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Objectives: We conducted a cluster-randomized-controlled trial (cRCT) in 18 German nursing homes (NH) to evaluate the cost-effectiveness of reinstruction and remotivation of nursing staff by dental assistants (DAs) over 13 months., Methods: In the intervention arm, dentists examined NH residents, identified oral health conditions, and prescribed individualized oral care interventions. Nursing staff delivered these interventions, with regular follow-up support from DAs (reinstruction and remotivation). In the control group, similar interventions were prescribed via a standardized form, without reinstruction and remotivation (standard of care). The primary outcome was Oral-Health-related Quality-of-Life (OHrQoL) using the Geriatric/General Oral Health Assessment Index (ADD-GOHAI). Secondary outcomes included Health-related Quality-of-Life (HrQoL) using the EQ-5D summary index and caries experience (DMFT index). Costs, including those for staff, materials, and travel, were assessed in Euro 2022. Cost-effectiveness ratios and bootstrapping simulations assessed cost-effectiveness-acceptability at different willingness-to-pay thresholds., Results: Of 358 recruited participants, 68 and 63 in the intervention and control group completed the study. No significant differences existed between groups in demographics or baseline health measures. After 13 months, changes in ADD-GOHAI and DMFT scores were minimal and non-significant, while EQ-5D scores decreased in the intervention group (p < 0.001). Total costs were higher in the intervention arm (median 121.10 Euro) versus the control (median 0 Euro, p < 0.001), mainly due to travel expenses. The intervention increased dental service use but demonstrated lower cost-effectiveness acceptability., Conclusions: DA-led reinstruction did not improve OHrQoL, negatively impacted HrQoL, and increased costs. Notably, our study was suffering from significant attrition, impacting on statistical power., Clinical Significance: Reinstruction and remotivation by dental assistants did not improve OHrQoL, but generated significant costs, mainly due to an uptake of dental services., Trial Registration: ClinicalTrials.gov (Trial registration number NCT04140929)., Competing Interests: Declaration of competing interest The authors have no conflicting interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways., Methods: This post-hoc, exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies. Both studies were international, multicentre, randomised, double-blind, placebo-controlled trials in patients with PAH. Efficacy and safety parameters common to both studies were analysed., Results: A total of 429 patients were randomised and treated; 237 received sotatercept and 192 received placebo. Adding sotatercept to background PAH therapy for 24 weeks improved exercise capacity (as assessed by 6-min walk distance), pulmonary vascular resistance, World Health Organization functional class, and delayed time to first occurrence of death or clinical worsening event. There were clinically important reductions in both pulmonary and right heart pressures; improvements in right ventricle (RV) size during both systole and diastole; and enhancements in RV contractility and RV-pulmonary artery coupling. The number of patients who experienced at least one adverse event of interest or special interest (increased haemoglobin, thrombocytopenia, bleeding events [mostly epistaxis], increased blood pressure, and telangiectasia) was higher in the sotatercept group than the placebo group., Discussion: This pooled analysis confirms that sotatercept delivers therapeutic benefit across a range of efficacy endpoints and has favourable safety in patients with PAH. Increased duration of follow-up will provide further insight into long-term outcomes of sotatercept in patients with PAH., (Copyright ©The authors 2025.)

Background: Living Labs, as a type of academic-practice partnerships, possess the potential to transform care and research into a participatory partnership and narrow the research-practice gap to improve evidence-based and Person-centred care. Given the lack of systematic investigations of Living Labs in healthcare, we will establish a dementia-specific academic-practice partnership (Living Lab Dementia) in Germany and conduct a process evaluation. The aim of this study is to gain insights into the intervention itself (mechanisms of impact) and its implementation process (degree of implementation, barriers, and facilitators)., Methods: This process evaluation of the multi-center research project PraWiDem (German acronym for linking professional nursing practice and research in dementia) will be conducted applying a convergent mixed methods design and will be based on the Medical Research Council (MRC) framework for the development and evaluation of complex interventions. The intervention is presented in a logic model which describes relevant basic theoretical assumptions, intervention components, implementation aspects, mechanisms of impact, relevant outcomes, and the context in which the intervention is delivered. Data will be collected before the intervention (T 0 ), during the intervention period, and at follow-up after 18 months (T 1 ). Qualitative data will be collected through semi-structured interviews and focus groups. Quantitative data sources will be process documents and questionnaires., Discussion: Our study will provide important insights into the Living Lab Dementia intervention and its implementation processes. The results of this evaluation will contribute to the refinement of the intervention and its implementation processes, and will enable to measure the impact of these processes in future studies., Competing Interests: Declarations. Ethics approval and consent to participate: The study is carried out according to the current data protection regulations (European General Data Protection Regulation and the German Federal Data Protection Regulation). The Ethics Committee of the German Society for Nursing Science has provided ethical approval for the project’s process evaluation (No. 22–035). In the event of protocol amendments, serious or unexpected adverse events or premature termination of the study, we will inform the Ethics Committee immediately. The participants, including the Linking Pins, staff, members of the management of the care facilities, people living with dementia and their legal representatives, will be informed about the study both verbally and in writing. Written informed consent will be obtained. Information about the procedures will be provided before the data collection begins. The participants are informed that the data obtained in the study will be published in scientific publications. In accordance with the consent, the researchers also reserve the right to reuse the collected data in further research work, such as secondary data analyses. Participants have the option to withdraw their consent at any point during the study. Given the variability in the ability of people living with dementia to remember, express themselves verbally, and relate to their diagnosis, the decision to conduct an interview will be made collaboratively in each case through joint discussions between the responsible nursing home staff and the project team during each data collection session. In cases where verbal or physical signs before or during data collection indicate discomfort or declining interest in the interview, ongoing and current consent [49] is obtained to verify the persistence of the initial consent [50]. If, by mutual agreement or if the initial consent is no longer affirmed, the interview will not commence or, if already started, will be promptly terminated. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: There are hardly any data on the extent to which nursing home residents are provided with palliative homecare. We want to add evidence by comparing nursing home residents (who had been living in a nursing home for at least one year) and nursing-care-dependent community dwellers in terms of utilization and quality of palliative homecare., Methods: We conducted a population-based study with nationwide claims data from deceased beneficiaries of a large German health insurance provider. First, we compared utilization rates of primary palliative care [PPC], specialized palliative homecare [SPHC], and no palliative care [noPC] between nursing home residents and community dwellers, both descriptively and adjusted for covariates. Second, we analyzed the (adjusted) relationship between PPC-only and SPHC (both: starting ≥ 30 days before death), and noPC with healthcare indicators (death in hospital, hospitalization, emergencies, intensive care treatment within the last 30 days of life), and compared these relationships between nursing home residents and community dwellers. Analyses were conducted using simple and multiple logistic regression. Data were standardized by age and gender., Results: From 117,436 decedents in 2019, 71,803‬ could be included in the first, 55,367‬ in the second analysis. The rate of decedents with noPC was higher in nursing home residents (61.3%) compared to community dwellers (56.6%). Nursing home residents received less SPHC (10.7% vs. 23.2%) but more PPC (30.3% vs. 27.0%) than community dwellers, and achieved better outcomes across all end-of-life healthcare indicators. Adjusted for covariates, both types of palliative homecare were associated with beneficial outcomes, in nursing home residents as well as in community dwellers, with generally better outcomes for SPHC than PPC-only. For most outcomes, the associations with palliative homecare were equal or smaller in nursing home residents than in community dwellers., Conclusions: The overall better performance in quality of end-of-life care in nursing home residents than in community dwellers may be due to the institutionally provided nursing and general practitioner care within nursing homes. This may also explain higher rates of PPC and lower rates of SPHC in nursing home residents, and why the relationship with both PPC and SPHC are smaller in nursing home residents., Trial Registration: German Clinical Trials Register (DRKS): [DRKS00024133, Date of registration: 28.06.2021]., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was granted by the Ethics Committee of Jena University Hospital (Reg.-Nr. 2021–2162-Daten). Access to data of statutory health insurance funds for research purposes was possible in accordance with the German Social Law (SGB V § 287). Patient consent was not necessary. The study was registered with the German Clinical Trials Register German Clinical Trials Register (German Clinical Trials Register (DRKS): [DRKS00024133, Date of registration: 28.06.2021]. All methods were carried out in accordance with relevant guidelines and regulations in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2025. The Author(s).)

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases.

Recent work has shown rapid microstructural brain changes in response to learning new tasks. These cognitive tasks tend to draw on multiple brain regions connected by white matter (WM) tracts. Therefore, behavioural performance change is likely to be the result of microstructural, functional activation, and connectivity changes in extended neural networks. Here we show for the first time that learning-induced microstructural change in WM tracts, quantified with diffusion tensor and kurtosis imaging (DTI, DKI) is linked to functional connectivity changes in brain areas that use these tracts to communicate. Twenty healthy participants engaged in a month of virtual reality (VR) systematic audiovisual (AV) training. DTI analysis using repeated-measures ANOVA unveiled a decrease in mean diffusivity (MD) in the SLF II, alongside a significant increase in fractional anisotropy (FA) in optic radiations post-training, persisting in the follow-up (FU) assessment (post: MD t(76) = 6.13, p < 0.001, FA t(76) = 3.68, p < 0.01, FU: MD t(76) = 4.51, p < 0.001, FA t(76) = 2.989, p < 0.05). The MD reduction across participants was significantly correlated with the observed behavioural performance gains. A functional connectivity (FC) analysis showed significantly enhanced functional activity correlation between primary visual and auditory cortices post-training, which was evident by the DKI microstructural changes found within these two regions as well as in the sagittal stratum including WM tracts connecting occipital and temporal lobes (mean kurtosis (MK): cuneus t(19)=2.3 p < 0.05, transverse temporal t(19)=2.6 p < 0.05, radial kurtosis (RK): sagittal stratum t(19)=2.3 p < 0.05). DTI and DKI show complementary data, both of which are consistent with the task-relevant brain networks. The results demonstrate the utility of multimodal imaging analysis to provide complementary evidence for brain changes at the level of networks. In summary, our study shows the complex relationship between microstructural adaptations and functional connectivity, unveiling the potential of multisensory integration within immersive VR training. These findings have implications for learning and rehabilitation strategies, facilitating more effective interventions within virtual environments., Competing Interests: Declaration of competing interest The authors report no relevant financial or non-financial conflicts in relation to this study., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALE extra ) epitopes, intracellular (ALE intra ) epitopes, anti-glutamic acid decarboxylase65 ALE (ALE GAD65 ), and ALE without detectable antibodies (ALE abneg ). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALE extra , 12 ALE intra , 28 ALE-GAD65, 37 ALE abneg ) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer's disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice. While ALE intra exhibited features of neuro-inflammation, ALE extra displayed features of neuro-inflammation as well as neuro-degeneration. Moreover, ALE GAD65 and ALE abneg lacked hallmarks of inflammation. This may explain the low efficacy of anti-inflammatory treatment regimens in ALE GAD65 and presumably also ALE abneg ., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [NMel has received honoraria for lecturing and travel expenses for attending meetings from Biogen Idec, GlaxoSmith Kline, Teva, Novartis Pharma, Bayer Healthcare, Genzyme, Alexion Pharmaceuticals, Fresenius Medical Care, Diamed, UCB Pharma, AngeliniPharma, BIAL and Sanofi-Aventis, has received royalties for consulting from UCB Pharma, Alexion Pharmaceuticals and Sanofi-Aventis and has received financial research support from Euroimmun, Fresenius Medical Care, Diamed, Alexion Pharmaceuticals, and Novartis Pharma. SR received travel grants from Merck Healthcare Germany GmbH, Bristol Myers Squibb, and Alexion Pharmaceuticals. She served on a scientific advisory board from Merck Healthcare Germany GmbH and received honoraria for lecturing from Roche. Her research was supported by Novartis, &lsquo;Stiftung zur F&ouml;rderung junger Neurowissenschaftler&lsquo;, and &#x0201A;Else Kr&ouml;ner-Fresenius-Stiftung&lsquo;. SGM receives honoraria for lecturing, and travel expenses for attending meetings from Academy 2, Argenx, Alexion, Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, BioNtech, BMS, Celgene, Datamed, Demecan, Desitin, Diamed, Diaplan, DIU Dresden, DPmed, Gen Medicine and Healthcare products, Genzyme, Hexal AG, IGES, Impulze GmbH, Janssen Cilag, KW Medipoint, MedDay Pharmaceuticals, Merck Serono, MICE, Mylan, Neuraxpharm, Neuropoint, Novartis, Novo Nordisk, ONO Pharma, Oxford PharmaGenesis, QuintilesIMS, Roche, Sanofi-Aventis, Springer Medizin Verlag, STADA, Chugai Pharma, Teva, UCB, Viatris, Wings for Life international and Xcenda. His research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut f&uuml;r Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Else Kr&ouml;ner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, DGM e.v., Fresenius Medical Care, Genzyme, Gesellschaft von Freunden und F&ouml;rderern der Heinrich-Heine-Universit&auml;t D&uuml;sseldorf e.V., HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. SK has received research funding from Biogen and speaker honoraria from UCB, Jazz Pharmaceutical and Eisai.]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of sexually transmitted infections (STI) continues to increase worldwide. Patient incentives are one proposed intervention to increase STI testing and treatment., Methods: We conducted a retrospective cohort study comparing incentivized versus routine care for STI outreach test and treat services between October 2018 and June 2019. Incentivized care included a $10 gift card for testing visits and an additional $10 gift card for results and/or treatment visits. Incentivized visits were offered to clients with a lack of housing, who were difficult to locate, or had a history of being lost to follow-up. All test and treatment visits included chlamydia, gonorrhea, syphilis, and HIV testing and/or treatment by Registered Nurses and outreach workers from an STI Clinic. Outreach visits were offered at subsidized housing locations, community-based organizations, and street outreach., Results: From October 2018 to June 2019, 2384 outreach clients were reached: 453 (19.0%) received incentives and 1931 (81.0%) received routine care. There were no significant differences in case-finding rates for chlamydia (4.8%), gonorrhea (2.9%), and HIV (0.1%); however, there was for syphilis (3.8% for incentivized vs. 1.9% for routine visits; P = 0.02). All newly diagnosed infections identified in the incentivized group received treatment compared with routine visits (chlamydia 100% vs 79.1%, P = 0.008, gonorrhea 100% vs 59.7%, P = 0.002, and syphilis 100% vs. 86.7%, P = 0.08)., Conclusions: Incentives were associated with increased case-finding rates of syphilis and were associated with 100% treatment rates. Incentives are a promising approach to decreasing the burden of STI among outreach populations., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)