Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.

Macroporosity-Heightened Mass Transfer Enabling Complete Benzene Oxidation over Pt/SiO Catalyst.

Mass transfer governs the overall catalytic performance of heterogeneous catalysts considerably; however, this fundamental research has often been ignored. Here, macroporous SiO-supported Pt nanoparticle (Pt/SiO-M) and mesoporous SiO-supported Pt nanoparticle (Pt/SiO-m) catalysts were specifically fabricated by a facile thermal reduction step to engineer the resultant Pt nanoparticles showing similar physiochemical properties while possessing completely different porous microstructures exclusively originating from SiO supports. On this basis, a platform to explore the crucial mass transfer difference affecting catalytic activity is then established by systematically practicing industry-important benzene oxidation measurements.

Non-canonical Wnt signaling pathway activated NFATC3 promotes GDF15 expression in MASH: prospective analyses of UK biobank proteomic data.

Background: Our previous research demonstrated that growth differentiation factor 15 (GDF15) exhibited superior predictive capability for metabolic dysfunction-associated steatohepatitis (MASH) development with an AUC of 0.86 at 10 years before disease diagnosis. However, the specific pathways and molecular mechanisms associated with GDF15 expression during MASH development remain to be fully investigated in humans.

Cytoophidium complexes resonate with cell fates.

Metabolism is a fundamental characteristic of life. In 2010, we discovered that the metabolic enzyme CTP synthase (CTPS) can assemble a snake like structure inside cells, which we call the cytoophidium. Including CTPS, an increasing number of metabolic enzymes have been found to form cytoophidia in cells.

A life course approach to examine cumulative impacts of parental migration on children's psychological well-being and education in Southeast Asia.

Researchers have raised concerns about parental migration's effects on various aspects of the left-behind children's development. However, there is limited understanding of how parental migration influences children over the life course. This study aimed to fill this gap by investigating how exposure to parental migration during childhood shapes later development in Indonesia and the Philippines, two major labor-sending countries in Southeast Asia.

The COVID-19 pandemic's impact on UK social workers working with people with learning disabilities: A mixed methods study.

The impact of the COVID-19 pandemic on the health and wellbeing of social workers working with people with learning disabilities has not been fully explored. This paper reports findings from a large United Kingdom study that surveyed health and care workers in six phases of the pandemic and shortly thereafter (2020-23) relating to 310 social workers who worked with people with learning disabilities. Mann-Whitney U tests revealed that these social workers experienced a decline in wellbeing over the pandemic period, but this lessened as time passed.

Effects of noise and metabolic cost on cortical task representations.

Cognitive flexibility requires both the encoding of task-relevant and the ignoring of task-irrelevant stimuli. While the neural coding of task-relevant stimuli is increasingly well understood, the mechanisms for ignoring task-irrelevant stimuli remain poorly understood. Here, we study how task performance and biological constraints jointly determine the coding of relevant and irrelevant stimuli in neural circuits.

Highly accurate real-space electron densities with neural networks.

Variational ab initio methods in quantum chemistry stand out among other methods in providing direct access to the wave function. This allows, in principle, straightforward extraction of any other observable of interest, besides the energy, but, in practice, this extraction is often technically difficult and computationally impractical. Here, we consider the electron density as a central observable in quantum chemistry and introduce a novel method to obtain accurate densities from real-space many-electron wave functions by representing the density with a neural network that captures known asymptotic properties and is trained from the wave function by score matching and noise-contrastive estimation.

Advances in the Release of Amide-Containing Molecules.

The ability to release a molecule from a larger construct in a controlled manner is of great importance to produce effective prodrugs, antibody-drug conjugates, and chemical probes. Amides are ubiquitous functional groups and yet methods to utilise them as molecular release handles are seldom reported. This concept article highlights the advances made in amide release strategies and how these approaches have been utilised.

Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression-Quantitative Trait Loci.

Asthma is a genetically complex inflammatory airway disease associated with over 200 Single nucleotide polymorphisms (SNPs). However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples.

Dynamic photosynthetic labeling and carbon-positional mass spectrometry monitor in vivo Rubisco carbon assimilation rates.

RIBULOSE-1,5-BISPHOSPHATE CARBOXYLASE/OXYGENASE (RUBISCO) is the most abundant enzyme and CO2 bio-sequestration system on Earth. Its in vivo activity is usually determined by 14CO2 incorporation into 3-phosphoglycerate (3PGA). However, the radiometric analysis of 3PGA does not distinguish carbon positions.

COPD Airway Epithelial Cell-derived Extracellular Vesicles Spread Cellular Senescence via MicroRNA-34a.

Chronic obstructive pulmonary disease (COPD) is associated with the acceleration of lung aging, and the accumulation of senescent cells in lung tissue. MicroRNA (miR)-34a induces senescence by suppressing the anti-aging molecule, sirtuin-1 (SIRT1). Senescent cells spread senescence to neighbouring and distant cells, favouring COPD progression and its comorbidities.

Germ cell quantification in human fetal and prepubertal testis tissues - a comparison of current methodologies.

Methods to quantify germ cell number in human immature testicular tissues are essential to evaluate the impact of chemotherapy exposures and for optimising cryopreservation protocols used in fertility preservation for prepubertal boys. Established quantification methods rely on the presence of round tubules within the tissue. However, round tubular cross sections are limited in human prepubertal testicular tissues, especially when using in vitro culture.

Reusable Intermittent Catheters are Acceptable but Product Innovation is Needed: An Interview Study of Catheter Users' Experiences.

Purpose: The purpose of this study was to explore the experiences of intermittent catheter users after using both reusable and single-use catheters, with a particular focus on factors that affected acceptability.

Design: Qualitative descriptive study following a clinical trial.

Participants And Setting: Thirty-six participants who had used both reusable and single-use catheters in a clinical trial were interviewed between June 2022 and March 2024.

Contrast-enhanced US of High-Risk Indeterminate Focal Liver Observations Categorized as LR-4 or LR-M at CT/MRI.

Background Indeterminate focal liver observations in patients at risk for hepatocellular carcinoma (HCC) may require invasive biopsy or follow-up, which could lead to delays in definitive categorization and to postponement of treatment. Purpose To examine clinical effect of contrast-enhanced US (CEUS) in participants with high-risk indeterminate liver observations categorized as Liver Imaging Reporting and Data System (LI-RADS) category LR-4 (probably HCC) or LI-RADS category LR-M (probably or definitely malignant but not HCC specific) at CT or MRI. Materials and Methods This was a secondary analysis of a prospective international multicenter validation study for CEUS LI-RADS (January 2018 to August 2021).

High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis.

Cytologically indeterminate thyroid nodules (Bethesda class III or IV) carry a 10-40% risk of malignancy. Diagnostic lobectomies are frequently performed but negative surgeries incur unnecessary costs on the healthcare system, potential complications, and negative impacts on quality of life. Molecular tests (MTs) have been developed to reduce unnecessary surgeries.

Parents' lived experience of support through their neonate's end of life and grief journey: An interpretative phenomenology study.

Medical and pharmacological advancements have influenced the ability to treat acutely ill neonates. However, complications of prematurity mean that death is unpreventable in some cases. The aim of this study was to explore parents' lived experiences of end of life care and their perceptions of support needs during and following the death of their baby in neonatal intensive care units in the United Kingdom.

Gesture screening in young infants: Highly sensitive to risk factors for communication delay.

Introduction: Children's early language and communication skills are efficiently measured using parent report, for example, communicative development inventories (CDIs). These have scalable potential to determine risk of later language delay, and associations between delay and risk factors such as prematurity and poverty. However, there may be measurement difficulties in parent reports, including anomalous directions of association between child age/socioeconomic status and reported language.

Abrupt transformation of west Greenland lakes following compound climate extremes associated with atmospheric rivers.

Arctic ecosystems are affected by accelerated warming as well as the intensification of the hydrologic cycle, yet understanding of the impacts of compound climate extremes (e.g., simultaneous extreme heat and rainfall) remains limited, despite their high potential to alter ecosystems.

The evolution of signaling and monitoring in plant-fungal networks.

Experiments have shown that when one plant is attacked by a pathogen or herbivore, this can lead to other plants connected to the same mycorrhizal network up-regulating their defense mechanisms. It has been hypothesized that this represents signaling, with attacked plants producing a signal to warn other plants of impending harm. We examined the evolutionary plausibility of this and other hypotheses theoretically.

Precision and accuracy of the dynamic endocast method for measuring volume changes in XROMM studies.

The X-ray Reconstruction of Moving Morphology (XROMM) workflow enables precise and accurate measurement of the 3D skeletal kinematics underlying animal behaviors. The dynamic endocast method built upon that workflow to measure the rate of volume change within a bounded region of interest. We measured the precision and accuracy of the dynamic endocast method, using a fish oropharyngeal cavity as a case study.

Safety and Tolerability of Pivmecillinam During More Than Four Decades of Clinical Experience: A Systematic Review.

The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions.