The full activation mechanism of the adenosine A1 receptor revealed by GaMD and Su-GaMD simulations.

The full activation process of G protein-coupled receptor (GPCR) plays an important role in cellular signal transduction. However, it remains challenging to simulate the whole process in which the GPCR is recognized and activated by a ligand and then couples to the G protein on a reasonable simulation timescale. Here, we developed a molecular dynamics (MD) approach named supervised (Su) Gaussian accelerated MD (GaMD) by incorporating a tabu-like supervision algorithm into a standard GaMD simulation. By using this Su-GaMD method, from the active and inactive structure of adenosine A1 receptor (A1R), we successfully revealed the full activation mechanism of A1R, including adenosine (Ado)-A1R recognition, preactivation of A1R, and A1R-G protein recognition, in hundreds of nanoseconds of simulations. The binding of Ado to the extracellular side of A1R initiates conformational changes and the preactivation of A1R. In turn, the binding of Gi2 to the intracellular side of A1R causes a decrease in the volume of the extracellular orthosteric site and stabilizes the binding of Ado to A1R. Su-GaMD could be a useful tool to reconstruct or even predict ligand-protein and protein-protein recognition pathways on a short timescale. The intermediate states revealed in this study could provide more detailed complementary structural characterizations to facilitate the drug design of A1R in the future.

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306.

BACKGROUND: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. METHODS: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. RESULTS: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. CONCLUSIONS: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

Simple tape-stripping method for highly reliable and quantitative analysis of skin microbiome.

The composition of human skin microbiome profoundly impacts host skin health and disease. However, the relationship between skin homeostasis or the development of skin diseases and daily changes in skin microbial composition is poorly understood. Longitudinal samplings at more frequent intervals would address this issue, while conventional sampling methods have technical difficulties, leading to limitations in sampling opportunities. Here, we developed a simple and stable tape-stripping method regardless of the operator's skill. Our method enables skin microbial sampling within 30 seconds and taking multiple skin microbial samples from the same body site. The amount of microbial DNA among multiple sampling sites could be measured within 13.5%. The sequencing results of multiple sampling showed high consistency, Pearson's correlation coefficient between multiple samples of 0.98. Furthermore, these results were comparable to those collected by the conventional swabbing method. These results demonstrate that our tape-stripping method enables simple microbiome collection and highly reliable quantitative skin microbiome analysis. These features of our method would lead to a further understanding of skin disease development or diagnosis of skin conditions in clinical research by increasing the opportunities for microbial sampling.

Person-specific and pooled prediction models for binge eating, alcohol use and binge drinking in bulimia nervosa and alcohol use disorder.

BACKGROUND: Machine learning could predict binge behavior and help develop treatments for bulimia nervosa (BN) and alcohol use disorder (AUD). Therefore, this study evaluates person-specific and pooled prediction models for binge eating (BE), alcohol use, and binge drinking (BD) in daily life, and identifies the most important predictors. METHODS: A total of 120 patients (BN: 50; AUD: 51; BN/AUD: 19) participated in an experience sampling study, where over a period of 12 months they reported on their eating and drinking behaviors as well as on several other emotional, behavioral, and contextual factors in daily life. The study had a burst-measurement design, where assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of three weeks. Afterwards, person-specific and pooled models were fit with elastic net regularized regression and evaluated with cross-validation. From these models, the variables with the 10% highest estimates were identified. RESULTS: The person-specific models had a median AUC of 0.61, 0.80, and 0.85 for BE, alcohol use, and BD respectively, while the pooled models had a median AUC of 0.70, 0.90, and 0.93. The most important predictors across the behaviors were craving and time of day. However, predictors concerning social context and affect differed among BE, alcohol use, and BD. CONCLUSIONS: Pooled models outperformed person-specific models and the models for alcohol use and BD outperformed those for BE. Future studies should explore how the performance of these models can be improved and how they can be used to deliver interventions in daily life.

Alcohol, Sexual Arousal, and Partner Familiarity as Predictors of Condom Negotiation: An Experience Sampling Study.

Numerous contextual factors contribute to risky sexual decision-making among men who have sex with men (MSM), with experimental laboratory-based studies suggesting that alcohol consumption, sexual arousal, and partner familiarity have the potential to impact condom negotiations during sexual encounters. The purpose of the current study was to extend this line of inquiry outside of the laboratory and into the everyday lives of MSM. We collected six weeks of daily data on alcohol consumption and sexual behaviors from 257 moderate- and heavy-drinking MSM to examine the within- and between-subjects effects of alcohol consumption, average daily sexual arousal, and partner familiarity on condom negotiation processes during sexual encounters. We hypothesized that alcohol consumption, higher levels of average daily sexual arousal, and greater partner familiarity would all contribute to a reduced likelihood of condom negotiation prior to sexual activity, and that they would also affect the difficulty of negotiations. Contrary to hypotheses, none of these three predictors had significant within-subjects effects on condom negotiation outcomes. However, partner familiarity and average daily sexual arousal did exert significant between-subjects effects on the incidence of negotiation and negotiation difficulty. These findings have important implications for risk-reduction strategies in this population. They also highlight the challenges of reconciling results from experimental laboratory research and experience sampling conducted outside of the laboratory on sexual risk behavior.

Comparative evaluation of two clinical sampling techniques for HPV detection in male genital sites: a randomized controlled study.

AIMS: The optimal sampling methods for detecting human papillomavirus (HPV) in male genital sites remain unclear. This study aimed to assess the performance, acceptability, and comfort of two sampling techniques for male genital HPV detection. METHODS AND RESULTS: A total of 490 men aged 18-45 were randomly assigned in a 1:1 ratio to undergo either the rub-brush (nail file followed by swab) or brush-only method (swab only) for sampling at external genitalia sites (PGS) and perineum/perianal (PA) sites. HPV distribution, specimen validity (ß-globin as a quality reference), and participant acceptability and comfort were evaluated between the two sampling methods. The brush-only method demonstrated non-inferiority in detecting 14 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/66/68) compared to the rub-brush method in both PGS (18.9% vs. 16.9%) and PA (10.5% vs. 11.9%). Although no significant differences were observed in positive rates for other HPV types, the brush-only method had a significantly higher invalid rate in PA (8.5% vs. 1.5%). Approximately 85.0% of participants reported good acceptability and comfort with both sampling methods, regardless of anatomical sites. CONCLUSIONS: This study suggests comparable performance, acceptability and comfort between the two sampling techniques for HPV detection. However, the rub-brush method may offer an advantage in higher sample validity.

Strategies, processes, outcomes, and costs of implementing experience sampling-based monitoring in routine mental health care in four European countries: study protocol for the IMMERSE effectiveness-implementation study.

BACKGROUND: Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users' daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia). METHODS: In this hybrid effectiveness-implementation study, a parallel-group, assessor-blind, multi-centre cluster randomized controlled trial (cRCT) will be conducted, combined with a process and economic evaluation. In the cRCT, 24 clinical units (as the cluster and unit of randomization) at eight sites in four European countries will be randomly allocated using an unbalanced 2:1 ratio to one of two conditions: (a) the experimental condition, in which participants receive a Digital Mobile Mental Health intervention (DMMH) and other implementation strategies in addition to treatment as usual (TAU) or (b) the control condition, in which service users are provided with TAU. Outcome data in service users and clinicians will be collected at four time points: at baseline (t0), 2-month post-baseline (t1), 6-month post-baseline (t2), and 12-month post-baseline (t3). The primary outcome will be patient-reported service engagement assessed with the service attachment questionnaire at 2-month post-baseline. The process and economic evaluation will provide in-depth insights into in-vivo context-mechanism-outcome configurations and economic costs of the DMMH and other implementation strategies in routine care, respectively. DISCUSSION: If this trial provides evidence on reach, effectiveness, adoption, implementation and maintenance of implementing ESM-based monitoring, reporting, and feedback, it will form the basis for establishing its public health impact and has significant potential to bridge the research-to-practice gap and contribute to swifter ecological translation of digital innovations to real-world delivery in routine mental health care. TRIAL REGISTRATION: ISRCTN15109760 (ISRCTN registry, date: 03/08/2022).

Momentary assessment of the relations between narcissistic traits, interpersonal behaviors, and aggression.

INTRODUCTION: This study explores the associations among narcissistic traits, interpersonal behaviors, and aggression using repeated, situation-based measurement. We examine narcissism's relations with aggression across three levels of its theorized hierarchy (level 1: narcissism; level 2: grandiose vs. vulnerable narcissism; level 3: antagonism, agentic extraversion, and narcissistic neuroticism). METHODS: Using an experience-sampling approach, the current study examined the effects of narcissism and its finer-grained components on daily affective experiences and aggressive behaviors in the context of interpersonal interactions. Data were collected from 477 undergraduate students who were instructed to complete four prompts a day for ten consecutive days. RESULTS: Narcissism at the global construct level positively predicted multiple indices of episodic aggression (i.e., aggressive temper, aggressive urge, verbal aggression). At the dual-dimension level, grandiose narcissism specifically predicted aggression, and then at the trifurcated level, interpersonal antagonism predicted aggression by itself and in interaction with event-level negative affect. Negative affect consistently exhibited both within- and between-person effects on aggression. CONCLUSION: In real-life social interactions, narcissism dimensions differentially affect the way individuals experience social interactions and process negative affect, and thus in both research and clinical practice, narcissism is best assessed as a heterogeneous, multidimensional construct.

Misremembering Solitude: The Role of Personality and Cultural Self-Concepts in Shaping Discrepancies Between Recalled and Concurrent Affect in Solitude.

BACKGROUND: Affect recall is key to psychological assessment and decision-making. However, self-concepts (self-beliefs) may bias retrospective affect reports such that they deviate from lived experiences. Does this experience-memory gap apply to solitude experiences? We hypothesized that individuals misremember how they feel overall and when in solitude, in line with self-concepts of introversion, self-determined/not-self-determined solitude motivations, and independent/interdependent self-construal. A pilot study comparing retrospective to daily affect reports captured over 2 weeks (N = 104 UK university students) provided preliminary evidence of introversion and not-self-determined solitude shaping affect recall. METHODS: In the main pre-registered study, participants aged 18-49 in the UK (N = 160) and Hong Kong (N = 159) reported their momentary affective states and social situations 5 times per day over 7 days, then recalled how they felt over the week. RESULTS AND DISCUSSION: Individuals higher in self-determined solitude were more prone to retrospectively overestimate their high- and low-arousal positive affect in solitude and showed less overestimation/more underestimation of negative affect in solitude. Higher not-self-determined solitude was associated with overestimating loneliness, and higher interdependent self-construal with overestimating loneliness and energy levels, in solitude. Comparisons based on residence/ethnicity suggest culture influences solitude-seeking and affective memory. Implications for well-being and affect measurement are discussed.

Feasibility of a novel blended-care intervention for fatigue after acquired brain injury: a pilot study of the Tied by Tiredness intervention.

PURPOSE: Evidence-based treatments for fatigue after brain injury are scarce and often not personalized. An approach to foster personalization is Experience Sampling Methodology (ESM), consisting of repeated daily measurements of fatigue and related factors in daily life. We investigated the feasibility and usability of a novel six-week ESM-based intervention for fatigue after brain injury. MATERIALS AND METHODS: Ten individuals with acquired brain injury (six men; four women) aged between 36-70 years (M = 53.3, SD = 12.9) used a mHealth application for three days each week during six-weeks; seven completed the intervention. Momentary fatigue, activities, mood, worrying, and social context were assessed with ESM and participants received weekly personalized feedback by a therapist.. RESULTS: 56% of ESM-questionnaires (568/1008) were completed, providing detailed insights into individual fatigue patterns. No statistically significant decrease in response rate was found over the course of treatment. Qualitative feedback from participants revealed increased insight into factors underlying fatigue, and no problems with treatment duration or difficulties using the app. Five participants showed a decline in fatigue level during treatment. CONCLUSIONS: This pilot study provides initial support for the feasibility and usability of this novel blended-care intervention, aimed at alleviating fatigue through personalized feedback and treatment strategies.

A closer look into the affect dynamics of adolescents with depression and the interactions with their parents: An ecological momentary assessment study.

Adolescents with depression tend to perceive behavior of parents as less positive than adolescents without depression, but conclusions are based on retrospective reports assessed once or over long time intervals, with the risk of memory biases affecting the recall. The current study used ecological momentary assessments to examine the link between adolescent affect and the amount of warmth and criticism expressed by both mothers and fathers in families with adolescents with depression versus adolescents without psychopathology in daily life. It also explored the possible bias by assessing parenting on the momentary, daily (EMA), and retrospective level. The sample consisted of 34 adolescents with depression and 58 parents and 80 healthy controls and 151 parents (adolescents: Mage = 15.8, SD = 1.41; 67.5% girls, parents: Mage = 49.3, SD = 5.73; 54.1% mothers). Participants completed retrospective questionnaires and four surveys a day for 14 consecutive days. Preregistered multilevel models showed that momentary parenting reports of adolescents with depression and healthy controls did not differ. The associations between perceived parenting of both mothers and fathers and adolescent affect did also not differ between the two groups. These results illustrate that adolescents generally benefit from supportive parenting, but substantial differences between individuals were found. In contrast to the momentary data, both adolescents with depression and their parents did report more negative parenting on retrospective questionnaires than healthy controls and their parents indicating that adolescents with depression may have a negativity bias in their retrospective recall. These findings are highly relevant for clinical practice and underscore the need for careful assessments on different time scales and including all family members.

Associations between childhood adversity, psychiatric symptoms, and self-esteem outcomes in adolescents and young adults: An experience sampling study.

OBJECTIVES: Self-esteem and self-esteem stability are important factors during adolescence and young adulthood that can be negatively impacted by childhood adversity and psychiatric symptoms. We examined whether childhood adversity and psychiatric symptoms are associated with decreased global self-esteem as well as increased self-esteem instability as measured with experience sampling method. In addition, we examined if childhood adversity moderates the association between psychiatric symptoms and self-esteem outcomes. METHODS: Our study consisted of 788 adolescents and young adults who were part of a twin pair. The twin structure was not of interest to the current study. Mean age was 16.8 (SD = 2.38, range: 14-25), 42% was male. We used a multilevel modeling approach to examine our hypotheses to account for the presence of twins in the data set. RESULTS: Childhood adversity and psychiatric symptoms were negatively associated with global self-esteem (respectively standardized ß = -.18, SE = 0.04, p < .0001 and standardized ß = -.45, SE = 0.04, p < .0001), with a larger effect for psychiatric symptoms. Similarly, both were associated with increased self-esteem instability (respectively standardized ß = .076, SE = 0.025, p = .002 and standardized ß = .11, SE = 0.021, p < .0001). In addition, interactions between childhood adversity and psychiatric symptoms on both global self-esteem (standardized ß = .06, SE = 0.01, p < .0001) and self-esteem instability (standardized ß = -.002, SE = 0.0006, p = .001) were found, showing that the negative association of psychiatric symptoms with self-esteem outcomes is less pronounced in young people with higher levels of childhood adversity, or formulated differently, is more pronounced in young people with little or no exposure to childhood adversity. CONCLUSION: Global self-esteem and self-esteem instability in young people are influenced by both current psychiatric symptomatology and exposure to childhood adversity. Those with more psychiatric symptoms show worse self-esteem and higher self-esteem instability, which is moderated by childhood adversity. For young people with high childhood adversity levels lower self-esteem and higher self-esteem instability are less influenced by reductions in psychiatric symptoms.

Real-time detection of mean and variance changes in experience sampling data: A comparison of existing and novel statistical process control approaches.

Retrospective analyses of experience sampling (ESM) data have shown that changes in mean and variance levels may serve as early warning signs of an imminent depression. Detecting such early warning signs prospectively would pave the way for timely intervention and prevention. The exponentially weighted moving average (EWMA) procedure seems a promising method to scan ESM data for the presence of mean changes in real-time. Based on simulation and empirical studies, computing and monitoring day averages using EWMA works particularly well. We therefore expand this idea to the detection of variance changes and propose to use EWMA to prospectively scan for mean changes in day variability statistics (i.e., s 2 , s , ln( s )). When both mean and variance changes are of interest, the multivariate extension of EWMA (MEWMA) can be applied to both the day averages and a day statistic of variability. We evaluate these novel approaches to detecting variance changes by comparing them to EWMA-type procedures that have been specifically developed to detect a combination of mean and variance changes in the raw data: EWMA- S 2 , EWMA-ln( S 2 ), and EWMA- X ¯ - S 2 . We ran a simulation study to examine the performance of the two approaches in detecting mean, variance, or both types of changes. The results indicate that monitoring day statistics using (M)EWMA works well and outperforms EWMA- S 2 and EWMA-ln( S 2 ); the performance difference with EWMA- X ¯ - S 2 is smaller but notable. Based on the results, we provide recommendations on which statistic of variability to monitor based on the type of change (i.e., variance increase or decrease) one expects.

Development of an open-source solution to facilitate the use of one-button wearables in experience sampling designs.

The experience sampling method (ESM) allows for a high degree of ecological validity compared to laboratory research, at the cost of greater effort for participants. It would therefore benefit from implementations that reduce participant effort. In the present paper, we introduce a screenless wrist-worn one-button wearable as an unobtrusive measurement method that can be employed in ESM designs. We developed an open-source Android application to make this commercially available wearable easily configurable and usable. Over the course of six pilot studies, we explored the technical viability (e.g., battery life, reliability of inputs) of this wearable. We compared data quality between wearables and smartphones in a within-subjects design, exploring both the input options of using the number of button presses as a Likert scale, as well as using the angle of the device as a Physical Analogue Scale. Assessments of Extraversion made with either of these methods were highly correlated to comparable assessments made with comparable methods on a smartphone (i.e., Likert scale or a Visual Analogue Scale, respectively). Furthermore, in a preregistered ESM field experiment (N = 134, 4 weeks), we compared compliance to real-life event triggers between wearable devices and smartphones. We found higher numbers of logged events in the wearable group, indicating better adherence to the event-contingent scheduling. Overall, despite the device's minimal capabilities and resulting limitations, one-button wearables can be beneficial for use in ESM designs.

Emotional food craving across the eating disorder spectrum: an ecological momentary assessment study.

PURPOSE: Emotional eating during negative emotions might underlie disordered eating behavior (i.e., binge eating and food restriction). Positive emotions, by contrast, seem to promote healthier eating behavior. Naturalistic research on the links between emotions and eating across individuals with binge-eating disorder (BED), bulimia nervosa (BN), binge-purge anorexia nervosa (AN-BP), and restrictive anorexia nervosa (AN-R) is, however, lacking. METHODS: Individuals without eating disorders (comparison group, CG, n = 85), and patients with BED (n = 41), BN (n = 50), AN-BP (n = 26), and AN-R (n = 29) participated in an ecological momentary assessment study. Six daily notifications over eight days prompted ratings of momentary food craving and emotional states differing in valence and arousal. RESULTS: Results supported specific emotion-food-craving patterns in each group. Compared to the CG, arousing negative emotions and higher cravings co-occurred in patients with BN. In patients with AN-BP (at trend level also in patients with AN-R) less arousing negative emotions and lower cravings co-occurred. In patients with AN, positive emotions and higher cravings co-occurred whereas in patients with BED less arousing positive emotions and lower cravings co-occurred. CONCLUSION: The found emotion-craving associations may underlie group-specific (dys-)functional eating behaviors, i.e., binge eating and food restriction during negative emotions in patients with BN and AN, and normalized appetitive responses during positive emotions in patients with BED and AN. Therapeutic efforts could target arousing negative emotions in patients with BN, and less arousing negative emotions in patients with AN. Positive emotions could be used in a salutogenetic approach in patients with BED and AN.

Influence of different cleaning methods on the concentration of airborne endotoxins and microbial aerosols in the oral clinical environment.

AIM: This study aims to evaluate the effectiveness of various cleaning methods in reducing airborne endotoxin and microbial aerosols during oral cleaning procedures. METHOD: Forty patients undergoing oral cleaning procedures were randomly assigned to one of four groups (n = 10 per group). Group A received strong suction alone; Group B received strong suction combined with an air disinfection machine; Group C received strong suction combined with a dental electric suction machine; Group D received strong suction in conjunction with both an air disinfection machine and a dental electric suction machine. Airborne aerosol concentrations were assessed at four-time points: before treatment, 30 min into treatment, immediately after treatment, and 60 min after treatment ended. Samples were collected at distances of 20 cm, 60 cm, and 1 m from the patient's oral cavity using the natural sedimentation method. T-test was used to evaluate the difference among tested groups. RESULTS: Airborne endotoxins and microbial aerosols levels increased significantly during treatment, with the highest levels observed at 20 cm from the patient's mouth. During treatment, groups with additional cleaning methods (Groups B, C, and D) exhibited higher levels of airborne endotoxins and microbial aerosols compared to Group A (strong suction alone). However, post-treatment analysis revealed that Group D demonstrated the lowest level of airborne endotoxins and microbial aerosols, while Group A exhibited the highest. CONCLUSIONS: Implementing effective aerosol management strategies can significantly reduce aerosol dispersion in the oral clinical environment. Continuous monitoring aerosol concentrations and the application of appropriate control measures are essential for minimizing infection risks for both patients and healthcare providers during oral cleaning procedures.

SEMA3: A free smartphone platform for daily life surveys.

Traditionally, behavioral, social, and health science researchers have relied on global/retrospective survey methods administered cross-sectionally (i.e., on a single occasion) or longitudinally (i.e., on several occasions separated by weeks, months, or years). More recently, social and health scientists have added daily life survey methods (also known as intensive longitudinal methods or ambulatory assessment) to their toolkit. These methods (e.g., daily diaries, experience sampling, ecological momentary assessment) involve dense repeated assessments in everyday settings. To facilitate research using daily life survey methods, we present SEMA3 ( http://www.SEMA3.com ), a platform for designing and administering intensive longitudinal daily life surveys via Android and iOS smartphones. SEMA3 fills an important gap by providing researchers with a free, intuitive, and flexible platform with basic and advanced functionality. In this article, we describe SEMA3's development history and system architecture, provide an overview of how to design a study using SEMA3 and outline its key features, and discuss the platform's limitations and propose directions for future development of SEMA3.

Using the experience sampling method to support clinical practice: An illustration with problematic cannabis use.

The experience sampling method (ESM) has been frequently used in clinical research; however, there is low translational uptake in clinical practice. This may be due to challenges with interpreting individual-level data at granular intervals. We provide an illustrative example of how ESM can be leveraged to generate personalized cognitive-behavioral strategies for problematic cannabis use.We conducted a descriptive case series analysis using ESM data from 30 individuals reporting on problematic cannabis use, craving, affect, and coping four times daily for 16-days (t = 64, T = 1,920).Analyzing ESM data using descriptive statistics and visualizations from individuals with similar clinical and demographic profiles supported a diverse array of personalized clinical insights and recommendations for each case. These recommendations included psychoeducation regarding affect- and boredom-regulation strategies, functional analyses of occasions during which cannabis was not used, and discussions on how cannabis use intersects with one's personal values.While many clinicians utilize measurement-based care, barriers have limited the incorporation of ESM towards personalized, data-informed approaches to treatment. We provide an illustrative example of how ESM data can be used to generate actionable treatment strategies for problematic cannabis use and highlight continued challenges with interpreting time-series data.

Introducing FRED: Software for Generating Feedback Reports for Ecological Momentary Assessment Data.

Ecological Momentary Assessment (EMA) is a data collection approach utilizing smartphone applications or wearable devices to gather insights into daily life. EMA has advantages over traditional surveys, such as increasing ecological validity. However, especially prolonged data collection can burden participants by disrupting their everyday activities. Consequently, EMA studies can have comparably high rates of missing data and face problems of compliance. Giving participants access to their data via accessible feedback reports, as seen in citizen science initiatives, may increase participant motivation. Existing frameworks to generate such reports focus on single individuals in clinical settings and do not scale well to large datasets. Here, we introduce FRED (Feedback Reports on EMA Data) to tackle the challenge of providing personalized reports to many participants. FRED is an interactive online tool in which participants can explore their own personalized data reports. We showcase FRED using data from the WARN-D study, where 867 participants were queried for 85 consecutive days with four daily and one weekly survey, resulting in up to 352 observations per participant. FRED includes descriptive statistics, time-series visualizations, and network analyses on selected EMA variables. Participants can access the reports online as part of a Shiny app, developed via the R programming language. We make the code and infrastructure of FRED available in the hope that it will be useful for both research and clinical settings, given that it can be flexibly adapted to the needs of other projects with the goal of generating personalized data reports.

Leveraging Single-Case Experimental Designs to Promote Personalized Psychological Treatment: Step-by-Step Implementation Protocol with Stakeholder Involvement of an Outpatient Clinic for Personalized Psychotherapy.

Our objective is to implement a single-case experimental design (SCED) infrastructure in combination with experience-sampling methods (ESM) into the standard diagnostic procedure of a German outpatient research and training clinic. Building on the idea of routine outcome monitoring, the SCED infrastructure introduces intensive longitudinal data collection, individual effectiveness measures, and the opportunity for systematic manipulation to push personalization efforts further. It aims to empower psychotherapists and patients to evaluate their own treatment (idiographic perspective) and to enable researchers to analyze open questions of personalized psychotherapy (nomothetic perspective). Organized around the principles of agile research, we plan to develop, implement, and evaluate the SCED infrastructure in six successive studies with continuous stakeholder involvement: In the project development phase, the business model for the SCED infrastructure is developed that describes its vision in consideration of the context (Study 1). Also, the infrastructure's prototype is specified, encompassing the SCED procedure, ESM protocol, and ESM survey (Study 2 and 3). During the optimization phase, feasibility and acceptability are tested and the infrastructure is adapted accordingly (Study 4). The evaluation phase includes a pilot implementation study to assess implementation outcomes (Study 5), followed by actual implementation using a within-institution A-B design (Study 6). The sustainability phase involves continuous monitoring and improvement. We discuss to what extent the generated data could be used to address current questions of personalized psychotherapy research. Anticipated barriers and limitations during the implementation processes are outlined.