Background: Clinical studies have long observed that neurodegenerative disorders display a range of symptoms and pathological features and, in some cases, overlap, suggesting that these diseases exist on a spectrum. Dementia with Lewy Bodies (DLB), a synucleinopathy, is a prominent example, where symptomatic similarities with tauopathy, Alzheimer's disease, are observed. Although tau pathology has been observed in DLB, the interplay between tau and α-synuclein is poorly understood at a molecular level.
View Article and Find Full Text PDFHospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery.
View Article and Find Full Text PDFmRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex.
View Article and Find Full Text PDFBackground: Concerns exist that long-term cardiac alterations occur after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, particularly in patients who were hospitalized in the acute phase or who remain symptomatic. This study investigates potential long-term functional and morphological alterations after SARS-CoV-2 infection.
Methods: The authors of this study investigated patients after SARS-CoV-2 infection by using a mobile 1.
Arterioscler Thromb Vasc Biol
January 2025
Atherosclerosis affects patients with systemic immune-mediated inflammatory diseases at an increased rate compared with the general population. In recent years, our understanding of the pathophysiology of atherosclerosis has advanced considerably. Nevertheless, cardiovascular imaging modalities that can adequately assess the biological background of atherosclerosis have not reached widespread clinical adoption.
View Article and Find Full Text PDFIntroduction: To improve the outcomes of thoracic endovascular aortic repair (TEVAR), we investigated the dynamic morphology of dilated and nondilated ascending aortas (AAs) to determine whether an appropriate proximal landing zone for TEVAR exists if the middle AA is dilated.
Materials And Methods: Patients with dilated (diameter 40-50 mm) and nondilated (<40 mm) AAs underwent electrocardiogram-gated computed tomography angiography of the entire AA in the systolic and diastolic phases. For each plane of each AA segment, the maximal and minimal diameters in systole and diastole were recorded.
Coronary anomalies occur in 0.2% to 1.2% of the population, with the anomalous aortic origin of the coronary arteries accounting for one third of these cases.
View Article and Find Full Text PDFMotivation: Accurate quantitative information about protein abundance is crucial for understanding a biological system and its dynamics. Protein abundance is commonly estimated using label-free, bottom-up mass spectrometry (MS) protocols. Here, proteins are digested into peptides before quantification via MS.
View Article and Find Full Text PDFBackground: The calculation of remaining growth in children and the timing of epiphysiodesis in those with leg-length discrepancy (LLD) is most often done with 4 methods: the Green-Anderson, White-Menelaus, Moseley straight-line graph, and multiplier methods. The aims of this study were to identify the most accurate method with use of bone age or chronological age and to evaluate the influence of including inhibition in the calculations.
Methods: One hundred and ninety-one children (10 to 17 years of age) with LLD who underwent surgical closure of the growth plate and were followed until skeletal maturity were identified from a local health register.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by highly heterogeneous manifestations ranging from asymptomatic cases to death for still incompletely understood reasons. As part of the IMmunoPhenotyping Assessment in a COVID-19 Cohort study, we mapped the plasma proteomes of 1117 hospitalized patients with COVID-19 from 15 hospitals across the United States. Up to six samples were collected within ~28 days of hospitalization resulting in one of the largest COVID-19 plasma proteomics cohorts with 2934 samples.
View Article and Find Full Text PDFBACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.
View Article and Find Full Text PDFAge is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics.
View Article and Find Full Text PDFCardiovascular diseases are the number one cause of death globally. The most important determinant of cardiovascular health is a person's age. Aging results in structural changes and functional decline of the cardiovascular system.
View Article and Find Full Text PDFAge is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti-interferon (IFN) autoantibodies.
View Article and Find Full Text PDFTau protein aggregation is associated with posttranslational modifications (PTMs) in 75% of all dementia cases. The distribution of tau pathology and the presence of specific tau phosphorylation sites of interest are typically visualized and measured using antibodies. However, previous knowledge of the target epitopes is required.
View Article and Find Full Text PDFPost-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.
View Article and Find Full Text PDF