Measuring interpersonal trauma: Development and validation of the German version of the victimization experience schedule (VES).

OBJECTIVE: Interpersonal victimization experiences (VEs) significantly affect mental and physical health, particularly in disorders associated with life-time adversities, like fibromyalgia syndrome (FMS) and major depressive disorder (MDD). However, assessing VEs comprehensively remains challenging due to limited tools that encompass sub-traumatic events, such as bullying or discrimination, and contextual dimensions. We aimed to address this gap by validating the Victimization Experience Schedule (VES) in German, examining its reliability, and assessing VEs in clinical populations with FMS and MDD. METHODS: We investigated the relationship between VEs and clinical symptoms in individuals with FMS, MDD and healthy controls (N = 105) in a case-control study. We also analyzed correlations between different types of VEs and categories of early childhood abuse and posttraumatic-stress-disorder instruments. Additionally, we validated our findings in an independent sample of individuals with FMS (N = 97) from a clinical study. RESULTS: We observed excellent inter-rater reliability (Kw = 0.90-0.99), and VEs assessed using the VES were in alignment with subcategories of early childhood abuse. The prevalence of VEs extended beyond the categories covered by traditional survey instruments and was higher in individuals with MDD (4.0 ± 2.6) and FMS (5.9 ± 3.1) compared to controls (1.5 ± 1.7). We consistently identified a significant association between the number of VEs, the associated subjective distress, and clinical scores. Furthermore, distinct correlation patterns between VEs and clinical outcomes emerged across different cohorts. CONCLUSION: Our study emphasizes the VES's value in understanding VEs within MDD and FMS. These experiences span from traumatic to sub-traumatic and correlate with posttraumatic-stress and clinical symptoms, underscoring the VES's importance as an assessment tool.

[Social pediatric care situation and needs during the COVID-19 pandemic from 2020 to 2022. What is needed now?] / Sozialpädiatrische Versorgungssituation und -bedarfe in Zeiten der COVID-19-Pandemie 2020 bis 2022. Was wird jetzt gebraucht?

BACKGROUND: Children and adolescents with social pediatric care needs represent a group with special challenges. The aim of this qualitative study was to describe social pediatric care during the pandemic from the perspective of experts. From this, conclusions were to be drawn for any social pediatric care needs that may have arisen. METHODS: Between May and November 2022, 25 experts from the field of social pediatrics were interviewed using guided interviews on the following topics: deviations in care, utilization behavior of families, individual burdens and resources, and sustainable needs. The interviews were analyzed by two research assistants. RESULTS: Overall, the social pediatric care offer was temporarily clearly limited. While families who were already well connected before the pandemic could be adequately cared for with the help of telephone/video contacts, an unreported number of at-risk groups, were described, for example, those with low competence to act, who did not make use of services or did so with delays. It was observed that there was a need for care for newly developed mental disorders and regression in therapy due to limited opportunities for support, as well as a need to catch up on missed opportunities for early support in the case of developmental disorders. DISCUSSION: To meet the needs that have arisen, underserved families should be identified and cared for promptly, taking individual characteristics into account. To this end, for example, more outreach services should be established that reach affected families unbureaucratically.

Compartmental exchange regulates steady states and stochastic switching of a phosphorylation network.

The phosphoregulation of proteins with multiple phosphorylation sites is governed by biochemical reaction networks that can exhibit multistable behavior. However, the behavior of such networks is typically studied in a single reaction volume, while cells are spatially organized into compartments that can exchange proteins. In this work, we use stochastic simulations to study the impact of compartmentalization on a two-site phosphorylation network. We characterize steady states and fluctuation-driven transitions between them as a function of the rate of protein exchange between two compartments. Surprisingly, the average time spent in a state before stochastically switching to another depends nonmonotonically on the protein exchange rate, with the most frequent switching occurring at intermediate exchange rates. At sufficiently small exchange rates, the state of the system and mean switching time are controlled largely by fluctuations in the balance of enzymes in each compartment. This leads to negatively correlated states in the compartments. For large exchange rates, the two compartments behave as a single effective compartment. However, when the compartmental volumes are unequal, the behavior differs from a single compartment with the same total volume. These results demonstrate that exchange of proteins between distinct compartments can regulate the emergent behavior of a common signaling motif.

Increased Digital Media Use in Preschool Children: Exploring the Links with Parental Stress and Their Problematic Media Use.

BACKGROUND: Intense or problematic media use behavior of parents could serve as a role model for their children's media use behavior. So far, knowledge is scarce about increased children's media use (ICMU) and its association with parental stress (PS) and problematic parental media use (PPMU). METHODS: ICMU was examined using a modified set of the DSM-5 criteria for Internet Gaming Disorder. PS was assessed via the widely used Parenting Stress Index, and PPMU was assessed using the Short Compulsive Internet Use Scale. A multiple linear regression analysis was conducted to evaluate the links between ICMU, PS, and PPMU. A mediation analysis was performed to examine if PPMU mediated the relationship between PS and ICMU. RESULTS: In sum, 809 parents (M = 36.89 years; SD = 4.87; 81.4% female) of preschool children (average age: 44.75 months, SD = 13.68) participated in the study. ICMU was statistically significantly related to higher age of the parent, greater PPMU, and higher PS. Furthermore, we found that the association between PS and ICMU was partially mediated by PPMU. CONCLUSIONS: The results indicate that more pronounced PS and PPMU are associated with ICMU, highlighting the necessity of considering these parental variables when developing early prevention strategies for preschool-age children.

Human REM sleep recalibrates neural activity in support of memory formation.

The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal-neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.

[Nociplastic pain in research and practice : Overview of biopsychosocial principles, possibilities and difficulties]. / Noziplastischer Schmerz in Forschung und Praxis : Übersicht über biopsychosoziale Grundlagen, Möglichkeiten und Schwierigkeiten.

Traditionally, two mechanistic pain categories were distinguished: nociceptive and neuropathic pain. After the definitions of these two mechanistic descriptors were refined more precisely in the International Association for the Study of Pain (IASP) taxonomy in 2011, a large group of patients remained whose pain could not be assigned to either of the two categories. Nociplastic pain was therefore proposed as a third mechanistic descriptor in 2016. This review article presents the current state of the integration of nociplastic pain into research and clinical practice. In particular, the possibilities and difficulties of applying this concept are addressed from a human and animal experimental research perspective.

Clinical Phenomenology of Fibromyalgia Syndrome in Male Patients: Same But Different.

The majority of knowledge about fibromyalgia syndrome (FMS) derives from studies of female patients. Little is known about the clinical characteristics and treatment outcomes of male patients with FMS. In this retrospective cohort study with a prospective posttreatment follow-up, we investigated whether male patients with FMS differ from female patients in terms of 1) symptom burden, 2) psychological characteristics, and 3) clinical treatment response. We identified 263 male (4%) out of 5,541 patients with FMS completing a 3-week multimodal pain-treatment program. Male patients (51.3 ± 9.1 years) were age- and time-matched (1:4) with female patients (N = 1,052, 51.3 ± 9.0 years). Data on clinical characteristics, psychological comorbidities, and treatment responses were obtained from medical records and validated questionnaires. Levels of perceived pain, psychological comorbidity, and functional capacity were similar between genders, although male patients with FMS showed a higher prevalence of alcohol abuse. Compared to female patients, male patients experienced themselves less often as overly accommodating (Cohen's d = -.42) but more often as self-sacrificing (d = .26) or intrusive (d = .23). Regarding pain coping, male patients were less likely to utilize mental distraction, rest- and relaxation techniques, or counteractive activities (d = .18-.27). Male patients showed a slightly worse overall response rate than women (69% vs 77%), although differences between individual outcome measures were small (d < .2). Although male and female patients in our cohort were similar in clinical presentation and treatment response, the gender-specific differences in interpersonal problems and pain coping suggest consideration of these aspects in the treatment of male patients with FMS. PERSPECTIVE: Knowledge about fibromyalgia mostly derives from studies of female patients. Identifying and understanding gender-specific differences in fibromyalgia is an important roadmap in the treatment of this syndrome by focusing on specific gender aspects such as differences in interpersonal problems and pain coping mechanisms.

[Children's mental health: the role of screen time, parenting behavior, and parenting stress-a secondary data analysis of KiGGS and BELLA data]. / Mental Health im Kindesalter: der Einfluss von Mediennutzung, Erziehungsverhalten und elterlichem Stresserleben ­ eine Sekundärdatenanalyse von KiGGS- und BELLA-Daten.

BACKGROUND: Previous studies established a link between high screen time and mental health problems in childhood. The role of possible influencing factors is currently unclear. This study aims at testing correlations among mental health problems, high screen time, parenting stress, and inconsistent and positive parenting behavior. METHODS: This study is based on data from the KiGGS and BELLA studies. For the present study, data from preschool children (age: 3-5 years, N = 417) and school children (age: 7-13 years, N = 239) were analyzed. Binary-logistic regressions were carried out to test for correlations between high screen time and children's mental health problems in cross-sectional and longitudinal analyses. Socioeconomic status, the child's gender, the parent's gender, parenting stress, and inconsistent and positive parenting behavior were used as control variables. RESULTS: In the cross-sectional analysis, mental health problems in preschool children were associated with high screen time (OR = 3.02; p = 0.003), parenting stress (OR = 17.00; p < 0.001), and positive parenting behavior (OR = 0.24; p < 0.001). In the longitudinal analysis, mental health problems in school children were associated with parenting stress (OR = 4.04; p < 0.001). Socioeconomic status and the child's and parent's gender were at no point associated with mental health problems. DISCUSSION: The sole existence of high screen time cannot explain mental health problems in children. Parental variables seem to be critical for children's mental health and should be considered in a holistic apporach on children's mental health in terms of strengthening parental competencies.

Patient-Assessed Quality of Virtual Consultations as Follow-Up on Long-Term Oxygen Therapy for Patients With COPD.

BACKGROUND: Long-term oxygen therapy (LTOT) can increase survival time and relieve symptom burden in patients with COPD and chronic hypoxemia. The Department of Respiratory Medicine at Odense University Hospital invites patients with LTOT and COPD to the out-patient clinic for treatment evaluation every 6 months to regulate or terminate treatment and support patients' treatment adherence. The out-patient clinic, however, experiences many absences or cancellations from patients. For that reason, patients were offered virtual consultation as an alternative to physical attendance. This study was initiated to uncover reasons for absences and the patients' experiences of virtual consultation to promote a more patient-centered clinical practice for patients with COPD and LTOT. METHODS: A qualitative study encompassing semi-structured interviews with 20 subjects was conducted in the winter of 2021. The subjects had tried or been given the opportunity of virtual consultation. Data were analyzed inspired by Kvale and Brinkmann focusing on the subject's perspectives on virtual consultation. RESULTS: The analysis resulted in 3 main themes: limitations and vulnerabilities, independence and quality of life, and personal strategies. Subjects expressed that everyday life with LTOT and COPD was characterized by limited resources in terms of energy, oxygen, and time. LTOT was perceived as a necessary means to maintain a sense of independence and quality of life. However, LTOT also meant additional limitations due to cumbersome equipment and feelings of isolation. Most subjects considered the virtual consultation to be oxygen-, energy-, and time-preserving, as it meant avoiding stressful transportation and handling of oxygen cylinders, COVID-19 exposure, waiting time, and not having to involve others for help. CONCLUSIONS: The subjects' perspective showed that follow-up on LTOT as a virtual consultation was considered a valuable offer. The chosen method was found to be relevant in uncovering subjects' attitudes toward clinical practice procedures.

Internet Use Disorders: Subjective Importance of Online Friends in the Context of Real-Life Social Support and Comorbid Mental Disorders.

INTRODUCTION: Previous studies analyzing friendships with people only known through the Internet mainly focused on quantitative aspects (e.g., the number of online friends or the time spent with them). Little is known about the perceived quality of online compared to real-life friends in individuals with an Internet use disorder (IUD). This study aimed to analyze associations of the increased subjective importance of online friends and IUD by controlling for the perceived real-life social support and comorbid mental disorders. METHODS: Based on a general population sample, 192 participants who were screened positive for risky Internet use took part in face-to-face clinical diagnostic interviews. IUD was assessed using the structure of the Munich-Composite International Diagnostic Interview (M-CIDI) and the adapted criteria of Internet gaming disorder in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The number and the increased subjective importance of online compared to real-life friends were assessed with the Online and Real-Life Friends scale (ORLF), real-life social support was assessed with the Berlin Social Support Scales (BSSS), and comorbidity was assessed with the M-CIDI. Data were analyzed with binary regression models. RESULTS: Of 192 participants with risky Internet use, 39 participants (19 men; age M = 29.9, SD = 12.2) fulfilled the criteria of IUD in the last 12 months. IUD was not associated with the number or perceived social support of online friends per se. In multivariate analyses, IUD was associated with increased subjective importance of online friends, independently from comorbid anxiety or mood disorders. However, when controlling for real-life social support, associations of IUD and increased subjective importance of online friends were no longer present. CONCLUSION: These findings highlight the necessity of therapeutic interventions aimed at strengthening social skills and engaging in real-life relationships in the prevention and therapy of IUD. Due to the small sample size and the cross-sectional analysis, however, further research is needed.

Psychometric Properties of Screening Instruments for Social Network Use Disorder in Children and Adolescents: A Systematic Review.

Importance: Children and adolescents spend considerable time on the internet, which makes them a highly vulnerable group for the development of problematic usage patterns. A variety of screening methods have already been developed and validated for social network use disorder (SNUD); however, a systematic review of SNUD in younger age groups has not been performed. Objective: To review published reports on screening tools assessing SNUD in children and adolescents with a maximum mean age of 18.9 years. Evidence Review: To identify instruments for the assessment of SNUD, a systematic literature search was conducted in the databases PsycINFO, PubMed, Web of Science, PsycArticles, and Scopus. The final search took place on May 2, 2022. Psychometric properties of available tools were examined and evaluated to derive recommendations for suitable instruments for individuals up to 18 years of age. Findings: A total of 5746 publications were identified, of which 2155 were excluded as duplicates. Of the remaining 3591 nonredundant publications, 3411 studies were assessed as not relevant after title and abstract screening. A full-text analysis of 180 remaining studies classified as potentially eligible resulted in a final inclusion of 29 studies revealing validation evidence for a total of 19 tools. The study quality was mostly moderate. With regard to validation frequency, 3 tools exhibited the largest evidence base: Social Media Disorder Scale (SMDS), the short version of the Bergen Facebook Addiction Scale, and Bergen Social Media Addiction Scale-Short Form (BSMAS-SF). Among these, 1 study tested a parental version (SMDS-P) for its psychometric properties. Taking all criteria into account, the strongest recommendation was made for the SMDS and BSMAS-SF. Conclusions and Relevance: Results suggest that the SMDS-SF and BSMAS-SF were appropriate screening measures for SNUD. Advantages of the SMDS are the availability of a short version and the possibility of an external parental rating.

[Transition-oriented patient education program for adolescents and young adults with ADHD]. / Transitionsorientierte Patientenschulung bei Adoleszenten und jungen Erwachsenen mit ADHS.

Transition-oriented patient education program for adolescents and young adults with ADHD Abstract. Background: The transition from child- to adult-centered treatment includes numerous challenges in the treatment of chronic disorders. This process can be further complicated by disease-specific characteristics of attention-deficit/hyperactivity disorders (ADHD). This secondary analysis evaluated a transition workshop in individuals with ADHD. Methods: In total, 56 adolescents and young adults with ADHD (age M = 17.3 years, SD = 1.1; 17.9 % female) and their parents were quasi-randomly assigned to a control group (CG, n = 28) or an intervention group (IG, n = 28). The CG received regular medical care, whereas the IG additionally participated in a one-and-a-half-day transition workshop (ModuS-T). Before and 4 weeks after the intervention, transition competence was assessed with the Transition Competence Scale (TKS), patient activation with the Patient Activation Measure 13 for Adolescents (PAM® 13), and satisfaction with care with the Patient Satisfaction Questionnaire (ZUF-8). Results: The IG showed significantly improved transition competence (p ≤ .001) compared to the CG. There was no significant intervention effect in terms of patient activation (p = .194). Overall, the IG was highly satisfied with the workshop. Discussion: To date, transition workshops have been evaluated predominantly in individuals with chronic somatic disorders. This secondary analysis indicates that a generic workshop is also associated with improved transition competence and high satisfaction in individuals with chronic mental disorders. The integration of such approaches into routine care needs to be discussed.

Motivational brief interventions for adolescents and young adults with Internet use disorders: A randomized-controlled trial.

Background: Adolescents and young adults (AYA) have an increased risk for Internet use disorders (IUD) compared to older individuals that may lead to functional impairments in daily life. To date, evidence-based brief interventions are lacking. This study aimed to test the efficacy of a low-threshold counseling approach based on Motivational Interviewing (MI) in a vocational school setting. Methods: Of 8.230 vocational students (age M=20.56, SD=4.68; 51.85% female) being proactively screened for IUD, 937 with positive screenings took part in telephone-based diagnostic interviews. IUD were assessed in line with the criteria of the Internet Gaming Disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Readiness to change, self-efficacy, and impairments in daily life were additionally assessed with standardized screening instruments. Participants fulfilling at least two IUD criteria were randomized to the intervention group (n=240, up to three MI-based counseling sessions via telephone) or the control group (n=257, information brochure on responsible Internet use). Follow-up interviews were conducted after five and ten months. The primary outcome was the reduction of IUD criteria. Secondary outcomes were improvements of readiness/ self-efficacy to change and the reduction of daily impairments. Data were analyzed with Intention-to-Treat (ITT) and complier average causal effect (CACE) analyses. Results: Overall, 153 (63.75%) individuals assigned to the intervention group participated at least in one counseling session (=compliers). Both groups reduced the number of IUD criteria over time. In ITT analyses, however, we did not find intervention effects for primary and secondary outcomes. Bayes statistics were inconclusive. Based on low participation rates in the intervention group, explorative CACE analyses were conducted to compare compliers in the intervention group to potential compliers in the control group. Again, we did not find intervention effects apart from improvements in self-efficacy after five months. Discussion: Telephone-based counseling seems not appropriate to address AYA at risk for IUD. Low participation rates in the intervention group caused underpowered analyses. Besides, dealing with the own Internet use during intensive assessments and receiving an information brochure led to behavioral changes also in the control group. Since the efficacy of brief interventions under the condition of higher participation rates cannot be fully ruled out, further research is required by taking the implications of this study into account.

Think-aloud analysis of commonly used screening instruments for Internet use disorders: The CIUS, the IGDT-10, and the BSMAS.

Background: Despite the constant publication of new screening instruments for Internet use disorders (IUD), little is known about their content validity. This study aimed to identify potential mismatches between the items' intention and young adults' interpretation of these items when answering three screening instruments that are commonly used in research and clinical settings: The Compulsive Internet Use Scale (CIUS), the 10 Item-Internet Gaming Disorder Test (IGDT-10), and the Bergen Social Media Addiction Scale (BSMAS). Methods: In total, 30 vocational students (50% female, age = 21.3; SD = 2.1) took part in individual think-aloud interviews. All participants were asked to report their thoughts while completing the CIUS. In addition, participants who reported online games (OG) as their main Internet activity (n = 11) answered the IGDT-10. Participants who reported social networks (SN) as their main Internet activity (n = 18) answered the BSMAS. One participant used OG and SN equally and completed both screening instruments. All interviews were audio-recorded, transcribed, and content-analysed. Results: Overall, four potential sources for errors were identified: (1) High scorings were often not congruent with the underlying diagnostic criteria. In particular, such discrepancies were found in items aimed to assess dysfunctional emotional regulation strategies and cognitive involvement. (2) Some participants were uncertain which time frame or Internet activity should be considered in their answers. (3) Long and complex items led to the building of mean values or the choice of the middle answer category. (4) Some wordings were perceived to be outdated and difficult to understand. Discussion: These findings might help to provide recommendations on how to improve screening instruments for IUD. Most important, items should more clearly distinguish between Internet use as a "normal" leisure activity and Internet use that leads to functional impairments in daily life.

Immune Response after mRNA COVID-19 Vaccination in Lung Transplant Recipients: A 6-Month Follow-Up.

BACKGROUND AND OBJECTIVE: This prospective cohort study analyzed the immune response to COVID-19 mRNA vaccines in lung transplant recipients (LuTRs) compared to healthy controls (HCs) at a 6-month follow-up. METHODS: After the first two doses of either BNT162b2 or mRNA-1273, SARS-CoV-2 antibodies were measured in LuTRs (n = 57) and sex- and age-matched HCs (n = 57). Antibody kinetics during a 6-month follow-up and the effect of a third vaccine dose were evaluated. Humoral responses were assessed using the Elecsys® Anti-SARS-CoV-2 S immunoassay. In 16 LuTRs, SARS-CoV-2-specific T cell responses were quantified using IFN-γ ELISpot assays. RESULTS: Seroconversion rates were 94% and 100% after the first and second vaccine dose, respectively, in HCs, while only 19% and 56% of LuTRs developed antibodies. Furthermore, 22 of 24 LuTRs who received the third vaccine dose showed seroconversion (five of seven primary non-responders and 17 of 17 primary responders). A T cell response against SARS-CoV-2-spike S1 and/or S2 was detected in 100% (16/16) of HCs and 50% (8/16) of LuTRs. CONCLUSIONS: The data suggest that LuTRs have reduced humoral and cellular immune responses after two doses of COVID-19 mRNA vaccination when compared to HCs. A third dose may be of substantial benefit.

Correction: A computational reproducibility study of PLOS ONE articles featuring longitudinal data analyses.

[This corrects the article DOI: 10.1371/journal.pone.0251194.].

[Attitudes of Medical Students Towards Alcohol-Related Disorders: Dependent on Intended Medical Specialization?] / Einstellungen von Medizinstudierenden gegenüber alkoholbezogenen Störungen: Abhängig von der angestrebten medizinischen Fachrichtung?

The aim of this study was to identify subjective attitudes of medical students towards alcohol-related disorders (ARD) compared to other mental and somatic disorders. Medical students taking part in an online survey (n = 1875) rated ARD less severe compared to other disorders (p < 0.001), had a greater wish for social distance towards those affected (p < 0.001), held them more responsible (p < 0.001), and chose ARD more often as a disorder with a potential for financial savings in the health care system. Prospective psychiatrists selectively reported an increased desire for social distance and readiness for structural discrimination in terms of ARD but not for mental disorders per se. Since these attitudes might have unfavorable effects on the medical-patient relationship, it is of importance to address this issue already during medicine studies.

Association of Increased Impulsiveness and Internet Use Disorder in Adolescents and Young Adults with Different Main Activities on the Internet.

Objective: Increased impulsiveness is a risk factor for health-endangering behavior patterns. Little is known about whether increased impulsiveness is associated with Internet Use Disorder (IUD) and whether individuals with various main activities on the internet differ in their levels of impulsiveness. Methods: In total, we screened 8,230 vocational students for problematic internet use with the Compulsive Internet Use Scale (CIUS). Participants scoring at least 21 points in the CIUS took part in an in-depth diagnostic interview. IUD was assessed according to the criteria of Internet Gaming Disorder (IGD) as suggested in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Impulsiveness was assessed with the Barratt Impulsiveness Scale (BIS-15). We analyzed the data using binary logistic regression models and nonparametric tests. Results: Participants with IUD (n = 144) showed increased impulsiveness (p = .005) compared to those without IUD (n = 774). Participants with different main activities on the internet did not differ in their levels of impulsiveness. Conclusions: Results indicate that impulsiveness is associated with IUD, independent of the main internet activity. This highlights the necessity to consider patients' impulsiveness in prevention and therapeutic approaches. Because of the cross-sectional study design, further research with longitudinal study designs is needed.

A computational reproducibility study of PLOS ONE articles featuring longitudinal data analyses.

Computational reproducibility is a corner stone for sound and credible research. Especially in complex statistical analyses-such as the analysis of longitudinal data-reproducing results is far from simple, especially if no source code is available. In this work we aimed to reproduce analyses of longitudinal data of 11 articles published in PLOS ONE. Inclusion criteria were the availability of data and author consent. We investigated the types of methods and software used and whether we were able to reproduce the data analysis using open source software. Most articles provided overview tables and simple visualisations. Generalised Estimating Equations (GEEs) were the most popular statistical models among the selected articles. Only one article used open source software and only one published part of the analysis code. Replication was difficult in most cases and required reverse engineering of results or contacting the authors. For three articles we were not able to reproduce the results, for another two only parts of them. For all but two articles we had to contact the authors to be able to reproduce the results. Our main learning is that reproducing papers is difficult if no code is supplied and leads to a high burden for those conducting the reproductions. Open data policies in journals are good, but to truly boost reproducibility we suggest adding open code policies.

Distribution and Cytokine Profile of Peripheral B Cell Subsets Is Perturbed in Pediatric IBD and Partially Restored During a Successful IFX Therapy.

BACKGROUND: The role of B cells in inflammatory bowel disease (IBD) is ambiguous, as B cells may have both pathogenic and protective functions in IBD. We studied B cell subsets before and after initiation of an anti-tumor necrosis factor alpha (anti-TNFα) therapy in pediatric IBD. The aim of the study was to examine the behavior of B cells in pediatric IBD patients undergoing an anti-TNFα therapy and, more specifically, to clarify their association with a successful or an unsuccessful infliximab (IFX) treatment. METHODS: A total of N = 42 pediatric IBD patients (Crohn disease, n = 30; ulcerative colitis, n = 12) for whom an anti-TNFα therapy with and without a concomitant azathioprine (AZA) medication was administered were recruited. Fourteen healthy age-matched children served as control patients. Blood samples were collected before initiation of the anti-TNFα therapy, before the fourth infusion at the end of the induction phase, and after 6 and 12 months under therapy maintenance. Flow cytometry (CD20, CD27, CD38, CD138) and intracellular staining (interleukin 10 [IL10], TNFα, granzyme B) were performed. Responders to successful IFX therapy were classified exhibiting a fecal calprotectin level of below 100 µg/g or achieving levels of <10% of the baseline value at initiation than at the end of the 12-month follow-up period. RESULTS: Before initiation of anti-TNFα therapy, flow cytometry revealed increased percentages of naïve B cells whereas transitional B cells were reduced compared with those in the healthy control patients. The IL10-producing B cells of both ulcerative colitis and Crohn disease patients were reduced at the initiation of IFX therapy, whereas TNFα-producing transitional CD24hiCD38hi B cells in ulcerative colitis patients were increased compared with those in healthy control patients. After 12 months of therapy, we detected a significant increase of IL10-producing transitional B cells in responding patients.The IFX trough levels in the responding patients showed a significant increase until 6 months after IFX initiation, attaining mean values of 9.9 µg/mL, whereas the IFX dosage was significantly lower than that in the nonresponding patients. The IFX trough levels in AZA-treated patients reached earlier therapeutic levels than in patients without AZA comedication, whereas during the course of the IFX therapy, comedication with AZA had no significant effect on the outcome. CONCLUSIONS: Attaining a normalization of IL10 production among CD24hiCD38hi B cells after 12 months of therapy may represent additional information about the reconstitution of a patient's immune system in responding patients. The achievement of an IFX trough level of ~10 µg/mL at 6 months of treatment is associated with a successful anti-TNFα therapy. In addition, AZA comedication supports an earlier achievement of therapeutic IFX trough levels.