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.

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype.

Objective: Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.

Design: Targeted and whole-genome low-coverage sequencing, genome-wide methylation and transcriptome analyses were applied on a final collective of 122 morphologically well-characterised low-grade and high-grade PDAC precursors, including intestinal and gastric intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasias (PanIN).

Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.

Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states.

Arthroscopic rod technique compared to stress ultrasound in the dynamic evaluation of lateral ligament instabilities of the elbow.

Introduction: The purpose was to compare the arthroscopic rod technique to stress ultrasound in the dynamic assessment of lateral elbow instabilities.

Materials And Methods: Fifteen elbows of eight specimen with a mean age of 66.4 ± 13.

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.

Biopsies of osseous jaw lesions using 3D-printed surgical guides: a clinical study.

Background: Bone biopsies are often necessary to make a diagnosis in the case of irregular bone structures of the jaw. A 3D-printed surgical guide may be a helpful tool for enhancing the accuracy of the biopsy and for ensuring that the tissue of interest is precisely removed for examination. This study was conducted to compare the accuracy of biopsies performed with 3D-printed surgical guides to that of free-handed biopsies.

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.

How to tame your genes: mechanisms of inflammatory gene repression by glucocorticoids.

Glucocorticoids (GCs) are widely used therapeutic agents to treat a broad range of inflammatory conditions. Their functional effects are elicited by binding to the glucocorticoid receptor (GR), which regulates transcription of distinct gene networks in response to ligand. However, the mechanisms governing various aspects of undesired side effects versus beneficial immunomodulation upon GR activation remain complex and incompletely understood.

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.

Myocarditis or inherited disease? - The multifaceted presentation of arrhythmogenic cardiomyopathy.

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is now usually referred to as arrhythmogenic cardiomyopathy (ACM) because of the possible left and biventricular affection. In recent years, it has been shown that early-stage ACM, especially in women carrying a disease-causing variant in the DSP gene, may present with clinical signs of myocarditis.

Case Presentation: The female patient was diagnosed with myocarditis based on arrhythmia and findings on magnetic resonance imaging at the age of 24 years.

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%.

Operative Volume of Newborn Surgery in German University Hospitals: High Volume Versus Low Volume Centers.

Introduction:  Adequate patient volume is essential for the maintenance of quality, meaningful research, and training of the next generation of pediatric surgeons. The role of university hospitals is to fulfill these tasks at the highest possible level. Due to decentralization of pediatric surgical care during the last decades, there is a trend toward reduction of operative caseloads.

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.

New insight into the CATIE study by constrained confidence partitioning. An innovative technique towards personalized antipsychotic drug therapy in schizophrenia treatment.

The CATIE schizophrenia trial was a very influential randomized controlled trial in patients with chronic schizophrenia. Patients were followed for up to 18 months under treatment with a randomly assigned antipsychotic. The primary endpoint, time to discontinuation of treatment for any reason, is influenced by individual patient characteristics, external factors as well as effects of drug treatment.

Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.

Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle.

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.

Effect of parental depressive symptoms on offspring's brain structure and function: A systematic review of neuroimaging studies.

Perinatal Depression (PND) is a severe mental disorder that appears during pregnancy or in the post-partum. Although PND has been associated with behavioral problems in the offspring, its effects on brain development are unclear. With this review we aimed at summarizing the existing literature on the effects of perinatal depressive symptoms on children's brains.

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.

Freeze-thaw stability of aluminum oxide nanoparticles.

The use of inorganic nanoparticles (NPs) gains interest for pharmaceutical applications, e.g. as adjuvants or drug delivery vehicles.