Intratumoral injection and retention hold promise to improve cytokine therapies for cancer.

As powerful activators of the immune system, cytokines have been extensively explored for treating various cancers. But despite encouraging advances and some drug approvals, the broad adoption of cytokine therapies in the clinic has been limited by low response rates and sometimes severe toxicities. This in part reflects an inefficient biodistribution to tumors or a pleiotropic action on bystander cells and tissues.

Meaning and prediction of 'excess mortality': a comparison of Covid-19 and pre-Covid-19 mortality data in 31 Eurostat countries from 1965 to 2021.

Determining 'excess mortality' makes it possible to compare the burden of disasters between countries and over time, and thus also to evaluate the success of mitigation measures. However, the debate on coronavirus disease 2019 (Covid-19) has exposed that calculations of excess mortalities vary considerably depending on the method and its specification. Moreover, it is often unclear what exactly is meant by 'excess mortality'.

Corrigendum: Psychometric evaluation and reference values for the German Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years.

[This corrects the article DOI: 10.3389/fneur.2023.

Psychometric evaluation and reference values for the German Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years.

Background: Post-concussion symptoms (PCS) are a common consequence of pediatric traumatic brain injury (pTBI). They include cognitive, emotional, and physical disturbances. To address the lack of age-adapted instruments assessing PCS after pTBI, this study examines the psychometric properties of the German 17-item post-TBI version of the Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years.

Missense Variant in a Lagotto Romagnolo Dog with Autosomal Recessively Inherited Limb-Girdle Muscular Dystrophy.

An 8-month-old female Lagotto Romagnolo dog was presented for a 1-month history of an initial severe reluctance to move, rapidly progressing to a marked stiff gait and progressive muscular weakness and evolving to tetraparesis, which persuaded the owner to request euthanasia. A primary muscle pathology was supported by necropsy and histopathological findings. Macroscopically, the muscles were moderately atrophic, except for the diaphragm and the neck muscles, which were markedly thickened.

Chemometrics in Protein Formulation: Stability Governed by Repulsion and Protein Unfolding.

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients.

Disorder-Induced Topological State Transition in the Optical Skyrmion Family.

Skyrmions endowed with topological protection have been extensively investigated in various platforms including magnetics, ferroelectrics, and liquid crystals, stimulating applications such as memories, logic devices, and neuromorphic computing. While the optical counterpart has been proposed and realized recently, the study of optical skyrmions is still in its infancy. Among the unexplored questions, the investigation of the topology induced robustness against disorder is of substantial importance on both fundamental and practical sides but remains elusive.

Systematic assessment of the replicability and generalizability of preclinical findings: Impact of protocol harmonization across laboratory sites.

The influence of protocol standardization between laboratories on their replicability of preclinical results has not been addressed in a systematic way. While standardization is considered good research practice as a means to control for undesired external noise (i.e.

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.

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.

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%.

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.

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.

Retinal Optical Coherence Tomography in Neuromyelitis Optica.

Background And Objectives: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts.

Methods: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs).

Single-step-fabricated disordered metasurfaces for enhanced light extraction from LEDs.

While total internal reflection (TIR) lays the foundation for many important applications, foremost fibre optics that revolutionised information technologies, it is undesirable in some other applications such as light-emitting diodes (LEDs), which are a backbone for energy-efficient light sources. In the case of LEDs, TIR prevents photons from escaping the constituent high-index materials. Advances in material science have led to good efficiencies in generating photons from electron-hole pairs, making light extraction the bottleneck of the overall efficiency of LEDs.