Mutations in tumor suppressor genes Vhl and Rassf1a cause DNA damage, chromosomal instability and induce gene expression changes characteristic of clear cell renal cell carcinoma.

RASSF1A is frequently biallelically inactivated in clear cell renal cell carcinoma (ccRCC) due to loss of chromosome 3p and promoter hypermethylation. Here we investigated the cellular and molecular consequences of single and combined deletion of the Rassf1a and Vhl tumor suppressor genes to model the common ccRCC genotype of combined loss of function of RASSF1A and VHL. In mouse embryonic fibroblasts and in primary kidney epithelial cells, double deletion of Rassf1a and Vhl caused chromosomal segregation defects and increased formation of micronuclei, demonstrating that pVHL and RASSF1A function to maintain genomic integrity.

Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries.

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet.

Oral health care pathways for patients with epidermolysis bullosa: A position statement from the European reference network for rare skin diseases.

Background: Inherited epidermolysis bullosa (EB) comprises a group of genetic disorders characterized by skin fragility and unique oral features. It requires interdisciplinary care from several health professionals, including oral health teams. Modern dentistry encompasses a wide range of therapeutic options performed by specialists from different fields.

Alterations in the microenvironment of junctional epidermolysis bullosa keratinocytes: a gene expression study.

Integrin α6β4 subunits and type XVII collagen are critical transmembrane proteins involved in cell-matrix adhesion in skin, while laminin 332 serves as their ligand in the basement membrane zone (BMZ). Those proteins contribute to the composition of hemidesmosomes (HDs) and pathogenic variants in their corresponding genes cause junctional epidermolysis bullosa (JEB). Although the genotype-phenotype relationships in JEB have been extensively studied, the pathogenetic changes of extracellular matrix (ECM) and cell-matrix adhesion resulting from gene mutations remain unclear.

Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study.

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses.

Enhancing patient activation: a controlled implementation study of an interprofessional evidence-based counseling program for complementary and integrative healthcare in cancer patients ('CCC-Integrativ').

Complementary and integrative healthcare (CIH) is increasingly recognized as a valuable approach to empowering and activating cancer patients. Studies have shown that higher patient activation is positively associated with improved health outcomes and reduced healthcare costs. The CCC-Integrativ study aimed to assess the implementation of an evidence-based counseling service on CIH at four Comprehensive Cancer Centers (CCC) in Germany.

Spontaneous brain abscess formation: challenge of a shifting pathogen spectrum over the last 21 years - a single center experience.

Background: Spontaneous intracerebral abscess formation is a rare condition presenting with a disabling sequela. The origin of infection can either be primary or secondary to an infection at another location. The site of primary infection - due to the proximity, often the oral cavity, the sinuses, and the orbit - determines the causative pathogens.

The value of self-reported variables in epilepsy monitoring and management. A systematic scoping review.

Purpose: Self-reported records of seizure occurrences, seizure triggers and prodromal symptoms via paper or electronic tools are essential components of epilepsy management. Despite recent studies indicating that this information could hold important clinical value, the adoption of self-reported information in clinical practice is inconsistent and of uncertain value.

Methods: We performed a systematic scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

User-Centered Evaluation of the Wearable Walker Lower Limb Exoskeleton; Preliminary Assessment Based on the Experience Protocol.

Using lower limb exoskeletons provides potential advantages in terms of productivity and safety associated with reduced stress. However, complex issues in human-robot interactions are still open, such as the physiological effects of exoskeletons and the impact on the user's subjective experience. In this work, an innovative exoskeleton, the , is assessed using the EXPERIENCE benchmarking protocol from the EUROBENCH project.

In Which Patients Do the 2023 Duke-ISCVID Criteria for Infective Endocarditis Increase the Diagnosis of "Definite Endocarditis"?-A Preliminary Analysis in the Prospectively Evaluated DERIVE Cohort.

Recently, an update of the Duke criteria for the diagnosis of infectious endocarditis has been published: the 2023 Duke-ISCVID criteria. To gain an insight into which proportion of patients are affected by the new criteria, and which criteria might be the most relevant for the expected increase in sensitivity, we analysed data from a registry of cardiovascular infections. The 2023 Duke-ISCVID criteria were applied to patients who were diagnosed with and treated for endocarditis after having been classified as "possible" endocarditis according to the 2015 ESC Modified Duke criteria.

Costs of Health Registries: An Exploration for Health Services Research.

Health registries are an established methodology in health services research. Regarded as cheap bidder for observation studies in earlier times, many registries now benefit from an appropriate funding. However, reference figures for costs of registries in health services research are missing.

Ascending Geometry After Thoracic Endovascular Aortic Repair for Descending Aortic Dissection.

Background: This study aimed to assess geometry changes of the ascending aorta after thoracic endovascular aortic repair (TEVAR) for descending aortic dissection and identify potential risk factors for diameter and length change.

Methods: Between April 2009 and July 2021, 102 patients were treated for acute descending aortic dissections (type B and non-A non-B) with TEVAR and were included in this analysis. Computed tomography angiographic scans were transferred to a dedicated imaging software and detailed aortic measurements (including length, diameter and area) were taken in multiplanar reconstruction postoperatively, after 6 months and annually thereafter.

Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study.

Objectives: Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences.

Methods: We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT).

Results: The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.

subsp. RadD binds Siglec-7 and inhibits NK cell-mediated cancer cell killing.

is an oral commensal bacterium that can colonize extraoral tumor entities, such as colorectal cancer and breast cancer. Recent studies revealed its ability to modulate the immune response in the tumor microenvironment (TME), promoting cancer progression and metastasis. Importantly, subsp.

MRI-based adrenal gland volume is associated with cardiovascular alterations in individuals without prior cardiovascular disease.

Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic-pituitary-adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular disease underwent a whole-body MRI.

Subacute Degeneration of Fibers After Vertical Parasagittal Hemispherotomy.

Purpose: After vertical parasagittal hemispherotomy a restricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective cohort study analyses the anatomic site and the time course of the diffusion restriction after vertical parasagittal hemispherotomy.

Methods: Fifty-nine patients were included into this study, all of them having had one pre-operative and at least one post-operative MRI, including diffusion imaging at b‑values of 0 and 1000 s/mm with a calculated ADC.

Associations of Urine and Plasma Metabolites With Kidney Failure and Death in a Chronic Kidney Disease Cohort.

Rationale & Objective: Biomarkers that enable better identification of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease.

Study Design: Prospective metabolome-wide association study.

Recommended data elements for health registries: a survey from a German funding initiative.

Background: The selection of data elements is a decisive task within the development of a health registry. Having the right metadata is crucial for answering the particular research questions. Furthermore, the set of data elements determines the registries' readiness of interoperability and data reusability to a major extent.

Joint recommendations on cost calculation and estimation in paediatric clinical trials.

The conduct of clinical trials in paediatrics is essential to improve drug therapy in children. In Europe, paediatric clinical trials have been supported by the European Paediatric Regulation since 2007, but there is still a great need for high-quality clinical trials. The personnel and time required to conduct clinical trials in accordance with EU Regulations 536/2014 and 745/2017 is considerably higher compared to other studies, such as observational studies.