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Abstract Despite increasing interest in using Artificial Intelligence (AI) and Machine Learning (ML) models for drug development, effectively interpreting their predictions remains a challenge, which limits their impact on clinical decisions. We address this issue by providing a practical guide to SHapley Additive exPlanations (SHAP), a popular feature‐based interpretability method, which can be seamlessly integrated into supervised ML models to gain a deeper understanding of their predictions, thereby enhancing their transparency and trustworthiness. This tutorial focuses on the application of SHAP analysis to standard ML black‐box models for regression and classification problems. We provide an overview of various visualization plots and their interpretation, available software for implementing SHAP, and highlight best practices, as well as special considerations, when dealing with binary endpoints and time‐series models. To enhance the reader's understanding for the method, we also apply it to inherently explainable regression models. Finally, we discuss the limitations and ongoing advancements aimed at tackling the current drawbacks of the method.

Behavioral researchers tend to study behavior in highly controlled laboratory settings to minimize the effects of potential confounders. Yet, while doing so, the artificial setup itself might unintentionally introduce noise or confounders, such as boredom. In this perspective, we draw upon theoretical and empirical evidence to make the case that (a) some experimental setups are likely to induce boredom in participants, (b) the degree of boredom induced might differ between individuals as a function of differences in trait boredom, (c) boredom can impair participants’ attention, can make study participation more effortful, and can increase the urge to do something else (i.e., to disengage from the study). Most importantly, we argue that some participants might adjust their behavior because they are bored. Considering boredom’s potential for adding noise to data, or for being an unwanted confound, we discuss a set of recommendations on how to control for and deal with the occurrence and effects of boredom in behavioral science research.

In the wake of the Coronavirus Disease 2019 (COVID-19), social distancing is instrumental for containing the pandemic. To maximize its effectiveness, it is paramount to investigate psychological factors that predict adherence to social distancing guidelines and examine corresponding interventions. We focused on individual differences in if-then planning, self-control, and boredom, and tested an intervention based on if-then planning. We conducted a two-wave longitudinal study combining observational and experimental methods. Participants (N = 574, 35.7% female, age: M = 37.5 years, SD = 10.8) reported their adherence to social distancing guidelines and the perceived difficulty of adherence at T1, along with trait measures of if-then planning, self-control, and boredom. Afterwards, they were randomly assigned to an if-then planning intervention to increase adherence, or to a control intervention. One week later at T2, participants again reported their adherence and the perceived difficulty of adhering. Multiple regression and structural equation modeling were used to establish whether trait if-then planning, self-control, and boredom predicted adherence, and to examine the effects of the if-then planning intervention. Trait if-then planning, self-control, and boredom were associated with T1 adherence, while only if-then planning and boredom predicted T2 adherence. No overall treatment effect of the if-then planning intervention emerged; however, participants who complied with the intervention (75.6%) maintained higher levels of adherence over time than control participants. In sum, individual differences in if-then planning, self-control, and boredom predicted adherence to social distancing guidelines. If-then planning interventions are promising but require further steps to ascertain compliance., Author(s): Maik Bieleke [sup.1] , Corinna S. Martarelli [sup.2] , Wanja Wolff [sup.1] [sup.3] Author Affiliations: (1) grid.9811.1, 0000 0001 0658 7699, Department of Sport Science, University of Konstanz, , [...]

A short course for high school students was converted from a two-week, in-person laboratory course to a remote and virtual four-week course due to the COVID-19 pandemic. Students met virtually each day to participate in activities that included the following: presentations, demonstrations, interviews, group discussions, lessons, and virtual tours and field trips. The virtual version of the course was able to maintain the same learning objectives and activities when compared to the in-person session and integrated additional expanded lessons, kitchen chemistry activities, and an emphasis on careers in science in order to increase student engagement. Student feedback indicated that interest in a career in STEM was increased overall, and the incorporation of some of the newly introduced activities can be implemented into future versions of the course.

A two-week summer camp was designed, implemented, and then updated for high school students focusing on organic chemistry, solar energy, and green chemistry principles. Students learn about laboratory safety, perform organic reactions, go on field trips, and take part in interactive lessons that focus on both fundamental chemistry topics as well as green chemistry. Each lab experiment implements at least one green chemistry principle by reducing waste or reagent use while employing additional safety measures. The course has been edited and modified on the basis of student feedback to include additional lessons, field trips, a student presentation, and other activities. Responses to postcourse surveys provided feedback on each component and also indicated that student interest in STEM increased as students gained physical laboratory and research skills.

Ongoing digital transformations facilitate the conduct of online courses and distance learning. In this study, it was aimed to investigate the role of learners' personalities and behaviors in their academic success (exam scores) in a blended learning setting (combination of distance learning and face-to-face learning). Next to individual differences in several variables (including intelligence), participants' (n = 62) learning time and learning motivation over 14 weeks (one term) using questionnaires for one learning module at the Swiss Distance University Institute was measured. Also, data on the participants' grades at the end of the course and the number of exercises they completed during the term were obtained. A stepwise regression analysis revealed that studying at the optimal time of the day and studying regularly are relevant predictors of academic success. The results and limitations of the study are discussed in the context of academic success prediction in higher education.

Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea exclusively in humans and uses multiple strategies to infect, including acquisition of host sialic acids that cap and mask lipooligosaccharide termini, while restricting complement activation. We hypothesized that gonococci selectively target human anti-inflammatory sialic acid-recognizing Siglec receptors on innate immune cells to blunt host responses and that pro-inflammatory Siglecs and SIGLEC pseudogene polymorphisms represent host evolutionary adaptations to counteract this interaction. N. gonorrhoeae can indeed engage multiple human but not chimpanzee CD33rSiglecs expressed on innate immune cells and in the genitourinary tract--including Siglec-11 (inhibitory) and Siglec-16 (activating), which we detected for the first time on human cervical epithelium. Surprisingly, in addition to LOS sialic acid, we found that gonococcal porin (PorB) mediated binding to multiple Siglecs. PorB also bound preferentially to human Siglecs and not chimpanzee orthologs, modulating host immune reactions in a human-specific manner. Lastly, we studied the distribution of null SIGLEC polymorphisms in a Namibian cohort with a high prevalence of gonorrhea and found that uninfected women preferentially harbor functional SIGLEC16 alleles encoding an activating immune receptor. These results contribute to the understanding of the human specificity of N. gonorrhoeae and how it evolved to evade the human immune defense.

Abstract During recall of visual information people tend to move their eyes even though there is nothing to see. Previous studies indicated that such eye movements are related to the spatial location of previously seen items on 2D screens, but they also showed that eye movement behavior varies significantly across individuals. The reason for these differences remains unclear. In the present study we used immersive virtual reality to investigate how individual tendencies to process and represent visual information contribute to eye fixation patterns in visual imagery of previously inspected objects in three-dimensional (3D) space. We show that participants also look back to relevant locations when they are free to move in 3D space. Furthermore, we found that looking back to relevant locations depends on individual differences in visual object imagery abilities. We suggest that object visualizers rely less on spatial information because they tend to process and represent the visual information in terms of color and shape rather than in terms of spatial layout. This finding indicates that eye movements during imagery are subject to individual strategies, and the immersive setting in 3D space made individual differences more likely to unfold.

We studied the role of time in the experience of boredom and its relationship with various psychological states using virtual reality. Sixty-six participants visited nine virtual waiting rooms and evaluated their perception of time and psychological experiences, including boredom, exhaustion, restlessness, amotivation, frustration, anger, unhappiness, spontaneous and deliberate mind-wandering, fantasy, and absorption. Results confirmed the relationship between boredom and time perception, showing that the higher the levels of boredom, the slower time seems to pass. However, manipulating time-related information via a slower/faster ticking clock did not affect boredom. We also found that boredom increased as participants progressed through the nine virtual rooms, and its affective characterisation over time remained stable, while its cognitive characterisation fluctuated. While boredom was consistently associated with exhaustion, restlessness, amotivation, and frustration, its relationship with fantasy, absorption, spontaneous mind-wandering and deliberate mind-wandering, evolved over time. These findings provide novel insights into the intricate and differentiated cognitive and affective consequences of being bored. [ABSTRACT FROM AUTHOR]

Despite increasing interest in using Artificial Intelligence (AI) and Machine Learning (ML) models for drug development, effectively interpreting their predictions remains a challenge, which limits their impact on clinical decisions. We address this issue by providing a practical guide to SHapley Additive exPlanations (SHAP), a popular feature‐based interpretability method, which can be seamlessly integrated into supervised ML models to gain a deeper understanding of their predictions, thereby enhancing their transparency and trustworthiness. This tutorial focuses on the application of SHAP analysis to standard ML black‐box models for regression and classification problems. We provide an overview of various visualization plots and their interpretation, available software for implementing SHAP, and highlight best practices, as well as special considerations, when dealing with binary endpoints and time‐series models. To enhance the reader's understanding for the method, we also apply it to inherently explainable regression models. Finally, we discuss the limitations and ongoing advancements aimed at tackling the current drawbacks of the method. [ABSTRACT FROM AUTHOR]

Recognition memory, the ability to recognise previously encountered information, correlates with pupil diameter changes during the recognition period. This physiological response, known as the pupil old/new effect, generally reflects the variation in pupil dilation when encountering previously studied (old) stimuli compared to new stimuli. To develop a more precise understanding of the pupil old/new effect, we conducted a meta-analysis of 17 eye-tracking experiments (across 12 articles spanning from 2008 to 2023) involving 560 healthy adults with a mean age of 22.31 years. Analysis of publication bias showed a rather low risk of bias in the selected articles. The main meta-analysis revealed a significant and large pooled pupil old/new effect (Cohen's dz = 0.73, 95% CI [0.50, 0.95]). Further analysis of moderators showed that the number of participants included in the experiments and the criteria for selecting trials (only correct trials vs. all trials) had a significant impact on the meta-analytic results. In general, the analyses revealed a robust pupil old/new effect across all selected articles. This finding underscores its potential utility as a marker of recognition memory across different stimuli type, and various experimental designs. [ABSTRACT FROM AUTHOR]

[micro]-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose.sup.1-3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown.sup.4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine consummatory response, while select enkephalin-containing nucleus accumbens ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of the endogenous MOPR ligand. Selective modulation of nucleus accumbens enkephalin neurons and CRISPR-Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent consumptive behaviour and suggest alternative mechanisms for opiate modulation of reward. Studies in mice show that [micro]-opioid peptide receptor regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection and requires enkephalin-producing neurons., Author(s): Daniel C. Castro [sup.1] [sup.2] [sup.3] [sup.4] , Corinna S. Oswell [sup.1] [sup.4] , Eric T. Zhang [sup.4] [sup.5] , Christian E. Pedersen [sup.4] [sup.5] , Sean C. Piantadosi [...]

Abstract In an effort to mitigate the impact of the COVID-19 pandemic, countries around the world have employed non-pharmaceutical containment measures. The effectiveness of such mitigation efforts relies on individual compliance (e.g., avoiding to travel or to gather). Crucially, adhering to the required behavioral recommendations places substantial burdens on those who are asked to follow them. One particularly likely outcome of adherence should be the experience of boredom. Thus, people might get bored by bothering. Drawing from research and theorizing on reward-based decision making, we conducted a high-powered study (N = 1553 US participants) to investigate whether the value and effort people ascribe to adherence to containment measures directly and indirectly (i.e., mediated by adherence) affects their experience of boredom. As expected, structural equation modeling revealed that high value and low effort predicted compliance with behavioral recommendations. Moreover, higher compliance was linked to more boredom, meaning that high value and low effort increased boredom via compliance. In contrast, high value and low effort had direct effects on boredom in the opposite direction (i.e., decreasing boredom). Attesting to their robustness and generalizability, these findings held for both prospective (with respect to upcoming winter holidays) and retrospective behavior (with respect to previous thanksgiving holidays), across US states, which had or had not enforced behavioral restrictions, individual differences in boredom proneness, and demographic variables. Taken together, our results provide evidence that people can indeed get bored by bothering: Complying with nonpharmacological containment measures like avoiding to travel and to gather can come at the cost of getting bored, an experience that was strongly linked to negative affect in our study.

Paired immune receptors display near-identical extracellular ligand-binding regions but have intracellular sequences with opposing signaling functions. While inhibitory receptors dampen cellular activation by recognizing self-associated molecules, the functions of activating counterparts are less clear. Here, we studied the inhibitory receptor Siglec-11 that shows uniquely human expression in brain microglia and engages endogenous polysialic acid to suppress inflammation. We demonstrated that the human-specific pathogen Escherichia coli K1 uses its polysialic acid capsule as a molecular mimic to engage Siglec-11 and escape killing. In contrast, engagement of the activating counterpart Siglec-16 increases elimination of bacteria. Since mice do not have paired Siglec receptors, we generated a model by replacing the inhibitory domain of mouse Siglec-E with the activating module of Siglec-16. Siglec-E16 enhanced proinflammatory cytokine expression and bacterial killing in macrophages and boosted protection against intravenous bacterial challenge. These data elucidate uniquely human interactions of a pathogen with Siglecs and support the long-standing hypothesis that activating counterparts of paired immune receptors evolved as a response to pathogen molecular mimicry of host ligands for inhibitory receptors.

Oxetanes, 4-membered oxygen-containing heterocycles, were identified to have pharmaceutical applications after the discovery of the chemotherapeutic drug taxol (Paclitaxel) and its analogues. Furthermore, oxetanes have been identified as bioisosteres for several common functional groups and are present in a number of natural products. However, oxetanes are one of the least common oxygen-containing heterocycles in active pharmaceutical ingredients on the market, which can be attributed, in part, due to challenges with their synthesis. Previous strategies rely on nucleophilic substitutions or [2+2]-cycloadditions, but are limited by the stepwise buildup of starting material and limitations in scope resulting from requirements for activated substrates. To address these limitations, we envisioned activating simple carbonyls to their corresponding α-oxy iodides to promote ketyl radical formation. These radicals can then undergo atom-transfer radical addition with alkenes followed by one-pot nucleophilic substitution to produce oxetanes. Herein, we present a proof-of-principle of this strategy in which fluoroalkyl carbonyls are successfully converted into the corresponding fluoroalkyl oxetanes. [ABSTRACT FROM AUTHOR]

Self-control is a highly adaptive human capacity and research on self-control is booming. To further facilitate self-control research, especially in conditions where time-constraints might render the use of multi-item measures of self-control problematic, a validated time-efficient single item measure would be an asset. However, such a measure has not yet been developed and tested. Here, we address this gap by reporting the psychometric properties of a single item measure of self-control and by assessing its localization within a larger theorized psychometric network consisting of self-control, boredom and if-then planning. In a high-powered (N = 1553) study with paid online workers from the US (gender: 47.3% female, 51.7% male, 1% other; age: 40.36 ± 12.65 years), we found evidence for the convergent validity (Brief Self-Control Scale), divergent validity (Short Boredom Proneness Scale and If-Then Planning Scale), and criterion validity (objective and subjective socio-economic status) of the single item measure of self-control (“How much self-control do you have?”). Network psychometrics further revealed that the single item was part of the self-control subnetwork and clearly distinguishable from boredom and if-then planning, which together with self-control form a larger psychometric network of psychological dispositions that are relevant for orienting goal directed behavior. Thus, the present findings indicate that self-control can be adequately captured with the single item measure presented here, thereby extending the methodological toolbox of self-control researchers by a highly-time efficient measure.

Abstract Coronavirus disease 2019 (COVID-19) caused by coronavirus (SARS-nCoV2) is currently spreading across the world. In response, different sets of pandemic containment measures have been employed by several countries. The effectiveness of non-pharmacological measures such as home confinement hinges on adherence by the population. While adherence to these social distancing measures appears to be high in general, adherence might be more challenging for some individuals and complying with these measures might become more difficult the longer they last. Here, we suggest that boredom and self-control are two important psychological concepts for understanding the challenges the COVID-19 pandemic containment measures pose to individuals. To maximize adherence to these measures, we propose to consider the specific and combined effects of boredom and self-control demands elicited by this situation on subsequent behavior.