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.

A Cross-Sectional Study: Systematic Quantification of Chemerin in Human Cerebrospinal Fluid.

Background: Dysregulation of adipokines is considered a key mechanism of chronic inflammation in metabolic syndrome. Some adipokines affect food intake by crossing the blood/brain barrier. The adipokine chemerin is associated with metabolic syndrome, cardiovascular diseases and immune response.

SGLT2 inhibition improves coronary flow velocity reserve and contractility: role of glucagon signaling.

Background: SGLT2 inhibitors, a T2DM medication to lower blood glucose, markedly improve cardiovascular outcomes but the underlying mechanism(s) are not fully understood. SGLT2i's produce a unique metabolic pattern by lowering blood glucose without increasing insulin while increasing ketone body and glucagon levels and reducing body weight. We tested if glucagon signaling contributes to SGLT2i induced improvement in CV function.

Implications of TRPM3 and TRPM8 for sensory neuron sensitisation.

Sensory neurons serve to receive and transmit a wide range of information about the conditions of the world around us as well as the external and internal state of our body. Sensitisation of these nerve cells, i.e.

Depolarization of mouse DRG neurons by GABA does not translate into acute pain or hyperalgesia in healthy human volunteers.

The majority of somatosensory DRG neurons express GABAA receptors (GABAAR) and depolarise in response to its activation based on the high intracellular chloride concentration maintained by the Na-K-Cl cotransporter type 1 (NKCC1). The translation of this response to peripheral nerve terminals in people is so far unclear. We show here that GABA (EC50 = 16.

Relation of life sciences students' metacognitive monitoring to neural activity during biology error detection.

Metacognitive calibration-the capacity to accurately self-assess one's performance-forms the basis for error detection and self-monitoring and is a potential catalyst for conceptual change. Limited brain imaging research on authentic learning tasks implicates the lateral prefrontal and anterior cingulate brain regions in expert scientific reasoning. This study aimed to determine how variation in undergraduate life sciences students' metacognitive calibration relates to their brain activity when evaluating the accuracy of biological models.

Isolation and identification of microplastics in infant formulas - A potential health risk for children.

Microplastics (MPs) are plastic particles between 0.1 and 5,000 µm in size that can contaminate food. Unfortunately, to date, little attention has been paid to analyzing the presence of such particles in baby foods.

Recruitment and retention of American Indian youth and caregivers in a culturally adapted prevention program.

This article seeks to understand to what extent cultural engagement and substance use risk factors influence families' decisions to participate, and ultimately complete, a culturally grounded substance use prevention program. Using data from a 14-week culturally oriented family-based substance use prevention program, we examine predictors of successful recruitment and retention of American Indian youth and their caregivers. Guided by the theoretical model for developing culturally specific preventions, the community-based approach to recruitment resulted in 85.

Non-covalent dyes in microscale thermophoresis for studying RNA ligand interactions and modifications.

Microscale Thermophoresis (MST) is a powerful biophysical technique that measures the mobility of biomolecules in response to a temperature gradient, making it useful for investigating the interactions between biological molecules. This study presents a novel methodology for studying RNA-containing samples using non-covalent nucleic acid-sensitive dyes in MST. This "mix-and-measure" protocol uses non-covalent dyes, such as those from the Syto or Sybr series, which lead to the statistical binding of one fluorophore per RNA oligo showing key advantages over traditional covalent labelling approaches.

A conceptual study on the relationship between daily stressors, stressful life events, and mental health in refugees using network analysis.

Introduction: There is growing recognition that daily stressors, such as social and material deficiencies, can be highly detrimental to the mental health of refugees. These stressors are in addition to stressful life events, which have been widely studied in the context of migration and forced displacement. Despite increasing evidence for an ecological model, there is still no consensus regarding the conceptualization of these highly influential factors.

"In a Religious Celebration"? The Religious Defense of LGBT Rights in U.S. Federal Courts.

This article advances scholarship on the relationship between sexuality, religion, and the law within the United States by analyzing case summaries and court opinions of the federal appellate cases decided between 1990 and 2020 that involve a religion-based claim being used to advance or defend gay and lesbian rights. Contrary to dominant public narratives that position religion uniformly in opposition to progressive sexual values, these cases show how Americans' religious beliefs and practices include diverse sexual identities. We find that the courts' reactions to such cases, however, illustrate the tension within legal discourse and hesitancy for the courts to equate religious and moral values with affirming LGBT identities, people, and rights.

Coping strategies of unaccompanied refugee minors shortly after arrival in Belgium.

Unaccompanied refugee minors (URMs) are a group in an especially vulnerable situation with heightened psychological suffering due to both stressful life events and current daily stressors. Research has shown that certain coping strategies such as avoidance can be adaptive in the face of ongoing stress. We conceptualize social support as an essential coping resource that these strategies tap into.

Lanthanide ions (Eu, Er, Pr) as luminescence and charge carrier centers in SrTiO.

A series of strontium orthotitanate (SrTiO) samples doped with 2% of a mole of europium, praseodymium, and erbium were obtained using the solid-state synthesis method. The X-ray diffraction (XRD) technique confirms the phase purity of all samples and the lack of the influence of dopants at a given concentration on the structure of materials. The optical properties indicate, in the case of SrTiO:Eu, two independent emission (PL) and excitation (PLE) spectra attributed to the Eu ions at sites with different symmetries: low - excited at 360 nm and high - excited at 325 nm, while, for SrTiO:Er and SrTiO:Pr, the emission spectra do not depend on the excitation wavelength.

External validation of a prediction model for timely implementation of innovations in radiotherapy.

Background And Purpose: The aim of this study was to externally validate a model that predicts timely innovation implementation, which can support radiotherapy professionals to be more successful in innovation implementation.

Materials And Methods: A multivariate prediction model was built based on the TRIPOD (Transparent Reporting of a multivariate prediction model for Individual Prognosis Or Diagnosis) criteria for a type 4 study (1). The previously built internally validated model had an AUC of 0.

Responses of Bunias orientalis to Short-term Fungal Infection and Insect Herbivory are Independent of Nutrient Supply.

Plants have to allocate their resources in both growth and defense under different environmental challenges. Several plant species have become invasive particularly in disturbed fertile habitats, which may influence their resource allocation. We studied the effects of nitrate fertilization (low versus high) on various plant responses towards a pathogenic fungus, Alternaria brassicae, and a herbivorous insect species, Mamestra brassicae, in a population of Bunias orientalis, which is invasive in parts of central Europe.

The impact of daily stressors on unaccompanied young refugees' mental health: A longitudinal study.

Previous research has shown the drastic impact of daily stressors on the mental health of unaccompanied young refugees (UYRs). This longitudinal study contributes to existing literature by distinguishing different kinds of daily stressors and examining their impact over time, in relation to stressful life events, legal status, and contact with family. We recruited = 189 UYRs from diverse backgrounds in Greece, Italy, and Belgium, and conducted two additional waves of interviews, accompanying them for approximately 2 years on their migratory and settlement trajectories throughout Europe.

Bradykinin-Induced Sensitization of Transient Receptor Potential Channel Melastatin 3 Calcium Responses in Mouse Nociceptive Neurons.

TRPM3 is a calcium-permeable cation channel expressed in a range of sensory neurons that can be activated by heat and the endogenous steroid pregnenolone sulfate (PS). During inflammation, the expression and function of TRPM3 are both augmented in somatosensory nociceptors. However, in isolated dorsal root ganglion (DRG) neurons application of inflammatory mediators like prostaglandins and bradykinin (BK) inhibit TRPM3.

Traumatic events, daily stressors and posttraumatic stress in unaccompanied young refugees during their flight: a longitudinal cross-country study.

Background: Unaccompanied young refugees constitute an especially vulnerable population, reporting high rates of trauma and mental health problems. There is a significant gap in the literature on trauma and posttraumatic stress symptoms (PTSS) in unaccompanied young refugees who are still on the move and live in precarious circumstances such as refugee camps. This study therefore aimed to contribute to this gap by investigating pre- and peri-migration (potentially) traumatic experiences of unaccompanied young refugees; longitudinal trajectories of trauma, daily stressors and PTSS; and the impact of gender, trauma, and daily stressors on PTSS over time.

Unraveling the Metabolic Derangements Occurring in Non-infarcted Areas of Pig Hearts With Chronic Heart Failure.

After myocardial infarction (MI), the non-infarcted left ventricle (LV) ensures appropriate contractile function of the heart. Metabolic disturbance in this region greatly exacerbates post-MI heart failure (HF) pathology. This study aimed to provide a comprehensive understanding of the metabolic derangements occurring in the non-infarcted LV that could trigger cardiovascular deterioration.

Uro-oncology in the era of social distancing: the principles of patient-centered online consultations during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic poses significant challenges to healthcare facilities and as per social distancing measures, many consultations are now being carried out via means of telemedicine. As some urologists may not be skilled with remote consultations, there is a need for recommendations on patient-centered online medical counseling.

Material And Methods: We have identified eight areas of excellence and defined the principles based on our experience.

The structural basis for an on-off switch controlling Gβγ-mediated inhibition of TRPM3 channels.

TRPM3 channels play important roles in the detection of noxious heat and in inflammatory thermal hyperalgesia. The activity of these ion channels in somatosensory neurons is tightly regulated by µ-opioid receptors through the signaling of Gβγ proteins, thereby reducing TRPM3-mediated pain. We show here that Gβγ directly binds to a domain of 10 amino acids in TRPM3 and solve a cocrystal structure of this domain together with Gβγ.

Diagnostic Laparoscopy and Abdominal Cytology Reliably Detect Peritoneal Metastases in Patients with Urachal Adenocarcinoma.

Background: Urachal adenocarcinoma (UrAC) is a rare malignancy that can cause peritoneal metastases (PM). Analogous to other enteric malignancies, selected patients with limited PM of UrAC can be treated by cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objective: The aim of this study was to address the value of diagnostic laparoscopy (DLS) and abdominal cytology (ACyt) for the detection and evaluation of the extent of PM in patients with UrAC.

Soft X-ray nanoscale imaging using a sub-pixel resolution charge coupled device (CCD) camera.

A sub-pixel 16 bit charge coupled device camera featuring superresolution for the soft X-ray regime is presented. Superresolution images (SRIs) are reconstructed from a set of 4 × 4 individual low-resolution images that are recorded for different sub-pixel shifts of the detector. SRIs have a 1.

Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases of urachal cancer.

Introduction: Urachal adenocarcinoma (UrAC) is a rare malignancy arising from persistent urachal remnants, which can cause peritoneal metastases (PM). Currently, patients with this stage UrAC are considered beyond cure. Our objective is to report long-term oncological outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with PM of urachal adenocarcinoma (UrAC).