AI-Powered Multimodal Modeling of Personalized Hemodynamics in Aortic Stenosis.

Aortic stenosis (AS) is the most common valvular heart disease in developed countries. High-fidelity preclinical models can improve AS management by enabling therapeutic innovation, early diagnosis, and tailored treatment planning. However, their use is currently limited by complex workflows necessitating lengthy expert-driven manual operations.

Cardiac diffusion-weighted and tensor imaging: A consensus statement from the special interest group of the Society for Cardiovascular Magnetic Resonance.

Thanks to recent developments in cardiovascular magnetic resonance (CMR), cardiac diffusion-weighted magnetic resonance is fast emerging in a range of clinical applications. Cardiac diffusion-weighted imaging (cDWI) and diffusion tensor imaging (cDTI) now enable investigators and clinicians to assess and quantify the tridimensional microstructure of the heart. Free-contrast DWI is uniquely sensitized to the presence and displacement of water molecules within the myocardial tissue, including the intracellular, extracellular, and intravascular spaces.

Control of dermatomyositis skin disease activity lags behind control of muscles disease activity during the early treatment stages of classic dermatomyositis: A retrospective, single-centre study.

This study aimed to retrospectively identify differences in relative control of cutaneous and muscular disease activity in adult dermatomyositis (DM) patients at a single, tertiary care centre following initiation of diagnosis and treatment. Our results demonstrated a significantly lower complete treatment response rate of skin disease compared to muscular disease at 6-months and persistent but not statistically significant lower skin disease response at 12 months. These results suggest DM skin disease activity may be more refractory to treatment than muscle disease activity, especially in the early disease phase.

A novel isoform associated with multiple sclerosis lesions induces P-body formation.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Current therapies primarily target the inflammatory component of the disease and are highly effective in early stages of MS while limited therapies have an effect in the more chronic progressive stages of MS where resident glia have a larger role. MS lesions tend to be inflammatory even after the initial peripheral immune cell invasion has subsided and this inflammation is known to cause alternative splicing events.

Hemispheric asymmetries in hippocampal volume related to memory in left and right temporal variants of frontotemporal degeneration.

In addition to Alzheimer's disease (AD), the hippocampus is now known to be affected in variants of frontotemporal degeneration (FTD). In semantic variant primary progressive aphasia (svPPA), characterized by language impairments, hippocampal atrophy is greater in the left hemisphere. Nonverbal impairments (e.

Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism.

Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion.

PDE5 inhibitor drugs for use in dementia.

Unlabelled: Alzheimer's disease and related dementias (ADRD) remain a major health-care challenge with few licensed medications. Repurposing existing drugs may afford prevention and treatment. Phosphodiesterase-5 (PDE5) is widely expressed in vascular myocytes, neurons, and glia.

Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease.

Background & Aims: Sex differences in muscle function and mass, dyspnea, and clinical outcomes have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD) despite a similar level of airflow obstruction. Protein and amino acid metabolism is altered in COPD, however, it remains unclear whether a difference in metabolic signature exists between males and females with COPD that may explain the observed differences in muscle health and clinical outcomes.

Methods: In 234 moderate to severe COPD patients (males/females: 113/121) and 182 healthy controls (males/females: 77/105), we assessed, besides presence of comorbidities and clinical features, muscle function by handgrip and leg dynamometry, and body composition by dual-energy x-ray absorptiometry.

Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome.

The gut microbiome is complex, raising questions about the role of individual strains in the community. Here, we address this question by constructing variants of a complex defined community in which we eliminate strains that occupy the bile acid 7α-dehydroxylation niche. Omitting Clostridium scindens (Cs) and Clostridium hylemonae (Ch) eliminates secondary bile acid production and reshapes the community in a highly specific manner: eight strains change in relative abundance by >100-fold.

Alzheimer's disease drug development pipeline: 2023.

Introduction: Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Methods: We searched ClinicalTrials.gov for all current Phase 1, 2 and 3 clinical trials for AD and mild cognitive impairment (MCI) attributed to AD.

Rigor, Reproducibility, and Transparency in Shared Research Resources: Follow-Up Survey and Recommendations for Improvements.

Rigor, reproducibility, and transparency (RR&T) are essential components of all scientific pursuits. Shared research resources, also known as core facilities, are on the frontlines of ensuring robust RR&T practices. The Association of Biomolecular Resource Facilities Committee on Core Rigor and Reproducibility conducted a follow-up survey 4 years after the initial 2017 survey to determine if core facilities have seen a positive impact of new RR&T initiatives (including guidance from the National Institutes of Health, new scientific journal requirements on transparency and data provenance, and educational tools from professional organizations).

Altered gene expression in excitatory neurons is associated with Alzheimer's disease and its higher incidence in women.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder involving interactions between different cell types in the brain. Previous single-cell and bulk expression Alzheimer's studies have reported conflicting findings about the key cell types and cellular pathways whose expression is primarily altered in this disease. We re-analyzed these data in a uniform, coherent manner aiming to resolve and extend past findings.

Aortic Valve Reconstruction With Autologous Pericardium Versus a Bioprosthesis: The Ozaki Procedure in Perspective.

Background We assessed the Ozaki procedure, aortic valve reconstruction using autologous pericardium, with respect to its learning curve, hemodynamic performance, and durability compared with a stented bioprosthesis. Methods and Results From January 2007 to January 2016, 776 patients underwent an Ozaki procedure at Toho University Ohashi Medical Center. Learning curves, aortic regurgitation (AR), and peak gradient, assessed by serial echocardiograms, valve rereplacement, and survival were investigated.

Adaptive exhaustion during prolonged intermittent hypoxia causes dysregulated skeletal muscle protein homeostasis.

Nocturnal hypoxaemia, which is common in chronic obstructive pulmonary disease (COPD) patients, is associated with skeletal muscle loss or sarcopenia, which contributes to adverse clinical outcomes. In COPD, we have defined this as prolonged intermittent hypoxia (PIH) because the duration of hypoxia in skeletal muscle occurs through the duration of sleep followed by normoxia during the day, in contrast to recurrent brief hypoxic episodes during obstructive sleep apnoea (OSA). Adaptive cellular responses to PIH are not known.

Multiparametric Quantitative Imaging Biomarker as a Multivariate Descriptor of Health: A Roadmap.

Multiparametric quantitative imaging biomarkers (QIBs) offer distinct advantages over single, univariate descriptors because they provide a more complete measure of complex, multidimensional biological systems. In disease, where structural and functional disturbances occur across a multitude of subsystems, multivariate QIBs are needed to measure the extent of system malfunction. This paper, the first Use Case in a series of articles on multiparameter imaging biomarkers, considers multiple QIBs as a multidimensional vector to represent all relevant disease constructs more completely.

Distinct Mechanisms of β-Arrestin-Biased Agonist and Blocker of AT1R in Preventing Aortic Aneurysm and Associated Mortality.

Background: Aortic aneurysm (AA) is a "silent killer" human disease with no effective treatment. Although the therapeutic potential of various pharmacological agents have been evaluated, there are no reports of β-arrestin-biased AT1R (angiotensin-II type-1 receptor) agonist (TRV027) used to prevent the progression of AA.

Methods: We tested the hypothesis that TRV027 infusion in AngII (angiotensin II)-induced mouse model of AA prevents AA.

Delineation of functionally essential protein regions for 242 neurodevelopmental genes.

Neurodevelopmental disorders (NDDs), including severe paediatric epilepsy, autism and intellectual disabilities are heterogeneous conditions in which clinical genetic testing can often identify a pathogenic variant. For many of them, genetic therapies will be tested in this or the coming years in clinical trials. In contrast to first-generation symptomatic treatments, the new disease-modifying precision medicines require a genetic test-informed diagnosis before a patient can be enrolled in a clinical trial.

The Alzheimer's Cell Atlas (TACA): A single-cell molecular map for translational therapeutics accelerator in Alzheimer's disease.

Introduction: Recent advances in generating massive single-cell/nucleus transcriptomic data have shown great potential for facilitating the identification of cell type-specific Alzheimer's disease (AD) pathobiology and drug-target discovery for therapeutic development.

Methods: We developed The Alzheimer's Cell Atlas (TACA) by compiling an AD brain cell atlas consisting of over 1.1 million cells/nuclei across 26 data sets, covering major brain regions (hippocampus, cerebellum, prefrontal cortex, and so on) and cell types (astrocyte, microglia, neuron, oligodendrocytes, and so on).

Multiparametric Quantitative Imaging Biomarkers for Phenotype Classification: A Framework for Development and Validation.

This manuscript is the third in a five-part series related to statistical assessment methodology for technical performance of multi-parametric quantitative imaging biomarkers (mp-QIBs). We outline approaches and statistical methodologies for developing and evaluating a phenotype classification model from a set of multiparametric QIBs. We then describe validation studies of the classifier for precision, diagnostic accuracy, and interchangeability with a comparator classifier.

Conserved patterns across ion channels correlate with variant pathogenicity and clinical phenotypes.

Clinically identified genetic variants in ion channels can be benign or cause disease by increasing or decreasing the protein function. As a consequence, therapeutic decision-making is challenging without molecular testing of each variant. Our biophysical knowledge of ion-channel structures and function is just emerging, and it is currently not well understood which amino acid residues cause disease when mutated.

Primary central nervous system lymphoma: Inter-compartmental progression.

There is limited understanding of the inter-compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18-92]; median follow-up 35 months [0.