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Background Despite approximately half of the German general population not meeting the physical activity (PA)-guidelines of the World Health Organization with further decreases noted during the pandemic, population-based intervention strategies to tackle this public health problem remain sparse. This study aimed to replicate the successfully delivered “10,000 Steps Ghent” intervention and research trial conducted in Belgium, two research questions were examined: (1) Do individuals located in the city that a complex PA intervention is implemented in (Duesseldorf) engage in more PA compared to individuals located in the control city (Wuppertal) after one year? (2) Is the proportion of those reaching 10,000 steps/day higher in the intervention than in the control city after the intervention? Methods A nonrandomized controlled intervention trial was conducted among residents of two German cities. The 12-month intervention ‘10,000 Steps Duesseldorf’ was designed as a multicomponent intervention targeting different socioecological levels: at the intrapersonal level, a website allowed participants to self-monitor their steps; at the organizational level, workplaces and community groups were engaged through step count competitions; and at the community and policy levels, a city-wide media campaign to increase awareness regarding PA benefits was rolled out and street signage indicating walking routes were posted in different city district of Duesseldorf. To investigate intervention effects, PA was assessed via pedometers in two representative samples of adults aged 25–75 years from Duesseldorf (intervention) and Wuppertal (control). Measurements were taken at baseline (April 2021-March 2022) and again one year later (May–November 2023) and the same participants recorded their steps over a 7-day period at both time points. Baseline differences in socio-demographic and health-related variables between intervention and control were adjusted for in a propensity score model with matching weights. Results 627 adults completed baseline and 553 the follow-up assessment (60% female, 60% intervention across both timepoints and cities). The results of the propensity score analyses revealed that intervention participants walked an average of 462 steps per day more (95% confidence interval: -146 to 1070) than controls at follow-up. However, the proportion of residents reaching 10,000 steps/day was comparable between intervention and control (Duesseldorf: 26.4%, Wuppertal: 25.6%) after the intervention (odds ratio 1.04, 95% confidence interval: 0.41 to 2.66). Conclusions Although the increase in step count detected in our study was promising, further intervention efforts and accompanying research are needed to meet the minimally relevant intervention effect of 1000 steps that was set in the original Ghent study. Trial registration German Clinical Trials Register DRKS00024873 (Date of registration: April 21st, 2021; URL: https://drks.de/search/de/trial/DRKS00024873 ).

The World Health Organization recommends 150 minutes of moderate to vigorous physical activity (PA), which translates to approximately 7000 to 10,000 steps per day for adults. In Germany, less than half of the population in this age range meets this recommendation, highlighting the need for population-based intervention approaches for promoting daily PA. The complex community-based PA intervention \"10,000 Steps Ghent,\" which was originally developed in Belgium and was shown to be effective for PA promotion, has been adapted for implementation and evaluation in 2 German cities. The original Belgian study is currently being replicated, and we aim to examine the effectiveness of the adapted intervention among adults living in intervention city districts in Duesseldorf when compared with those living in control city districts in Wuppertal, over the course of 1 year. A controlled intervention trial examining the effects of an intervention addressing multiple levels (eg, individual level: website; organizational level: PA promotion in companies; community level: media campaigns and environmental changes) is being conducted. PA and various secondary outcomes will be assessed in 2 random samples of adults aged 25 to 75 years (n=399 in each city) at baseline and after 1 year. Funding for this study was obtained in March 2020. Recruitment for this study and baseline data collection were conducted from May 2021 to March 2022 (as of March 2022, 626 participants were enrolled in the study). The intervention will be implemented in Duesseldorf for 1 year from April 2022 onward, and follow-up assessments will be conducted, starting in May 2023 (until September 2023). Data analysis will be performed in fall 2023, and the results will be published in spring 2024. To our knowledge, this is the first research project (currently underway in Germany) that is aimed at replicating the effects of a complex intervention for PA promotion that was previously shown to be effective in another European country. German Clinical Trials Register DRKS00024873; https://tinyurl.com/4c9e8azh. DERR1-10.2196/39175.

Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5–235 mg/d for a period of 1–36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality.

Severe autoimmune-mediated neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and paranodopathies, often remain refractory to established immunotherapies. 1–3 Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promising therapeutic potential in autoimmune conditions through substantial and sustained B-cell depletion. 4,5 Here, we report treatment of two patients with severe, treatment-refractory autoimmune neuropathies using autologous anti-CD19 CAR T cells ( appendix pp 2–3). In March, 2023, the patient first presented to our university hospital with rapid progression to symmetric tetraplegia despite extensive immunotherapy (intravenous immunoglobulin, corticosteroids, plasmapheresis, cyclophosphamide, rituximab, obinutuzumab, and bortezomib; appendix pp 4–6). JM declares stock ownership from Amgen, Bayer, and Sanofi; travel grants from Alnylam, Biogen Idec, Novartis, Teva, Eisai, Neuraxpharm, Bristol Myers Squibb, and Kyverna; consulting fees from Novartis and Alnylam; and research funding from Klaus Tschira Foundation, Ruhr-University Bochum (FoRUM program), Deutsche Multiple Sklerose Gesellschaft, Hertie Foundation, Novartis, and Kyverna, not related to this work.

The statistical problem of estimating the total number of distinct species in a population (or distinct elements in a multiset), given only a small sample, occurs in various areas, ranging from the unseen species problem in ecology to estimating the diversity of immune repertoires. Accurately estimating the true richness from very small samples is challenging, in particular for highly diverse populations with many rare species. Depending on the application, different estimation strategies have been proposed that incorporate explicit or implicit assumptions about either the species distribution or about the sampling process. These methods are scattered across the literature, and an extensive overview of their assumptions, methodology and performance is currently lacking. We comprehensively review and evaluate a variety of existing methods on real and simulated data with different compositions of rare and abundant elements. Our evaluation shows that, depending on species composition, different methods provide the most accurate richness estimates. Simpler methods, like the Chao 1 and Chiu estimators, yield accurate predictions for many of the tested species compositions, but tend to underestimate the true richness for heterogeneous populations and small (containing 1% to 5% of the population) samples. When the population size is known, upsampling estimators such as PreSeq and RichnEst often yield more accurate results. Source code for data simulation and richness estimation is available at https://gitlab.com/rahmannlab/speciesrichness.

Motivation: Automated chromatin segmentation based on ChIP-seq data reveals insights into the epigenetic regulation of chromatin accessibility. Existing segmentation methods are constrained by simplifying modeling assumptions, which may have a negative impact on the segmentation quality. Results: We introduce EpiSegMix, a novel segmentation method based on a hidden Markov model with flexible read count distribution types and state duration modeling, allowing for a more flexible modeling of both histone signals and segment lengths. In a comparison with two existing tools, ChromHMM, Segway and EpiCSeg, we show that EpiSegMix is more predictive of cell biology, such as gene expression. Its flexible framework enables it to fit an accurate probabilistic model, which has the potential to increase the biological interpretability of chromatin states. Availability and implementation: Source code: https://gitlab.com/rahmannlab/episegmix.Competing Interest StatementThe authors have declared no competing interest.Footnotes* The Results section has been extensively revised after obtaining very helpful reviewer feedback. The evaluation focuses on genome-wide quantitative aspects, while examples have been moved to the supplement. The other sections have been clarified and shortened where possible.* https://gitlab.com/rahmannlab/episegmix

Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression. We therefore tested the hypothesis that the peripheral inflammation markers IL-6 and TNF-α correlate with neural resting state network functional connectivity in depression using functional magnetic resonance imaging (fMRI) and compared it with healthy controls. We used fMRI to investigate the functional connectivity (FC) of the resting state Default Mode Network (DMN) and Salience/Ventral Attention Network (SAL) and their association with the peripheral inflammation markers IL-6 and TNF-α in 25 patients with depression and compared it to 24 healthy subjects. Results of this imaging study revealed that both DMN and SAL resting state networks are differentially associated with distinct immunological pathways depending on whether a person has a depressive phenotype or is healthy. While the DMN FC correlated with the concentration of the cytokine IL-6 in healthy subjects, SAL FC’s connectivity correlated with the cytokine TNF-α's concentration. This study highlights the importance of peripheral inflammatory processes in depression and suggests a modulatory effect on neural resting state networks depending on the state of depression.

This study explored the impact of an art of living intervention within group psychotherapy for depression, focusing on constructs like life satisfaction, self-efficacy, and depression. Mental illness prevalence often exceeds available treatment options, particularly in Germany, where group psychotherapy is a viable alternative. While less researched, group therapy effectively improves well-being, especially through interpersonal exchange. Meta-analyses confirm cognitive behavioral group therapy’s effectiveness against depression, encouraging further investigation. This study employed a two-factor experimental design with randomized group allocation. The control group (CG) participated in weekly 50 min sessions for four weeks, while the experimental group (EG) received identical therapy plus reflective life-stimulating questions. Measures of depression, art of living, life satisfaction, and self-efficacy were taken before, after, and three months post-intervention. Among 107 participants, 52 were in the EG and 55 were in the CG. The results showed a significant 24% reduction in depression scores in the experimental group, a significant 16% increase in the art of living and a significant 19% increase in life satisfaction, while the CG showed no significant changes. Self-efficacy did not significantly improve in the EG. Follow-up data indicated sustained improvements in depression and art of living for the EG. The limitations of this study include a limited scope, practical constraints, randomization challenges and confounding variables, which are typical for experimental studies. These findings highlight the intervention’s potential, suggesting future research focusing on long-term effects, personality factors and disorder-specific applications.

Treatments for Cocaine Use Disorder (CUD) are variably effective, and there are no FDA-approved medications. One approach to developing new treatments for CUD may be to investigate and target poor prognostic signs. One such sign is anhedonia (i.e. a loss of pleasure or interest in non-drug rewards), which predicts worse outcomes in existing CUD treatments. Inflammation is thought to underlie anhedonia in many other disorders, but the relationship between anhedonia and inflammation has not been investigated in CUD. Therefore, we assessed peripheral genome-wide gene expression in n = 48 individuals with CUD with high (n = 24) vs. low (n = 24) levels of anhedonia, defined by a median split of self-reported anhedonia. Our hypothesis was that individuals with high anhedonia would show differential gene expression in inflammatory pathways. No individual genes were significantly different between the low and high anhedonia groups when using t-tests with a stringent false discovery rate correction (FDR-corrected p < 0.05). However, an exploratory analysis identified 166 loci where t-tests suggested group differences at a nominal p < 0.05. We used DAVID, a bioinformatics tool that provides functional interpretations of complex lists of genes, to examine representation of this gene list in known pathways. It confirmed that mechanisms related to immunity were the top significant associations with anhedonia in the sample. Further, the two top differentially expressed genes in our sample, IRF1 and GBP5, both have primary inflammation and immune functions, and were significantly negatively correlated with total scores on our self-report of anhedonia across all 48 subjects. These results suggest that prioritizing development of anti-inflammatory medications for CUD may pay dividends, particularly in combination with treatment-matching strategies using either phenotypic measures of anhedonia or biomarkers of inflammatory gene expression to individualize treatment.

Epicardial adipose tissue (EAT) has the unique property to release mediators that nourish the heart in healthy conditions, an effect that becomes detrimental when volume expands and proinflammatory cytokines start to be produced. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a proinflammatory mediator involved in atherosclerosis, is also produced by visceral fat. Due to the correlation of inflammation with PCSK9 and EAT enlargement, we evaluated whether PCSK9 was expressed in EAT and associated with EAT inflammation and volume. EAT samples were isolated during surgery. EAT thickness was measured by echocardiography. A microarray was used to explore EAT transcriptoma. The PCSK9 protein levels were measured by Western Blot in EAT and ELISA in plasma. PCSK9 was expressed at both the gene and protein levels in EAT. We found a positive association with EAT thickness and local proinflammatory mediators, in particular, chemokines for monocytes and lymphocytes. No association was found with the circulating PCSK9 level. The expression of PCSK9 in EAT argues that PCSK9 is part of the EAT secretome and EAT inflammation is associated with local PCSK9 expression, regardless of circulating PCSK9 levels. Whether reducing EAT inflammation or PCSK9 local levels may have beneficial effects on EAT metabolism and cardiovascular risk needs further investigations.