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Background Mindfulness-based cognitive therapy (MBCT) seems a promising intervention for bipolar disorder (BD), but there is a lack of randomised controlled trials (RCT) investigating this. The purpose of this multicentre, evaluator blinded RCT was to investigate the added value of MBCT to treatment as usual (TAU) in BD up to 15 months follow-up (NCT03507647). Methods A total of 144 participants with BD type I and II were randomised to MBCT + TAU (n = 72) and TAU (n = 72). Primary outcome was current depressive symptoms. Secondary outcomes were current (hypo)manic and anxiety symptoms, recurrence rates, rumination, dampening of positive affect, functional impairment, mindfulness skills, self-compassion, and positive mental health. Potential moderators of treatment outcome were examined. Results MBCT + TAU was not more efficacious than TAU in reducing current depressive symptoms at post-treatment (95% CI [−7.0 to 1.8], p = 0.303, d = 0.24) or follow-up (95% CI [−2.2 to 6.3], p = 0.037, d = 0.13). At post-treatment, MBCT + TAU was more effective than TAU in improving mindfulness skills. At follow-up, TAU was more effective than MBCT + TAU in reducing trait anxiety and improving mindfulness skills and positive mental health. Exploratory analysis revealed that participants with higher depressive symptoms and functional impairment at baseline benefitted more from MBCT + TAU than TAU. Conclusions In these participants with highly recurrent BD, MBCT may be a treatment option in addition to TAU for those who suffer from moderate to severe levels of depression and functional impairment. Trial registration ClinicalTrials.gov, NCT03507647. Registered the 25 April 2018, https://www.clinicaltrials.gov/ct2/show/NCT01126827.

Muscle-specific kinase (MuSK) is crucial for acetylcholine receptor (AChR) clustering and thereby neuromuscular junction (NMJ) function. NMJ dysfunction is a hallmark of several neuromuscular diseases, including MuSK myasthenia gravis. Aiming to restore NMJ function, we generated several agonist monoclonal antibodies targeting the MuSK Ig-like 1 domain. These activated MuSK and induced AChR clustering in cultured myotubes. The most potent agonists partially rescued myasthenic effects of MuSK myasthenia gravis patient IgG autoantibodies in vitro. In an IgG4 passive transfer MuSK myasthenia model in NOD/SCID mice, MuSK agonists caused accelerated weight loss and no rescue of myasthenic features. The MuSK Ig-like 1 domain agonists unexpectedly caused sudden death in a large proportion of male C57BL/6 mice (but not female or NOD/SCID mice), likely caused by a urologic syndrome. In conclusion, these agonists rescued pathogenic effects in myasthenia models in vitro, but not in vivo. The sudden death in male mice of one of the tested mouse strains revealed an unexpected and unexplained role for MuSK outside skeletal muscle, thereby hampering further (pre-) clinical development of these clones. Future research should investigate whether other Ig-like 1 domain MuSK antibodies, binding different epitopes, do hold a safe therapeutic promise.

In recent years platinum (Pt) drugs have been found to be especially efficient to treat patients with cancers that lack a proper DNA damage response

In recent years, platinum (Pt) drugs have been found to be especially efficient to treat patients with cancers that lack a proper DNA damage response, for example, due to dysfunctional BRCA1. Despite this knowledge, we are still missing helpful markers to predict Pt response in the clinic. We have previously shown that volume-regulated anion channels, containing the subunits LRRC8A and LRRC8D, promote the uptake of cisplatin and carboplatin in BRCA1-proficient cell lines. Here, we show that the loss of LRRC8A or LRRC8D significantly reduces the uptake of cisplatin and carboplatin in BRCA1;p53-deficient mouse mammary tumor cells. This results in reduced DNA damage and in vivo drug resistance. In contrast to Lrrc8a, the deletion of the Lrrc8d gene does not affect the viability and fertility of mice. Interestingly, Lrrc8d−/− mice tolerate a 2-fold cisplatin MTD. This allowed us to establish a mouse model for intensified Pt-based chemotherapy, and we found that an increased cisplatin dose eradicates BRCA1;p53-deficient tumors, whereas eradication is not possible in wild-type mice. Moreover, we show that decreased expression of LRRC8A/D in patients with head and neck squamous cell carcinoma, who are treated with a Pt-based chemoradiotherapy, leads to decreased overall survival of the patients. In particular, high cumulative cisplatin dose treatments lost their efficacy in patients with a low LRRC8A/D expression in their cancers. Our data therefore suggest that LRRC8A and LRRC8D should be included in a prospective trial to predict the success of intensified cisplatin- or carboplatin-based chemotherapy.Significance:We demonstrate that lack of expression of Lrrc8a or Lrrc8d significantly reduces the uptake and efficacy of cisplatin and carboplatin in Pt-sensitive BRCA1;p53-deficient tumors. Moreover, our work provides support to confirm the LRRC8A and LRRC8D gene expression in individual tumors prior to initiation of intensive Pt-based chemotherapy.

gRNA oligos used for the generation of Lrrc8a or Lrrc8d-knockout cell lines, organoids and tumors

TIDE analysis and tumor growth curves of Kaplan Meyer survival graphs shown in main Figure 3

Analysis of publicly available ovarian cancer dataset to identify the association of LRRC8A or LRRC8D expression with outcome of chemotherapy with cisplatin

Lrrc8d KO mice tolerate higher cisplatin doses than wild type mice

Generation of monoclonal knockout cell lines of Lrrc8a or Lrrc8d used in main Figure

Pt-drug treatment of polyclonal cell lines with wild type as well as Lrrc8a or Lrrc8d knockout alleles shows positive selection for knockout alleles

Blasticidin and Pt treatment of Lrrc8a or Lrrc8d rescue cell lines data associated with main Figure 1

Primer sequences used for Lrrc8a or Lrrc8d knockout control in 2D cell lines or Lrrc8d knockout mice or reconstitution experiments

The BRCA1 tumor suppressor gene encodes a multidomain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks, which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered variants of uncertain clinical significance (VUS). Using genetically engineered mice, we show here that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupts the interaction with PALB2 and leads to embryonic lethality. Brca1 p.L1363P led to a similar acceleration in the development of Trp53-deficient mammary tumors as Brca1 loss, but the tumors showed distinct histopathologic features, with more stable DNA copy number profiles in Brca1 p.L1363P tumors. Nevertheless, Brca1 p.L1363P mammary tumors were HRR incompetent and responsive to cisplatin and PARP inhibition. Overall, these results provide the first direct evidence that a BRCA1 missense variant outside of the RING and BRCT domains increases the risk of breast cancer.Significance:These findings reveal the importance of a patient-derived BRCA1 coiled-coil domain sequence variant in embryonic development, mammary tumor suppression, and therapy response.See related commentary by Mishra et al., p. 6080

Included are the supplementary methods, tables, and figures.

Supplementary Table S1 from An Inducible Mouse Model of Melanoma Expressing a Defined Tumor Antigen

Cancer immunotherapy based on vaccination with defined tumor antigens has not yet shown strong clinical efficacy, despite promising results in preclinical models. This discrepancy might result from the fact that available preclinical models rely on transplantable tumors, which do not recapitulate the long-term host-tumor interplay that occurs in patients during progressive tumor development and results in tumor tolerance. To create a faithful preclinical model for cancer immunotherapy, we generated a transgenic mouse strain developing autologous melanomas expressing a defined tumor antigen recognized by T cells. We chose the antigen encoded by P1A, a well-characterized murine cancer germ line gene. To transform melanocytes, we aimed at simultaneously activating the Ras pathway and inactivating tumor suppressor Ink4a/Arf, thereby reproducing two genetic events frequently observed in human melanoma. The melanomas are induced by s.c. injection of 4-OH-tamoxifen (OHT). By activating a CreER recombinase expressed from a melanocyte-specific promoter, this treatment induces the loss of the conditional Ink4a/Arf gene in melanocytes. Because the CreER gene itself is also flanked by loxP sites, the activation of CreER also induces the deletion of its own coding sequence and thereby allows melanocyte-specific expression of genes H-ras and P1A, which are located downstream on the same transgene. All melanomas induced in those mice with OHT show activation of the Ras pathway and deletion of gene Ink4a/Arf. In addition, these melanomas express P1A and are recognized by P1A-specific T lymphocytes. This model will allow to characterize the interactions between the immune system and naturally occurring tumors and thereby to optimize immunotherapy approaches targeting a defined tumor antigen. (Cancer Res 2006; 66(6): 3278-86)

Supplementary Methods, Figures 1-6 from Tumor-Initiated Inflammation Overrides Protective Adaptive Immunity in an Induced Melanoma Model in Mice

Background Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD. Methods The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted. Discussion This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions. Trial registration: ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.

We evaluated a digital cognitive assessment platform, Philips IntelliSpace Cognition, in a cross-sectional cohort of patients diagnosed with mild cognitive impairment (MCI). Performance on individual neuropsychological tests, cognitive domain scores, and Alzheimer’s disease (AD) specific composite scores in MCI were compared with a cohort of cognitively normal adults (CN). The cohorts were matched for age, sex, and education. The performance on all but two neuropsychological tests was worse in the MCI group. After ranking the cognitive domains by effect size, we found that the memory domain was most impaired, followed by executive functioning. The Early AD/MCI Alzheimer’s Cognitive Composite (EMACC) and Preclinical Alzheimer’s Cognitive Composite (PACC) scores were constructed from the digital tests on Philips IntelliSpace Cognition. Both AD-specific composite scores showed greater sensitivity and specificity than the Mini-Mental State Examination, as well as individual neuropsychological tests and individual cognitive domain scores. Together, these results demonstrate the diagnostic value of Philips IntelliSpace Cognition in patients with MCI.

Contains fulltext : 293885.pdf (Publisher’s version ) (Open Access) BACKGROUND: Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness-Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD. METHODS: The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted. DISCUSSION: This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.

The BRCA1 tumor suppressor gene encodes a multidomain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks, which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered variants of uncertain clinical significance (VUS). Using genetically engineered mice, we show here that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupts the interaction with PALB2 and leads to embryonic lethality. Brca1 p.L1363P led to a similar acceleration in the development of Trp53-deficient mammary tumors as Brca1 loss, but the tumors showed distinct histopathologic features, with more stable DNA copy number profiles in Brca1 p.L1363P tumors. Nevertheless, Brca1 p.L1363P mammary tumors were HRR incompetent and responsive to cisplatin and PARP inhibition. Overall, these results provide the first direct evidence that a BRCA1 missense variant outside of the RING and BRCT domains increases the risk of breast cancer. Significance: These findings reveal the importance of a patient-derived BRCA1 coiled-coil domain sequence variant in embryonic development, mammary tumor suppression, and therapy response. See related commentary by Mishra et al., p. 6080

Background Preliminary evidence suggests that Mindfulness-Based Cognitive Therapy (MBCT) is a promising treatment for bipolar disorder (BD). A proposed working mechanism of MBCT in attenuating depressive symptoms is reducing depressive rumination. The primary aim of this study was to investigate the effect of MBCT on self-reported trait depressive rumination and an experimental state measure of negative intrusive thoughts in BD patients. Exploratively, we investigated the effect of MBCT on positive rumination and positive intrusive thoughts. Methods The study population consisted of a subsample of bipolar type I or II patients participating in a multicenter randomized controlled trial comparing MBCT + treatment as usual (TAU) (N = 25) to TAU alone (N = 24). Trait depressive rumination (RRS brooding subscale) and intrusive thoughts (breathing focus task (BFT)) were assessed at baseline (full subsample) and post-treatment (MBCT + TAU; n = 15, TAU; n = 15). During the BFT, participants were asked to report negative, positive and neutral intrusive thoughts while focusing on their breathing. Results Compared to TAU alone, MBCT + TAU resulted in a significant pre- to post-treatment reduction of trait depressive rumination (R2 = .16, F(1, 27) = 5.15, p = 0.031; medium effect size (f2 = 0.19)) and negative intrusive thoughts on the BFT (R2 = .15, F(1, 28) = 4.88, p = 0.036; medium effect size (f2 = 0.17)). MBCT did not significantly change positive rumination or positive intrusive thoughts. Conclusions MBCT might be a helpful additional intervention to reduce depressive rumination in BD which might reduce risk of depressive relapse or recurrence. Considering the preliminary nature of our findings, future research should replicate our findings and explore whether this reduction in rumination following MBCT indeed mediates a reduction in depressive symptoms and relapse or recurrence in BD.

Contains fulltext : 252777.pdf (Publisher’s version ) (Open Access) Negative self-referential processing has fruitfully been studied in unipolar depressed patients, but remarkably less in patients with bipolar disorder (BD). This exploratory study examines the relation between task-based self-referential processing and depressive symptoms in BD and their possible importance to the working mechanism of mindfulness-based cognitive therapy (MBCT) for BD. The study population consisted of a subsample of patients with BD (n = 49) participating in an RCT of MBCT for BD, who were assigned to MBCT + TAU (n = 23) or treatment as usual (TAU) (n = 26). Patients performed the self-referential encoding task (SRET), which measures (1) positive and (2) negative attributions to oneself as well as (3) negative self-referential memory bias, before and after MBCT + TAU or TAU. At baseline, all three SRET measures were significantly related to depressive symptoms in patients with BD. Moreover, repeated measures analyses of variance revealed that negative self-referential memory bias diminished over time in the MBCT + TAU group, compared with the TAU group. Given the preliminary nature of our findings, future research should explore the possibly mediating role of reducing negative self-referential memory bias in preventing and treating depressive symptoms in BD through MBCT. 18 p.

Mindfulness-based cognitive therapy (MBCT) has been found effective in reducing depressive symptoms in adults suffering from recurrent depression. However, sustained recovery after MBCT is modest and may require additional, sequential treatment. Basing such additions on known working mechanisms of MBCT, like increases in (self-)compassion, is likely to reap further benefits. Mindfulness-based compassionate living (MBCL) is designed as a follow-up to MBCT and has been shown effective in reducing depressive symptoms. It has a similar format to MBCT: eight weekly group sessions and additional home practice. MBCL has a more explicit focus on cultivating (self-)compassion in response to difficult experiences. Little is known about the potential experiential added value of MBCL after MBCT. The current study aims to fill this gap. A grounded theory approach was used to analyze in-depth interviews, which were held post-intervention with a purposive sample of patients who participated in a randomized controlled trial of MBCL for recurrent depression. Participants indicated that MBCL particularly had added value in terms of its immediate applicability in situations of deep suffering. Four themes emerged: (1) the container of kindness, (2) exposure to the difficult, (3) empowerment, and (4) common humanity. This study shows that participants experienced an additional value of MBCL over and above MBCT. The results provide insight into the processes underlying the efficacy of MBCL in reducing depressive symptoms and may help address underlying mechanisms of vulnerability in this population as well as tap into mechanisms that enhance resilience.

Merciful Augusta. Margaret of Brabant as counselor, mediator and saint in Italy (1310-1311) This article shows that Margaret of Brabant (1276-1311), Queen of the Romans, played an influential diplomatic and moral role on the international stage and had great influence on her husband, the Holy Roman Emperor Henry VII, in the perception of her contemporaries, who glorified the love between the two. A study of several letters addressed to her shows how Margaret helped her spouse to build a stable political network based on personal relations. This article then discusses the perception of Margaret in contemporary historiography and it demonstrates that early humanists Albertino Mussato and Giovanni de Cermenate both acknowledge her importance as a political counselor and mediator crucial to Henry’s reign. This view contrasts with other accounts of her life, in which she is solely remembered for her piety and holiness. Indeed, these aspects came to dominate the memory of Margaret soon after her death, as the Franciscans promoted her cult as ‘Holy Empress’.

Wastewaters can be analyzed to generate population-level data for public health surveillance, such as antibiotic resistance monitoring. To provide representative data for the contributing population, bacterial isolates collected from wastewater should originate from different individuals and not be distorted by a selection pressure in the wastewater. Here we use Escherichia coli diversity as a proxy for representativeness when comparing grab and composite sampling at a major municipal wastewater treatment plant influent and an untreated hospital effluent in Gothenburg, Sweden. All municipal samples showed high E. coli diversity irrespective of the sampling method. In contrast, a marked increase in diversity was seen for composite compared to grab samples from the hospital effluent. Virtual resampling also showed the value of collecting fewer isolates on multiple occasions rather than many isolates from a single sample. Time-kill tests where individual E. coli strains were exposed to sterile-filtered hospital wastewater showed rapid killing of antibiotic-susceptible strains and significant selection of multi-resistant strains when incubated at 20 °C, an effect which could be avoided at 4 °C. In conclusion, depending on the wastewater collection site, both sampling method and collection/storage temperature could significantly impact the representativeness of the wastewater sample.

Organ-specific autoimmunity is often characterized by autoantibodies targeting proteins expressed in the affected tissue. A subgroup of autoimmunopathies has recently emerged that is characterized by predominant autoantibodies of the IgG4 subclass (IgG4-autoimmune diseases; IgG4-AID). This group includes pemphigus vulgaris, thrombotic thrombocytopenic purpura, subtypes of autoimmune encephalitis, inflammatory neuropathies, myasthenia gravis and membranous nephropathy. Although the associated autoantibodies target specific antigens in different organs and thus cause diverse syndromes and diseases, they share surprising similarities in genetic predisposition, disease mechanisms, clinical course and response to therapies. IgG4-AID appear to be distinct from another group of rare immune diseases associated with IgG4, which are the IgG4-related diseases (IgG4-RLD), such as IgG4-related which have distinct clinical and serological properties and are not characterized by antigen-specific IgG4. Importantly, IgG4-AID differ significantly from diseases associated with IgG1 autoantibodies targeting the same organ. This may be due to the unique functional characteristics of IgG4 autoantibodies (e.g. anti-inflammatory and functionally monovalent) that affect how the antibodies cause disease, and the differential response to immunotherapies of the IgG4 producing B cells/plasmablasts. These clinical and pathophysiological clues give important insight in the immunopathogenesis of IgG4-AID. Understanding IgG4 immunobiology is a key step towards the development of novel, IgG4 specific treatments. In this review we therefore summarize current knowledge on IgG4 regulation, the relevance of class switching in the context of health and disease, describe the cellular mechanisms involved in IgG4 production and provide an overview of treatment responses in IgG4-AID.

Background: Value Based Health Care (VBHC) is a well-known strategy in most countries, amongst whom the Netherlands, to improve patient-relevant outcomes and reduce healthcare costs. However, a met...

Contains fulltext : 220962.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Mindfulness-Based Cognitive Therapy (MBCT) has been shown to reduce depressive symptoms in patients with recurrent or chronic depression. However, sequential, follow-up interventions are needed to further improve outcome for this group of patients. One possibility is to cultivate mechanisms thought to support recovery from depression, such as (self-)compassion. The current study examined the efficacy of mindfulness-based compassionate living (MBCL) in recurrently depressed patients who previously received MBCT, and consolidation effects of MBCL at follow-up. METHODS: Part one is a randomized controlled trial (RCT) comparing MBCL in addition to treatment as usual (TAU) with TAU alone. The primary outcome measure was severity of depressive symptoms. Possible mediators and moderators of treatment outcome were examined. Part two is an uncontrolled study of both intervention- and control group on the consolidation of treatment effect of MBCL over the course of a 6-months follow-up period. RESULTS: Patients were recruited between July 2013 and December 2014 (N = 122). MBCL participants (n = 61) showed significant improvements in depressive symptoms (Cohen's d = 0.35), compared to those who only received TAU (n = 61). The results at 6-months follow-up showed a continued improvement of depressive symptoms. LIMITATIONS: As MBCL was not compared with an active control condition, we have little information about the possible effectiveness of non-specific factors. CONCLUSION: MBCL appears to be effective in reducing depressive symptoms in a population suffering from severe, prolonged, recurrent depressive symptoms. To optimise the (sequential) treatment trajectory, replication of the study in a prospective sequential trial is needed. Registered at ClinicalTrials.gov:NCT02059200.

Objectives Gaining knowledge of dynamic processes of mechanisms underlying mindfulness-based cognitive therapy (MBCT) for recurrent depression could help to improve treatment efficacy. The current study examined the overall course and week-to-week associations of mindfulness and positive/negative affect during MBCT for recurrent depression. Methods Using data from the MOMENT study, 235 patients with recurrent depression in (partial) remission allocated to MBCT were included. Prior to each MBCT session, self-reports were obtained on mindfulness, positive affect, and negative affect. Results Autoregressive latent trajectory (ALT) modeling revealed that, across the MBCT course, larger increases in mindfulness were associated with larger increases in positive affect (r = .80,p < .050). Higher general levels of negative affect were associated with smaller increases in mindfulness over time (r = -.26,p < .001). Week-to-week effects showed no reciprocal cross-lagged effects between mindfulness and positive affect or negative affect, except for positive affect at session 2 which was positively associated with mindfulness at session 3 (r = .11,p < .050). Conclusions The current study supports a positive association in strength of increase between mindfulness and positive affect, while higher general levels of negative affect might be associated with smaller increases of mindfulness during MBCT for recurrent depression. For future research, experience sampling methods (ESMs) are recommended to capture dynamics on a smaller time scale. ALT modeling techniques are advised to be better able to interpret the processes of stability and change during MBCT for recurrent depression.

Additional file 2: Table S1. Sociodemographic and clinical characteristics, and baseline measures for patients that agreed or refused to perform the experimental tasks. Table S2. Sociodemographic and clinical characteristics, and baseline measures for patients who performed, or did not perform the experimental tasks. Table S3. Sociodemographic and clinical characteristics, and baseline measures for patients who completed baseline and post-treatment BFT versus patients who completed baseline BFT only. Table S4. No influence of time between measures of depressive/manic symptoms (T0), self-report questionnaires (T0a), and the BFT scores (T0b), on the association between those measures at baseline. Table S5. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the brooding subscale of the RRS: RRS_br.T1 – RRS_br.T0 = group + intercept. Table S6. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the number of negative intrusive thoughts: BFT.neg.T1 – BFT.neg.T0 = group + intercept. Table S7. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the number of positive intrusive thoughts: BFT.pos.T1 – BFT.pos.T0 = group + intercept. Table S8. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the number of neutral intrusive thoughts: BFT.neutral.T1 – BFT.neutral.T0 = group + intercept. Table S9. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the number of total intrusive thoughts: BFT.total.T1 – BFT.total.T0 = group + intercept. Table S10. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the emotion-focused subscale of the RPA: RPA_ER.T1 – RPA_ER.T0 = group + intercept. Table S11. Bootstrapped BCa 95% confidence intervals of B for the regression model regarding the self-focused subscale of the RPA: RPA_SR.T1 – RPA_SR.T0 = group + intercept