Crucial aspects for maintaining rAAV stability.

The storage of rAAV vectors for gene therapy applications is critical for ensuring a constant product quality and defined amount of medication at the time of administration. Therefore, we determined the influence of different storage conditions on the physicochemical and biological properties of rAAV8 and rAAV9 preparations. Particular attention was paid to short-term storage, which plays a crucial role in both the manufacturing process and in clinical applications.

Shared principles for disentangling heterogeneity in neuroscience and psychopathology.

A primary goal of clinical neuroscience is to identify associations between individual differences in psychopathology and the brain. However, despite a significant amount of resources invested in this endeavor, few reliable neural correlates of psychopathology have been identified. A common suspect for this lack of success is the significant heterogeneity in symptoms observed in psychiatric disorders.

How to make cardiology clinical trials more inclusive.

Cardiovascular clinical trials continue to under-represent children, older adults, females and people from ethnic minority groups relative to population disease distribution. Here we describe strategies to foster trial representativeness, with proposed actions at the levels of trial funding, design, conduct and dissemination. In particular, trial representativeness may be increased through broad recruitment strategies and site selection criteria that reflect the diversity of patients in the catchment area, as well as limiting unjustified exclusion criteria and using pragmatic designs that minimize research burden on patients (including embedded and decentralized trials).

In-situ relative calibration of Bragg crystals with Monte Carlo line ratio analysis.

X-ray line emission spectra can thoroughly characterize hot plasmas, especially when line shapes and ratios convey distinct aspects of plasma conditions. However, the high spectral resolution required for observing line shapes is often at odds with the large bandwidth required to observe many line ratios across a wide spectral range. One strategy to obtain high spectral resolution over a wide bandwidth is to use multiple crystals with calibrated reflectivity so that line intensities across different crystals can be compared.

X-ray sources for in situ wavelength calibration of x-ray imaging crystal spectrometers.

X-ray sources for a range of wavelengths are being considered for in situ calibration of X-ray Imaging Crystal Spectrometers (XICSs) and for monitoring line shifts due to changes in the crystal temperature, which can vary during experimental operation over a day [A. Ince-Cushman et al., Rev.

Factors affecting rAAV titers during triple-plasmid transient transfection in HEK-293 cells.

The efficiency of triple-plasmid transfection in recombinant Adeno-Associated Virus (rAAV) production was analyzed by examining two distinct HEK-293 cells lines. These were categorized as high producer (HP) and low producer (LP) based on their differing levels of productivity under identical conditions. Analysis of RNA expression levels of viral genes revealed disparities in plasmid derived gene expression between the cell lines.

Cas-CLOVER-mediated knockout of STAT1: A novel approach to engineer packaging HEK-293 cell lines used for rAAV production.

In addressing the limitations of CRISPR-Cas9, including off-target effects and high licensing fees for commercial use, Cas-CLOVER, a dimeric gene editing tool activated by two guide RNAs, was recently developed. This study focused on implementing and evaluating Cas-CLOVER in HEK-293 cells used for recombinant adeno-associated virus (rAAV) production by targeting the signal transducer and activator of transcription 1 (STAT1) locus, which is crucial for cell growth regulation and might influence rAAV production yields. Cas-CLOVER demonstrated impressive efficiency in gene editing, achieving over 90% knockout (KO) success.

Statistical data analysis of x-ray spectroscopy data enabled by neural network accelerated Bayesian inference.

Bayesian inference applied to x-ray spectroscopy data analysis enables uncertainty quantification necessary to rigorously test theoretical models. However, when comparing to data, detailed atomic physics and radiation transfer calculations of x-ray emission from non-uniform plasma conditions are typically too slow to be performed in line with statistical sampling methods, such as Markov Chain Monte Carlo sampling. Furthermore, differences in transition energies and x-ray opacities often make direct comparisons between simulated and measured spectra unreliable.

The Spinal Cord Injury Self-Management Program: A Pilot.

People with chronic spinal cord injury (SCI) experience a higher rate of secondary health conditions (SHCs) which affect their health and well-being. Self-management (SM) is a proven intervention approach, but formal programs may need to be tailored for the SCI population to reflect their needs and values. We sought to examine the feasibility and acceptability of the Spinal Cord Injury Self-Management (SCISM) Program and estimate its effect.

Orthogonal characterization of rAAV9 reveals unexpected transgene heterogeneity.

Recombinant adeno-associated virus (rAAV) is the most widely used viral vector for in vivo human gene therapy. To ensure safety and efficacy of gene therapy products, a comprehensive analytical profile of the rAAVs is needed, which provides crucial information for therapeutic development and manufacturing. Besides information on rAAV quantities and possible contaminating DNA and protein species, assessing rAAV quality is of utmost importance.

"The Other Thousand Hours": A Spinal Cord Injury Self-Management Program Qualitative Analysis.

People with spinal cord injury experience secondary health conditions (SHCs) at a high rate which impacts life expectancy and functional performance. Self-management (SM) is an evidence-based approach to reduce the negative effects of SHCs, but prior SM programs have not been successful for the spinal cord injury (SCI) population. We sought to describe the experiences of participants completing a group-based telehealth program that is tailored to the SCI population: The Spinal Cord Injury Self-Management (SCISM) Program.

Ultrasound education across European Federation of Radiographers Societies (EFRS) countries: Similarities and differences.

Introduction: Ultrasound education varies greatly across European healthcare systems. This paper focuses on ultrasound academic education as a part of wider suite of surveys on radiographers working in ultrasound. The aim was to investigate sonography educational levels, methods of training, course duration and other factors in European Federation of Radiographers Societies (EFRS) member countries.

The impact of culture on emotion suppression: Insights from an electrophysiological study of emotion regulation in Japan.

Prior theory and evidence suggest that native East Asians tend to down-regulate their emotional arousal to negatively valenced experiences through expressive suppression, an emotion regulation technique focused on suppressing one's emotional experience. One proposed explanation for this choice of regulation strategy and its efficacy is rooted in their commitment to the cultural value of interdependence with others. However, prior work has not yet thoroughly supported this hypothesis using in vivo neural correlates of emotion regulation.

Indistinguishability of Identical Bosons from a Quantum Information Theory Perspective.

Using tools from quantum information theory, we present a general theory of indistinguishability of identical bosons in experiments consisting of passive linear optics followed by particle number detection. Our results do neither rely on additional assumptions on the input state of the interferometer, such as, for instance, a fixed mode occupation, nor on any assumption on the degrees of freedom that potentially make the particles distinguishable. We identify the expectation value of the projector onto the N-particle symmetric subspace as an operationally meaningful measure of indistinguishability, and derive tight lower bounds on it that can be efficiently measured in experiments.

How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.

Introduction: Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear.

Methods: We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimated glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy or death due to kidney disease) in EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses.

Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Preserved.

Aims: Renal function (estimated glomerular filtration rate [eGFR]) changes early after the introduction of empagliflozin have not been described in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to describe early eGFR changes, assess its determinants and its clinical impact on cardiovascular and renal outcomes in patients with HFpEF enrolled in EMPEROR-Preserved.

Methods And Results: Estimated glomerular filtration rate changes (absolute and relative) from randomization to week 4 were calculated and landmark analyses performed.

Sonographers' perspectives on research - A worldwide online questionnaire study.

Introduction: Research has been performed by sonographers (also known as ultrasound reporting radiographers) for many years for improving diagnosis of disease, developing new imaging approaches, and enhancing patient outcomes. Despite this, sonographers' perspectives on research have not been well studied. To understand the views of sonographers is essential, as they have an important role in the successful implementation of research outcomes during their daily work.

Sulfate limitation increases specific plasmid DNA yield and productivity in E. coli fed-batch processes.

Plasmid DNA (pDNA) is a key biotechnological product whose importance became apparent in the last years due to its role as a raw material in the messenger ribonucleic acid (mRNA) vaccine manufacturing process. In pharmaceutical production processes, cells need to grow in the defined medium in order to guarantee the highest standards of quality and repeatability. However, often these requirements result in low product titer, productivity, and yield.

Differential Modulation of Markers of Oxidative Stress and DNA Damage in Arterial Hypertension.

Patients with arterial hypertension have an increased risk of developing tumors, particularly renal cell carcinoma. Arterial hypertension is linked to DNA damage via the generation of oxidative stress, in which an upregulated renin-angiotensin-aldosterone system plays a crucial role. The current study investigated surrogates of oxidative stress and DNA damage in a group of hypertensive patients (HypAll, n = 64) and subgroups of well (HypWell, n = 36) and poorly (HypPoor, n = 28) controlled hypertensive patients compared to healthy controls (n = 8).