Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.

Predicting T cell receptor functionality against mutant epitopes.

Cancer cells and pathogens can evade T cell receptors (TCRs) via mutations in immunogenic epitopes. TCR cross-reactivity (i.e.

Carbon and oxygen isotopes in mummified wood reveal warmer and wetter winters in the Siberian Arctic 3000 years ago.

Paleoclimate reconstructions from the Holocene are important for defining baseline conditions in order to interpret and contextualize the effects of modern climate change. Such records are particularly lacking for Siberia, a region that represents ~ 50% of the Arctic. In addition, the majority of proxy-based paleoclimate reconstructions for the Holocene represent mean annual conditions, and few quantify winter temperature, which is particularly important for predicting the effects of global warming in Arctic environments.

Quality of life after immune suppressive therapy in aplastic anemia.

Acquired aplastic anemia (AA) is a rare form of immune-mediated bone marrow failure, which can result in life-threatening infections or bleeding if left untreated. Treatment consists of either immune suppressive therapy (IST) or allogeneic stem cell transplantation (alloHSCT). While considerable research has been published regarding survival, response rate and toxicity of both treatments, knowledge on the impact on quality of life (QoL) is scarce.

Analysis of Variation in the Origin of the Obturator Artery in Midwestern American Donor Bodies.

The obturator artery (OA) is typically a branch of the anterior division of the internal iliac artery. However, an aberrant obturator artery origin may lead to clinical complications. Because of its location in the pelvic cavity, the OA is at high risk of injury or laceration during a variety of pelvic surgeries.

COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.

Introduction: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.

Methods: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4).

Guideline for the management of myasthenic syndromes.

Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature.

Mitogenomic analysis of a late Pleistocene jaguar from North America.

The jaguar (Panthera onca) is the largest living cat species native to the Americas and one of few large American carnivorans to have survived into the Holocene. However, the extent to which jaguar diversity declined during the end-Pleistocene extinction event remains unclear. For example, Pleistocene jaguar fossils from North America are notably larger than the average extant jaguar, leading to hypotheses that jaguars from this continent represent a now-extinct subspecies (Panthera onca augusta) or species (Panthera augusta).

Colorimetric Sensor Reading and Illumination Correction via Multi-Task Deep-Learning.

Colorimetric sensors represent an accessible and sensitive nanotechnology for rapid and accessible measurement of a substance's properties (e.g., analyte concentration) via color changes.

Automated MRI Lung Segmentation and 3D Morphologic Features for Quantification of Neonatal Lung Disease.

Purpose: To analyze the performance of deep learning (DL) models for segmentation of the neonatal lung in MRI and investigate the use of automated MRI-based features for assessment of neonatal lung disease.

Materials And Methods: Quiet-breathing MRI was prospectively performed in two independent cohorts of preterm infants (median gestational age, 26.57 weeks; IQR, 25.

MRI pulmonary artery flow detects lung vascular pathology in preterms with lung disease.

Background: Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension. Our objectives were to associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification.

Methods: Preterms <32 weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3 T MRI in spontaneous sleep near term (AIRR (Attention to Infants at Respiratory Risks) study).

A 10-year experience in testicular tissue cryopreservation for boys under 18 years of age: What can be learned from 350 cases?

Background: A growing number of centers worldwide are preserving testicular tissue (TT) of young boys at risk of fertility loss to preserve their fertility. Data in this regard are scarce and experience sharing is essential to the optimization of the process.

Objectives: This report of our 10-year activity of pediatric fertility preservation (FP) has the objective to (1) improve knowledge regarding the feasibility, acceptability, safety, and potential usefulness of the procedure; (2) analyze the impact of chemotherapy on spermatogonia in the cryopreserved TT.

Morphometric Analysis of Pyramidalis Muscle in Midwestern Americans: A Cadaveric Approach.

The pyramidalis muscle (PM) is an abdominal muscle with unclear function. The current study determined the presence of the PM in Midwestern American cadavers. Of 33 cadavers, 22 had bilateral PM (12 [54.

Brownian translation and rotation from the ballistic to the diffusive limit and derivation of the physical properties of dust agglomerates.

We analyzed the translational and rotational Brownian motion of aggregates of micrometer-sized silica spheres under microgravity conditions and in rarefied gas. The experimental data was collected in the form of high-speed recordings using a long-distance microscope as part of the ICAPS (Interactions in Cosmic and Atmospheric Particle Systems) experiment on board of the sounding rocket flight Texus-56. Our data analysis shows that the translational Brownian motion can be used to determine the mass and translational response time of each individual dust aggregate.

Early Emergence of Rumination has no Association with Performance on a Non-affective Inhibitory Control Task.

Rumination is a vulnerability for depression and potentially linked to inhibitory control weaknesses. We aimed to replicate the association observed in adults between inhibitory control and rumination in adolescents, and to examine putative moderating roles of childhood maltreatment and perceived family cohesion in an adolescent sample at risk for depression due to familial/personal history. Ninety adolescents aged 11-17 (M = 14.

Spermatozoa isolation with Felix™ outperforms conventional density gradient centrifugation preparation in selecting cells with low DNA damage.

Background: The optimization of spermatozoa preparation techniques in order to obtain cell fractions enriched with structurally and functionally "superior" spermatozoa is a key objective of the assisted reproduction industry.

Objectives: The purpose of this study was to evaluate a recent development of an electrophoretic spermatozoa separation device (Felix™, Memphasys Ltd, Sydney, Australia) and to compare its performance with conventional spermatozoa preparation by density gradient centrifugation (DGC). Particular attention was paid to the evaluation of sperm DNA/nuclear integrity.

Effects of Bacteriophages on IRAK3 Knockdown/Knockout THP-1 Monocyte Cell Lines.

Bacterial sepsis characterised by an immunosuppressive and cytokine storm state is a challenge to treat clinically. While conventional antibiotics have been associated with exacerbating the cytokine storm, the role that bacteriophages may play in immune modulation of sepsis remains unclear. Bacteriophages are bacterial viruses that have the capacity to lyse specific bacteria and hence provide a natural alternative to antibiotics.

Magnetic resonance imaging-based scoring of the diseased lung in the preterm infant with bronchopulmonary dysplasia: UNiforme Scoring of the disEAsed Lung in BPD (UNSEAL BPD).

Neonatal chronic lung disease lacks standardized assessment of lung structural changes. We addressed this clinical need by the development of a novel scoring system [UNSEAL BPD (UNiforme Scoring of the disEAsed Lung in BPD)] using T2-weighted single-shot fast-spin-echo sequences from 3 T MRI in very premature infants with and without bronchopulmonary dysplasia (BPD). Quantification of interstitial and airway remodeling, emphysematous changes, and ventilation inhomogeneity was achieved by consensus scoring on a five-point Likert scale.

Proteomics reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients.

SARS-CoV-2 remains an acute threat to human health, endangering hospital capacities worldwide. Previous studies have aimed at informing pathophysiologic understanding and identification of disease indicators for risk assessment, monitoring, and therapeutic guidance. While findings start to emerge in the general population, observations in high-risk patients with complex pre-existing conditions are limited.

Position-specific carbon isotope analysis of serine by gas chromatography/Orbitrap mass spectrometry, and an application to plant metabolism.

Rationale: Position-specific C/ C ratios within amino acids remain largely unexplored in environmental samples due to methodological limitations. We hypothesized that natural-abundance isotope patterns in serine may serve as a proxy for plant metabolic fluxes including photorespiration. Here we describe an Orbitrap method optimized for the position-specific carbon isotope analysis of serine to test our hypothesis and discuss the generalizability of this method to other amino acids.

Increased sensitivity of insula to supraliminal faces in adults with histories of mood disorders and self-injury.

Background: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms.