Effects of time-of-day on the noradrenaline, adrenaline, cortisol and blood lipidome response to an ice bath.

While the effect of time-of-day (morning versus evening) on hormones, lipids and lipolysis has been studied in relation to meals and exercise, there are no studies that have investigated the effects of time-of-day on ice bath induced hormone and lipidome responses. In this crossover-designed study, a group of six women and six men, 26 ± 5 years old, 176 ± 7 cm tall, weighing 75 ± 10 kg, and a BMI of 23 ± 2 kg/mhad an ice bath (8-12 °C for 5 min) both in the morning and evening on separate days. Absence from intense physical exercise, nutrient intake and meal order was standardized in the 24 h prior the ice baths to account for confounders such as diet or exercise.

PTMNavigator: interactive visualization of differentially regulated post-translational modifications in cellular signaling pathways.

Post-translational modifications (PTMs) play pivotal roles in regulating cellular signaling, fine-tuning protein function, and orchestrating complex biological processes. Despite their importance, the lack of comprehensive tools for studying PTMs from a pathway-centric perspective has limited our ability to understand how PTMs modulate cellular pathways on a molecular level. Here, we present PTMNavigator, a tool integrated into the ProteomicsDB platform that offers an interactive interface for researchers to overlay experimental PTM data with pathway diagrams.

Predicting cell morphological responses to perturbations using generative modeling.

Advancements in high-throughput screenings enable the exploration of rich phenotypic readouts through high-content microscopy, expediting the development of phenotype-based drug discovery. However, analyzing large and complex high-content imaging screenings remains challenging due to incomplete sampling of perturbations and the presence of technical variations between experiments. To tackle these shortcomings, we present IMage Perturbation Autoencoder (IMPA), a generative style-transfer model predicting morphological changes of perturbations across genetic and chemical interventions.

Fracture load of feldspar ceramic crowns: effects of surface treatments and aging.

Objectives: To compare the impact of intaglio surface treatments - airborne particle abrasion and hydrofluoric acid (HF) etching - of feldspar ceramic (FEL) crowns on the fracture load (FL) and to investigate the effects of abutment materials and artificial aging. The aim was to assess whether etching could be replaced by an alternative surface roughening method.

Materials And Methods: FEL crowns had their intaglio surfaces either abraded (25 µm AlO, 0.

GOLD grade-specific characterization of COPD in the COSYCONET multi-center trial: comparison of semiquantitative MRI and quantitative CT.

Objectives: We hypothesized that semiquantitative visual scoring of lung MRI is suitable for GOLD-grade specific characterization of parenchymal and airway disease in COPD and that MRI scores correlate with quantitative CT (QCT) and pulmonary function test (PFT) parameters.

Methods: Five hundred ninety-eight subjects from the COSYCONET study (median age = 67 (60-72)) at risk for COPD or with GOLD1-4 underwent PFT, same-day paired inspiratory/expiratory CT, and structural and contrast-enhanced MRI. QCT assessed total lung volume (TLV), emphysema, and air trapping by parametric response mapping (PRM, PRM) and airway disease by wall percentage (WP).

Society for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing.

Objectives: Multiplex immunohistochemistry and immunofluorescence (mIHC/IF) are emerging technologies that can be used to help define complex immunophenotypes in tissue, quantify immune cell subsets, and assess the spatial arrangement of marker expression. mIHC/IF assays require concerted efforts to optimize and validate the multiplex staining protocols prior to their application on slides. The best practice guidelines for staining and validation of mIHC/IF assays across platforms were previously published by this task force.

Molecular insights into myelomeningocele via proteomic analysis of amniotic fluid.

Despite numerous studies on fetal therapy for myelomeningoceles (MMC), the pathophysiology of this malformation remains poorly understood. This study aimed to analyze the biochemical profile and proteome of amniotic fluid (AF) supernatants from MMC fetuses to explore the prenatal pathophysiology. Biochemical analysis of 61 AF samples from MMC fetuses was compared with 45 healthy fetuses' samples.

Precursors of exhausted T cells are preemptively formed in acute infection.

T cell exhaustion limits effector T cell function in chronic infection and tumors. The development of these hypofunctional T cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T cell populations in the early phase of acute infections.

Training and validating a treatment recommender with partial verification evidence.

Background: Current clinical decision support systems (DSS) are trained and validated on observational data from the clinic in which the DSS is going to be applied. This is problematic for treatments that have already been validated in a randomized clinical trial (RCT), but have not yet been introduced in any clinic. In this work, we report on a method for training and validating the DSS core before introduction to a clinic, using the RCT data themselves.

Linear Plasmids in Micrococcus: Insights Into a Common Ancestor and Transfer by Conjugation.

Actinobacteria have frequently been reported in the Andean Puna, including strains of the genus Micrococcus. These strains demonstrate resistance to high levels of UV radiation, arsenic, and multiple antibiotics, and possess large linear plasmids. A comparative analysis of the sequences and putative functions of these plasmids was conducted.

CO and Temperature Induced Switching of a Flexible Metal-Organic Framework with Surface-Mounted Nanoparticles.

Within the material family of metal-organic frameworks (MOFs) the subclass of flexible MOFs (flexMOFs) has attracted great attention, showing structural flexibility as a response to external stimuli such as guest adsorption, temperature, and pressure. Hybrid composites like nanoparticle (NP) loaded flexible MOFs, which stand to potentially combine advantageous properties of both are yet largely unexplored. Here the synthesis of flexMOFs with surface mounted nanoparticles, e.

Noninvasive blood-brain barrier integrity mapping in patients with high-grade glioma and metastasis by multi-echo time-encoded arterial spin labeling.

Purpose: In brain tumors, disruption of the blood-brain barrier (BBB) indicates malignancy. Clinical assessment is qualitative; quantitative evaluation is feasible using the K leakage parameter from dynamic susceptibility contrast MRI. However, contrast agent-based techniques are limited in patients with renal dysfunction and insensitive to subtle impairments.

Transcriptionally downregulated GABAergic genes associated with synaptic density network dysfunction in temporal lobe epilepsy.

Purpose: Temporal lobe epilepsy (TLE) is a brain network disorder closely associated with synaptic loss and has a genetic basis. However, the in vivo whole-brain synaptic changes at the network-level and the underlying gene expression patterns in patients with TLE remain unclear.

Methods: In this study, we utilized a positron emission tomography with the synaptic vesicle glycoprotein 2 A radioligand [F]SynVesT-1 cohort and two independent transcriptome datasets to investigate the topological properties of the synaptic density similarity network (SDSN) in TLE and its correlation with significantly dysregulated risk genes.

Are oligodendrocytes bystanders or drivers of Parkinson's disease pathology?

The major pathological feature of Parkinson 's disease (PD), the second most common neurodegenerative disease and most common movement disorder, is the predominant degeneration of dopaminergic neurons in the substantia nigra, a part of the midbrain. Despite decades of research, the molecular mechanisms of the origin of the disease remain unknown. While the disease was initially viewed as a purely neuronal disorder, results from single-cell transcriptomics have suggested that oligodendrocytes may play an important role in the early stages of Parkinson's.

Environmental enrichment is associated with favorable memory-related functional brain activity patterns in older adults.

Background: In humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13-30 years) and midlife (30-65 years) is associated with better preserved memory-related brain activity patterns in older age.

Methods: In total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated.

C-X-C motif chemokine receptor 4-directed PET signal in the arterial tree is not consistently linked to calcified plaque burden and cardiovascular risk.

To establish the extent, distribution and frequency of in-vivo vessel wall [Ga]Ga-PentixaFor uptake and to determine its relationship with calcified atherosclerotic plaque burden (CAP) and cardiovascular risk factors (CVRF). 65 oncological patients undergoing [Ga]Ga-PentixaFor PET/CT were assessed. Radiotracer uptake (target-to-background ratio [TBR]) and CAP burden (including number of CAP sites, calcification circumference and thickness) in seven major vessel segments per patient were determined.

Intravitreal enzyme replacement therapy slows retinopathy in late infantile ceroid lipofuscinosis type 2.

Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the TPP1 gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.

Expression of vesiculation-related genes is associated with a tumor-promoting microenvironment: a pan-cancer analysis.

Background: Small extracellular vesicles (sEV) released by tumor cells (tumor-derived sEV; TEX) mediate intercellular communication between tumor and non-malignant cells and were shown to impact disease progression. This study investigates the relationship between the expression levels of the vesiculation-related genes linked to sEV production and the tumor microenvironment (TME).

Methods: Two independent gene sets were analyzed, both previously linked to sEV production in various non-malignant or malignant cells.

Clinical Outcomes According to the Extent of Atherosclerotic Disease in Female Patients Undergoing Transcatheter Aortic Valve Replacement: An Analysis From the WIN-TAVI Registry.

Background: Limited data exist on the impact of polyvascular disease (PolyVD) on clinical outcomes in female patients undergoing transcatheter aortic valve replacement (TAVR). We therefore sought to investigate clinical outcomes in women with versus without PolyVD undergoing TAVR.

Methods: Female participants from the multicentre Women's International Transcatheter Aortic Valve Implantation (WIN-TAVI) registry were categorized based on the presence or absence of PolyVD.

Evaluation of Glutathione T in the Human Brain Using J-Difference MRS at 3 T: Multicenter Multivendor Study.

The need to quantify brain glutathione (GSH) accurately by J-difference spectroscopy has stimulated assessment of the TE effects on GSH edited signals at the popular field strength 3 T. We performed multiple-TE J-difference MRS at two sites to evaluate the GSH T relaxation and TE dependence of the GSH signal resolution. Two 10-ms spectrally selective Gaussian editing RF pulses were implemented in 3 T MEGA-PRESS sequences at two sites having different vendors.

Real-World Prevalence, Incidence and Management of Systemic Lupus Erythematosus in Germany: A Retrospective Claims Data Analysis.

Introduction: This study evaluated the prevalence and incidence of systemic lupus erythematosus (SLE) in Germany and explored real-world data on sequence of therapy (SOT; sequence of drugs as prescribed in clinical practice).

Methods: This retrospective, observational, longitudinal cohort study using German claims data from the WIG2 GmbH Scientific Institute for Health Economics and Health System Research database (January 2011-December 2019), extrapolated to the statutory health insurance (SHI)-insured population, evaluated prevalence and incidence in an epidemiological analysis group and SLE treatment patterns in an incident cohort (subgroup ≥ 18 years of age with incident disease and ≥ 24-month follow-up post index date). Analyses were descriptive.

Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders.

Importance: As an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.

Objective: To determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.

Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.