From extraction to end-uses and waste management: Modeling economy-wide material cycles and stock dynamics around the world.

Material stocks of infrastructure, buildings, and machinery are the biophysical basis of production and consumption. They are a crucial lever for resource efficiency and a sustainable circular economy. While material stock research has proliferated over the last years, most studies investigated specific materials or end-uses, usually not embedded into an economy-wide perspective.

Therapeutic Drug Monitoring of Long-Acting Rilpivirine and Cabotegravir for Treatment of HIV-1 Infection-A Case Series of Five Patients With One Virologic Failure After Development of Two-Class Resistance.

Virologic failure of long-acting rilpivirine/cabotegravir is rare but may result in severely limited treatment options. Known risk factors cannot predict all cases. Therapeutic drug monitoring (TDM) may help identify patients at risk, but reliable thresholds are missing.

Challenges in the analysis of pharmaceutical lentiviral vector products by orthogonal and complementary physical (nano)particle characterization techniques.

Lentiviral vectors (LVVs) are used as a starting material to generate chimeric antigen receptor (CAR) T cells. Therefore, LVVs need to be carefully analyzed to ensure safety, quality, and potency of the final product. We evaluated orthogonal and complementary analytical techniques for their suitability to characterize particulate matter (impurities and LVVs) in pharmaceutical LVV materials at development stage derived from suspension and adherent manufacturing processes.

Epirubicin for the Treatment of Sepsis and Septic Shock (EPOS-1): study protocol for a randomised, placebo-controlled phase IIa dose-escalation trial.

Introduction: Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial.

Evaluation of an English language phoneme-based imagined speech brain computer interface with low-cost electroencephalography.

Introduction: Paralyzed and physically impaired patients face communication difficulties, even when they are mentally coherent and aware. Electroencephalographic (EEG) brain-computer interfaces (BCIs) offer a potential communication method for these people without invasive surgery or physical device controls.

Methods: Although virtual keyboard protocols are well documented in EEG BCI paradigms, these implementations are visually taxing and fatiguing.

Pilotins are mobile T3SS components involved in assembly and substrate specificity of the bacterial type III secretion system.

In animal pathogens, assembly of the type III secretion system injectisome requires the presence of so-called pilotins, small lipoproteins that assist the formation of the secretin ring in the outer membrane. Using a combination of functional assays, interaction studies, proteomics, and live-cell microscopy, we determined the contribution of the pilotin to the assembly, function, and substrate selectivity of the T3SS and identified potential new downstream roles of pilotin proteins. In absence of its pilotin SctG, Yersinia enterocolitica forms few, largely polar injectisome sorting platforms and needles.

Cytosolic sorting platform complexes shuttle type III secretion system effectors to the injectisome in Yersinia enterocolitica.

Bacteria use type III secretion injectisomes to inject effector proteins into eukaryotic target cells. Recruitment of effectors to the machinery and the resulting export hierarchy involve the sorting platform. These conserved proteins form pod structures at the cytosolic interface of the injectisome but are also mobile in the cytosol.

Current and Expected Trends for the Marine Chitin/Chitosan and Collagen Value Chains.

Chitin/chitosan and collagen are two of the most important bioactive compounds, with applications in the pharmaceutical, veterinary, nutraceutical, cosmetic, biomaterials, and other industries. When extracted from non-edible parts of fish and shellfish, by-catches, and invasive species, their use contributes to a more sustainable and circular economy. The present article reviews the scientific knowledge and publication trends along the marine chitin/chitosan and collagen value chains and assesses how researchers, industry players, and end-users can bridge the gap between scientific understanding and industrial applications.

Genome length determination in adeno-associated virus vectors with mass photometry.

Recombinant adeno-associated viruses (rAAVs) are attractive therapeutic viral vectors for gene delivery. To ensure the efficacy and safety of rAAV-based therapies, comprehensive characterization of the adeno-associated virus (AAV) capsids is essential. Mass photometry (MP) provides the advantage of short analysis times, low sample consumption, and high accuracy of molecular mass determination.

Three-Dimensional Homodyne Light Detection (3D-HLD) for High-Throughput Submicron Particle Analysis in (Highly Concentrated) Protein Biopharmaceuticals, Viral Vectors, and LNPs.

During biopharmaceutical development, particle monitoring and characterization are crucial. Notably, particles can be impurities considered as critical quality attribute, or active pharmaceutical ingredient (e.g.

Macrocephaly and developmental delay caused by missense variants in RAB5C.

Rab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C.

HbA1c as a shared treatment goal in type 2 diabetes? A secondary analysis of the DEBATE trial.

Background: Type 2 diabetes mellitus (T2DM) is a major health problem in the western world. Despite a widespread implementation of integrated care programs there are still patients with poorly controlled T2DM. Shared goal setting within the process of Shared Decision Making (SDM) may increase patient's compliance and adherence to treatment regimen.

Imaging Flow Cytometry for Sizing and Counting of Subvisible Particles in Biotherapeutics.

Imaging flow cytometry (IFC), a technique originally designed for cellular imaging, is featured by the parallel acquisition in brightfield (BF), fluorescence (FL), and side scattering channels. Introduced to the field of subvisible particle analysis in biopharmaceuticals roughly ten years ago, it has the potential to yield additional information, e.g.

Combining Machine Learning and Backgrounded Membrane Imaging: A Case Study in Comparing and Classifying Different Types of Biopharmaceutically Relevant Particles.

This study investigates how backgrounded membrane imaging (BMI) can be used in combination with convolutional neural networks (CNNs) in order to quantitatively and qualitatively study subvisible particles in both protein biopharmaceuticals and samples containing synthetic model particles. BMI requires low sample volumes and avoids many technical complications associated with imaging particles in solution, e.g.

Particles in Biopharmaceutical Formulations, Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins, Viruses, Vaccines and Cells.

Particles in biopharmaceutical formulations remain a hot topic in drug product development. With new product classes emerging it is crucial to discriminate particulate active pharmaceutical ingredients from particulate impurities. Technical improvements, new analytical developments and emerging tools (e.

In vitro culture of freshly isolated Trypanosoma brucei brucei bloodstream forms results in gene copy-number changes.

Most researchers who study unicellular eukaryotes work with an extremely limited number of laboratory-adapted isolates that were obtained from the field decades ago, but the effects of passage in laboratory rodents, and adaptation to in vitro culture, have been little studied. For example, the vast majority of studies of Trypanosoma brucei biology have concentrated on just two strains, Lister 427 and EATRO1125, which were taken from the field over half a century ago and have since have undergone innumerable passages in rodents and culture. We here describe two new Trypanosoma brucei brucei strains.

Comparison of Syringes With Intravitreal Anti-VEGF Drugs: Particle Burden and Protein Aggregates in Brolucizumab, Aflibercept and Bevacizumab.

Purpose: In a benchwork particle counting analytical evaluation, the number and type of particles in intravitreal injection formulations of three different agents against vascular endothelial growth factor were investigated.

Methods: Commercially available ready-to-use aflibercept and brolucizumab glass syringes, vials containing bevacizumab (off-label use in ophthalmology), and repackaged ready-to-use plastic syringes containing bevacizumab were tested without filtration. Total visible, subvisible, and nanoparticles numbers and size distributions were quantified using light obscuration, flow imaging, resonant mass measurement (RMM), tunable resistive pulse sensing, and dynamic light scattering.

Shared decision making and patient-centeredness for patients with poorly controlled type 2 diabetes mellitus in primary care-results of the cluster-randomised controlled DEBATE trial.

Background: We investigate whether an educational intervention of GPs increases patient-centeredness and perceived shared decision making in the treatment of patients with poorly controlled type 2 diabetes mellitus?

Methods: We performed a cluster-randomized controlled trial in German primary care. Patients with type 2 diabetes mellitus defined as HbA1c levels ≥ 8.0% (64 mmol/mol) at the time of recruitment (n = 833) from general practitioners (n = 108) were included.

Patterns and Facilitators for the Promotion of Glaucoma Medication Adherence-A Qualitative Study.

Primary open-angle glaucoma (POAG) is a chronic optic neuropathy causing irreversible nerve fiber damage. Initially asymptomatic, it progresses slowly without any notable sign of vision loss, thus early detection and treatment is essential. The standard treatment being non-invasive topical administration of eye drops harbors the problem of patients not being adherent.

Insights into the functions and RNA binding of ZC3H22, RBP9 and DRBD7.

Trypanosoma brucei is unusually reliant on mRNA-binding proteins to control mRNA fate, because its protein-coding genes lack individual promoters. We here focus on three trypanosome RNA-binding proteins. ZC3H22 is specific to Tsetse fly forms, RBP9 is preferentially expressed in bloodstream forms; and DRBD7 is constitutively expressed.

Treatment Complexity in Primary Open-Angle Glaucoma (POAG): Perspectives on Patient Selection in Micro-Invasive Glaucoma Surgery (MIGS) Using Stents.

Background: Primary open-angle glaucoma (POAG) is still one of the most common causes of impaired vision worldwide, despite the further development of therapy options, and can lead to blindness. Micro-invasive glaucoma surgery (MIGS) using stents aims at reducing intraocular pressure (IOP), as it is the main risk factor. With regard to adherence and adverse drug reactions it also aims at reducing the drug burden on patients.

Hospitalization for Acute Respiratory Tract Infection in a Low-Antibiotic-Prescribing Setting: Cross-Sectional Data from General Practice.

Background: Acute respiratory tract infections (ARTI) are the main cause of inappropriate antibiotic prescribing. To date, there is limited evidence concerning whether low levels of antibiotic prescribing may impact patient safety. We investigate whether antibiotic prescribing for patients seeking primary care for ARTI correlates with the odds for hospitalization.

Global Metal Use Targets in Line with Climate Goals.

Metals underpin essential functions in modern society, yet their production currently intensifies climate change. This paper develops global targets for metal flows, stocks, and use intensity in the global economy out to 2100. These targets are consistent with emissions pathways to achieve a 2 °C climate goal and cover six major metals (iron, aluminum, copper, zinc, lead, and nickel).

The IL-33-induced p38-/JNK1/2-TNFα axis is antagonized by activation of β-adrenergic-receptors in dendritic cells.

IL-33, an IL-1 cytokine superfamily member, induces the activation of the canonical NF-κB signaling, and of Mitogen Activated Protein Kinases (MAPKs). In dendritic cells (DCs) IL-33 induces the production of IL-6, IL-13 and TNFα. Thereby, the production of IL-6 depends on RelA whereas the production of IL-13 depends on the p38-MK2/3 signaling module.