SV-AUC as a stability-indicating method for the characterization of mRNA-LNPs.

During the SARS-CoV2 pandemic mRNA vaccines in the form of lipid nanoparticles (LNPs) containing the mRNA, have set the stage for a new area of vaccines. Analytical methods to quantify changes in size and structure of LNPs are crucial, as changes in these parameters could have implications for potency. We investigated the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) as quantitative stability-indicating method to detect structural changes of mRNA-LNP vaccines upon relevant stress factors (freeze/thaw, heat and mechanical stress), in comparison to qualitative dynamic light scattering (DLS) analysis.

Using digital interventions to reduce digitalization-related stress: does it work?

Digitalization entails positive and negative consequences for employees. In a longitudinal, randomized control group design over 14 days ( = 95 participants), we piloted and expected each of three app-based interventions to positively influence general well-being, well-being related to information and communication technology (ICT) and recovery compared to the control group with no intervention. The meditation intervention significantly increased general well-being (satisfaction) and recovery (detachment) compared to the control group but did not reduce general stress.

Is Covid-19 a dread risk? The death toll of the pandemic year 2020 in long-term and transnational perspective.

"Dread risks" are threats that can have catastrophic consequences. To analyse this issue we use excess mortality and corresponding life years lost as simple measures of the severity of pandemic events. As such, they are more robust than figures from models and testing procedures that usually inform public responses.

Utility of Three Flow Imaging Microscopy Instruments for Image Analysis in Evaluating four Types of Subvisible Particle in Biopharmaceuticals.

Subvisible particles (SVPs) are a critical quality attribute of parenteral and ophthalmic products. United States Pharmacopeia recommends the characterizations of SVPs which are classified into intrinsic, extrinsic, and inherent particles. Flow imaging microscopy (FIM) is useful as an orthogonal method in both the quantification and classification of SVPs because FIM instruments provide particle images.

Biopsy Characteristics, Subtypes, and Prognostic Features in 107 Cases of Feline Presumed Immune-Mediated Polyneuropathy.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up.

Computational fluid dynamic simulations of temperature, cryoconcentration, and stress time during large-scale freezing and thawing of monoclonal antibody solutions.

Purpose: Large-scale freezing and thawing experiments of monoclonal antibody (mAb) solutions are time and material consuming. Computational Fluid Dynamic (CFD) modeling of temperature, solute composition as well as the stress time, defined as the time between start of freezing and reaching T' at any point in the container, could be a promising approach to ease and speed up process development.

Methods: Temperature profiles at six positions were recorded during freezing and thawing of a 2L rectangular bottle and compared to CFD simulations via OpenFOAM.

Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity.

The centrosome provides an intracellular anchor for the cytoskeleton, regulating cell division, cell migration, and cilia formation. We used spatial proteomics to elucidate protein interaction networks at the centrosome of human induced pluripotent stem cell-derived neural stem cells (NSCs) and neurons. Centrosome-associated proteins were largely cell type-specific, with protein hubs involved in RNA dynamics.

High-Q collective Mie resonances in monocrystalline silicon nanoantenna arrays for the visible light.

Dielectric optical antennas have emerged as a promising nanophotonic architecture for manipulating the propagation and localization of light. However, the optically induced Mie resonances in an isolated nanoantenna are normally with broad spectra and poor -factors, limiting their performances in sensing, lasing, and nonlinear optics. Here, we dramatically enhance the -factors of Mie resonances in silicon (Si) nanoparticles across the optical band by arranging the nanoparticles in a periodic lattice.

Excessive local host-graft connectivity in aging and amyloid-loaded brain.

Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment on transplant connectivity. To explore the effect of amyloid pathology in Alzheimer's disease (AD) and aging, we examined graft connectivity using monosynaptic rabies virus tracing in APP/PS1 mice and in 16- to 18-month-old wild-type (WT) mice. Transplanted neurons differentiated within 4 weeks and integrated well into the host visual cortex, receiving input from the appropriate brain regions for this area.

Comparative Study of the Role of Interepithelial Mucosal Mast Cells in the Context of Intestinal Adenoma-Carcinoma Progression.

Mast cells (MCs) are crucial players in the relationship between the tumor microenvironment (TME) and cancer cells and have been shown to influence angiogenesis and progression of human colorectal cancer (CRC). However, the role of MCs in the TME is controversially discussed as either pro- or anti-tumorigenic. Genetically engineered mouse models (GEMMs) are the most frequently used in vivo models for human CRC research.

Selective plasticity of callosal neurons in the adult contralesional cortex following murine traumatic brain injury.

Traumatic brain injury (TBI) results in deficits that are often followed by recovery. The contralesional cortex can contribute to this process but how distinct contralesional neurons and circuits respond to injury remains to be determined. To unravel adaptations in the contralesional cortex, we used chronic in vivo two-photon imaging.

Design of freeze-drying cycles: The determination of heat transfer coefficient by using heat flux sensor and MicroFD.

The complexity of biopharmaceuticals requires often the freeze-drying as stabilizing process. Inadequate parameters in the primary drying phase can impair product quality, besides, increasing time and costs. Therefore, the process requires a thorough characterization and with this purpose, heat flux sensor (HFS) and miniaturized freeze-dryers conceived to emulate larger equipment, were recently introduced.

Evaluation and Utility of Submaximal Stimulation Intensity in Transcranial Magnetic Stimulation in the Standing Horse.

Transcranial magnetic stimulation (TMS) has been successfully used in horses to evaluate function and integrity of descending motor pathways in patients affected by neurological gait abnormalities. In preceding studies, lengthening latency times (LT) of cranially evoked limb muscle potentials have been considered a reliable diagnostic parameter. Standardized settings use device output signal intensities of 100%.

A deep learning-based toolbox for Automated Limb Motion Analysis (ALMA) in murine models of neurological disorders.

In neuroscience research, the refined analysis of rodent locomotion is complex and cumbersome, and access to the technique is limited because of the necessity for expensive equipment. In this study, we implemented a new deep learning-based open-source toolbox for Automated Limb Motion Analysis (ALMA) that requires only basic behavioral equipment and an inexpensive camera. The ALMA toolbox enables the consistent and comprehensive analyses of locomotor kinematics and paw placement and can be applied to neurological conditions affecting the brain and spinal cord.

Minor stroke in large vessel occlusion: A matched analysis of patients from the German Stroke Registry-Endovascular Treatment (GSR-ET) and patients from the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR).

Background And Purpose: Reperfusion treatment in patients presenting with large vessel occlusion (LVO) and minor neurological deficits is still a matter of debate. We aimed to compare minor stroke patients treated with endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or IVT alone.

Methods: Patients enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) and the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) between June 2015 and December 2019 were analyzed.

TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation and Neurite Formation by Modulating Calcium Dynamics.

Long noncoding RNAs (lncRNAs) are regulatory molecules which have been traditionally considered as "non-coding". Strikingly, recent evidence has demonstrated that many non-coding regions, including lncRNAs, do in fact contain small-open reading frames that code for small proteins that have been called microproteins. Only a few of them have been characterized so far, but they display key functions in a wide variety of cellular processes.

The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - part 2: Aggregate formation and oxidation.

We examined the impact of monoclonal antibody (mAb) and buffer concentration, mimicking the cryoconcentration found upon freezing in a 2 L bottle, on mAb stability during frozen storage. Upon cryoconcentration, larger protein molecules and small excipient molecules freeze-concentrate differently, resulting in different protein to stabiliser ratios within a container. Understanding the impact of these shifted ratios on protein stability is essential.

The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - Part 1: Higher molecular weight species and subvisible particle formation.

Cryoconcentration upon large-scale freezing of monoclonal antibody (mAb) solutions leads to regions of different ratios of low molecular weight excipients, like buffer species or sugars, to protein. This study focused on the impact of the buffer species to mAb ratio on aggregate formation after frozen storage at -80 °C, -20 °C, and - 10 °C after 6 weeks, 6 months, and 12 months. An optimised sample preparation was established to measure T' of samples with different mAb to histidine ratios via differential scanning calorimetry (DSC).

Evaluation of Two Novel Scale-Down Devices for Testing Monoclonal Antibody Aggregation During Large-Scale Freezing.

There is a need for representative small volume devices that reflect monoclonal antibody (mAb) aggregation during freezing and thawing (FT) in large containers. We characterised two novel devices that aim to mimic the stress in rectangular 2 L bottles. The first scale-down device (SDD) consists of a 125 mL bottle surrounded by a 3D printed cover that manipulates heat exchange.

The year in cardiovascular medicine 2021: interventional cardiology.

Since last year's report in the European Heart Journal, we have witnessed substantial progress in all aspects of interventional cardiology. Of note, the practice of interventional cardiology took place amidst successive waves of the COVID-19 pandemic, which continues to be a major burden for all healthcare professionals around the globe. In our yearly review, we shall revisit the developments in percutaneous coronary intervention (PCI), structural heart interventions, and adjunctive pharmacotherapy.

Bridging the Species Gap: Morphological and Molecular Comparison of Feline and Human Intestinal Carcinomas.

Limited availability of in vivo experimental models for invasive colorectal cancer (CRC) including metastasis and high tumor budding activity is a major problem in colorectal cancer research. In order to compare feline and human intestinal carcinomas, tumors of 49 cats were histologically subtyped, graded and further characterized according to the human WHO classification. Subsequently, feline tumors were compared to a cohort of 1004 human CRC cases.

Adjustment of specific residual moisture levels in completely freeze-dried protein formulations by controlled spiking of small water volumes.

The residual moisture (RM) level strongly impacts the stability of freeze-dried biopharmaceuticals. On the one hand, the RM should not be too high to keep the reaction potential of water molecules low and to avoid a decrease in the glass transition temperature through the plasticizing effect of water. On the other hand, overdrying has been described to negatively impact protein stability.

Scaling Down Large-Scale Thawing of Monoclonal Antibody Solutions: 3D Temperature Profiles, Changes in Concentration, and Density Gradients.

Purpose: Scale-down devices (SDD) are designed to simulate large-scale thawing of protein drug substance, but require only a fraction of the material. To evaluate the performance of a new SDD that aims to predict thawing in large-scale 2 L bottles, we characterised 3D temperature profiles and changes in concentration and density in comparison to 125 mL and 2 L bottles. Differences in diffusion between a monoclonal antibody (mAb) and histidine buffer after thawing were examined.

Potential effect of pre-activated muscles under a far-side lateral impact.

Objective: The goal of this study is to evaluate the potential effect of muscle pre-activation under a lateral impact scenario, in this case focusing on a far-side impact, using an Active Human Body Model.

Methods: In total fourteen simulations were run, out of these, twelve were computed with an Active Human Body Model and two with a passive one. The models were subjected to a far-side impact scenario reaching up to 14 g's.