Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.

Targeting the Type I Interferon Pathway in Glomerular Kidney Disease: Rationale and Therapeutic Opportunities.

Type I interferons (IFNs) are immunostimulatory molecules that can activate the innate and adaptive immune systems. In cases of immune dysfunction, prolonged activation of the type I IFN pathway has been correlated with kidney tissue damage in a wide range of kidney disorders, such as lupus nephritis (LN) and focal segmental glomerulosclerosis (FSGS). Genetic mutations, such as risk variants in conjunction with elevated type I IFN expression, are also associated with higher rates of chronic kidney disease in patients with LN and collapsing FSGS.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis.

Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Microcomputed tomographic analysis of the trabecular and cortical architecture of the proximal femur and hip bone of cats and small breed dogs.

This study aims to provide an initial database to gain more detailed knowledge of the trabecular and cortical bone structure of pelvic and femur bones in cats and smaller dogs. Additionally, the bony microarchitecture between cats and smaller dogs was compared to identify possible differences between those species. These findings could potentially improve the development of non-cemented total hip replacement (THR).

Diagnostic Efficacy of Iodo-Metaiodobenzylguanidine SPECT/CT in Cardiac vs. Neurological Diseases: A Comparative Study of Arrhythmogenic Right Ventricular Cardiomyopathy and α-Synucleinopathies.

: Iodo-metaiodobenzylguanidine single photon emission computed tomography/computed tomography (I-MIBG SPECT/CT) is used to evaluate the cardiac sympathetic nervous system in cardiac diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and α-synucleinopathies such as Parkinson's diseases. A common feature of these diseases is denervation. We aimed to compare quantitative and semi-quantitative cardiac sympathetic innervation using I-MIBG imaging of ARVC and α-synucleinopathies.

Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review.

Borna disease, which is a severe encephalitis that primarily affects horses and sheep, has been recognised for over two centuries. Borna disease virus 1 (BoDV-1) has been identified as a cause of a predominantly fatal encephalitis in humans. Little scientific data exist regarding the virus' transmission, entry portal, and excretion routes.

Response of Differently Structured Dental Polymer-Based Composites to Increasingly Aggressive Aging Conditions.

Objective: It is hypothesized that the way nano- and micro-hybrid polymer-based composites are structured and cured impacts the way they respond to aging.

Material And Methods: A polymer-ceramic interpenetrating network composite (Vita Enamic/VE), an industrially polymerized (Brillinat CriosST/BC), and an in situ light-cured composite with discrete inorganic fillers (Admira Fusion5/AF5) were selected. Specimens (308) were either cut from CAD/CAM blocks (VE/BC) or condensed and cured in white polyoxymethylene molds (AF5) and subjected to four different aging conditions ( = 22): (a) 24 h storage in distilled water at 37 °C; (b) 24 h storage in distilled water at 37 °C followed by thermal cycling for 10,000 cycles 5/55 °C (TC); (c) TC followed by storage in a 75% ethanol-water solution; and (d) TC followed by a 3-week demineralization/remineralization cycling.

Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.

Twins with at least one with CHD and their immunisation status in direct comparison-are both twins complying with the German immunisation recommendations?

Background: Patients with congenital heart defects (CHDs) are at higher risk for infectious diseases. This may partly be due to frequent hospital stays and the associated exposure to pathogens. This study aims to provide a comprehensive overview of immunisation coverage among twins in which at least one twin has CHD.

GOLD grade-specific characterization of COPD in the COSYCONET multi-center trial: comparison of semiquantitative MRI and quantitative CT.

Objectives: We hypothesized that semiquantitative visual scoring of lung MRI is suitable for GOLD-grade specific characterization of parenchymal and airway disease in COPD and that MRI scores correlate with quantitative CT (QCT) and pulmonary function test (PFT) parameters.

Methods: Five hundred ninety-eight subjects from the COSYCONET study (median age = 67 (60-72)) at risk for COPD or with GOLD1-4 underwent PFT, same-day paired inspiratory/expiratory CT, and structural and contrast-enhanced MRI. QCT assessed total lung volume (TLV), emphysema, and air trapping by parametric response mapping (PRM, PRM) and airway disease by wall percentage (WP).

Intravitreal Enzyme Replacement Therapy Slows Retinopathy in Late Infantile Ceroid Lipofuscinosis Type 2.

Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.

Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.

Rapid Development of Modified Vaccinia Virus Ankara (MVA)-Based Vaccine Candidates Against Marburg Virus Suitable for Clinical Use in Humans.

Background/objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics.

Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.

The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.

Cellular EMT-status governs contact guidance in an electrospun TACS-mimicking model.

In this study, an advanced nanofiber breast cancer model was developed and systematically characterized including physico-chemical, cell-biological and biophysical parameters. Using electrospinning, the architecture of tumor-associated collagen signatures (TACS5 and TACS6) was mimicked. By employing a rotating cylinder or static plate collector set-up, aligned fibers (TACS5-like structures) and randomly orientated fibers (TACS6-like structures) fibers were produced, respectively.

Conceptual foundations of a REFRAME-based approach to discriminate across total knee implant designs based on the positions of functional centres of rotation.

In modern knee arthroplasty, surgeons increasingly aim for individualised implant selection based on data-driven decisions to improve patient satisfaction rates. The identification of an implant design that optimally fits to a patient's native kinematic patterns and functional requirements could provide a basis towards subject-specific phenotyping. The goal of this study was to achieve a first step towards identifying easily accessible and intuitive features that allow for discrimination between implant designs based on kinematic data.

Successful pregnancy of an SMA type 3 sitter on Nusinersen therapy - a case report.

Background: Due to improved treatment options, more SMA patients reach childbearing age. Currently, limited data on pregnant SMA patients is available, especially in relation to disease-modifying therapies (DMT). This case report helps to elucidate new approaches for future guidelines in the management of pregnancy and SMA.

Perioperative outcomes in an age-adapted analysis of the German StuDoQ|Pancreas registry for PDAC.

Background: Pancreatic ductal adenocarcinoma (PDAC) typically occurs in an older patient population. Yet, early-onset pancreatic cancer (EOPC) has one of the fastest growing incidence rates. This study investigated the influence of age and tumor location on postoperative morbidity and mortality in a large, real-world dataset.

Accelerometry-assessed sleep clusters and obesity in adolescents and young adults: a longitudinal analysis in GINIplus/LISA birth cohorts.

Background: Some studies have revealed various sleep patterns in adolescents and adults using multidimensional objective sleep parameters. However, it remains unknown whether these patterns are consistent from adolescence to young adulthood and how they relate to long-term obesity.

Methods: Seven-day accelerometry was conducted in German Infant Study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development (GINIplus) and Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany (LISA) birth cohorts during the 15-year and 20-year follow-ups, respectively.