Which clinical trial designs and statistical approaches have been used in assessments of orphan maintenance by the European Medicines Agency between 2012 and 2022? A cross-sectional study.

Objectives: In the European Union, a new orphan medicinal product must demonstrate 'significant benefit' over approved medicinal products targeting the same indication. To demonstrate a significant benefit, comparisons between the new product and the already approved medicinal products-either directly by a head-to-head comparison within a clinical trial or indirectly as a cross-trial comparison-are necessary. In this study, we investigate the types of trial designs and statistical approaches used for demonstrating a significant benefit of a new orphan medicinal product against approved comparators used between 2012 and 2022.

Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation.

Background: The conversion of primary bile acids to secondary bile acids by the gut microbiota has been implicated in colonic inflammation. This study investigated the role of gut microbiota related bile acid metabolism in colonic inflammation in both patients with inflammatory bowel disease (IBD) and a murine model of dextran sulfate sodium (DSS)-induced colitis.

Methods: Bile acids in fecal samples from patients with IBD and DSS-induced colitis mice, with and without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS).

Radiation exposure during cardiac interventions in CHD: German Registry 2012-2020.

Background: Since patients with congenital heart defects (CHD) frequently require life-long medical care and repeat invasive treatment, radiation exposure during interventional procedures is a relevant issue concerning potential radiation related risks. Therefore, an analysis on radiation data from the German Registry for Cardiac Operations and Interventions in patients with CHD was performed.

Methods: From January 2012 until December 2020 a total of 28,374 cardiac catheter interventions were recorded.

Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields.

Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)).

Characterization of Thin Polymer Layer Prepared from Liposomes and Polyelectrolytes for TGF-β Release in Tissue Engineering.

Implant-integrated drug delivery systems that enable the release of biologically active factors can be part of an in situ tissue engineering approach to restore biological function. Implants can be functionalized with drug-loaded nanoparticles through a layer-by-layer assembly. Such coatings can release biologically active levels of growth factors.

Machine learning-based blood pressure estimation using impedance cardiography data.

Objective: Accurate blood pressure (BP) measurement is crucial for the diagnosis, risk assessment, treatment decision-making, and monitoring of cardiovascular diseases. Unfortunately, cuff-based BP measurements suffer from inaccuracies and discomfort. This study is the first to access the feasibility of machine learning-based BP estimation using impedance cardiography (ICG) data.

Investigating Ultrafiltration Membranes and Operation Modes for Improved Lentiviral Vector Processing.

The demand for lentiviral vectors (LVs) as tools for ex vivo gene therapies is ever-increasing. Despite their promising applications, challenges in LV production remain largely due to the fragile envelope, which challenges the maintenance of vector stability. Thus, downstream processing optimization to enhance efficiency, yield, and product quality is necessary.

Microplastic Materials for Inhalation Studies: Preparation by Solvent Precipitation and Comprehensive Characterization.

Assessing the inhalation hazard of microplastics is important but necessitates sufficient quantity of microplastics that are representative and respirable (<4 µm). Common plastics are not typically manufactured in such small sizes. Here, solvent precipitation is used to produce respirable test materials from thermoplastics polyurethane (TPU), polyamide (PA-6), polyethylene terephthalate (PET), and low-density polyethylene (LDPE).

Uncovering the genetic basis of antiviral polyketide limocrocin biosynthesis through heterologous expression.

Background: Streptomyces roseochromogenes NRRL 3504 produces clorobiocin, an aminocoumarin antibiotic that inhibits DNA replication. No other natural products have been isolated from this bacterium so far, despite the presence of a rich repertoire of specialized metabolite biosynthesis gene clusters (smBGCs) within its genome. Heterologous expression of smBGCs in suitable chassis speeds up the discovery of the natural products hidden behind these sets of genes.

Depletion of alloreactive B cells by drug-resistant chimeric alloantigen receptor T cells to prevent transplant rejection.

Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.

C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis.

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients.

Neural processing of auditory stimuli in rats: Translational aspects using auditory oddball paradigms.

Background: The three-class oddball paradigm allows to investigate the processing of behaviorally relevant and irrelevant auditory stimuli. In humans, event-related potentials (ERPs) are used as neural correlate of behavior. We recorded local field potentials (LFPs) within the medial prefrontal cortex (mPFC) in rats during three-class and passive two-class oddball paradigms and analyzed the ERPs focusing on similarities to human recordings.

Genetic parameters and single-step genome-wide association analysis for trematode (Fasciola hepatica and Calicophoron/Paramphistomum spp.) infections in German dairy cows.

Infections with the liver fluke (Fasciola hepatica) cause economic losses in cattle production worldwide. Also, infections with rumen flukes (Calicophoron/Paramphistomum spp.) are gaining importance in grazing cattle in Europe.

Pelvic packing - status 2024.

Patients with unstable hemodynamics and unstable pelvic ring injuries are still demanding patients regarding initial treatment and survival. Several concepts were reported during the last 30 years. Mechanical stabilization of the pelvis together with hemorrhage control offer the best treatment option in these patients.

Exploring Dietary- and Disease-Related Influences on Flatulence and Fecal Odor Perception in Inflammatory Bowel Disease.

: Inflammatory bowel disease (IBD) affects gastrointestinal function and may alter fecal and flatulence odor (intestinal odor) due to changes in inflammation, the gut microbiome, and metabolism. Investigating the relationship between dietary habits and intestinal odor in IBD is critical given the relationship between diet, gut health, and microbiome diversity. : We performed a cohort analysis of a monocentric, cross-sectional study at a tertiary referral center and compared the perception of fecal and flatulence odor in 233 IBD patients (n = 117 women) with that of 96 healthy controls (HCs) (n = 67 women).

Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.

Respiratory viral infections continue to cause pandemic and epidemic outbreaks in humans and animals. Under steady-state conditions, alveolar macrophages (AlvMϕ) fulfill a multitude of tasks in order to maintain tissue homeostasis. Due to their anatomic localization within the deep lung, AlvMϕ are prone to detect and react to inhaled viruses and thus play a role in the early pathogenesis of several respiratory viral infections.

Prolonged Hypoxia in Rat Living Myocardial Slices Affects Function, Expression, and Structure.

Ischemic heart disease is the leading cause of death worldwide. Reduced oxygen supply and myocardial hypoxia lead to tissue damage and impairment of the heart function. To the best of our knowledge, the primary functional effects of hypoxia in the multicellular model of living myocardial slices (LMSs) have not been investigated so far.

A Design of Experiments Approach to the Radical-Induced Oxidation of Dimeric C4-C8 Linked B-Type Procyanidins.

This study systematically investigated the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical induced oxidation of all dimeric C4-C8 linked B-type procyanidins (PCs) B1-B4 to maximise the formation of the oxidation products using a Design of Experiments (DoE) approach. The C4-C8 linked B1 and B2 formed the A1 () and A2 () (/ 575 [M-H]) with an ether bridge between C2u-O-C7t as expected. Interestingly, the oxidation of the C4-C8 linked dimers B3 and B4 yielded for each two main oxidation products with / 575 [M-H].

Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis.

Background And Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for treatment of compensated chronic hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.

Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a European retrospective multicenter real-life study (SAVE-D). Patient characteristics before and during BLV treatment were collected.

Tissue concepts: Supervised foundation models in computational pathology.

Due to the increasing workload of pathologists, the need for automation to support diagnostic tasks and quantitative biomarker evaluation is becoming more and more apparent. Foundation models have the potential to improve generalizability within and across centers and serve as starting points for data efficient development of specialized yet robust AI models. However, the training of foundation models themselves is usually very expensive in terms of data, computation, and time.

infection accelerates postnatal maturation of the intestinal epithelium.

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.