TumFlow: An AI Model for Predicting New Anticancer Molecules.

Melanoma is the fifth most common cancer in the United States. Conventional drug discovery methods are inherently time-consuming and costly, which imposes significant limitations. However, the advent of Artificial Intelligence (AI) has opened up new possibilities for simulating and evaluating numerous drug candidates, thereby mitigating the requisite time and resources. In this context, normalizing flow models by employing machine learning techniques to create new molecular structures holds promise for accelerating the discovery of effective anticancer therapies. This manuscript introduces TumFlow, a novel AI model designed to generate new molecular entities with potential therapeutic value in cancer treatment. It has been trained on the NCI-60 dataset, encompassing thousands of molecules tested across 60 tumour cell lines, with an emphasis on the melanoma SK-MEL-28 cell line. The model successfully generated new molecules with predicted improved efficacy in inhibiting tumour growth while being synthetically feasible. This represents a significant advancement over conventional generative models, which often produce molecules that are challenging or impossible to synthesize. Furthermore, TumFlow has also been utilized to optimize molecules known for their efficacy in clinical melanoma treatments. This led to the creation of novel molecules with a predicted enhanced likelihood of effectiveness against melanoma, currently undocumented on PubChem.

The impact of free will beliefs on implicit learning.

A growing number of studies demonstrate that belief in free will (FWB) is dynamic, and can be reduced experimentally. Most of these studies assume that doing so has beneficial effects on behavior, as FWBs are thought to subdue unwanted automatic processes (e.g. racial stereotypes). However, relying on automatic processes can sometimes be advantageous, for instance during implicit learning (e.g. detecting and exploiting statistical regularities in the environment). In this registered report, we tested whether experimentally reducing FWBs positively affected implicit motor learning. We hypothesized that reducing FWBs would lead to both faster and stronger implicit learning, as measured using the alternating serial reaction time (ASRT) task. While we did show a manipulation effect on free will beliefs, there was no detectable effect on implicit learning processes. This finding adds to the growing body of evidence that free will belief manipulations do not meaningfully affect downstream behavior.

The impact of implicit and explicit suggestions that 'there is nothing to learn' on implicit sequence learning.

We can sometimes efficiently pick up statistical regularities in our environment in the absence of clear intentions or awareness, a process typically referred to as implicit sequence learning. In the current study, we tried to address the question whether suggesting participants that there is nothing to learn can impact this form of learning. If a priori predictions or intentions to learn are important in guiding implicit learning, we reasoned that suggesting participants that there is nothing to learn in a given context should hamper implicit learning. We introduced participants to random contexts that indicated that there was nothing to learn, either implicitly (i.e., by presenting blocks of random trials in "Experiment 1"), or explicitly (i.e., by explicitly instructing them in "Experiment 2"). Next, in a subsequent learning phase, participants performed an implicit sequence learning task. We found that these implicit or explicit suggestions that 'there was nothing to learn' did not influence the emergence of implicit knowledge in the subsequent learning phase. Although these findings seem consistent with simple associative or Hebbian learning accounts of implicit sequence learning (i.e., not steered by predictions), we discuss potential limitations that should inform future studies on the role of a priori predictions in implicit learning.

Belief in free will affects causal attributions when judging others' behavior.

Free will is a cornerstone of our society, and psychological research demonstrates that questioning its existence impacts social behavior. In six studies, we tested whether believing in free will is related to the correspondence bias, which reflects people's automatic tendency to overestimate the influence of internal as compared to external factors when interpreting others' behavior. All studies demonstrate a positive relationship between the strength of the belief in free will and the correspondence bias. Moreover, in two experimental studies, we showed that weakening participants' belief in free will leads to a reduction of the correspondence bias. Finally, the last study demonstrates that believing in free will predicts prescribed punishment and reward behavior, and that this relation is mediated by the correspondence bias. Overall, these studies show that believing in free will impacts fundamental social-cognitive processes that are involved in the understanding of others' behavior.

Free will beliefs predict attitudes toward unethical behavior and criminal punishment.

Do free will beliefs influence moral judgments? Answers to this question from theoretical and empirical perspectives are controversial. This study attempted to replicate past research and offer theoretical insights by analyzing World Values Survey data from residents of 46 countries (n = 65,111 persons). Corroborating experimental findings, free will beliefs predicted intolerance of unethical behaviors and support for severe criminal punishment. Further, the link between free will beliefs and intolerance of unethical behavior was moderated by variations in countries' institutional integrity, defined as the degree to which countries had accountable, corruption-free public sectors. Free will beliefs predicted intolerance of unethical behaviors for residents of countries with high and moderate institutional integrity, but this correlation was not seen for countries with low institutional integrity. Free will beliefs predicted support for criminal punishment regardless of countries' institutional integrity. Results were robust across different operationalizations of institutional integrity and with or without statistical control variables.

The hand of God or the hand of Maradona? Believing in free will increases perceived intentionality of others' behavior.

The question of whether free will actually exists has been debated in philosophy for centuries. However, how belief in free will shapes the perception of our social environment still remains open. Here we investigate whether belief in free will affects how much intentionality we attribute to other people. Study 1a and 1b demonstrate a weak positive relation between the strength of belief in free will and the perceived intentionality of soccer players committing handball. This pattern even holds for behavior that is objectively not intentional (i.e., when the player touches the ball accidentally). Going one step further, in Study 2 we find a weak correlation between belief in free will and perceiving intentions in very abstract geometrical shapes. These findings suggest that whether individuals believe in free will or not changes the way they interpret others' behavior, which may have important societal consequences.

Fake feedback on pain tolerance impacts proactive versus reactive control strategies.

It is well-known that beliefs about one's own ability to execute a task influence task performance. Here, we tested the hypothesis that beliefs about a specific self-control capacity, namely pain tolerance, modulate basic cognitive control processes. Participants received fake comparative social feedback that their ability to tolerate painful stimulations was either very poor or outstanding after which they performed an unrelated go/no-go task. Participants receiving low-tolerance feedback, relative to high-tolerance feedback, were less successful at inhibiting their responses and more influenced by previous trial conditions, as indicated by an increased slowdown following errors and more failed inhibitions following go-trials. These observations demonstrate a shift from a more proactive to a more reactive control mode. This study shows that providing feedback about one's own capacity to control impulsive reactions to painful stimulations directly influences low-level cognitive control dynamics.

Imaging volition: what the brain can tell us about the will.

The question of how we can voluntarily control our behaviour dates back to the beginnings of scientific psychology. Currently, there are two empirical research disciplines tackling human volition: cognitive neuroscience and social psychology. To date, there is little interaction between the two disciplines in terms of the investigation of human volition. The aim of the current article is to highlight recent brain imaging work on human volition and to relate social psychological concepts of volition to the functional neuroanatomy of intentional action. A host of studies indicate that the medial prefrontal cortex plays a crucial role in voluntary action. Accordingly, we postulate that social psychological concepts of volition can be investigated using neuroimaging techniques, and propose that by developing a social cognitive neuroscience of human volition, we may gain a deeper understanding of this fascinating and complex aspect of the human mind.

Top-down modulation of brain activity underlying intentional action and its relationship with awareness of intention: an ERP/Laplacian analysis.

Intentional actions are executed with the peculiar experience of "I decide to do that." It has been proposed that intentional actions involve a specific brain network involving the supplementary motor areas (SMAs). Here, we manipulated the internal representation participants attended to (intention vs. movement) in order to (1) examine the activity of SMAs and of the primary motor cortex (M1) during intentional action preparation and execution, and (2) investigate the temporal relationship between activity in these structures and intention awareness. Participants performed self-paced key presses. After each key press, participants were asked to report either the time they had the first intention to press the key (W-condition) or the time they actually started the movement (M-condition). We then estimated surface Laplacians from brain electrical potentials recorded while participants were performing the task. Activity in SMAs was greater in the W-condition than in the M-condition more than 1 s before electromyographic (EMG) activation, suggesting that this region is indeed associated to the formation of conscious intention. Conversely, activity in primary motor cortex (M1) contralateral to the responding hand was larger in the M-condition than in the W-condition, revealing that this region is also modulated by top-down processes. In addition, waveforms time-locked to the W-judgement revealed that M1 as well as EMG activation preceded the time at which participants become aware of their intention by about 0.3 s. This observation argues against the possibility that the temporal delay between motor-related activation and intention awareness results from smearing artifacts.

Reducing self-control by weakening belief in free will.

Believing in free will may arise from a biological need for control. People induced to disbelieve in free will show impulsive and antisocial tendencies, suggesting a reduction of the willingness to exert self-control. We investigated whether undermining free will affects two aspects of self-control: intentional inhibition and perceived self-control. We exposed participants either to anti-free will or to neutral messages. The two groups (no-free will and control) then performed a task that required self-control to inhibit a prepotent response. No-free will participants showed less intentional inhibitions than controls, suggesting a reduction of self-control. We assessed perceived self-control by asking participants whether the response resulted from a deliberate intention or from an impulsive reaction. Perceived self-control was lower in the no-free will group than in control group. Our findings show that undermining free will can degrade self-control and provide insights into how disbelieving in free will leads to antisocial tendencies.

The detection and the neural correlates of behavioral (prior) intentions.

Prior intentions are abstract mental representations that are believed to be the prime cause of our intentional actions. To date, only a few studies have focused on the possibility that single prior intentions could be identified in people's minds. Here, for the first time, we used the autobiographical Implicit Association Test (aIAT) in order to identify a specific prior intention on the basis of a pattern of associations derived from reaction times (Experiment 1). The aIAT is based on two critical blocks: the block associating intentions with true sentences (congruent block) gave rise to faster reaction times (RTs) than the block associating intentions with false sentences (incongruent block). Furthermore, when comparing intentions with hopes, it was revealed that the reported effect was intention-specific: The pattern of associations reflected a congruency effect when intentions and the logical category "True" were paired, but not when hopes and the "True" category were paired (Experiment 2). Finally, we investigated the neural bases of the congruency effect that leads to the identification of an intention (Experiment 3). We found a reduced late positive component (LPC) for the incongruent with respect to the congruent block, suggesting that the incongruent block needs additional resources of cognitive control with respect to the congruent block.

Inducing disbelief in free will alters brain correlates of preconscious motor preparation: the brain minds whether we believe in free will or not.

The feeling of being in control of one's own actions is a strong subjective experience. However, discoveries in psychology and neuroscience challenge the validity of this experience and suggest that free will is just an illusion. This raises a question: What would happen if people started to disbelieve in free will? Previous research has shown that low control beliefs affect performance and motivation. Recently, it has been shown that undermining free-will beliefs influences social behavior. In the study reported here, we investigated whether undermining beliefs in free will affects brain correlates of voluntary motor preparation. Our results showed that the readiness potential was reduced in individuals induced to disbelieve in free will. This effect was evident more than 1 s before participants consciously decided to move, a finding that suggests that the manipulation influenced intentional actions at preconscious stages. Our findings indicate that abstract belief systems might have a much more fundamental effect than previously thought.

"Free won't" after a beer or two: chronic and acute effects of alcohol on neural and behavioral indices of intentional inhibition.

BACKGROUND: Response inhibition can be classified into stimulus-driven inhibition and intentional inhibition based on the degree of endogenous volition involved. In the past decades, abundant research efforts to study the effects of alcohol on inhibition have focused exclusively on stimulus-driven inhibition. The novel Chasing Memo task measures stimulus-driven and intentional inhibition within the same paradigm. Combined with the stop-signal task, we investigated how alcohol use affects behavioral and psychophysiological correlates of intentional inhibition, as well as stimulus-driven inhibition. METHODS: Experiment I focused on intentional inhibition and stimulus-driven inhibition in relation to past-year alcohol use. The Chasing Memo task, the stop-signal task, and questionnaires related to substance use and impulsivity were administered to 60 undergraduate students (18-25 years old). Experiment II focused on behavioral and neural correlates acute alcohol use on performance on the Chasing Memo task by means of electroencephalography (EEG). Sixteen young male adults (21-28 years old) performed the Chasing Memo task once under placebo and once under the influence of alcohol (blood alcohol concentration around 0.05%), while EEG was recorded. RESULTS: In experiment I, AUDIT (Alcohol Use Disorder Identification Test) total score did not significantly predict stimulus-driven inhibition or intentional inhibition performance. In experiment II, the placebo condition and the alcohol condition were comparable in terms of behavioral indices of stimulus-driven inhibition and intentional inhibition as well as task-related EEG patterns. Interestingly, a slow negative readiness potential (RP) was observed with an onset of about 1.2 s, exclusively before participants stopped intentionally. CONCLUSIONS: These findings suggest that both past-year increases in risky alcohol consumption and moderate acute alcohol use have limited effects on stimulus-driven inhibition and intentional inhibition. These conclusions cannot be generalized to alcohol use disorder and high intoxication levels. The RP might reflect processes involved in the formation of an intention in general.

Automatic imitation: A meta-analysis.

Automatic imitation is the finding that movement execution is facilitated by compatible and impeded by incompatible observed movements. In the past 15 years, automatic imitation has been studied to understand the relation between perception and action in social interaction. Although research on this topic started in cognitive science, interest quickly spread to related disciplines such as social psychology, clinical psychology, and neuroscience. However, important theoretical questions have remained unanswered. Therefore, in the present meta-analysis, we evaluated seven key questions on automatic imitation. The results, based on 161 studies containing 226 experiments, revealed an overall effect size of gz = 0.95, 95% CI [0.88, 1.02]. Moderator analyses identified automatic imitation as a flexible, largely automatic process that is driven by movement and effector compatibility, but is also influenced by spatial compatibility. Automatic imitation was found to be stronger for forced choice tasks than for simple response tasks, for human agents than for nonhuman agents, and for goalless actions than for goal-directed actions. However, it was not modulated by more subtle factors such as animacy beliefs, motion profiles, or visual perspective. Finally, there was no evidence for a relation between automatic imitation and either empathy or autism. Among other things, these findings point toward actor-imitator similarity as a crucial modulator of automatic imitation and challenge the view that imitative tendencies are an indicator of social functioning. The current meta-analysis has important theoretical implications and sheds light on longstanding controversies in the literature on automatic imitation and related domains. (PsycINFO Database Record

Sensory Prediction Errors Are Less Modulated by Global Context in Autism Spectrum Disorder.

BACKGROUND: Recent predictive coding accounts of autism spectrum disorder (ASD) suggest that a key deficit in ASD concerns the inflexibility in modulating local prediction errors as a function of global top-down expectations. As a direct test of this central hypothesis, we used electroencephalography to investigate whether local prediction error processing was less modulated by global context (i.e., global stimulus frequency) in ASD. METHODS: A group of 18 adults with ASD was compared with a group of 24 typically developed adults on a well-validated hierarchical auditory oddball task in which participants listened to short sequences of either five identical sounds (local standard) or four identical sounds and a fifth deviant sound (local deviant). The latter condition is known to generate the mismatch negativity (MMN) component, believed to reflect early sensory prediction error processing. Crucially, previous studies have shown that in blocks with a higher frequency of local deviant sequences, top-down expectations seem to attenuate the MMN. We predicted that this modulation by global context would be less pronounced in the ASD group. RESULTS: Both groups showed an MMN that was modulated by global context. However, this effect was smaller in the ASD group as compared with the typically developed group. In contrast, the P3b, as an electroencephalographic marker of conscious expectation processes, did not differ across groups. CONCLUSIONS: Our results demonstrate that people with ASD are less flexible in modulating their local predictions (reflected in MMN), thereby confirming the central hypothesis of contemporary predictive coding accounts of ASD.

Mimicry and automatic imitation are not correlated.

It is widely known that individuals have a tendency to imitate each other. However, different psychological disciplines assess imitation in different manners. While social psychologists assess mimicry by means of action observation, cognitive psychologists assess automatic imitation with reaction time based measures on a trial-by-trial basis. Although these methods differ in crucial methodological aspects, both phenomena are assumed to rely on similar underlying mechanisms. This raises the fundamental question whether mimicry and automatic imitation are actually correlated. In the present research we assessed both phenomena and did not find a meaningful correlation. Moreover, personality traits such as empathy, autism traits, and traits related to self- versus other-focus did not correlate with mimicry or automatic imitation either. Theoretical implications are discussed.

Happiness in action: the impact of positive affect on the time of the conscious intention to act.

The temporal relationship between our conscious intentions to act and the action itself has been widely investigated. Previous research consistently shows that the motor intention enters awareness a few 100 ms before movement onset. As research in other domains has shown that most behavior is affected by the emotional state people are in, it is remarkable that the role of emotional states on intention awareness has never been investigated. Here we tested the hypothesis that positive and negative affects have opposite effects on the temporal relationship between the conscious intention to act and the action itself. A mood induction procedure that combined guided imagery and music listening was employed to induce positive, negative, or neutral affective states. After each mood induction session, participants were asked to execute voluntary self-paced movements and to report when they formed the intention to act. Exposure to pleasant material, as compared to exposure to unpleasant material, enhanced positive affect and dampened negative affect. Importantly, in the positive affect condition participants reported their intention to act earlier in time with respect to action onset, as compared to when they were in the negative or in the neutral affect conditions. Conversely the reported time of the intention to act when participants experienced negative affect did not differ significantly from the neutral condition. These findings suggest that the temporal relationship between the conscious intention to act and the action itself is malleable to changes in affective states and may indicate that positive affect enhances intentional awareness.

'Why should I care?' Challenging free will attenuates neural reaction to errors.

Whether human beings have free will has been a philosophical question for centuries. The debate about free will has recently entered the public arena through mass media and newspaper articles commenting on scientific findings that leave little to no room for free will. Previous research has shown that encouraging such a deterministic perspective influences behavior, namely by promoting cursory and antisocial behavior. Here we propose that such behavioral changes may, at least partly, stem from a more basic neurocognitive process related to response monitoring, namely a reduced error detection mechanism. Our results show that the error-related negativity, a neural marker of error detection, was reduced in individuals led to disbelieve in free will. This finding shows that reducing the belief in free will has a specific impact on error detection mechanisms. More generally, it suggests that abstract beliefs about intentional control can influence basic and automatic processes related to action control.

When errors do not matter: weakening belief in intentional control impairs cognitive reaction to errors.

The belief that one can exert intentional control over behavior is deeply rooted in virtually all human beings. It has been shown that weakening such belief - e.g. by exposure to 'anti-free will' messages - can lead people to display antisocial tendencies. We propose that this cursory and irresponsible behavior may be facilitated by a breakdown of neurocognitive mechanisms underlying behavioral adjustments. In the study reported here, we tested the hypothesis that weakening belief in intentional control reduces cognitive markers of behavioral control. Participants performed a Simon task before and after reading a scientific text either denying free will (no-free will group) or not mentioning free will (control group). Results showed that the post-error slowing, a cognitive marker of performance adjustment, was reduced in the no-free will group. This reduction was proportional to a decrease of the belief in intentional control. These observations indicate that weakening the belief in free will can impact behavioral adjustment after an error, and could be the cause of antisocial and irresponsible behavior.

Attitudes towards end-of-life decisions and the subjective concepts of consciousness: an empirical analysis.

BACKGROUND: People have fought for their civil rights, primarily the right to live in dignity. At present, the development of technology in medicine and healthcare led to an apparent paradox: many people are fighting for the right to die. This study was aimed at testing whether different moral principles are associated with different attitudes towards end-of-life decisions for patients with a severe brain damage. METHODOLOGY: We focused on the ethical decisions about withdrawing life-sustaining treatments in patients with severe brain damage. 202 undergraduate students at the University of Padova were given one description drawn from four profiles describing different pathological states: the permanent vegetative state, the minimally conscious state, the locked-in syndrome, and the terminal illness. Participants were asked to evaluate how dead or how alive the patient was, and how appropriate it was to satisfy the patient's desire. PRINCIPAL FINDINGS: We found that the moral principles in which people believe affect not only people's judgments concerning the appropriateness of the withdrawal of life support, but also the perception of the death status of patients with severe brain injury. In particular, we found that the supporters of the Free Choice (FC) principle perceived the death status of the patients with different pathologies differently: the more people believe in the FC, the more they perceived patients as dead in pathologies where conscious awareness is severely impaired. By contrast, participants who agree with the Sanctity of Life (SL) principle did not show differences across pathologies. CONCLUSIONS: These results may shed light on the complex aspects of moral consensus for supporting or rejecting end-of-life decisions.