Cardiac Damage in Patients Infected with Different SARS-CoV-2 Variants of Concern.

Coronavirus Disease 2019 causes significant morbidity, and different variants of concern (VOCs) can impact organ systems differently. We conducted a single-center retrospective cohort analysis comparing biomarkers and clinical outcomes in hospitalized patients infected with the wild-type or Alpha (wt/Alpha) VOC against patients infected with the Omicron VOC. We included 428 patients infected with the wt/Alpha VOC and 117 patients infected with the Omicron VOC.

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma.

Telomere maintenance in neuroblastoma is linked to poor outcome and caused by either telomerase reverse transcriptase (TERT) activation or through alternative lengthening of telomeres (ALT). In contrast to TERT activation, commonly caused by genomic rearrangements or MYCN amplification, ALT is less well understood. Alterations at the ATRX locus are key drivers of ALT but only present in ∼50% of ALT tumors.

Knockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice.

Glycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice.

Multidomain Protein-Urea Interactions: Differences in Binding Behavior Lead to Different Destabilization Tendencies for Monoclonal Antibodies.

We study the influence of urea on the stability of monoclonal antibodies (mAbs) using molecular dynamics (MD) simulations in combination with differential scanning fluorimetry (DSF). We show that a denaturing cosolute such as urea binds strongly to the protein, which can lead to denaturation and enhanced aggregation behavior at high temperatures. The interaction between protein and urea crucially depends on the surface properties of the individual mAb domains and therefore affects the general binding to the protein differently.

Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial.

Background: Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury.

Methods: In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.

Bedside-focused transthoracic echocardiography in acute atraumatic thoracic aortic syndrome: a systematic review and meta-analysis of diagnostic accuracy.

The objective of this review was to assess the diagnostic accuracy of bedside-focused transthoracic echocardiography (TTE) in acute atraumatic thoracic aortic syndrome in adults. We performed a systematic review and meta-analysis of publications that described the use of bedside-focused TTE on adults presenting to emergency care settings with suspected atraumatic thoracic aortic syndrome. Studies were identified using keyword and MeSH on relevant databases as well as grey literature, followed by abstract screening and study selection by two independent reviewers.

Effective and Successful Quantification of Leukemia-Specific Immune Cells in AML Patients' Blood or Culture, Focusing on Intracellular Cytokine and Degranulation Assays.

Novel (immune) therapies are needed to stabilize remissions or the disease in AML. Leukemia derived dendritic cells (DCleu) can be generated ex vivo from AML patients' blasts in whole blood using approved drugs (GM-CSF and PGE-1 (Kit M)). After T cell enriched, mixed lymphocyte culture (MLC) with Kit M pretreated (vs.

Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection.

Research into the molecular basis of disease trajectory and Long-COVID is important to get insights toward underlying pathophysiological processes. The objective of this study was to investigate inflammation-mediated changes of metabolism in patients with acute COVID-19 infection and throughout a one-year follow up period. The study enrolled 34 patients with moderate to severe COVID-19 infection admitted to the University Clinic of Innsbruck in early 2020.

The Radcliffe Wave is oscillating.

Our Sun lies within 300 parsecs of the 2.7-kiloparsecs-long sinusoidal chain of dense gas clouds known as the Radcliffe Wave. The structure's wave-like shape was discovered using three-dimensional dust mapping, but initial kinematic searches for oscillatory motion were inconclusive.

Impact of Urea on Monoclonal Antibodies: Multiple Destabilization and Aggregation Effects for Therapeutic Immunoglobulin G Proteins.

We performed nano differential scanning fluorimetry (nanoDSF) measurements of immunoglobulin G (IgG) in urea gradient solutions under thermal unfolding. Our results show that the denaturing effect of urea on individual IgG domains can be monitored via a linear mapping of thermal shift curves to the corresponding urea concentrations. Assignment of IgG domains to each thermal shift curve allows for a reliable differentiation of the underlying mechanisms.

Deep learning-based image analysis identifies a DAT-negative subpopulation of dopaminergic neurons in the lateral Substantia nigra.

Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously quantify cell numbers, and fluorescence signals within cellular compartments, derived from RNAscope or immunohistochemistry. We utilised DLAP to analyse subtypes of tyrosine hydroxylase (TH)-positive dopaminergic midbrain neurons in mouse and human brain-sections. These neurons modulate complex behaviour, and are differentially affected in Parkinson's and other diseases.

Comparison of methylation estimates obtained via MinION nanopore sequencing and sanger bisulfite sequencing in the TRPA1 promoter region.

Background: Bisulfite sequencing has long been considered the gold standard for measuring DNA methylation at single CpG resolution. However, in recent years several new approaches like nanopore sequencing have been developed due to hints for a partial error-proneness of bisulfite sequencing. Since these errors were shown to be sequence-specific, we aimed to verify the methylation data of a particular region of the TRPA1 promoter from our previous studies obtained by bisulfite sequencing.

Mutational topography reflects clinical neuroblastoma heterogeneity.

Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although clinical risk-defining genomic alterations exist in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography and mutational signatures derived from all variant classes, we identified co-occurring mutational footprints, which we termed mutational scenarios.

Sustainable approach to recover β-carotene and astaxanthin from Phaffia rhodozyma grown in a stirred-tank bioreactor under the influence of magnetic fields.

This study aimed to produce carotenoids by Phaffia rhodozyma in a stirred-tank bioreactor under the influence of magnetic fields (MF) and to evaluate a sustainable approach to recover them from the yeast biomass. MF application proved to be effective in increasing 8.6 and 22.

Establishing a nationwide pediatric heart transplantation program with mid-term results comparable to worldwide data - The Czech experience.

Background: Heart transplantation (HTx) is an established therapeutic option for children with end-stage heart failure. Comprehensive pediatric nationwide HTx program was introduced in 2014 in the Czech Republic. The aim of this study was to evaluate its mid-term characteristics and outcomes and to compare them with international data.

Itaconic Acid as a Comonomer in Betulin-Based Thermosets via Sequential and Bulk Preparation.

The inherent chemical functionalities of biobased monomers enable the production of renewably sourced polymers that further advance sustainable manufacturing. Itaconic acid (IA) is a nontoxic, commercially produced biobased monomer that can undergo both UV and thermal curing. Betulin is a biocompatible, structurally complex diol derived from birch tree bark that has been recently studied for materials with diverse applications.

Investigation of Inkjet-Printed Masks for Fast and Easy Photolithographic NIL Masters Manufacturing.

Modern optical systems often require small, optically effective structures that have to be manufactured both precisely and cost-effectively. One option to do this is using nanoimprint lithography (NIL), in which the optical structures are replicated as masters using a stamping process. It would also be advantageous to manufacture the master structures quickly and easily.

Outcome of Application of Cryopreserved Amniotic Membrane Grafts in the Treatment of Chronic Nonhealing Wounds of Different Origins in Polymorbid Patients: A Prospective Multicenter Study.

To compare the therapeutic efficacy of cryopreserved amniotic membrane (AM) grafts and standard of care (SOC) in treating nonhealing wounds (NHW) through a prospective multicenter clinical trial, 42 patients (76% polymorbid) with 54 nonhealing wounds of various etiologies (mainly venous) and an average baseline size of 20 cm were included. All patients were treated for at least 6 weeks in the center before they were involved in the study. In the SOC group, 29 patients (36 wounds) were treated.

Interaction Between Determinants Governing Urine Volume in Patients With ADPKD on Tolvaptan and its Impact on Quality of Life.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic cause of kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the first drug with proven disease-modifying activity. Long-term treatment adherence is crucial, but a considerable fraction of patients discontinue treatment, because of aquaretic side effects.

First Measurement of Hard Exclusive π^{-}Δ^{++} Electroproduction Beam-Spin Asymmetries off the Proton.

The polarized cross-section ratio σ_{LT^{'}}/σ_{0} from hard exclusive π^{-}Δ^{++} electroproduction off an unpolarized hydrogen target has been extracted based on beam-spin asymmetry measurements using a 10.2  GeV/10.6  GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab.

Quantification of Analgesic and Anti-Inflammatory Lipid Mediators in Long-Term Cryopreserved and Freeze-Dried Preserved Human Amniotic Membrane.

The aim of this study was to compare concentrations of endogenous N-acylethanolamine (NAE) lipid mediators-palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA)-in fresh, decontaminated, cryopreserved, and freeze-dried amniotic membrane (AM) allografts, thereby determining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPAR-α receptor.