confirmatory Factor Analysis. We then evaluated how correlated was the FSS with the Flow State Scale and Flow Core Scale. Finally, we evaluated how well the FSS distinguished Flow-inducing experiences from boring (non-Flow-inducing) experiences. Taken together, our results show that an 8-item, two-factor version of the scale was a justified instrument with good psychometric properties.

Online 8-week cognitive therapy for problem gamblers: The moderating effects of depression symptoms and perceived financial control.

BACKGROUND AND AIMS: Online interventions for problem gambling are increasingly popular, but not everyone benefits from them. We describe 12 years of real-world data from an online intervention for gambling problems and aim to find out the extent to which depression, alcohol use, and sense of financial control influence the effectiveness of the program. METHODS: We analyzed treatment effectiveness and moderators in the Finnish "Peli Poikki" program (2007-2018)-an 8-week cognitive behavioral therapy and follow-up program for problem gambling. Participants were Finnish-speaking adults over 18 years of age (N = 2011, 66.9% males). We measured the self-reported level of problem gambling, depression, alcohol use, and sense of financial control across four treatment phases (baseline, post-treatment, 6-month follow-up, and 12-month follow-up), as well as the presence of gambling debt, psychological and physiological health, years suffered from gambling problems, and demographic variables. RESULTS: Participation grew across years with retention rates of 55%, 30%, and 19% for post-treatment and the two follow-ups, respectively. The average problem gambling scores declined significantly following treatment and remained low throughout the follow-ups. However, this decline (the beneficial treatment effect) was reversed after the follow-ups for those with high depression scores and those who felt they had no control over their finances. DISCUSSION AND CONCLUSIONS: The Peli Poikki program is a well-functioning online intervention but less effective in the long term for participants with persisting symptoms of depression or without a sense of financial control. More attention is needed to screen and direct people with comorbidities to the appropriate services.

Reduced Power in Fronto-Parietal Theta EEG Linked to Impaired Attention-Sampling in Adult ADHD.

Attention-deficit/hyperactivity disorder (ADHD) in adults is understudied, especially regarding neural mechanisms such as oscillatory control of attention sampling. We report an electroencephalography (EEG) study of such cortical mechanisms, in ADHD-diagnosed adults during administration of Test of Variables of Attention (TOVA), a gold-standard continuous performance test for ADHD that measures the ability to sustain attention and inhibit impulsivity. We recorded 53 adults (28 female, 25 male, aged 18-60), and 18 matched healthy controls, using 128-channel EEG. We analyzed sensor-space features established as neural correlates of attention: timing-sensitivity and phase-synchrony of response activations, and event-related (de)synchronization (ERS/D) of α and θ frequency band activity; in frontal and parietal scalp regions. TOVA test performance significantly distinguished ADHD adults from neurotypical controls, in commission errors, response time variability (RTV) and d' (response sensitivity). The ADHD group showed significantly weaker target-locked and response-locked amplitudes, that were strongly right-lateralized at the N2 wave, and weaker phase synchrony (longer reset poststimulus). They also manifested significantly less parietal prestimulus 8-Hz θ ERS, less frontal and parietal poststimulus 4-Hz θ ERS, and more frontal and parietal prestimulus α ERS during correct trials. These differences may reflect excessive modulation of endogenous activity by strong entrainment to stimulus (α), combined with deficient modulation by neural entrainment to task (θ), which in TOVA involves monitoring stimulus spatial location (not predicted occurrence onset which is regular and task-irrelevant). Building on the hypotheses of θ coding for relational structure and rhythmic attention sampling, our results suggest that ADHD adults have impaired attention sampling in relational categorization tasks.

Online betting intensity is linked with Extraversion and Conscientiousness.

INTRODUCTION: Extraversion and Conscientiousness are well-studied personality traits associated with reward processing and goal prioritization, respectively, and bear on individual differences in financial risk-taking. Using unique large datasets, we investigated the link between these traits and male online gamblers' actual betting participation and intensity. METHOD: We combined datasets containing online horse betting data (during 2015-2016) from the Finnish monopoly betting company, administrative registry data from Statistics Finland, and personality trait measures from the Finnish Defence Forces corresponding to Extraversion and Conscientiousness as defined in the five-factor model. We modelled associations between these traits and betting participation (n = 471,968) and intensity (n = 11,217) among male horse bettors (age = 36-53). RESULTS: Controlling for demographics and IQ, individuals scoring high on Conscientiousness (or Extraversion) were less (or more) likely to bet and less (or more) intensive bettors-even when personality was measured 16-34 years before betting occurred. One SD personality score increase represented an annual decrease (Conscientiousness) or increase (Extraversion) of €570-754 in spending. CONCLUSIONS: Extraversion and Conscientiousness are implicated in real-life financial behavior with tangible consequences for individuals. These effects are stronger than for many known demographic variables used in gambling studies and persist up to 34 years after personality has been measured.

Positive affect state is a good predictor of movement and stress: combining data from ESM/EMA, mobile HRV measurements and trait questionnaires.

Personality describes the average behaviour and responses of individuals across situations; but personality traits are often poor predictors of behaviour in specific situations. This is known as the "personality paradox". We evaluated the interrelations between various trait and state variables in participants' everyday lives. As state measures, we used 1) experience sampling methodology (ESM/EMA) to measure perceived affect, stress, and presence of social company; and 2) heart rate variability and 3) real-time movement (accelerometer data) to indicate physiological stress and physical movement. These data were linked with self-report measures of personality and personality-like traits. Trait variables predicted affect states and multiple associations were found: traits neuroticism and rumination decreased positive affect state and increased negative affect state. Positive affect state, in turn, was the strongest predictor of observed movement. Positive affect was also associated with heart rate and heart rate variability (HRV). Negative affect, in turn, was not associated with neither movement, HR or HRV. The study provides evidence on the influence of personality-like traits and social context to affect states, and, in turn, their influence to movement and stress variables.

Flow Experiences During Visuomotor Skill Acquisition Reflect Deviation From a Power-Law Learning Curve, but Not Overall Level of Skill.

Flow is a state of "optimal experience" that arises when skill and task demands match. Flow has been well studied in psychology using a range of self-report and experimental methods; with most research typically focusing on how Flow is elicited by a particular task. Here, we focus on how the experience of Flow changes during task skill development. We present a longitudinal experimental study of learning, wherein participants (N = 9) play a novel steering-game task designed to elicit Flow by matching skill and demand, and providing clear goals and feedback. Experimental design involves extensive in-depth measurement of behavior, physiology, and Flow self-reports over 2 weeks of 40 game trials in eight sessions. Here we report behavioral results, which are both strikingly similar and strong within each participant. We find that the game induces a near-constant state of elevated Flow. We further find that the variation in Flow across all trials is less affected by overall performance improvement than by deviation of performance from the expected value predicted by a power law model of learning.

Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection.

A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from the Nordic countries. Finland's history includes at least two major waves of human migration, suggesting the potential for diverse viruses to persist in the population. Here, we used HSV-1 clinical isolates from Finland to test the relationship between viral phylogeny, genetic variation, and phenotypic characteristics. We found that Finnish HSV-1 isolates separated into two distinct phylogenetic groups, potentially reflecting historical waves of human (and viral) migration into Finland. Each HSV-1 isolate harbored a distinct set of phenotypes in cell culture, including differences in the amount of virus production, extracellular virus release, and cell-type-specific fitness. Importantly, the phylogenetic clusters were not predictive of any detectable pattern in phenotypic differences, demonstrating that whole-genome relatedness is not a proxy for overall viral phenotype. Instead, we highlight specific gene-level differences that may contribute to observed phenotypic differences, and we note that strains from different phylogenetic groups can contain the same genetic variations.IMPORTANCE Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences.

Experience and Passion in Poker: Are There Well-Being Implications?

Previous studies on gambling passion have identified that obsessive passion is related to negative consequences, including gambling pathology, whereas harmonious passion is mostly related to positive outcomes both during and after engagement in gambling activity. In the present study, we focused on poker players (N = 311) and investigated the associations between the two types of gambling passion and subjective well-being, while taking into account acquired poker experience. We found that harmonious passion toward poker was associated with higher levels of well-being, whereas the reverse was true for obsessive passion. Poker experience was positively related to harmonious but not obsessive passion, and moderated the relationship between harmonious passion and quality of life. Our findings contribute to extant literature on passion and further solidify its application in a gambling context. Most importantly, our results underline the relevance of accounting for poker experience when studying gambling among poker players.

Evaluating the replicability of the uncanny valley effect.

The uncanny valley (UV) effect refers to an eerie feeling of unfamiliarity people get while observing or interacting with robots that resemble humans almost but not quite perfectly. The effect is not well understood, and it is also unclear how well results from previous research on the UV can be replicated. In six studies, both in the laboratory and online (N = 1343), we attempted to replicate the UV effect with various stimuli used in previous research. In Studies 1 and 2 we failed to replicate the UV effect with CGI stimuli created using the so-called morphing technique (a robot image morphed into a human image, resulting in a supposedly creepy robot-human image). In Studies 3a and 3b we found a prominent UV effect using pre-evaluated, non-morphed and photorealistic robot pictures. Finally, in exploratory Studies 4a and 4b we found the UV effect using morphed and photorealistic human and robot pictures. Our results suggest that the UV effect is more robust when elicited by pre-validated or prima facie uncanny robot pictures than by non-photorealistic images generated using the morphing technique. We argue that photorealistic pictures are more suitable than less realistic CGI pictures as stimuli for research attempting to elicit the UV effect - however, our results do not invalidate any previous research on the UV effect using morphing techniques, but point to their domain of applicability and context sensitivity.

We will make you like our research: The development of a susceptibility-to-persuasion scale.

Psychological and other persuasive mechanisms across diverse contexts are well researched, with many studies of the effectiveness of specific persuasive techniques on distinct types of human behaviour. In the present paper, our specific interest lies in the development of a generalized modular psychometric tool to measure individuals' susceptibility to persuasion. The scale is constructed using items from previously developed and validated particulate scales established in the domains of social psychology and behavioural economics. In the first study we establish the Susceptibility to Persuasion-II (StP-II) scale, containing 54 items, 10 subscales and further 6 sub-sub scales. In Study 2 we establish the scale's construct validity and reconfirm its reliability. We present a valid and reliable modular psychometric tool that measures general susceptibility to persuasive techniques. Since its inception, we have successfully implemented the StP-II scale to measure susceptibility to persuasion of IT security officers, the role of psychology of persuasion in cybercrime victims and general persuadability levels of Facebook users; these manuscripts are in preparation. We argue that the StP-II scale shows promise in measuring individual differences in susceptibility to persuasion, and is applicable across diverse contexts such as Internet security and cybercrime.

Money for microbes-Pathogen avoidance and out-group helping behaviour.

Humans have evolved various adaptations against pathogens, including the physiological immune system. However, not all of these adaptations are physiological: the cognitive mechanisms whereby we avoid potential sources of pathogens-for example, disgust elicited by uncleanliness-can be considered as parts of a behavioural immune system (BIS). The mechanisms of BIS extend also to inter-group relations: Pathogen cues have been shown to increase xenophobia/ethnocentrism, as people prefer to keep their societal in-group norms unaltered and "clean." Nonetheless, little is known how pathogen cues influence people's willingness to provide humanitarian aid to out-group members. We examined how pathogen cues affected decisions of providing humanitarian aid in either instrumental (sending money) or non-instrumental form (sending personnel to help, or accepting refugees), and whether these effects were moderated by individual differences in BIS sensitivity. Data were collected in two online studies (Ns: 188 and 210). When the hypothetical humanitarian crisis involved a clear risk of infection, participants with high BIS sensitivity preferred to send money rather than personnel or to accept refugees. The results suggest that pathogen cues influence BIS-sensitive individuals' willingness to provide humanitarian aid when there is a risk of contamination to in-group members.

"To Bluff like a Man or Fold like a Girl?" - Gender Biased Deceptive Behavior in Online Poker.

Evolutionary psychology suggests that men are more likely than women to deceive to bolster their status and influence. Also gender perception influences deceptive behavior, which is linked to pervasive gender stereotypes: women are typically viewed as weaker and more gullible than men. We assessed bluffing in an online experiment (N = 502), where participants made decisions to bluff or not in simulated poker tasks against opponents represented by avatars. Participants bluffed on average 6% more frequently at poker tables with female-only avatars than at tables with male-only or gender mixed avatars-a highly significant effect in games involving repeated decisions. Nonetheless, participants did not believe the avatar genders affected their decisions. Males bluffed 13% more frequently than females. Unlike most economic games employed exclusively in research contexts, online poker is played for money by tens of millions of people worldwide. Thus, gender effects in bluffing have significant monetary consequences for poker players.

Emotional and Social Factors influence Poker Decision Making Accuracy.

Poker is a social game, where success depends on both game strategic knowledge and emotion regulation abilities. Thus, poker provides a productive environment for studying the effects of emotional and social factors on micro-economic decision making. Previous research indicates that experiencing negative emotions, such as moral anger, reduces mathematical accuracy in poker decision making. Furthermore, various social aspects of the game­such as losing against "bad players" due to "bad luck"­seem to fuel these emotional states. We designed an Internet-based experiment, where participants' (N = 459) mathematical accuracy in five different poker decision making tasks were assessed. In addition, we manipulated the emotional and social conditions under which the tasks were presented, in a 2 × 2 experimental setup: (1) Anger versus neutral emotional state­participants were primed either with an anger-inducing, or emotionally neutral story, and (2) Social cue versus non-social cue­during the tasks, either an image of a pair of human eyes was "following" the mouse cursor, or an image of a black moving box was presented. The results showed that anger reduced mathematical accuracy of decision making only when participants were "being watched" by a pair of moving eyes. Experienced poker players made mathematically more accurate decisions than inexperienced ones. The results contribute to current understanding on how emotional and social factors influence decision making accuracy in economic games.