Publications by authors named "Steen H"

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.

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Hospitalized 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.

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Article Synopsis
  • Chronic viral infections can reactivate during acute illnesses, and this study looked at how SARS-CoV-2 infection affects latent viruses like Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) in over 1,154 hospitalized COVID-19 patients.* -
  • The analysis showed significant reactivation of multiple virus families during the acute stage of COVID-19, which correlated with disease severity, demographics, and clinical outcomes, including higher mortality rates.* -
  • Additionally, persistent viral reactivation after recovery was linked to ongoing symptoms of Post-Acute Sequelae of COVID-19 (PASC), emphasizing the importance of understanding these interactions for better treatment and management strategies.*
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mRNA 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.

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Background: 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.

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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.

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Introduction: 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.

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  • Neonatal sepsis is a serious condition with vague symptoms, making early diagnosis challenging; researchers aimed to identify gene expression biomarkers at birth to improve early detection.
  • In a study of 720 healthy full-term newborns, they compared gene expression data from those later hospitalized for early-onset sepsis (EOS) and others who remained healthy, identifying significant genetic differences.
  • A 4-gene signature (HSPH1, BORA, NCAPG2, PRIM1) was developed, showing high predictive accuracy for EOS at birth, indicating that even healthy-appearing infants may already exhibit signs of future sepsis through gene expression changes.
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  • Patients with coronary artery bypass grafts (CABG) are at higher risk for serious heart issues, and this study investigates the safety of high-dose dobutamine stress cardiovascular magnetic resonance (DCMR) imaging for these patients.
  • A total of 336 CABG patients were reviewed, noting adverse events and symptoms during DCMR compared to a control group of 200 individuals without CABG.
  • The findings revealed similar rates of adverse events and aborted DCMR examinations between CABG patients and controls, suggesting that DCMR may be safely performed in patients with CABG.
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  • Extensive research has shown that cardiovascular magnetic resonance (CMR) is effective for diagnosing and monitoring cardiovascular diseases but is underused in clinical settings due to reimbursement issues.
  • A survey of 144 healthcare professionals revealed that while respondents recognized social impacts and some CMR benefits, significant gaps in knowledge about its full capabilities and advantages were present.
  • Despite these gaps, there was a positive attitude towards CMR, with many participants willing to travel and pay for the procedure, indicating a need for better awareness and educational strategies to enhance its use in healthcare.
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  • Early life adaptations in immune system function are crucial for infant health, with newborns facing environmental challenges that test their immune response.
  • Adenosine deaminases (ADAs), specifically ADA-1 and ADA-2, play important roles in immune modulation, and infants typically show lower ADA activity, resulting in higher levels of plasma adenosine and an anti-inflammatory bias.
  • A study comparing plasma ADA activity in infants from Papua New Guinea to those from The Gambia found that PNG infants had lower ADA levels at birth but these levels increased and converged by the one-month mark, highlighting the importance of genetic and environmental factors in immune development.
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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.

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  • Left ventricular global longitudinal strain (LV-GLS) is a promising early marker for heart failure, and this study aimed to establish cut-off points to distinguish healthy hearts from those affected by heart failure using different imaging techniques.
  • The study analyzed data from healthy subjects and heart failure patients to determine LV-GLS cut-offs, finding values of -19.3% for fast strain-encoded imaging (fSENC) and -15.1% for feature tracking (FT) to differentiate healthy individuals from those with heart failure.
  • Both techniques effectively identify heart failure with consistent results, and a conversion factor was established to translate LV-GLS between fSENC and FT, suggesting a simplified threshold of -15% for FT
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Motivation: 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.

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Background: 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.

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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.

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BACKGROUNDPatients 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.

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Age 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.

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Cardiovascular 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.

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Age 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.

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  • - The NIAID organized a workshop focusing on the use of various omics approaches (like genomics, transcriptomics, and microbiomics) to study asthma and allergic diseases, bringing together experts from different fields.
  • - Participants discussed the current trends, challenges, and emerging strategies in asthma and allergy research, emphasizing the need for integrated and rigorous analytic frameworks.
  • - The workshop highlighted the importance of cross-disciplinary collaboration to enhance understanding and improve care for asthma and allergic conditions.
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Tau 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.

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  • Cardiac magnetic resonance (CMR) is really important for doctors to check heart problems and predict risks for patients.
  • The study looked at a specific type of MRI called Strain-encoded MR (SENC) to see how well it can predict serious heart issues.
  • It found that SENC can help identify patients at risk for major heart events, even in people who don’t show symptoms, and it can accurately predict outcomes like death or heart attacks.
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Post-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.

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