John W.

Millions globally suffer from rare diseases, often genetic and affecting children. This study explores using antisense oligonucleotides to fix incorrect RNA splicing, a common result of disease-causing genetic mutations. The results showed that tailored ASOs could correct incorrect splicing for various mutation types, showing this technology′s potential in treating rare genetic diseases. The team chose five mutation types disrupting normal splicing and created specific ASOs to correct these errors in cell models. They created minigenes to simulate the mutations and tested different ASOs′ effectiveness. This method was key to understanding ASOs′ ability to restore normal gene function, crucial for developing targeted treatments for rare genetic disorders. This research could lead to new, targeted treatments for rare genetic disorders, offering hope to millions of patients and their families facing limited treatment options. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Abstract Global change is associated with variable shifts in the annual production of aboveground plant biomass, suggesting localized sensitivities with unclear causal origins.

Abstract Early patterning of DNA methylation (DNAm) may play an important role in later disease development.

Although much information can be gained about thermally induced microstructural changes in metals through the measurement of their thermophysical properties using a differential scanning calorimeter (DSC), due to competing influences on the signal, not all microstructural changes can be fully characterised this way. For example, accurate characterisation of recrystallisation, tempering, and changes in retained delta ferrite in alloyed steels becomes complex due to additional signal changes due to the Curie point, oxidation, and the rate (and therefore the magnitude) of transformation. However, these types of microstructural changes have been shown to invoke strong magnetic and electromagnetic (EM) responses; therefore, simultaneous EM measurements can provide additional complementary data which can help to emphasise or deconvolute these complex signals and develop a more complete understanding of certain metallurgical phenomena. This paper discusses how a DSC machine has been modified to incorporate an EM sensor consisting of two copper coils printed onto either side of a ceramic substrate, with one coil acting as a transmitter and the other as a receiver. The coil is interfaced with a custom-built data acquisition system, which provides current to the transmit coil, records signals from the receive coil, and is controlled by a graphical user interface which allows the user to select multiple excitation frequencies. The equipment has a useable frequency range of approximately 1–100 kHz and outputs phase and magnitude readings at a rate of approximately 50 samples per second. Simultaneous DSC-EM measurements were performed on a nickel sample up to a temperature of 600 °C, with the reversable ferromagnetic to paramagnetic transition in the nickel sample invoking a clear EM response. The results show that the combined DSC-EM apparatus has the potential to provide a powerful tool for the analysis of thermally induced microstructural changes in metals, feeding into research on steel production, development of magnetic and conductive materials, and many more areas.

Understanding transformations of non-equilibrium materials is a key open scientific question. Here the pathway by which different polar supertextures undergo dynamical correlations and collectively transform into a metastable supercrystal state is revealed experimentally and theoretically over seven orders of magnitude timescale.

Abstract Background The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials.

Abstract Sympathetic efferent renal nerves have key roles in the regulation of kidney function and blood pressure.

Abstract In the 465,000 km Canadian Prairies ecozone, robust hydrological input data for hydraulic model applications are uncommon because

Background: Acute pancreatitis (AP) can be life-threatening with unpredictable severity. Despite advances in management, its pathogenesis remains unclear. This study investigated metabolites and lipoprotein profiles in AP patients of African descent to understand the underlying pathophysiological conditions so as to inform prognosis and management. Methods: Serum samples were collected from 9 healthy controls (HCs) and 30 AP patients (8 with mild AP, 14 with moderately severe AP, and 8 with severe AP) on days 1, 3, 5, and 7 post epigastric pain and subjected to nuclear magnetic resonance (NMR) spectroscopy. Wilcoxon and Kruskal–Wallis rank-sum tests compared numerical covariates. Lipoprotein characterization was performed using the Liposcale test, and Spearman’s rank test assessed data correlations. The p-values < 0.05 indicated significance. Results: Thirty-eight metabolic signals and information on lipoprotein subclasses were identified from the NMR spectra. The severity of AP correlated with increased levels of 3-hydroxybutyrate and acetoacetate and decreased levels of ascorbate. Distinct metabolic phenotypes were identified and characterized by unique inflammatory and lipoprotein profiles. High-density lipoprotein cholesterol (HDL-C) decreased across all the metabolic phenotypes of AP when compared with the HC, while elevated immediate density lipoprotein cholesterol (IDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels were observed. Time-dependent changes in metabolites were indicative of responsiveness to therapy. Conclusions: Our findings indicate that dysregulated metabolites and lipoproteins can be used to differentiate AP disease state and severity. Furthermore, integrating clinical parameters with data on metabolic and lipoprotein perturbations can contribute to a better understanding of the complex pathophysiology of AP.

Neuromyelitis optica spectrum disorders (NMOSD) comprise autoimmune diseases imposing substantial disability. We compared an NMOSD-targeted disability assessment of mobility, vision, and self-care domains (individually and composite) with the multiple sclerosis-targeted Expanded Disability Status Scale (EDSS) to assess NMOSD disease burden. An overall cohort (n = 505) and a subset of these patients with an enriched dataset (n = 198) were analyzed from the CIRCLES longitudinal, observational database of patients with AQP4-IgG–seropositive or –seronegative NMOSD in North America. Multinomial modeling was used to identify temporal correlates of disability improvement, stability, and worsening. Prior on-study relapse correlated with worsening mobility (OR, 3.08; 95% CI: 1.61–5.90), vision (OR, 3.99; 95% CI: 2.03–7.86), self-care disability (OR, 1.90; 95% CI: 1.07–3.38), and mean composite index disability (OR, 4.20; 95% CI: 1.71–10.34). Higher vision disability was associated with Black race, shorter time on-study, and AQP4-IgG–seropositive status in patients ≥ 18 years (p < 0.05). Disease onset phenotype and sex correlated with pain interference (p < 0.05). These correlates of NMOSD disability were undetected by EDSS. The CIRCLES real-world experience supports the need for NMOSD-specific disability assessment to improve recognition of disease burden, facilitate proactive clinical management, offer insights into resilience, and inform clinical trial design.