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Multi-organ autoimmunity belongs to a group of ultrarare diseases characterized by complex autoimmune or autoinflammatory processes affecting multiple organs. In addition to adequate medical care for patients with multi-organ autoimmunity, the understanding of patients' treatment preferences and the measurement of their health-related quality of life are essential for improving therapy for these patients. This study has three goals: (1) to compile a modular questionnaire package using established instruments to assess health-related quality of life and health status; (2) to develop, through a participatory process, and conduct psychometric testing of a new self-report questionnaire assessing patients' treatment preferences; and (3) to evaluate quality of life and patients' preferences in a longitudinal study. To address our goals, we are conducting a mixed methods study involving 300 adult patients undergoing treatment for multi-organ autoimmune diseases; the study includes qualitative interviews with patients and their physicians and a quantitative longitudinal study with 4 measurement time points (at study enrollment and at 3, 6, and 9 months later). We will address our first goal by conducting psychometric analyses to assess the applicability of the modularized questionnaire package to our target population. We will determine item characteristics and conduct exploratory factor analyses and internal consistency analyses with the scales used to assess generic and disease-specific quality of life, as well as disease-specific health status. To address our second goal, we will conduct (1) qualitative interviews with patients and their physicians to explore the preferences of our target population, (2) a 2-round Delphi study to select preferences that are highly relevant to most patients, (3) cognitive pretests to ensure the acceptability and comprehensibility of the scale items and instructions, and (4) psychometric analyses to guide item selection and evaluate the reliability and validity of the final scales. This paper describes the protocol for the longitudinal cohort study of the research project Qualy-GAIN (German Multi-Organ Auto-Immunity Network), which was funded from January 2023 to December 2025. Data were collected at 4 measurement points from July 2024 to June 2025. First results are expected to be submitted for publication in spring 2026. A result of this study will be a package of questionnaires that can be used to assess health-related quality of life, disease-specific health status, and treatment preferences. Due to the voluntary nature of participation and the low burden associated with participation, we believe that the benefits of the study outweigh potential risks. In case the questionnaires evaluated in this study prove to be reliable, valid, and useful in practice, they can be transferred to the routine treatment of patients with multi-organ autoimmune diseases to improve treatment and promote patient-centered care.

Response cost and token approach (RCT) within the scope of a summer camp training is an effective treatment program for attention deficit hyperactivity disorder (ADHD). It is likely that intensive RCT training influences networks responsible for ADHD symptoms. Functional magnetic resonance imaging (fMRI) was carried out in 12 children with ADHD before and after the RCT program and in 12 healthy control children twice. For fMRI, a Go/No-go paradigm was used to investigate the influence of RCT training on attention and impulsivity. The No-go condition revealed only weak activation in the dorsal part of the anterior cingulate cortex (ACC), parietal and dorsolateral prefrontal cortex (DLPFC) before the training in children with ADHD compared to healthy children. However, this activation in these brain regions was significantly more pronounced after the training. This increase in hemodynamic response cannot be attributed merely to repetition of the measurement since the effect was not observed in healthy children. The increase in hemodynamic response in the ACC and right DLPFC was significantly associated with a reduction in response time variability and clinical symptoms in ADHD patients. After the RCT training, the children with ADHD demonstrated more pronounced activation of cortical structures which are typically related to response monitoring and self-control. It seems likely that children with ADHD learned more cognitive control in a continuous performance task as was revealed by both neuropsychological outcome and fMRI.

Purpose Patients with rare diseases often undergo a long diagnostic odyssey. However, there is little empirical evidence on the cost incurred during the diagnostic pathway for patients with suspected rare diseases. This study provides a comprehensive analysis of healthcare costs and utilization during the diagnostic pathway for a heterogeneous sample of patients with suspected rare diseases but unclear diagnosis. Methods Using claims data from five German statutory health insurance organizations for the years 2014–2019, we analyzed costs and healthcare utilization of 1,243 patients (aged 0 to 82 years) with suspected rare diseases referred to a rare disease center. A control cohort was assigned using 1:75 exact matching on age, sex and place of residence. Results In the years prior to referral to an expert center, healthcare utilization of patients with suspected rare diseases was, on average, substantially and significantly higher compared to a matched control cohort during the same observation period – e.g. in terms of the number of hospitalizations (3.1 (95%CI: 2.9–3.4) vs. 0.5 (95%CI: 0.5–0.5)), different diagnoses (50.0 (95%CI: 48.1–51.9) vs. 26.4 (95%CI: 26.2–26.5)), different active substances prescribed (12.7 (95%CI: 12.2–13.3) vs. 8.2 (95%CI: 8.2–8.3)) and the number of genetic tests (14.7 (95%CI: 12.6–16.7) vs. 0.3 (95%CI: 0.3–0.3)). We found evidence of heterogeneity in utilization by age and sex. On average, direct costs (inpatient, outpatient and prescription drug costs) of patients with suspected rare diseases during the diagnostic pathway were 7.6-fold higher than the costs of matched controls (€26,999 (95%CI: €23,751 − 30,247) vs. €3,561 (95% CI: € 3,455-3,667)). Inpatient costs were the main cost component, accounting for 62.5% of total costs. Conclusions The diagnostic odyssey of patients with suspected rare diseases is associated with extensive healthcare utilization and high cost. Against this background, new ways to shorten the diagnostic journey have a high potential to decrease the financial burden related to rare diseases.

This article examines the way in which the future of Europe is imagined in European cinema, especially in European speculative fiction and science fiction. The first part of this article discusses the dynamics and parameters within which European science fiction and European science fiction cinema navigate when they imagine the future face of Europe and the construction of pan-European identities. The second part of the article focuses on one example as a case study of cultural transfer to illustrate these processes: Damir Lukačević's film Transfer (2010, Germany), an adaptation of Mil euros por tu vida (2003), a short story by the Spanish science fiction writer Elia Barceló. The discussion pays attention to the cultural translation process from literature to film, from a Spanish to a German context, and to the changing image of the future. In drawing on other examples from contemporary European science fiction cinema for comparison, the analysis shows that both texts align with a wider European discourse on migration and race and, more specifically, are examples of a European imaginary that envision the future of Europe as shaped by Europe's colonial past, persistent racism, and continuing exploitation of the Global South.

While scholars recognize both museums and films as sites where historical knowledge and cultural memory are created, the convergence between their methods of constructing the past has only recently been acknowledged. The essays in Exhibiting the German Past examine a range of films, museums, and experiences which blend the two, considering how authentic objects and cinematic techniques are increasingly used in similar ways by both visual media and museums. This is the first collection to focus on the museum–film connection in German-language culture and the first to approach the issue using the concept of “musealization,” a process that, because it engages the cultural destruction wrought by modernization, offers new means of constructing historical knowledge and shaping collective memory within and beyond the museum’s walls. Featuring a wide range of valuable case studies, Exhibiting the German Past offers a unique perspective on the developing relationship between museums and visual media.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs) 1 , 2 , conferring a predisposition to life-threatening COVID-19 pneumonia 3 . Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52 LOF /IκBδ GOF ). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52 LOF /IκBδ LOF ) or gain-of-function of p52 (hereafter, p52 GOF /IκBδ LOF ). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases. Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

EGFP oligomers are convenient standards for experiments on fluorescent protein-tagged biomolecules. In this study, we characterized their hydrodynamic and fluorescence properties. Diffusion coefficients D of EGFP 1–4 were determined by analytical ultracentrifugation with fluorescence detection and by fluorescence correlation spectroscopy (FCS), yielding 83.4…48.2 μm 2 /s and 97.3…54.8 μm 2 /s from monomer to tetramer. A “barrels standing in a row” model agreed best with the sedimentation data. Oligomerization red-shifted EGFP emission spectra without any shift in absorption. Fluorescence anisotropy decreased, indicating homoFRET between the subunits. Fluorescence lifetime decreased only slightly (4%) indicating insignificant quenching by FRET to subunits in non-emitting states. FCS-measured D, particle number and molecular brightness depended on dark states and light-induced processes in distinct subunits, resulting in a dependence on illumination power different for monomers and oligomers. Since subunits may be in “on” (bright) or “off” (dark) states, FCS-determined apparent brightness is not proportional to that of the monomer. From its dependence on the number of subunits, the probability of the “on” state for a subunit was determined to be 96% at pH 8 and 77% at pH 6.38, i.e., protonation increases the dark state. These fluorescence properties of EGFP oligomeric standards can assist interpreting results from oligomerized EGFP fusion proteins of biological interest.

Background The Perinatal Center of the University Hospital Carl Gustav Carus Dresden has initiated the telemedical healthcare network “SAFE BIRTH” to coordinate and improve specialized care in non-metropolitan regions for pregnant women and newborns. The network incorporates five intervention bundles (IB): (1) Multi-professional, inter-disciplinary prenatal care plan; (2) Neonatal resuscitation; (3) Neonatal antibiotic stewardship; (4) Inter-facility transfer of premature and sick newborns; (5) Psycho-social support for parents. We evaluate if the network improves care close to home for pregnant women, premature and sick newborns. Methods To evaluate the complex healthcare intervention “SAFE BIRTH” we will conduct a cluster-randomized controlled stepped-wedge trial in five prenatal medical outpatient offices and eight non-metropolitan hospitals in Saxony, Germany. The offices and hospitals will be randomly allocated to five respectively eight sequential steps over a 30-month period to implement the telemedical IB. We define one specific primary process outcome for each IB (for instance IB#1: “ Proportion of patients with inclusion criterion IB#1 who have a prenatal care plan and psychosocial counseling within one week” ). We estimated a separate multilevel logistic regression model for each primary process outcome using the intervention status as a regressor (control or intervention group). Across all IB, a total of 1,541 and 1,417 pregnant women or newborns need to be included in the intervention and control group, respectively, for a power above 80% for small to medium intervention effects for all five hypothesis tests. Additionally, we will assess job satisfaction and sense of safety of health professionals caring for newborns (questionnaire survey) and we will assess families’ satisfaction, resilience, quality of life and depressive, anxiety and stress symptoms (questionnaire surveys). We will also evaluate the cost-effectiveness of ”SAFE BIRTH” (statutory health insurance routine data, process data) and barriers to its implementation (semi-structured interviews). We use multilevel regression models adjusting for relevant confounders (e.g. socioeconomic status, age, place of residence), as well as descriptive analyses and qualitative content analyses. Discussion If the telemedical healthcare network “SAFE BIRTH” proves to be effective and cost-efficient, strategies for its translation into routine care should be developed. Trial registration German clinical trials register. DRKS-ID: DRKS00031482.

Glioblastoma is a highly aggressive brain tumor for which there is no cure. The dire prognosis of this disease is largely attributable to a high level of heterogeneity, including the presence of a subpopulation of tumor‐initiating glioblastoma stem‐like cells (GSCs), which are refractory to chemo‐ and radiotherapy. Here, in an unbiased marine‐derived fungal extract screen, together with bioguided dereplication based on high‐resolution mass spectrometry, we identified malformin C to preferentially induce cell death in patient‐derived GSCs and explore the potential of this cyclic peptide as a therapeutic agent for glioblastoma. Malformin C significantly reduced tumor growth in an in vivo xenograft model of glioblastoma. Using transcriptomics and chemoproteomics, we found that malformin C binds to many proteins, leading to their aggregation, and rapidly induces the unfolded protein response, including autophagy, in GSCs. Crucially, chemical inhibition of translation using cycloheximide rescued malformin C‐induced cell death in GSCs, demonstrating that the proteotoxic effect of the compound is necessary for its cytotoxicity. At the same time, malformin C appears to accumulate in lysosomes, disrupting autophagic flux, and driving cells to death. Supporting this, malformin C synergizes with chloroquine, an inhibitor of autophagy. Strikingly, we observed that autophagic flux is differentially regulated in GSCs compared with normal astrocytes. The sensitivity of GSCs to malformin C highlights the relevance of proteostasis and autophagy as a therapeutic vulnerability in glioblastoma. In a fungal extract screen, malformin C was identified as a compound which selectively kills glioblastoma stem‐like cells while sparing normal cells. Malformin C induces proteotoxic stress and disrupts autophagy, exploiting a vulnerability in glioblastoma stem‐like cells. This discovery highlights the therapeutic potential of malformin C for treating this aggressive brain cancer.